Koilocyte
"Shrunken raisin" seen in HPV infection.
Transformation of bacteria
1. Cell lysis & release of DNA fragments.2. Uptake by naturally competent bacteria3. Integration into host genome.
Pulmonary hypertension due to hypertensive heart disease
1.Increased diastolic filling pressure. 2. increased Lt atrial pressure. 3. Pulm venous congestion. 4. increased pulm arterial pressure. 5. vasoconstriction. 6. Intimal thickening & medial hypertrophy.
21/11/17-hydroxylase deficiency
17= ambiguous genitalia in males21= ambiguous gen. in females.
heparin mechanism of action- which is most effective in inactivating thrombin? Enoxaparin (LMWH), Fondaparinux or Unfractioned Heparin?
A. Unfractioned hep. Unfractioned & LMWH can bind to antithrombin to increase its activity against Xa. Only Unfractioned hep is able to bind to BOTH antithrombin & thrombin to inactivate thrombin. HAs better antithrombotic activity then LMWH.Fondaparinux is a synthetic pentasaccharide Xa inhibitor. It has none of reqd long saccharide units that bind to thrombin.
Traumatic brain injury. Arterial blood gases.
ABGs have a powerful effecton cerebral blood flow, PaCO2 is most imp regulator. A drop in PaCO2 due to hyperventilation causes vasoconstriction. The resulting reduction in cerebral blood volume leads to decreased ICP. Lowering PaCO2 reduces ICP in mechanically ventilated patients w cerebral edema.
ADH action in nephrons
ADH primarily acts on collecting ducts, increasing their permeability to water.In absence of ADH tubular fluid is most concentrated at junction bw descending & ascending limbs of loop of Henle & most dilute in the collecting ducts.
Paraventricular nuclei
ADH, CRH, oxytocin & TRH secretion
G protein-coupled receptors & their signal transducers
ADRENERGIC- a1 - Gq, a2 - Gi, B1 - Gs, B2 - GsCHOLINERGIC- M1 - Gq, M2 - Gi, M3 - GqDOPAMINERGIC - D1 - Gs, D2 - Gi
Aromatase Def.
AR disorder manifests early in embryonal life, w high androgen & low estrogen levels in FEMALE fetus. Maternal virilization commonly occurs in pregnancy due to transfer of excess androgens into maternal circulation. Affected girls have normal internal genitalia, & ambiguoug or male type external genitalia. At puberty impaired ovarian estrogen synthesis causes primary amenorrhea, osteoporosis, tall stature (low estrogen delays fusion of epiphyses). Men w/ aromatase def have tall stature & osteoporosis but no genital abnormalities.
PKU
AR disorder. Severe def. of Phenylalanine hydroxylase. It converts Phe to Tyr. Tyr becomes an ESSENTIAL amino acid in these patients as it cannot be synthesized for Phe.
alpha-glucosidase inhibitors
Acarbose, MiglitolMOA- reduces intestinal disaccharide absorptions/e- diarrhea, flatulence
Interferon gamma
Activates Th1 and supresses Th2 production. Activates macrophages (phagocytosis & killing)More MHC I & II expression.
TNF-alpha
Activates endothelium. Causes WBC recruitment, vascular leak. Secreted by macrophages. Causes cachexia in malignancy. Maintains granulomas in TB. IL-1, IL-6 & TNF alpha mediate sepsis.
Tongue - gustation
Ant 2/3 - Chorda tympani of CN VIIPost 1/3- CN IXPost area of tongue root & taste buds of larynx & upper esophagus - CN X
Oxygen induced hypercapnia in COPD
Administration of excessively high O2 concentrations in pts w/ COPD can lead to increased CO2 retention (o2 induced hypercapnia), resulting in confusion & depressed consciousness. This is due in part to reversal of hypoxic pulmonary voasoconstriction, which increases physiologic dead space as the poorly ventilated alveoli are perfused (ventilation-perfusion mismatch)
Pernicious Anemia
Affects layer B. Parietal cells are lost w/ marked lymphocytic & plasma cell infiltration. Parietal cells are oxyntic (palepink), round, plate like cells found in layer B, that secrete Gastric Acid & Intrinsic Factor.Layer A- simple columnar epi cells that secrete mucus to protect gastric lining from acid.Layer C- Has a preponderence of small basophilic, granular chief cells that synthesize & secrete pepsinogen
Risk factors for cervical cancer
Alcohol causes breast ca, not cervical ca. Early Age of menarche effects breast & endom ca. Parity has no effect on cerv ca, nulliparity increases risk of endometrial ca.Fam history not a risk factor for cervical ca, also no genetic component to it.
Systolic heart failure
Alcoholic cardiomyopathy, doxorubicin therapy, selenium def & viral myocarditis can all lead to dilated cardiomyopathy w LV systolic dysfunction. SHF is typically characterized by increased LV volume & shifting the pressure-volume curve to right due to thinning of vent wall (increased compliance)
Tongue sensory innervation
Ant 2/3 - mandibular branch of CN V3Post 1/3 - CN IXPost area of tongue root - CN X
Extrapyramidal symptoms
Antipsychotic D2 receptor antagonism in nigrostriatal pathway can cause variety of reactions aka EPS. These can be condused w/ neuroleptic malignant syndrome. No altered sensorium & hyperthermia
Head bobbing
Aortic Regurgitation
Thyroid hormone inhibition
Blue circle at bottom lt hand corner is peripheral tissue.
# of Pterion (region where frontal, parietal, temporal, & sphenoid bones meet in skull)
Bone here is thin. # there risks acerating middle meningeal artery, and causing epidural hematoma. Mid meningeal artery is branch of Maxillary art. (one of terminal branches of ext carotid art) which enters skull at foramen spinosum & supplies dura mater & periosteum.
Knudson's 2-Hit hypothesis
Both copies of gene must be knocked out in order to promote malignancy.
RER & SER
RER is involved in transfer of proteins to the cell membrane & Extra Cellular space. Ribosomes attach to RER via the translocon, a protein complex containing ribophorins that bind the large 60S subunit.
Clinical diagnosis of Narcolepsy
Can be confirmed by low CSF levels of Hypocretin-1 or shortened REM sleep latency on polysomnography.
Dynein vs Kinesin
D= retrograde (downwards,towards nucleus)K= Anterograde (upwards)
Benedikt syndrome
Damage to CN 3, medial lemniscus, red nucleus. Oculomotor palsy. contralateral loss of proprioception/ vibration. Involuntary movements - ataxia & tremors
Clavicle origin or insertion
Deltoid - inferolateral aspectPec major - infermedial aspectSubclavius - inferolateral aspectSternohyoid - inferomedial aspectTrapezius - superolateral aspectSternocleidomastoid - superomedial aspect
Strongyloides stercoralis
Diagnosis made by finding rhabditiform larvae in stool, as eggs & adult parasites usually seen in intestinal biopsies. Rx= Ivermectin
in/direct inguinal hernia
Direct= acquired protrusion of abd contents through weakness of abd wall (hessselbach triangle). Don't pass through inguinal canal and located MEDIAl to inf epigastric vesselsIndirect= common in children. contents pass through deep inguinal ring are covered by spermatic fascia & locared LATERAL to in epigastric vessels.Can be due to failure to obliterate processus vaginalis. IF communication through peritoneal cavity & scrotum is large, it will allow for passage of abd organs. this causes indirect hernia. If only fluid leaks it is termed hydrocele.
Serotonin syndrome
Drugs assoc w 5HT syndrome = SSRIs, SNRIs, MAOIs, St. john's wort, kava kava, tryptophan, cocaine, amphetaminesTreat w/ Benzodiazepines, Cyproheptadine
EBV absorption
EBV envelope glycoprotein gp350 binds to CD21 (aka CR2), cellular receptor for C3d complement component. CD21 normally present on surface of B cells (CD-19 +ve cells) & nasopharyngeal epi cells. Exposure to a monoclonal anti-CD21 antibody could interfere w EBV attachment to B cells.CD4 w HIV gp120, CD21 w EBV gp350, & Erythrocyte P antigen w Parvovirus B19.
Cardiac Tamponade
Electrical alternans, JVP increased, BP decreased, Pulse ~120, pulsus paradoxus increased. Heart can't fill properly so, preload decreased, Hypotension & tachycardia ensues.
Types of Hb
Embryonic:- Gower 1= zeta2 epsilon2- Portland= zeta2 gamma2- Gower 2= Alpha2 epsilon2Fetal:- F= alpha2 gamma2Adult:-A= Alpha2 beta2-A2= alpha2 delta2a-thalassemia intermedia:- H= Beta4a-thalassemia major:- Barts= gamma 4
Meralgia Paresthetica
Entrapment of lateral femoral cutaneous nerve. It travels under the inguinal ligament. Provides sensory innervation to the anterolateral thigh. Most commonly occurs in obese or pregnant people or in those who wear tight garments around the hip.
SBP, DBP, HR, Contractility, & RBF changes
Epinephrine (α+β)= SBP-incr., DBP-decreased, HR-incr., Contractility-incr, RBF-decreasedPhenylephrine (α1)= S-incr., D-incr., HR-decr., Contr-no change, RBF-decr.Dopamine low dose (β1+D1)= S-incr., D-no change, HR-incr., Contr-increased, RBF-incr.
Inheritance of Down Syndrome
Most common casue if meiotic non disjunction ~95% cases.Unbalanced translocations occur in 2-3% cases.Mosaicism accounts for <2% cases.
Beta thalassemia
HbA2 is elevated
Pregnancy anti-caogulants
Increase in factors I, II, VII, VIII, IX & X. Decrease in Protein S leads to a hypercoagulable state.
Fanconi Anemia
Increased risk of AML
Renal clearance
Inulin & Mannitol- no tubular reabsorption or secretion (filtered amount = excreted amount) Inulin clearance used to calculate GFR.Glucose, Na & Urea- Net tubular reabsorption (excreted amount <<< filtered amount)PAH & Creatinine- net tubular secretion (excreted amount >>> filtered amount) PAH used to calculate RPF.
Nephrotic Syndrome pathogenesis
Involves increased permeability of glomerular capillary wall to plasma proteins (leads to massive urine loss)decreased plasma oncotic pressure of blood, fluid shift into interstitium- causing edema, increased aldosterone synthesis bc RAAS is activated, increased ADH release , with resulting Na & H2O retention. This exacerbates edema,To compensate liver synthesis of proteins increased including lipoproteins. Increases levels of cholesterol, TGs, VLDL, LDL, lipoprotein, & apoproteins. hyperlipidemia & subsequent lipiduria.
Multiple sclerosis autoimmune response
It is T cell & antibody mediated. targets oligodendrocytes & myelin in CNS. This decreases nerve conduction velocity.
Mosaicism Germline & Somatic
It is defined as the presence of multiple, genetically different cell likes within the body. Can result from several processes including chromosomal nondisjunction or a mutation during the 1st stages of embryonic development. Somatic mosaicism results in a mixture of normal and mutated somatic cells, often leading to a milder form of the disease.
Holiday heart syndrome
It is seen after excessive alcohol consumption. Can precipitate Atrial fibrillation.A.fib = absence of Pwaves, irregularly irregular rhythm w/ varying R-R intervals. Some may have irregular low amplitude fine fibrillatory waves (f waves) b/w QRS complexes, these reprsent chaotic atrial activation.
Erythema Infectiosum aka 5th disease aka Parvovirus B19
It's a single stranded DNA virus. 1-2 week ncubation period a nonspecific prodrome if followed by an erythematous rash on cheeks. Aka slapped cheek rash, spares nasolabial folds ad develops after initial symptoms have resolved. A lacy rash then follows spreading along trunk and extremeties. Rash may result from immune complex deposition, the timing which coincides with increasing levels of serum virus specific igM & IgG.B19 replicates in erythrocyte precursors in bone marrow. These cells express blood group P antigen aka globoside. Viral replication in nucleus leads to cell lysis.
PCOS
LH increased at ovary (increased Lh receptor expression) Estrogen increased chronically. May cause endometrial hyperplasia/ carcinoma.Insulin levels increased. Increased adrenal androgen production.
HSV reactivation involves, Dynein orKinesin?
Kinesin. It is a microtubule assoc motor protein that functions in anterograde transport of materials & organelles w/in cells. Reactivation of latent HSV requires anterograde transport of viral particles from neuronal cell bodies in sensory ganglia to skin & oral mucosa.
Kozak consensus sequence
Kozak consensus sequence occurs on Eukaryotic mRNA & is defined by the following sequence,- (gcc)gccRccAUGG - in which R is either adenine or guanine. This sequence helps initiate translation at methionine start codon (AUG)
Pressure tracings aortic stenosis
L- NormalR- ASPeak murmur intensity at point B
Leukocyte adhesion disorder
LAD type 1 is caused by CD18 absence. Inability to synthesize beta-2 integrins Mac-1 & LFA 1, affecting tight adhesion, crawling & transmigration. Clinical manifestations include recurrent skin infection w/out pus formation, delayed attachment of the umbilical cord, & poor wound healing. LAD2 is milder, no delay in seperation of umbilical cord & less severe & fewer inf. LAD 3 similar type 1, & causes severe, recurrent bac inf, delayed separation of umbilical cord & bleeding complications (due to affected beta-3 integrins on platelets)
Femoral nerve
Leg flexion at hip, leg extension at knee. involves iliopsoas & quadriceps
Blunt aortic injury
Like traumatic aortic rupture, commonly caused by motor vehicle collisions. Injury most commonly occurs at aortic isthmus, which is tethered by lig. arteriosum & relatively fixed & immobile compared to adjacent desc. aorta.
cephalosporin resistant organisms
Listeria, MRSA, Enterococci. bc of resistance to penicillin binding proteinsAtypical bac. (mycoplasma, chlamydia etc.) bc of lack of cell wall
Femoral head arteries
Medial circumflex artery & its branches provide majority blood supply to femoral head & neck. Injury to these vessls occurs due to displaced femoral neck # & can cause osteonecrosis of femoral head.
Parkinsons treatment issues
Long term rx of parkinsons w/ levodopa can be complicated by periodic & sometimes unpredictable fluctuations in motor function. On-Off phenomena is consequence of progressive NIGROSTRIATAL NEURODEGENERATION leading to decrease therapeutic window. In advanced Parkinsons motor fluctuations can occur independently of medication dosing and may become unpredictable.Drug holidays are not effective in preventing motor fluctuations.
Pathogenesis of PAH
Longstanding PAH leads to hypertrophy &/or dilation of Rt. ventricle (cor pulmonale). Pts typically have progressive dyspnea, exertional angina, or syncope. As PAH progresses signs of Rt heat failure may become prominent. Common cause of death in PAH is Rt heart failure w/ circulatory collapse & resp failure.
Major depressive disorder w psychotic features.
MDD w psychotic features. pt develops psychotic features during the depressive episode. Such as delusions & hallucinations. Diagnosis is differentiated from psychotic disorders in that psychotic symptoms are present only during episode of major depression. Rx= combination of antidepressants & antipsychotics or ECT.
Opioid Intoxication
MIosis, Bradycardia, hypotension, Tight chest pain. Decreased RR, decreased bowelsounds. These symptoms are seen bc of histamine release.
Classification of Multiple endocrine Neoplasia
MTC= medullary thyroid carcinoma
Fidaxomicin
Macrocyclic antibiotic (related to amcrolides). It inhibits sigma unit of RNA Polymerase, leading to protein synthesis impairment & cell death (bacteriocidial activity against C.diff) Oral admin, minimal systemic absorption, has high fecal conc. Narrow spectrum of activity w/ lesser effect on normal colonic flora. Used in patients w/ recurrent c.dif colitis and have increased risk kof recurrence.
IL-12 Receptor defeciency
Makes "naive" T helper cells unable to differentiate into Th1 subpopulation. W/out th1 cells the synthesis of IFN-gamma required for activation of macrophages does not occur. Activated macrophages are necessary for delayed hypersensitivity reactions and cytotoxicity against intracellular organisms, such as mycobacteria. Thus ppl w/ IL-12 receptor defeciency suffer severe mycobacterial infections. Admin IFN-gamma is indicated.
DCIS
Malignant clonal cell proliferation contained by surrounding ductal basement membrane. (Basal) Myoepithelial layer of duct is preserved & uninvolved
Confounding Bias
Matching is generally used in design stage of case control studies to control Confounding bias. Intial step in matching involves selecting variables that can be confounders eg: age, race etc. Cases & controls are then selected based on matching variables so that both groups have similar distribution in accordance w/ variables.
lifecycle of hepatitis B
Mature virion aka Dane particle. has both RNA & DNA dependent DNA polymerase activity. Mature capsid is partially ds circular DNA and contains reverse transcriptase.
Lateral nuclei
Mediates hunger, destruction leads to anorexia
H. influenzae most common infection?
Meningitis. The polyribosyl ribitol phosphate (PRP) capsule of Hib, serves as an imp virulence factor, facilitating invasion by evading mucosal immunity & inhibiting complement mediated killing & phagocytosis. This may be why Hib has predilection to meninges.
Sickle Cell Anemia
Missense mutation. Glutamic Acid to Valine substitution at position 6.
Trastuzumab
Monoclonal antibody used in management of pts w/ HER2+ breast ca. Binds to extracellular domain of HER2 and prevents activation of a transmembrane tyrosine kinase. This downregulates cellular proliferation and promotes apoptosis.
Atypical depression
Mood reactivity (main distinguishing factor), leaden paralysis, rejection hypersensitivity, reversed vegetative signs of increased sleep & apetite.
Dermatomyositis may occur as a paraneoplastic syndrome.
Most commonly assoc malignancies include ovarian, lung, colorectal, non-Hodgkins lymphoma. Symtpoms mau precede diagnosis of malignancy, but usually parallel to cancer.
Temporal bone #
Most commonly results in epidural hematoma. Caused by rupture/ tear of middle meningeal artery.
Chron's disease (NOD2 MUTATION)
NO@ (encodes an intracellular microbial receptor), resulting in decreased activity of NF-kB protein (proinflammatory transcription factor) w reduced cytokine production. This impairs innate barrier function of intestinal mucosa & allows intestinal microbes to induce an exaggerated response by adaptive immune system, resulting in chronic GI inflammation
adverse effects of some HIV antiretroviral medications
NRTI = lactic acidosis, lipodystrophy, hypersensitivity (abacavir), Pancreatitis (didanosine), Bone marrow suppression (zidovudine)NNRTI = rash (including SJS), heptotoxicity, neuropsych effects & teratogenicity (efavirenz)PI = Metabolic complications (lipodystrophy, dyslipidemia, insulin resistance), inhibition of CYP450Integrase inhibitor = myopathy
Atropine
No action on nicotinic receptors.
Maternal Parvovirus
Non enveloped ss DNA virus. Fetal infection leads to interruption of erythropoeisis, causing profound anemia & CHF. Fetal CHF causes pleaurl effusions. pericardial effusions, & ascites. Fetal autopsy represnts hydrops.
Neuroblastoma
Non rhythmic conjugate eye movements assoc w myoclonus describe opsoclonus-myoclonus syndrome. In young children its assoc w neuroblastoma. Most common extracranial childhood ca. It develops from neuroblasts located in medulla.Small round blue cell tumors. Neuritic process called neuropil is a pathognomonic feature. Neuron Specific Enolase, chromogranin, synaptophysin, S-100 stains are usually +ve. More than 90% ptshave elevated urine homovanilic acid &/or vanillylmandelic acid. N-MYC/MYCN present on Chr 2
Neuromuscular monitoring with train of four stimulation
Nondepolarizing NMJ blocker (eg:Vecuronium), when added competetive inhibition of post synaptic Ach receptors at motor endplate prevents some of these fibers from activating, decreasing strength of twitch. Train of Four(TOF) shows preogressive reduction as a result of less Ach being released w/ each subsequent impulse.Depolarizing blockers (eg: Succinylcholine) intially function ny preventing repolarization of motor endplate & show equal reduction of all 4 twitches during TOF stimulation (Phase 1 blockade). Responses remain equal bc the presynaptic Ach receptor stimulation helps to mobilize presynaptic Ach vesicles for release. Persistent or prolonged exposure to Succinylcholine results in eventual transition to Phase 2 blockade as Ach rceptors become desensitized & inactivated.
Candida albicans
Normal flora. Can appear as pseudohyphae of budding yeat on Pap smear.
Gallstone ileus
Not a true ileus. Caused by mech. obstr. caused when large gallstone (>2.5cm) erodes into the intestinal lumen through a cholecystoenteric fsitula. As it obstructs the lumen, it causes episodic symptoms. Eventually gallstone may rest in the ILEUM, it has smallest lumen of intestinal tract.Abd. radiographs reveal dilated bowel loops w air fluid levels. May also reveal air in biliary tree (pneumobilia) due to retrograde passage of intestinal gas through fistula.
anticoagulants mechanism of action
PT/ INR monitored for WarfarinaPTT for unfractioned heparin.
OCD vs OCPersonalityD
OCPD= involves lifelong pattern of insistense on control, orderliness, perfection & doesn't involve compulsions performed in response to intrusive obsessions.
Subclavian steal
Occurs due to severe stenosis of proximal subclavian artery, which leads to reversal in blood flow from contralateral vertebral artery to the ipsilateral vertebral arter. May have symptoms related to arm ischemia in affected extremity (exercise induced fatigue, ppain, paraesthesias) or vertebrobasilar insufficiency (dizziness, vertigo)
Phenotypic mixing v Reassortment.
PM- The first gen progeny contain nucleocapsid proteins from both parental virus & other virus. The 2nd gen progeny only contains parental proteins bc there is no change in underlying viral genomes (no genetic exchange).--purely superficialRA- Changes in genomic composition. There is exchange of whole genomic segments. Any 1st gen progeny genomic changes will also be present in future generations.---kind of like having mixed race kids.
Osteoclast differentiation
Osteoclasts originate from mononuclear phagocytic cell lineage & ultimately formed when several precursor cells fuse to create a multinucleated mature cell.2 most imp factors for diff. are --- M-CSF (macrophage colony stimulating factor), RANK-L. Are produced by osteoblasts & bone marrow stromal cells.TGF-beta decreases bone resorption by increasing osteoclastic apoptosis.
Osgood Schlatter disease
Overuse injury of 2dary ossification center (apophysis) of tibial tubercle. Very common cause of knee pain in young adolescent athletes after a recent growth spurt. OSD presents as pain & swelling at tibial tubercle, the insertion point of patellar ligament.
Oxygen-dissociation curves of hemoglobin & myoglobin
P50 of Hb is 26 mmHg while P50 of myoglobin is 1mm Hg. This indicates that myoglobin has a higher affinity for O2 than Hb.
renal tubular solute concentrations
PAH is primarily secreted into nephron by PCT but some is also freely filtered by glomerulus. PAH is not reabsorbed by any portion of nephron. Therefore tubular fluid conc. of PAH is lowest in bowmans space.
Classification of PAH
PAH primary- Idiopathic, HereditaryPulm. HTN (secondary)- Lt heart failure, Chronic lung disease &/or hypoxia. Chronic pulm. thromboembolism
A-a gradient calculation & interpretation
PAO2 - PaO2. Normally 10-15mmHg. Increased A-a gradient may occur in hypoxemia; causes include R-L shunting, V˙/Q˙mismatch, fibrosis(impairs diffusion)Normal A-a = high altitude, hypoventilation
mTOR pathway
PI3K/ Akt/ mTOR pathway is an intracellular signaling pathway important for anti-apoptosis, cellular proliferation & angiogenesis. Mutations in growth factor receptors, Akt, mTOR pr PTEN that enhance activity of this pathway contribute to cancer pathogenesis.mTOR inhibitors include Rapamycin (sirolimus)
Lung volumes and pulmonary vascular resistance
PVR is lowest at functional residual capacity. Increased lung volumes increase PVR due to longitudinal stretching of alveolar capillaries by expanding alveoli. Decreased lung volumes also increase PVR due to decreased radial traction from adjacent tissues on large extra alveolar vessels.
Cardiac AP blocking drugs & phases.
Phase 0/ Upstroke= Class I antiarrhythmics (Procainamide, Flecainide, Lidocaine)Phase 1/ Dip= Nothing significantPhase 2/ Plateau= Ca channel blockers (Verapamil, Diltiazem) are Class IV antiarryhthmicsPhase 3/ Downstroke= Class III antiarrhythmics (Amiodarone, Sotalol, Dofetilide)Phase 4= No antiarrhythmics affect. B-blockers & Ca channel blockers can slow diastolic depolarization.
Mechanisms of common antiseizure drugs
Phenytoin & carbamazepine - Blocks Na channelsValproic acid - Blocks Na channels & increases GABA levelsBZPs & Phenobarbital - Increase GABA-A actionLevetiracetam - Modulates GABA & Glutamate releaseEthosuximide - Blocks thalamic T-type Ca channels
Thiazolidinediones
Pioglitazone, RosiglitazoneMOA- activates transcription regulator PPAR-gamma, decreasing insulin resistances/e- fluid retention/ heart failure, weight gain
Parinaud syndrome
Post midbrain. Sup colliculus & pretectal area (Vertical gaze palsy - can't look up). Pseudo Argyll-robertson pupil. Often from pinealoma/ germinoma of pineal region. Can cause cerebral aqueduct obstr. (non-comm hydrocephalus, compression from pineal tumor)
Mitral Valve prolapse w/ mitral regurgitation.
Presence of mid-systolic click followed by a mid to late systolic murmur at cardiac apex, that disappears w/ squatting is indicative of MVP w/ mitral regurgitation.Primary MVP- most commonly a sporadic disorder & characterized by myxomatous degeneration, affecting MV leaflets & chordae tendinae.Secondary MVP- assoc w/ inherited connective tissue disorders. eg:Marfans, Ehlers-Danlos, Osteogenesis Imperfecta.
Primary & Secondary structure
Primary (amino acids) - linked by peptide bonds2ndary (alpha-helix & Beta sheet) - A-helix linked by Hydrogen bond bw every 4th amino acid. B sheet linked by H bonds bw all residues of antiparallel strands.Tertiary = many forces combined, including ionic bonds, hydrophobic interactions, Hydrogen bonds, disulfide bonds.
Protein Kinase A
Primary intracellular effector enzyme in G-protein/ Adenylate cyclase 2nd messenger system. Gluacgon acts through this pathway to stimulate Glycogen breakdown. Protein Kinase A activates glycogen phosphorylase via activation of glycogen phosphorylase kinase.
Renal blood flow
RPF = RBF x (1- Hct)
Proteinase / antiproteinase balance
Proteinases- Elastase, Cathepsin G, Matrix mettaloproteinasesAntiproteinases- a1-antitrypsin, a2-macroglobulin, TIMPs (tissue inhibitors of mettaloproteinases)Elastase is a neutral protease contained in macrophage lysosomes & azurophilic granules of neutrophils. Normally elastase release from macrophages & infiltrating neutrophils is balanced by serum & tissue protease inhibitors.
Urea cycle disorders. Treat by restricting intake of what?
Proteins must be restricted in diet. NOT PURINES.
Ureters blood supply.
Proximal ureter recieves blood supply from renal artery, whereas distal ureter is supplied by Superior vesical artery. Circulation to middle portions of ureter are variable and anastomotic.
Glioblastoma Multiforme
Pseudopalisading necrosis (foci of necrosis surrounded by tumorcells). New vessel formation. Small round cells, bizzare giant cells, large number of mitoses.
Zollinger ellison syndrome
Pt usually has high-normal gastrin levels that rise in response to Secretin admin. are suggestive of ZE syndrome.Secretin normally inhibits release of Gastrin from normal G cells & increases pancreatic HCO3. However secretin paradoxically stimulates gastrin release from gastrinomas due to abnormal adenylate cyclase activation.
Ataxia telangectesia
Pts have repeated sinopulmonary infections.
Manic Episode
Pts w 1 or more lifetime manic episodes are diagnosed w Bipolar I disorder.
Pelvic innervation
Pudendal N->S2-4 ->Function:Sensory:perineum, motor:urethral & anal sphinctersLat femoral cutaneous->L2-3 ->Sensory: ant & lat thighInf. gluteal-> L5-S2-> Motor:gluteus maximusGenitofemoral-> L1-2-> sensory: scrotu/labia majora, medial thighObturator-> L3-4-> sensory: medial thigh, motor:adductionIliohypogastric-> T12-L1-> Sensory:suprapubic
An/aerobic glycolysis
Pyruvate--->LActate requires Lactate Dehydrogenase (anaerobic)Pyr--->Acetyl CoA requires Pyr. dehydrogenase (aerobic)
Starling equation
Q.id 1354
Glycolysis in erythrocytes
RBCs use as major pathway bc they dont have mitochondria, so they can't use citric acid cycle. During Normal glycolysis ATP is generated when 1,3 BPG is converted to 3-phosphoglycerate by enzyme phosphoglycerate kinase. RBCs bypass this by using bisphosphoglycerate mutase, and enzyme that converts 1,3BPG to 2,3 BPG in a step that produces NO ATP. 2,3BPG decreases Hb affinity for O2. Therefore in presence of lower blood o2 concentratioons higher 2,3-BPG levels within RBCs enable increased o2delivery to peripheral tissues. 2,3-BPG is produced from 1,3-BPG by enzyme bisphosphoglycerate mutase, This reaction bypasses an ATP generating step of glycolysis causing no net ATP gain.
Fick principle
Rate of O2 consumption / (Arterial O2 content - Venous O2 content)
Temporality of different study designs
Red= pastYellow= presentFuture= Blue
Reassortment
Refers to changes in genomic composition that occur when host cells are co infected w 2 SEGMENTED viruses that exchange whole genome segments. This process can cause sudden alterations in surface antigens of viral progeny, as observed w highly mutagenic influenza virus.
lac Operon
Regulated by two distinct mechanisms: negatively by binding of the repressor protein to the operator locus and positively by cAMP-CAP binding upstream from the promoter region. Constitutive expression of the structural genes of the lac operon occurs with mutations that impair the binding of the repressor protein (Lac 1) to it's regulatory sequence in the operator region.works by 2 distinct mechanisms:-negatively binding of repressor protein to the operator locus-positively by cAMP-CAP binding upstream from promoter region.
Duration of action of common Benziodiazepines
Short (<6hrs) - Triazolam, oxazepam, midazolamIntermediate (6-24hrs) - Alprazolam, lorazepam, temazepamLong (>24hrs) - Diazepam, Chlordiazepoxide, Flurazepam
Small cell Ca of lung
Show neuroendocrine differentiation. Tumors stain for markers such as NCAM/neural cell adhesion molecule aka CD56, neuron specific enolase, chromogranin, & synaptophysin. Some small cell ca express neurofilaments.
Pyruvate dehydrogenase complex
Requires 5 cofactors- Thiamine (b1)- Lipoic Acid- Coenzyme A (B5)- FAD (B2)-NAD (B3)"Tender love & care for nancy"a-ketoglutarate dehydrogenase requires same co factors
Opioid intoxication
Resp rate is best predictor of intoxication & is also a frequent cause of mortality
Wright-Giemsa stain on microscopy.
Reticulocytes are immature RBCs that are slightly larger & bluer than mature RBC. Lacks cell nucleus, but retains basophilic, reticular (mesh like) network of residual rRNA. rRNA appears blue microscopically after Wright-Giemsa stain.
Prophylaxis for Neisseria meningitis
RifampinCiprofloxacin ( not routinely used in kids bc of concerns for conenctive tissue injury)IM ceftriaxoneSulfamethoxazole (not used anymore due to widespread resistance)
Drug treatment for TB- MOA
Rifampin- inhibition of bac DNA dependent RNA polymerase. s/e include GI side effects, rash, red orange body fluids, cytopenias.Isoniazid- inhibition of mycolic acid synthesis. s/e neurotoxicity (treat w/ B6), hepatotoxicity.Pyrazinamide- unclear moa. s/e hepatotoxicity, hyperuricemia.Ethambutol- inhibition of arabinosyl transferase. s/e optic neuropathy
Renal cell carcinoma
Rounded & polygonal cells w abundant clear cytoplasm. <--Most common histo finding for Clear cell carcinoma, most common type of RCC. Cytoplasm is clear due to high glycogen & lipid content of tumor. This is why it is gold-yellow on gross exam. nuclei can be eccentric or central in CCC.
Ascending colon cancer
Rt sided colon cancer tend to grow as large, bulky masses that protrude into the colonic lumen due to relatively large caliber of asc colon. These cancers are more likely to bleed & cause iron def anemia.
elastin structure
Rubber like properties of elastin are due to extensive cross linking bw elastin monomers, which is facilitated by lysl oxidase. lysl oxidase oxidatively deaminates some of lysine residues of tropoelastin facilitating the formation of Desmosine cross links bw neighbouring polypeptides. Elsatin os synthesized as a large polypeptide precursor (tropoelastin) composed of 700 mostly non polar amino acids (glycine, valine, alanine) Elastin also continues proline & lysine residues however in contrast to collagen few of these amino acids are hydroxylated.
Skin rashes
Rubella- Togavirus. German measles, rash on face & spreads to trunk & extremities. post auriculor lymphadenopathy more common than rubeola.Rubeola- Paramyxovirus. Measles
IFN-gamma
Secreted by NK cells & T cells in response to antigen or IL12 from macrophages, stimulates macrophages to kill phagocytosed pathogens. Inhibits differentiation of Th2 cells.Also activates NK cells to kill virus infected cells. Increases MHC expression & antigen presentation by all cells.From Th1 cells.
Supraoptic nuclei
Secretion of ADH & oxytocin
Lumbar spinal stenosis
Seein in pts over 60yo. Overtimeintervertebral disc degenretaes and begins to protruse, resulting corresponding loss in disc height. Leads to formation of facet joint in osteophytes & hypertrophy of LIGAMENTUM FLAVUM. Lower extremity pain, numbness/paraesthesia, weakness. Onset of pain w/ walking aka neurogenic claudication. Symptoms are posture dependent. Lumbar flexion (leaning forward, walking uphill) relieves pain.
Apoptosis of effector cells
Seen after resolution of immunologic reaction. Decreased IL-2 mediates this by, proliferating effector cells via intrinsic pathway.
Functional hypothalamic amenorrhea
Seen in anorexics, amenorrhea caused by hypothalamic suppression. Not primary ovarian failure.
Haptoglobin
Serum protein tgat binds to FREE Hb & promotes uptake by reticuloendothelial system. Levels decrease when significant quantity of Hb is rekeased into circulation (DIC)
SSRIs
Sexual dysfunction= decreased libido, decreased arousal, anorgasmia in woman, increased ejaculation latency in men. occurs in 50% pts.
Vitamin D in Renal failure
Sick kidney--->elevated phosphate--->decreased calcium from Plasma--->Hypocalcemia--->increased PTHSick kidney--->decreased 1,25-OH Vit D--->decreased calcium from gut--->Hypocalcemia--->increased PTH
Involuntary head bobbing
Sign of widened Pulse pressure.(Pulse pressure = peak systolic arterial pressure - enddiastolic arterial pressure)Most likely cause of repetetive widened pulse pressure together w/ unusually large LV stroke volumes & heart murmur is aortic regurg.
Coronary subclavian steal phenomenon
Similar to subclavian steal, bloodflow through IMA can reverse & steal flow from Coronary circulation during increased demand (eg; upper extremity exercise). However symptoms are typically related to coronary ischemia (eg; angina pectoris)
Medullary carcinoma of breast
Solid sheets of vesicular, pleomorphic, mitotically active cells w a significant lymphoplasmacytic infiltrate around & within tumor & a pushing, non infiltrating border.
Pupillary light reflex
The Optic(II) nerve is responsible for afferent limb of this reflex, the oculomotor (III) nerve is responsible for efferent limb.
Desmosomes (maculae adherentes)
Spotlike junctions that anchor adjacent cells together via keratin intermediate filament interactions. Autoantibodies against desmosomes in the striatum spinosum of skin cause pemphigus vulgaris.
Tumor stage v Grade
Stage is more imp. in determining prognosis than grade.
IL-2
Stimulates growth of helper, cytotoxic, & regulatory T cells, & NK cellsSecreted by all T cells
Baroreceptors
Stretch receptors (more fluid in vessels, more baroreceptors fire) For eg, a pt. in hypovolemi shock decrease baroreceptor firing rate. Activation of RAAS will result in increased vascular resistance (vasoconstriction) in order to maintain BPIn hypovolemia, decreased Atrial baroreceptor firing, increased systemic Vasc. resistance. increased Pulm. vasc. resistance.
Disaccharides
Sucrose, Lactose, Maltose
Nutrient deficiencies associated with malabsorption
Sudan III stain can quickly and easily identify unabsorbed fat & confirm malabsorption.
Insulin secretagogues
Sulfonylureas, Meglitinides.MOA- Increases insulin secretion by inhibiting B-cell Potassium ATP channelss/e- hypoglycemia & weight gain
Erythema multiforme
Target lesions. Seen in severe cases can affect oral mucosa & tongue. Target lesions. It is predominated by Cytotoxic CD8+ lymphocytes. assoc w HSV & mycoplasma, and maybe due to immune response against antigens deposited in skin. Also can caused by sulfa drugs, cancer, collagen vasc diseases.DO NOT confuse w dermatitis herpetiforms or HIV inf. (this is well circumscribed & involves trunk, face & palms and soles)
Differences bw th1 & th2 cell
Th1- cell mediated. Activates macrophages and cytotoxic T cells. Secreted substances- IL2, IFN gamma, lymphotoxin-beta. Results in cytotoxicity, delayed hypersensitivityTh2- Humoral (ab mediated) immunity. Activates B cells, promote class switching. secretes- IL4, 5, 10 &13. Results in secretion of antibodies.
A-a gradient
The Alveolar-arterial gradient (A-aO2, or A-a gradient), is a measure of the difference between the alveolar concentration (A) of oxygen and the arterial (a) concentration of oxygen. It is used in diagnosing the source of hypoxemia. A normal A-a gradient for a young adult non-smoker breathing air, is between 5-10 mmHg. Normally, the A-a gradient increases with age. For every decade a person has lived, their A-a gradient is expected to increase by 1 mmHg. An abnormally increased A-a gradient suggests a defect in diffusion, V/Q (ventilation/perfusion ratio) mismatch, or right-to-left shunt.
Long thoracic nerve injury
damage to serratus ant. muscle. winging of scapula.
Congenital TORCH infections
read up
Pulmonary embolism
westermark= area of lucency due to reduced perfusionorHamptons hump= wedge shaped opacity adjacent to pleura
Monocyte-macrophage cell lineage
express CD14. Caseating granulomas of TB almost always contain large epitheloid macrophages w/ pale pink granular cytoplasm & CD14 at periphery.
CD 31 aka PECAM
expressed on surface of endothelial cells & functions in leukocyte migration through endothelium. Endothelial cell marker. eg: elevated in lover angiosarcoma.
Medial epicondylitis aka Golfers elbow
involved in WRIST FLEXION
Clopidogrel
irreversibly blocks the P2Y12 component of ADP receptors on platelet surface & prevents platelet aggregation. Clopidogrel is as effective as aspirin in the prevention of CV events in pts w coronary heart disease.
Enoxaparin
is a LMW heparin. Binds to antithrombin III. ATIII binds to Xa & stops Xa from converting prothrombin to thrombin
ANOVA
is used to determine whether there are significant difeerences bw the means of 2 or more independent groups. ANOVA compares the means bw groups relative to variability w/in groups & determines whether any of thoses means are significantly different from one another.
Path of CSF flow
lat ventricles--> intraventricular foramenof Monro---> 3rd ventricle--> Cerebral aqueduct--->4th ventricle--> foramina of Luschka & Magendie--> Subarachnoid space.
Posterior nuclei
mediates heat conservation, destruction leads to hypothermia
MVP w regurgitation
most common cause of native valve Infective Endocarditits in developed nations. Rheumatic heart disease most common in developing nations,
Thyroid peroxidase
multifunctional enzyme responsible for catalyzing oxidation of iodide, the iodination of thyroglobulin & the coupling reaction b/w 2 iodized tyrosine residues that froms T3 &T4. Antibodies against this present in more than90% of pts w autoimmune (Hashimotos) thyroiditis
GLP-1 (Glucagon like peptide) agonists
Exenatide, LiraglutideMOA- increases glucose-dependent insulin secretion, decreases glucagon secretion, delays gastric emptyings/e- Pancreatitis
Heterophile Antibodies / Monospot test
- present in EBV/ +ve monospot test- Not usually present in CMV/ -ve monospot test
Lateral epicondylitis aka Tennis elbow
Caused by overuse of extensor carpi radialis brevis & extensor digitorum (involved in WRIST EXTENSION)& is characterized by angiofibroblastic tendinosis at its origin on lat. epicondyle. No or little true inflam. infiltrate.
Isotype switching
(from IgM to other types of IG's) also occurs in germinal centers late in primary response, providing activated B cells the ability to produce Ag specific antibodies of differing isotypes. Heavy chain constant regions are isotype specific & distinguish 5 isotypes (IgG, M, A, E, D) while variable regions are Ag specific.Light chains are ag specific & don't determine isotype. Isotype switching 1st requires interaction of CD40 receptor on activated B cells w the CD40 ligant (CD154) expressed by activated T cells. Afterwards isotype switching can occur through genetic rearrangement of heavy chain constant regions. This process is modulated by T cell cytokines such as IL2, 4, 5, 6 & IFN-gamma. After primary immune response subsequent encoutners w the saame ag generate a predominantly IgG response or IgA in case of a mucosa response.
West nile virus
+ sense SS flavivirus. Can present as encephalitis, meningitis, or flaccid paralysis. Coarse hand tremor, Morbiliform rash on trunk & arms.
Causes of Gram -ve (cocci) meningitis
- Bean shaped diplococci (N. menigitidis) = 2nd most common cause in adults, causes outbreaks
Causes of Gram -ve (rods) meningitis
- E.Coli
Causes of Gram -ve (coccobacilli) meningitis
- H. influenzae = Rare now w/ Hib Vaccine
Reduced pulse pressures
- Restriction of LV filling results in reduced LV EDV (reduced preload). This would reduce stroke volume. Low SV = low PP-Impaired LV contractility reduces SV for given preload. Low PP-LV outflow tract obstr. (caused by Aortic stenosis or HCM) can cause murmur but reduces SV & PP
Different types of culture media
- Selective- eg; VPN/VCNT for Neisseria. These antibiotics kill potential contaminants.- Differential- help identify cultured organisms based on their metabolic & biochemical properties. eg; MacConkey agar, eosin metheylene blue agar.-Enrichment- contain special growth factors required for some organisms. eg; X & V factors reqd by haemophilus or anaerobic conditions needed by clostridium- Reducing- remove O2 & are used to culture anaerobic organisms. eg; thioglycolate broth
Sarcomere
- Thin actin filaments bound to structural proteins at Z line.- Thick myosin filaments bound at M Line
Skin pigmentation diseases.
-Absence of melanocytes - Vitiligo. NOT poor melanin formation-Poor melanin production - Albinism. -Diminished pigment transfer to keratinocytes - Post. inflammatory hypopigmentation-Melanosome aggregates in cytoplasm of melanocytes - Cafe au lait spots.-Linear pattern of melanocyte proliferation - Lentigo.
Common triggers for Candida vaginitis
-Antibiotic use (depletes lactobailli pop.)-High estrogen levels-Systemic corticosteroid therapy-Uncontrolled DM-Immunosuppression
Antibiotics effective against Pseudomonas Aeuroginosa
-Antipseudomonal penicillins- Ticarcillin, Piperacillin-Cephalosporins- Ceftazidime, Cefipime-Aminoglycosides- Amikacin, Gentamicin, Tobramycin-Fluoroquinolones- Ciprofloxacin, Levofloxacin. Moxiflox has poor anti-pseudomonal activity-Monobactams- Aztreonam-Carbapenems- Imipenem, Meropenem
RAAS
-B-blockers= decreased renin/AT I/AT II/ Aldosterone. No change in bradykinin- Direct renin inhibitors(aliskrein)= Increased renin. decreased AT I/ ATII/ Aldosterone, no change in bradykinin- ACE Inhibitors= increased renin/ AT I/ bradykinin. Decreased AT II/ Aldosterone. - ARB's= increased renin/ ATI/ ATII. decreased aldosterone. no change in bradykinin- Aldosterone antagonists= increased renin/ ATI/ ATII/ Aldosterone. no change bradykinin
Virions & corresponding cellular receptor binding site
-CMV = Cellular integrins-EBV = CR2 (CD21)-HIV = CD4 & CXCR4/ CCR5-RAbies = Nicotinic acetylcholine receptor-Rhinovirus = ICAM1 (CD54)
Characteristics of pathogenic yeast
-Candida - Pseudohyphae w blastoconidia. Wide range of superficial or invasive infections-Blastomyces - Broad based budding. Inhaled can disseminate to skin & bone-Coccidioides - Spherules w endospores. Trypically transient pulm. syndrome, can progress to meninges & bone. Endemic to SW US-Cryptococcus - Capsule (india ink stain). Meningitis among immunocompromised patients-Histoplasma - Small oval yeasts w/in macrophages. Most subclinical. Can become invasive in immunocompromised. Endemic to MS & OH river valleys.
Resp. epithelium types
-Ciliated pseudostratified, columnar--Nasal cavity, upper pharynx, false vocal cords, trachea, bronchi.---Mucus secreting cells moisten air & trap debris/pathogens. Ciliary beating sweeps debris towards pharynx for swallowing.-Startified squamous-- True vocal cords---protects from abrasion & chemical attack.-Cuboidal--Bronchioles---Conduct air to alveoli-Simple squamous--Alveoli---Gas exchange
fungal infections, geography
-Coccidioides immitis- dimorphic fungus endemic to SW USA (AZ). Exists in environment as mold (w/ hyphae) that form spores. Spores are inhaled & turn into spherules in the lungs- Cryptococcus neoformans- pigeon droppings. Can cause pulm disease & meningoencephalitis in immunocompromised.- Histoplasma Capsulatum- Endemic to MS & OH river basins. found in bird & bat droppings. -Aspergillus fumigatus- "fungus ball" seen in colonized old lung cavities
Anti-parasitic drugs
-DEC = ndicated in Loa Loa, W.Bancrofti-Ivermectin = Strongyloides stercoralis, Onchocerca volvulus-Nifurtimox = Trypanasomas-Praziquantel = Schistosomiasis, Clonorchis sinensis, Paragonium westermani- Pyrantel pamoate = Enterobius vermicularis (in pregnant pts. or else can treat w/ albendazole)-Most others are treated w/ albendazole & mebendazole.
Some transplant reaction facts
-GRAFT B CELL SENSITIZATION AGAINST HOST MHC ANTIGENS--> doesn't occur in any clinical relevant processes.-GRAFT T CELL SENSITIZATION AGAINST HOST MHC ANTIGENS--> occurs in graft vs host disease, in which host lacks competent T lymphocytes. Transplanted T lymphocytes attack host antigens that are recognized as foreign. Exact HLA matching reduces likelihood of GVHD-HOST T LYMPHOCYTES SENSITIZATION AGAINST DONOR MHC (HLA) ANTIGENS--> Occurs in acute cellular rejection. characterized by dense infiltrate of mononuclear infiltrate on histopath & graft dysfunction. Prevention w calcineurin inhibitors & rx includes systemic steroids.-HOST B& T CELL SENSITIZATION AGAINST GRAFT MHC ANTIGENS--> play a role in both acute antibody mediated & chronic rejection. However acute rejection causes necrotizing vasculitis w a neutrophilic infiltrate.-PREFORMED ANTIBODIES AGAINST GRAFT ABO ANTIGENS--> cause hyperacute graft rejection. transplanted organ becomes mottled immediately after blood vessel anastomosis, and intense inflam response is seen w/in hours. Screening 4 ABO blood group incompatibility virtually eliminates hyperacute rej.
Alcohol effects- hypoglycemia
-Gluconeogenesis is inhibited bc oxaloacetate is shunted to malate. Glycogen becomes main source bc of this. (so you should eat while consuming alochol to maintain glucose levels)eg: a person goes out to run, comes back home and drinks alcohol. at risk for extreme hypoglycemia bc no food has been consumed.
TCA side effects
-Inhibition of presynaptic neurotransmitter reuptake (norepi & 5HT) --Tremor & insomnia-Blockade of cardiac fast sodium channels -- Conduction defects, arrhythmias, hypotension.-Antagonism ofcentral & peripheral muscarinic Ach receptors -- Confusion,dry mouth, constipation, intestinal ileus, hyperthermia,flushing, urinary retention.-Antagonism of peripheral alpha-1-adrenergic receptors -- Orthostatic hypotension, falls-Antagonism of H1 receptors -- Sedation
Jimsonweed(datura) poisoning aka Gardeners mydriasis
-JW produces toxins (belladonna alkaloids), they possess strong anticholinergic properties. It casues a blockade of visceral muscarinic receptors.Similar to atropine poisoning.Antimusc. effects can be counteracted by increasing conc of Ach n synaptic cleft. Increased Ach conc are produced by cholinesterase inhibitors that suppress Ach degradation. Physostigmine can used for RX of atropine overdose.
ANP actions on tissues
-Kidney - dilates afferent arterioles, increasing GFR &urinary excretion of Na & H2O. In addition ANP limits Na reabsorption (in PCT & innermedullary collecting duct) & inhibits renin secretion.-Adrenals - restricts aldosterone secretion, leading to increase in Na &H2O excretion by kidneys-Blood vessels - relaxes vasc. smooth muscle in arterioles & venules, prroducing vasodilation. Also increases capillary permeability, leading to fluid extravasation into interstitium & a decrease in circulating blood volume.
Pituitary adenomas
-Lactotrophs - Hypogonadism (infertility). Galactorrhea, Amenorrhea-Corticotroph (ACTH) - Cushings disease-Somatotrophs (GH) - Acromegaly (adults), GIgantism (children)-Thyrotroph (TSH) - Thyrotoxicosis- Gonadotrophs (LH, FSH) - Nonfunction (hypopituitarism), Mass effect
Causes of Gram +ve (cocci) bacterial meningitis
-Lancet shaped diplococci (Strep. pneumo) = most common cause in Adults- In clusters (S.Aureus) = Penetrating skull injury, neurosurgery- Chains (strep agalactiae- Group B Strep) = Neonatal meningitis, sepsis
Causes of Gram +ve (rods) meningitis
-Listeria = neonates, immunocompromised & elderly
Common brain cancers of childhood
-Pilocytic Astrocytoma (most common) oftern located in cerebellum. Low grade tumors. Histo = pilocytic astrocytes & rosenthal fibers.-Medulloblastoma 2nd most common. Located in the cerebellum, often at vermis. Poorly differentiated & have bad prognosis. Histo= sheets of amll, blue cells, w many mitotic figures.-Ependymomas 3rd most common. Arise in walls of ventriculi & can hamper CSF flow & cause hydrocephalus. Histo= gland ilke structures called rosettes.
Norovirus (ppl at chipotle got it)
-SS RNA. most common cause of viral gastroenteritis in developed countries.-Acute onset, resolves in 2-3 days. Vomiting &/ or diarrhea (no blood or mucus)- Incubation period is 1-2 d. PCR can be done to confirm outbreak.*** Differentiate from Rotavirus!!- both have similar presentation. But rotavirus is unlikely in vaccinated kids/ adults. Not as common n developed countries.
DNA binding proteins
-Transcription factors (Myc etc.)-Steroid receptors (cortisol, aldosterone, progesterone, cortisol)-Thyroid hormone receptor-Fat soluble vit. receptors ( Retinoic acid, Vit D)-DNA transcription & replication proteins
Drugs to avoid in Hypertrophic cardiomyopathy
-Vasodilators - Dihydropyridine Ca channel blockers, Nitroglycerin, ACE inhibitors.-Diuretics-Negative inotropes such as Beta blockers, non-dihydropyridine Ca channel blockers, disopyramide are HELPFUL IN HCM.
Physiologic defense against hypoglycemia
-decreased insulin = decreased peripheral glucose utilization & increased heaptic gluconeogenesis & glycogenolysis- increased glucagon = increased heaptic gluconeogenesis & glycogenolysis-increased epinephrine = increased mobilization of gluconeogenic substrates, increased heaptic gluconeogenesis & glycogenolysis-increased cortisol & GH = alters transcription of many genes to conserve glucose.
Rib fracture- Post view
12th rib # = Kidney injury. Rib also overlies parietal pleuraR 8-11th ribs # = liver injuryL 9-10-11th ribs # = Spleen injuryVisceral Pleura injury = most likely w/ 1-6th rib #
Dietary energy
1g of protein = 4 cal1g of carbohydrates = 4 cal1g fat = 9 cal1g ethanol = 7 cal
Antipsychotics
1st gen APs can be classified as HIGH or LOW potency, and have differing s/e. LOW= sedation, anticholinergic side effects, orthostatic hypotension. eg: Chlorpromazine, ThioridazoneHIGH= extrapyramidal s/e. eg: Haloperidol, Fluphenazine
Duodenum segments
1st part= emerges from pylorus of stomach & is horizontally oriented over 1st lumbar vertebra. Only part of duodenum that is not retroperitoneal.2nd= courses inferiorly from level of L1-L3. This part of duodenum is in close relation to head of pancreas & contains ampulla of Vater, site where pancreatic & common bile duct secretions are release3rd- horizontally courses over L3, the abd aorta, & IVC. Close assoc w uncinate process of pancreas & SMA and vein. Small bowel ca is rare but when they occur in 3rd part ant tumor invasion could compromise sup. mesenteric vessels4th= courses superiorly & to left of L2 & L3, & becomes jejunum past ligament of Treitz.
Twinning
2 cell stage (0-4d) = Dichorionic & diamniotic. 25%Morula (4-8d) = Monochorionic & diamniotic. 75%Blastocyst (8-12) = Monochorionic & monoamniotic.RAREFormed embryonic disc (>13d) = Monochorionic & monoamniotic-conjoined. V RARE
Candida Albicans host defense mechanisms
2 immune types w/ distinct functions--T lymphocytes (TH cells)- imp. in preventing superficial Candidiasis. Conditions such as HIV (low T cell count) increase risk of superficial candidiasis.Neutrophils - prevent hematogenous spread. Disseminated candidiasis is more likely in pts who are neutropenic or otherwise immunocompromised and in those w inherited impairments of phagocytosis.
Mayer Rokitansky Kuster Hauser Syndrome
46XX female w/ Mullerian aplasia aka vaginal agenesis. Short vaginal. Normal 2ndary sex characteristics.Vs Androgen Insensitivity syndrome- 46XY males who appear female due to androgen receptor defect. They have minimal axillary or pubic hair (unlike MRKH syndrome above). Due to adnrogen resistence. Pts have cryptorchid testes & no uterus or ovaries.
Infectious dose(ID)
50% ID corresponds to min. orhanisms reqd to cause disease.-Low ID50- Shigella (dysenteriae= 10, flexneri= 100, sonnei= 500), C. jrjuni (500), E.histolytica (1-10), Giardia (1-10)-High ID50- Salmonella, Vibrio, C. perfringens, E.Coli
Roseola Infantum
<2yo kids. Rx= supportive careRash starts on trunk & spreads to face & extremeties
Normal pressure tracings
A Swan Ganz catheter is often used to obtain hemodynamic measurements in pts w shock & certain Cardiopulm conditions During Pulm artery (Rt heart) catheterization, the cath is advanced to small branch of pulm artery & balloon is inflated to obstruct blood flow in that vessel & its distal branches (which eventually form pulm veins). Bc blood flow toward LA is obstructed beyond this point of occlusion the pressure at tip of cath becomes nearly equal to LA pressure & LVEDP. This is referred to as PCWP. During normal diastole LA pressure nearly equal to LVEDP as open mitral valve offers minimal resistance to flow bw 2 chambers.
IVC union
IVC lies just ant. to rt. renal artery & to the right of the aorta. IVC is formed by union of Rt & lt common iliac veins at L4-5 level & drains into rt. atrium.
Nephrotic Syndrome - Renal vein thrombosis
A pt w membranous nephropathy, flank pain, hematuria, & lt varicocele has Lt renal vein thrombosis (RVT) as result of nephrotic syndrome.Bc of increased glomerular capillar wall permeability n nephrotic syndrome, many imp substances are lost in urine. Loss of anticoagulant factors, escpecially Antithrombin III leads to hypercoagulable state. pts with RVT can develop sudden onset abd or flank pain & gross hematuria w elevated LDH as a result of renal infarction.
Hibernating myocardium
A state of chronic myocardial ischemia in which myocardial metabolism & function are reduced to match a concitant reduction in coronary blood flow. This new equilibrium prevents myocardial necrosis. Chronically demonstrates decreased expression & disorganization of contractile & cytoskeletal proteins, altered adrenergic control, and reduced Ca reponsiveness. These changes lead to decreased contractility & LV systolic dysfunction. However revascularization & subsequent restoration of blood flow improves contractility & function
46 yo w easy fatigability & exertional dyspnea. Auscultation shows diminished 1st heart sound & apical holosystolic murmur radiating to axilla. Diffuse pulm crackles heard bilaterally. No elevation of JVP or peripheral edema. What would most likely increase ratio of forward flow volume to regurgitant flow volume?
A, Decreasing Lt ventricular afterload. Lt ventricular afterload is a major determinant of the forward to regurgitant flow ratio in pts w mitral regurgitation. Decreasing afterload will increase forward flow while reducing regurgitant flow. An increase in Lt ventricular EDV can contribute to or worsen mitral regurgitation when the degree of regurgitation is dependent on Lt ventricular size
Test result is negative in 95% pts who dont have disease. If new assay used on 8 samples taken from pts w/out disease what is probability of ALL 8 results are -ve??
A. 0.95^8. Other wrong options are 0.05 x 8, 0.95 x 8, 0.05 ^ 8, 0.95 ^ 8, 1 - 0.05^8, 1 - 0.95^8.Each sample is independent event, one pts result has no impact on another. w/ 95% probability of correctly testing -ve and a 0.05% probability of testing +ve. [1-P]. To calc. multiply probability of each test returning a -ve result. eg: 0.95 x 0.95 x 0.95 x 0.95 x 0.95 x 0.95 x 0.95 x 0.95 = 0.95^8Probability of all 8 samples testing incorrectly positive is 0.05^8probability of atleast 1 sample testing +ve is 1 - 0.95^8probability of atleast 1 sample testing -ve is 1 - 0.05^8
Endogenous compounds in CSF measured after noxious stimuli. Elevated compound is a pentapeptide w/ strong affinity to delta and mu receptors. What does it share a common molecular origin with?
A. ACTH. Enkephalins, endorphins & dynorphins are endogenous opiod peptides. Beta endorphin is one endogenous opioid peptide derived POMC. POMC is a polypeptide precursor that goes through enzymatic cleavage and modification to produce not only beta endorphins but also ACTH & MSH.
In vitro studies show tumor cell ines can become resistant after exposure to various anti cancer agents. These cells express a specific cell surface glycoprotein that has what function?
A. ATP dependent transporter. The human MDR1 gene codes for P-glycoprotein, a transmembrane ATP dependent efflux pump protein that has broad specificity for hydrophobic compunds. This protein can both reduce the influx of drugs into cytosol & can increase efflux from cytosol thereby preventing action of chemotherapeutic agents.
Which drug may precipitate opioid withdrawal symptoms if used? Pt is using oral morphine sulphate for back pain
A. Buprenorphine- it is a partial agonist w/ low intrinsic activity (efficacy). But has high potency (affinity). Full agonist don't typically cause withdrawal. In long term opioid therapy it can displace other opi. & precipitate withdrawal.Opioids selectively bind to g protein coupled receptors, mimicking endogenous opioids. Long term activation of mu receptors on noviveption transmitting neurons is assoc w/ increased pain sensitivity, due to -- increased turnover of inhibitory opioid receptors (receptor downregulation) & decoupling of receptors from 2nd messenger. Upregulation of NMDA receptors.
43yo M evaluated for occasional retrosternal chest pressure that occurs during mod. and sometimes during rest. Angio shows mild luminal irregularities but no significant obstr. lesions. Ach infusion during procedure results in dilation of epicardial coronary vessels. Reaction involving which amino acid is most responsible for observed dilation?? WTFFFFFFFFFFFFFFFFFFFFFFFFFFF
A. Arginine. Vasodilation mediated by Ach, bradykinin, 5-HT, Substance P, & shear forces. They activate specific membrane recepors present on endothelial cells, increasing cytosolic Ca levels. Nitric oxide is synthesized from arginine, NADPH, 02. This then activates guanylyl cyclase & increases formation of cGMP. high levels of cGMP activate protein kinase G, which reduces cytosolic calcium levels & relaxation of vasc, smooth muscle cells.
67yo M presents with h/o progressive dyspnea. He can't tolerate moderate exertion & sleeps in 1/2 sitting position due to orthopnea. He has noticed some swelling of his ankles. Doesn't smoke or alcohol. Pmh is significant for hypercholesterolemia & recurrent chest pain. What is increase in this pt?
A. Arteriolar Resistance. Pt has Congestive heart failure. Lt sided CHF frequently presents w/dyspnea on exertion, orthopnea, PND. Symptoms of rt. sided CHF include lower extremity edema & hepatomegaly. Most common cause of Rt heart failure is Lt heart failure.Decreased cardiac output triggers a number of compensatory mechanisms. R-A-A-S activation & increased sympathetic output raise arterial resistence(afterload) and exacerbate heart failure by making it more difficult for failing heart to pump blood to tissue.RAAS activation--> sodium retention (direct effect), Aldosterone production, Vasoconstriction
Analysis of progeny viruses demonstrate that phospholipid composition of viral particle surface is highly similar to that of cell nuclear membrane, Pt is most likely infected w/ ?
A. CMV. Virion containing particle surface is likely an enveloped virus. Most enveloped nucleocapsid viruses acquire lipid bilayer envelops by budding through plasma membrane of host cell. Except for herpesviruses, which bud through & acquire their envelope from host cell nuclear membrane.
Rt ureter injured during hysterectomy. Later partial obstruction of rt ureter is observed w/ mild dilation of proximal collecting system. What changes seen in rt kidney?
A. GFR decreased & FF decreased. Acute ureteral obstruction increases hydrostatic pressure proximal to constriction. In acute obstruction RPF may transiently increase, however with time efferent arteriolar constriction in response to reduced GFR will decrease RPF. At later stages GFR remains depressed to a greater extent than the RPF resulting in reduced FF
34yo F w/ months of moderate hearing loss. Ringing noise in left ear. NO recent infections. No trauma or cotton swab usage. Dad had b/l hearing loss attributed to old age. On exam auditory canals N. Pt has lt sided face numbness, assymetric smile, decreased afferent & efferent corneal reflex in Lt eye. Where is the intracranial mass located?
A. B/w cerebellum & lat. Pons. Pt has acoustic schwannoma (assoc. w/ NF type 2). They arise from CNVIII. CN VII & CN V are in close proximity so can be affected by compression. Craniopharyngiomas arise above the sellar (suprasellar) region. Germ cell tumors frequntly arise from pineal gland, which is part of Dorsal Midbrain. Meningiomas found at falcine/parasaggital region & over convexities of cerebral hemispheres.Medulloblastomas primarily arise in Post. fossa (cerebellum)
Biologists studying signal transduction apply an agent to human cells that activates G-protein-dependent Phospholipase C. What intracellular substance is most likely to increase immediately after exposure to this agent?
A. Ca2+. A variety of hormone receptors are known to exert their intracellular effects voa Phosphoinositol system. Examples include a1-adrenergic, M1 & M3 cholinergic, V1, H1, Oxytocin, Angiotensin II, TRH, GnRh receptors. It proceeds through following steps---Binding of ligand to its cell surface receptor causes exchange of GDP to GTP on a-subunit of Gq protein assoc. w the receptor. The activates a-subunit undergoes a conformational change & exposes phospholipase C (PLC) activating site-After activation PLC hydrolyzes PIP2 into DAG & IP3.-DAG is able to directly stimulate protein kinase C, but major activator of PKC is increased intracellular Ca2+, that occurs due to IP3 mediated release of intracellular Ca2+ stores from ER. PKC is major effector molecule in this pathway, it directly modulates activity of other proteins via phosphorylation.
47yo M has elevated BP. BP- 154/107, pulse-86. Np physical changes. Pt is started on low dose atenolol. What changes occur bc of this?
A. Cardiomyocyte [cAMP] - decreased, JG Cell [cAMP] - decreased, Vascular smooth muscle [cAMP] - no significant change.B1 adrenergic receptors are found in cardiac tissue and or Renal JG cells, but not in vasc. smooth muscle. Selective blockade of B1 receptor (atenolol) leads to decreased cAMP levels in cardiac & renal tissue w/out significantly affecting cAMP levels in vasc. smooth muscle.
36yo undergoing major surgery under gen anaesthesia. Fluorinated inhaled anesthetic (isoflurane) used to achieve desirable depth of CNS depression. Increase what parameter is most likely to happen during anesthesia in this pt?
A. Cerebral blood flow. Inhaled anesthetics effect most systems in body.-CVS - Myocardial depression that leads to decrease in CO & increase in atrial & ventricular pressures. Hypotension assoc w fluorinated anesthetics is result of decrease in CO-Resp - all inhaled anesthetics except NO are resp depressents. They decrease tidal volume & minute ventilation & cause hypercapnia. Another undesirable effect is suppresiion of mucociliary clearance, which may predispose to post-op atelectasis. Halothane & sevofluorane have bronchodilation properties & are preferred in pts w asthma-Brain- decrease vascular resistance & this increases cerebral blood flow. It is an UNDESIRABLE effect as it results in increased intracranial pressure. -Renal- decrease GFR, increase vasc resistance & decrease renal plasma flow -Liver- decrease blood flow
65yo M came to hosp after stroke. You give diazepam to this pt in order to decrease muscle spasticity of onvolved extremities. This pt should primarily be cautioned to avoid which drug?
A. Chlorpheniramine. 1st gen H1-histamine receptor antagonists,including diphenhydramine & chlorpheniramine, can cause significant sedation, especially when used w other medications that cause CNS depression (such as BZPs). 1st gen antihistamines easily cross BBB & sccumulate in CNS.
M is give low dose Chlorthalidone monotherapy. Serum level of what will increase bc of his therapy?
A. Cholesterol. Thiazides decrease secretion of insulin & reduce glucose uptake in peripheral tissues. As a result blood glucose levels often rise in diabetic pts taking thiazides. Thiazides also cause increased LDL cholesterol & TG levels, possibly due to altered lipid metabolism from increased peripheral insulin resistance.Thiazide s/e--hyponatremia (inhibition of Na/Cl co transporters in DCT), hypokalemia (compensatory rise in renin & aldosterone secretion), hypercalcemia (Increased reabsorption in distal tubule), Hyperglycemia/cholesterolemia (decreased insulin secretion & increased insulin resistance), hyperuricemia (increased reabsorption in PCT)
Bronchi are llined w/ pseudostratified epithelium. Airways continue distally, the epithelium changes. Which feature is last to disappear as epi changes along resp. tube?
A. Cilia. By terminal bronchioles the airwy epi. is changed from pseudostratified ciliated columnar to ciliated simple cuboidal. Cilia are present through the resp. bronchioles but are not present in alveolar ducts or in alveoli themselves. Bronchi have pseudostratified columnar ciliated epi. w/ goblet cells & submucosal mucoserous glands & cartilage. Bronchioles, terminal bronchioles, and resp bronchioles genreally lack goblet cells, glands, and cartilage. By level of terminal bronchioles airway epi is ciliated simple cuboidal.
24yo mountain climber, has rt arm pain after a fall. Fell on his rt arm. Externsive bruising over lat. rt.arm and a total inability to extend rt wrist. X-ray shows midshaft fracture of rt. humerus. Which artery is injured?
A. Deep brachial artery. NOT brachial artery. Pt has wrist drop due to radial nerve injury.Deep artery aka profunda brachii branches off brachial artery high in arm, passes inferior t teres major & courses along humerus w/ radial nerve.Supracondylar fractures may injure brachial artery. Axillary art. gives off post. circumflex humeral art & becomes brachial artery.# of surgical neck of humerus may damage axillary N and post. circumflex art.
guy has fever, cough 7 cold. Lungs clear, nose swab done. Naked viral particles seen, and purified RNA is extracted from these particles. Once introduced into human cells the purified RNA molecules induce viral protein synthesis & viral genomes replication. What type of virus is causing this?
A. Rhinovirus. For a purified RNA molecule to induce viral protein synthesis in a host cell, it must be able to act directly as mRNA using the host's intracellular machinery for translation. There fore in general, purified Single stranded positive sense aka SS+ RNA can be infectious.SS- or dsRNA IS NOT.
34 yo M treated for Acute leukemia develops oliguria. Serum creatinine is 2.7. Renal bipsy reveals multiple uric acid crystals obstructing renal tubular lumen. Principal sire of uric acid precipitation would be which?
A. Collecting ducts due to low urine pH. dude has tumor lysis syndrome. It develops due to rapid cell turnover & high sensitivity to chemotherapy. When large number of cells are destroyed intracellular ions, such a K, Phosphorous, Uric acid ( as metabolite of tumor nucleic acid) released into serum and are then filtered by kidneys.Uric acid is soluble at physiological pH, but precipitates in acidic environment. Lowest pH along nephron fond in distal tubules & collecting ducts, so these are segments of nephron that become obstructed by uric acid crystals. risk of tumor lysis can be reduced by alkalinization & hydration, as high urine & high pH along nephron prevent crystallization & precipitation of uric acid.
Admins. of certain meds can cause redistribution of blood flow away from ischemic areas, exacerbating existing myocardial ischemia. The drug assoc w/ this phenomena casues what effect?
A. Coronary arteriolar dilation. Drugs such as Dipyridamole, and adenosine are selective vasodilators of coronary vessels. These drugs are used in myocardial perfusion imaging studies to simulate the generalized coronary vasodilation caused by exercise. This allows for detection of ischemic areas that would otherwise not be seen in resting heart.
1 wk old boy is brought to ER w/ recurrent vomiting & poor feeeding. Infant was born full term w/out any complications. he is dehydrated & hypotensive. Serum Na= 122, K= 5.7, BUN= 25, Creatinine= 0.6. Further evaluation shows what/
A. Cortisol=decreased. Aldosterone= decreased, Serum ACTH= increased, 17-hydroxyprogesterone= increased.Pt has 21 hydroxylase def. salt wasting type. MALE Infants have normal genitalia & present 1-2wks after birth w/ vomiting, hypotension, hyponatremia & hyperkalemia. FEMALE Infants present at birth w/ ambiguous genitalia.
35yo M ate flat beans after business trip from egypt. Jaundice & pallor +. Hb=8. deficiency in enzyme converting G-6-P to ribulose-5-phosphate. Substance generated during this conversion reqd. for what?
A. fatty acid synthesis. G6PD Deficiency.
Holoprosencephaly. What is mechanism for this?
A. Developmental Field defect. Which is when an embryonic disturbance leads to multiple malformations b disrupting the development of adjacent tissues & structures within particular region.
Pt is started on new anti epileptic med that selectively blocks voltage gated Ca channels. Medication most likely affects which of the following steps of neurotransmission?
A. Fusion & release of neurotransmitter vesicles. Voltage gated Na channels are imp. for generation & propagation of action potentials. When the AP reaches axon terminal, voltage gated ca channels open & allow influx of Ca which is essential for fusion & release of Neurotransmitter vesicles into synaptic cleft.
Dude has exam, rt. wrist hurts when typing. He has asthma. Impaired dorsiflex. of rt wrist, lt wrist normal. Serum Ab's against neutrophil myeloperoxidase positive. what does he have?
A. Eosinophilic granulomatosis w/ polyangitis aka Churg Strauss/ It's small/ medium vessel vasculitis characterized by late onset asthma, rhinosinusitis, & esoniphilia. Can involve, Renal, GI & CVS. Asymmetric multifocal neuropathy aka mononeuritis multiplex can cause wrist drop due to radial nerve involvement. P-anca +ve. Can have skin nodules, migratory/transient pulm. infiltrates and paranasal sinus abnormalities.
What drug mechanism is used for treatment for PCOS related infertility?
A. Estrogen receptor modulation. Clomiphine citrate used for those who want get pregnant. It is SERM that prevents negative feedback inhibition on hypothalamus and pituitary by circulating estrogen, resulting in increased gonadotropin production (FSH & LH) and ovulation. Those who don't want kids can use dual estrogen-progestin OCPs (minimize endometrial proliferation reduce androgenic symptoms). Androgen receptor anatagonists (SPirinolactone) used in those who don't respond to OCPs, not used for pregnancy bc of fetal abormalities.
32yo M evaluated for fever, night sweats, and chills over last few days. He has been using IV drugs recently as he is stressed. Temp-38.3, BP-120/80, pulse-105. Further evaluation reveals aortic valve endocarditis w/ an intracardiac abscess & small fistula formation between the aortic root & rt. ventricle. Doppler reveals what pattern?
A. Flow from aortic root to Rt. ventricle continuously. Aortocavitary fistulas are an uncommon complication of bacterial endocarditis caused by extension of the infection from valve to adjacent myocardium. During the normal cardiac cycle, central aortic pressure is higher than rt. vent. pressure during systole & diastole. Consequently an intracardiac fistula bw the aortic root & rt. ventricle will most likely demonstrate a lt-to-rt cardiac shunt as blood continuously flows from aortic root (high pressure) to rt. ventricle (low pressure)
43 yo M w/ several month h/o fatigue, rash, flushing & abd cramps. Rash is worse w/ rubbing or scratching and has diffuse itching after hot showers. Frequently feels dizzy and light headed after prolonged standing & had an episode of syncope while standing under hot sun. Doesn't smoke, drink or drugs. Vital signs normal. Maculopapular rash +. Skin biopsy shows clusters of mast cells +ve for KIT (CD 117). Which additonal finding is present?
A. Gastric Hypersecretion. In systeminc mastocytosis clonal mast cell proliferation occurs in bone marrow, skin & other organs. Mast cell proliferations are assoc w/ KIT receptor tyrosine kinase mutations. These cells are charcterized by prominent expression of mast cell tryptase. Excessive histamine release mediates many symptoms of disease, such as Syncope, flushing, hypotension, pruritis, & urticaria. In addition histamine induces gastric acid secretion, which can lead to gastric ulceration. excess acid also inactivates pancreatic & intestinal enzymes causing diarrhea.
Enterococci Drug resistance
A. Gentamicin resistant. Aminoglycoside resistance develops through bac. production of aminogly. modifying enzymes that transfer acetyl/ adenyl/ phosphate groups to aminoglycoside antibiotic molecule outside of bacteria, thereby decreasing ability to bind to ribosomes & exert anti-microbial effects. It is not chromosomally mediated, its acquired mediated by plasmids or transposons.Vancomycin resistance is mediated by plasmids or transposons, can develop when bac. proteins serving as ligases alter D-ala D-ala cell wall precursors. VanA ligase replaces D-alanyl D-alanine w/ D-alanine D-lactate thereby preventing vancomycin binding.
Pt has severe pyelonephritis & needs to be started on antibiotic that depends mainly on non renal clearance. What characteristics should antibiotic have if hepatic metabolism & clearance is desired?
A. High lipophilicity. Wrong answers = low Volume of distribution,Poor oral absorption, low rate of redistribution, poor penetration into CNS.While kidney is primary site of elimination of most drugs, liver is main site of BIOTRANSFORMAtION of these agents in prep for elimination. Drugs that are more lipophilic (high Vd, good CNS penetration) are preferentially processed by liver into more polar compunds for easier elimination in bile & urine. Liver disease or concomitant use of other drugs may limit or enhance clearance of drugs metabolized in liver.
63yo M comes to ER w/ muscle weakness & severe cramping in lower extremeties. Cramps disrupt sleep. Had to suspend exercise bc of symptoms. chlorthalidone & amlodipine started 4 wks ago. BP in ER is 140/86 & PR is 90. Heart rate & rhythm are regular. Has palpable pedal pulses, noperipheral edema. What is cause for muscular syptoms?
A. Hypokalemia. Thiazide decrease IV fluid volume, which stimulates aldosterone secretion & leads to increased excretion of K & H ions in urine. Results in hypokalemia & met. alkalosis.Note- 3Na - 2K ATP pump. Ca - 3Na pump. Both actat interstitial fluid to distal tubule cells.
Anticoagulated blood falls at rate of 35mm/hr. This is related to action of what substance?
A. IL-6. NOT bradykinin, LTB4, EPO, Platelet activating factor, TXA2. During injury, local neutrophils & macrophages release TNF-a, IL-1, Il-6 into circulation. They mediate systemic inflam. response, in part by stimulating hepatic production of acute phase reactants. eg-CRP, amyloid A, amyloid P, fibrinogen, ferritin, & complement factors. High levels increase EDR which is a nonspecific marker of inflam.
54 yo F unconscious at grocery store. Breathing, palpable pulse, but not arousable. Has Type 1 DM. Glucose level shows 34. Ambulance called but takes time. U are given First aid kit, what do you give to normalize glucose meanwhile?
A. IM Glucagon. Mild to moderate hypoglyc. can be self treates w/ oral intake of 15-30 g fast acting carbs. (eg: glucose tabs, sweet juices, hard candy etc). In MEDICAL SETTING severe hypogly. treated w/ IV glucose (50% dextrose amp). In NON MEDICAL SETTING Glucagon may be used for rapid correction, can be given IM or SC. It acts by increasing hepatic glycogenolysis & gluconeogenesis. Pt typically regains consciousness in 10-15 mins. If Glucagon UNAVAILABLE buccal or sublingual glucose or sucrose (sweet things) can be used, but oral absorption is slow and erratic and maybe ineffective.
Isolated Diastolic heart failure findings
A. INCREASED- Lt ventricular end diastolic pressure. NORMAL- Lt ventricular end diastolic volume & lt. vent. ejection fraction.
44yo mandrug addict has fever & chills. Blood cultures +ve for S. Aureus and the pt was diagnosed w infective endocarditis. Treated w long course of antibiotics. 3mo later returnsfor eval. No current symptoms & reports good exercise tolerance. ECG shows Severe aortic regurgitation as sequela to prior infection. What change is responsible for maintaining CO in the setting of this valvular abnormality?
A. Increase in Lt. Ventricular Stroke volume. Regurgitant blood flow from Aorta into Lt ventricle in chronic aortic regurgitation leads to an increase in lt ventricular end diastolic volume (preload) & wall stress withresultant eccentric hypertrophy. The gradual increase in Lt ventricular chamber size increases total stroke volume & helps maintain CO.
What indicates a pt has both mitral and aortiv valve involvemnt , rather than exclusive mitral inv.? CXR shows pulm vascular congestion and edema.
A. Increased lt. vent. diastolic pressure. eg: rheumatic fever.
53yo M w/ prog exertional dyspnea. AP diameter increassed. Decresased breath sounds and scattered wheezes. Mild dilation of rt ventricle and increased cvp. How can you explain absence of peripheral edema in this pt?
A. Increased tissue lymphatic drainage. Guy has COPD. And increased CVP predisposees to developing noninflammatory edema. Causes excessive accumulation of transudative fluid fluid in interstitial tissues & occurs in following--1. elevated cap. hydrostatic pressure, 2. decreased plasma oncotic pressure, 3. sodium & water retention, 4. lymphatic obstr.Rt heart failure increases CVP which leads to a rise in capillary hydrostatic pressure, net plasma filtration and interstitial fluid pressure. As interstitial fluid pressure increases so does lymphatic drainage, which can compensate for moderate CVP elvations and prevent development of clinically apparent edema. LArge CVP elevations can overwhelm lymphatic reabsorptive capacity leading to development of overt edema.
In experiment RBC precursor cells are incubated in a medium containing radiolabeled cysteine. These cysteine residues are attached to their appropriate tRNAs by enzyme aminoacyl-tRNA synthetase. The bound cysteine residues are them chemically modified to form alanine. The end product of this reaction is a tRNA molecule that contains the cysteine anticodon but is mischargd w alanine. What is most likely to occur to this alanine residue during polypeptide synthesis of alpha Hb?
A. It will be incorporated into polypeptide chain at site requiring cysteine. The sequence of amino acids in a growing polypeptide chain is dedicated by te interaction of mRNA codon w the tRNA anticodon. tRNA that is mischarged w the incorrect amino acid (& not corrected by aminoacyl-tRNA synthetase proofreading) will incorporate w wrong amino acid into the growing polypeptide chain.
Kegel exercises in 52yo F, postmenopausal, has 3 vaginal deliveries & has a cystocele. What do kegels target?
A. Levator Ani muscles (Iliococcygeus, pubococcygeus, puborectalis) aka pelvic floor muscles. They hold bladder & urethra in appropriate anatomic position. Injury here results in urethral hypermobility & or pelvic organ prolapse (cystocele). Damage to Uterosacral ligaments causes Uterine & vaginal apical prolapse. These ligaments run along lat. pelvic wall & anchor uterus & vag. apex by attaching to sacrum.
A 70yo M w/ severe midback pain several hrs ago. Excruciating pain, nausea, diaphoresis, & lightheadedness. Has HTN &CKD. Medical compliance is poor. BP-220/105. ECG- Sinus tachycardia and voltagr criteria for Lt Vent. hypertrophy, w/ secondary ST segment & T wave changes. Transesophageal echo shows dissection flap in desc. aorta but no evidence of dissection asc. aorta. Where does this dissection originates?
A. Lt. Subclavian Artery. This pt has Stanford typeB aortic dissection, typically originate at Lt. subclavian artery. Type A= refers to aortic dissections that involve any part of asc. aorta. Type B= refers all other dissections involving desc. aorta.Distal propagation of Type A or proximal propagation of type B dissection can effect aortic arch (eg: Brachiocephalic artery, lt. common carotid artery, lt. subclavian artery). Either type can propagate distally into thoracoabdominal aorta, involving the origins of the celiac trunk, intercostal arteries, and renal arteries.
32yo M w/ high grade fever, dyspnea, fatigue. Temp-102.9, BP- 122/70, Pulse- 102 and regular. New holosystolic murmur, blowing, heard at apex. Skin shows non tender lesions on sole of feet. (Giant red dots), what do they represent?
A. Microemboli to skin vessels. Pt has Inf. Endocarditis, these are Janeway lesions (located on palms & soles. nontender). Also seen are oslers nodes (Painful violaceous nodes on fingertips & toes), splinter hemorrhages, Roth spots(edematous & hemmorhagic lesions of retina). Vascular phenomena= mycotic aneurysm & systemic emboli.oslers nodes are caused by immune complex deposition in skin.
What drugs are used to improve survival in Congestive HF & reduced LV ejection fraction?
A. Mineralocorticoid receptor antagonists (spironolactone, eplerenone) prevent aldosterone from binding to its receptor in distal renal tubules. Leads to increased Na & H2O excretion while conserving K ions. They also block deleterious effect of alsoterone on heart, causing regression of myocardial fibrosis & improvement in ventricular remodeling.These drugs reduce morbidity & improve survival in pts. They are recommended in addition to ARBs, ACE inhibitors & B-blockers. SHOULD NOT be used in pts w/ hyperkalemia or renal failure.
Clip to pigs to Rt renal artery, which significantly reduces blood flow to kidney. after 6mo Rt nephrectomy is done, & glomeruli is examined. What cell type would most likely undergo hyperplasia as a result of the clip placement?
A. Modified smooth muscle cells of afferent arterioles.Reduced blood flow is sensed by JG apparatus & macula densa. Significant renal hypoperfusion leads to compensatory increse in renin secretion by JG cells w/in afferent arterioles. This activates RAAS leading to increased circulating levels of ATII & aldosterone. Long term renal hypoperfusion causes JG cells of affected kidney to undergo hyperplasia.
56yo M hearing loss both ears.Worked in loud factory. Rt ear air conduction, bone conduction decreased. Whats damaged?
A. Organ of Corti. Noise induced hearing loss assoc from trauma to stereociliated hair cells or Organ of Corti. Acoustic reflex normally dampens the effects of loud noise by causing stapedius and tensor tympani muscles to contract, which lessens responsiveness of ossicles to sound. However prolonged noise exposure can cause distortion or fracture of stercocilia due to shearing forces against tectorial membrane. High frequency hearing lost first, regardless of frequency of sounds causing damage.defects in mid ear ossicles is otosclerosis. affects air conduction across all frequencies. This pt has air & bone conduction defect.
Pt has sickle cell disease. Pt Hb is most likely aggregate upon what??
A. Oxygen unloading. HbS aggregates in deoxygenated state. HbS polymers form fibrous strands the reduce red blood cell membrane flexibility & promote sickling. Sickling occurs under conditions assoc w anoxia including low pH & high levels of 2,3-BPG, low blood volume (dehydration). These inflexible rbc predispose to microvascular occlusion & microinfarcts.
68yo M is on treatment recieving monoclonal antibody infusions that were approved for advanced melanoma management after clinical trials. The monoclonal Abs block a specific cell surface receptor found on T lymphocytes to facilitate destruction of cancer cells by T cells capable of recognizing tumor antigens. What cell surface receptor is most likely blocked??
A. PD-1 (Programmed death receptor 1). It is expressed on surface of activated T cells. Binds to programmed death ligand 1(PD-L1) downregulating immune response against tumor cells primarily by inhibiting cytotoxic T cells (similar to CTLA-4 aka cytotoxic T lymphocyte assoc protein 4) Many types of cancer cells evade the immune system byincreasing expression of PD-L1. Monoclonal ab's against PD-1 have been developed that prevent binding of PD-1 to PD-L1, this blocks Tcell inhibition. Thereby restoring cytotoxic response and promoting apoptosis of tumor cells. Anti PD-1 therapy is used in advanced melanoma and certain type of Lung Ca.
14 yo boy, comes to ER w/ excessive thirst and urination. Lost 4.5kg in 3 weeks. Dad has DM Type1. Dry mucous membranes. Glucose-455mg/dl. N anion gap, HbA1c-11.3% Insulin is started. Insulin icreases glycogen synthesis in hepatocytes. Activation What molecule Promotes this effect?
A. PROTEIN PHOSPHATASE. Insulin decreses glucose levels by increasing glucose uptake into Skeletal muscle and adipocytes. Insulin inhibits glycogenolysis and gluconeogenesis. Surface receptor for Insulin is transmembrane protein w/ Intrinsic tyrosine kinase activity in cytoplasm. Insulin binding activates tyr kinase, leading to phosphorylation of insulin receptor substrate1 (IRS-1). IRS1 activates several intracellular pathways that induce phys. effects of insulin. Activation od MAP kinsae promotes mitogenic functions such as DNAsynthesis and cell growth. In contrast activation of PI3k stimulates metabolic fucntions such as translocation of GLUT 4 to cell membrane, glycogen synthesis and fat synthesis. P13K promotes glycogen sythesis by activating protein phosphatase, an enzyme that dephosphorylates glycogen synthase leading to its activation.
vertical midline episiotomy is given through vaginal & subvaginal mucosa. What structure is invovled?
A. Perineal body.
43yo man w/muscle weakness. Pain bean 6wks ago & worst in hips and shoulders. Progressive. Can't comb hair and has difficulty getting up from chairs. Muscle biposy shows MHC 1 overexpression on sarcolemma w/ CD8 lymphocyte infiltration
A. Polymyositis. Causes symmetric proximal muscle weakness. Muscle biopsy reveals inflammation, necrosis and regengeration of muscle fibers, and endomysial mononuclear infiltrste,patchy necrosis. Ovrexpression of MHC 1 on sarcolemma leads to infiltration w/ CD8 T lymphocytes and myocyte damage. Elevated muscle enzymes (CK, aldolase), Autoantibodies (ANA, anti-Jo1). Complications- Interstitial lung disease, Myocarditis. Differentiate from Dermatomyositis bc of lack of skin findings.
30 yo F comes to ER w acute shortness of breath. Analysis of pt. expiratory gases reveal following- Tracheal po2=150mmHG, Alveolar po2= 145, alveolar pco2= 5. What best explains this pts. pulm gas analysis?
A. Poor alveolar perfusion. Under normal conditions p02 of inspired air is approx 160. this decreases to approx 150 in trachea due to partial pressure of water vapor. pt.s expiratory tracheal p02 is normal, which indicates she is breathing room air w/out supplemental o2. Normal alveolar p02 is 104, which is bw tracheal(150) & venous blood (40) conc. Normal pco2 is 40, bw it's respective tracheal (o) & venous blood (45) conc. situations in which 02 equilibrium can become diffusion limited include disease states such as emphysema & pulm. fibrosis, & physiologically in states of very high pulm blood flow, such as during exercise.
70yo man is treated w metoprolol for HTN, and enalapril is added. BP normalizes but creatinine levels increase. What is the reason for this abnormality?
A. Reduction in renal filtration fraction. Many drugs cause nephrotoxicity & acute renal failure by diff mechanisms. In particular ACE inhibitors can cause an acute rise in serum Creatinine by blocking angiotensin mediated efferent arteriole vasoconstriction. This leads to a reduction in renal filtration fraction. For pts dependent on effernt arteriole constriction to maintain renal perfusion (those w renal artery stenosis) ACE inhibitors can be detrimental by precipitating acute renal failure.
12yo white boy has wide, fixed splitting of 2nd heart sound (S2) on routine physical exam. Denies any symptoms. If present, the congenital hert disease in this patient may require surgical repair to prevent IRREVERSIBLE changes in what?
A. Pulm. vessels. Pt has ASD, ASD creates a L-R shunt bc of high pressure in lt atrium. This increases blood flow through pulm. artery. Musc. pulm arteries may develop laminated medial hypertrophy that can become so severe over time as to increase the pulm vascular resistence above total systemic vascular resistance. At t his point the original L-R intracardiac shunt reverses and flow becomes R-L. This switch to r-l shunting manifests as late onset cyanosis, w/ clubbing & polycythemia. Eisenmenger syndrome occurs as a result of chr. pulm. HTN, itis the reversal of shunt flow through cong. cardaic defect. Over time pulm vascular sclerosis becomes irreversible &closure of cardiac septal defect no longer can be tolerated byrt. ventricle.
External stimulus applied to cell increases activity of several enzymes including dihydrofolate reductase & DNA polymerase. What precedes the observed effect?
A. Rb protein phosphorylation. proliferation signals activate CDK4 resulting in hyperphosphorylation of Rb protein. Because hyperphos Rb is inactive, cells are allowed to transition unchecked from G1 to S phase.
SOme unknown factors may interrupt normal migration of neural crest cells to intestine. This migration is typicallycompleted by 12 weeks. If interrupted during final week of migration which organ is most likely to be affected?
A. Rectum. Hirschsprung disease is a result of abnormal migration of neural crest cells during embryogenesis. These cells are precursors of ganglion cells of intestinal wall plexi. Since neural crest cells migrate caudally, the rectum is always affected in Hirschsprung disease.Bowel is filled w stool but rectum is empty. Anal sphincter tone is increased. Rectal biopsy reveals aganglionic segment of bowel.Sigmoid colon involved in 75% cases. REctum & anus always involved. Duodenum, jejunum, ileum & cecum involvement extremely rare. Although total intestinal aganglionosis can occur, but extremely rare.
19 yo M w/ watery diarrhea for 4 months. Used antibiotics but no improvement. Persistent nausea, bloating, 6.8 kg wt. loss. Impairment of which defense mechanisms would most likely predispose to this pts condition.
A. Secretory IgA production. Diagnosis of Giardia can be confirmed by stool microscopy for ova & parasites, or fecal Immunoassays for antigens. Small bowel biopsy is sometimes performed when stool studeis are nondiagnostic, can show varying degrees of Villus Atrophy & Crypt hyperplasia depending on disease severity. MAJOR immune mech. against Giardia involve CD4 T helper cells & Secretory IgA production. Children with IgA defeciency, X Linked agammaglobulinemia, & Common Variable Immune def. have a predisposition to developing chronic Giardiasis. CD8 T Cells are not important in giardiasis, more important in Cryptosporidium parvum & T. gondii
lab animals are exposed to toxin that targets kinesin protein. What is most likely absent from tissues on histological exam as a result?
A. Secretory vessels in nerve terminals. Kinesin in microtubule assoc ATP powered motor protein that facilitates anterograde transport of neurotransmitter containing secretory vesicles down axons to synaptic terminals.
MPTP is a toxic substance that causes Parkinsonism like syndrome by destroying dopaminergic neurons in CNS. A series of experiments demonstrated that MPTP per se is minimally toxic. It is a metabolite of MPTP, produced by MAO type B & called MPP+, it causes the neuro damage. Pretretment by what minimizes damage caused by MPTP consumption?
A. Selegiline. It is an inhibitor of MAO type B and can prevent MPTP induced damge pf dopaminergic neurons. It is used clinically to delay progression of parkinsons. Many favor use of combinations of selegiline, anticholinergics & amantadine until they no longer provide control of symptoms. Only then is levodopa/ carbidopa introduced.
Ppl are studying mechanism of signal transduction involved in patho of type 2 DM. Research focuses on intracellular signaling cascade that begins when insulin binds to receptor. They demonstrate that pre-rx w/ TNF alpha results in decreased insulin mediated glucose uptake. TNF alpha effect is mediated through upregulation of which of the following processes?
A. Serine residue phosphorylation. Insulin receptor is tetramic structure consisting of 2 alpha & 2 beta subunits. Alpha are extracellular and provide binding site for insulin. Beta are intracellular and contain tyr. kinase domains that are activated when insulin attaches to alpha subunits. Series of downstream signaling is trigerred, starting w/ autophosphorylation of insulin receptor (IR), phospho. of IR substrates 1 &2 (IRS 1/2) and ultimately translocation of GLUT4 to cell membrane.TNF Alpha is proinflam. cytokine that induces insulin resistance through activation of Serine kinases, which then phospho. serine residues on beta subunits of IR &IRS1. This inhibits tyr. phosphor. of IRS1 by IR & subsequently hinders downstream signaling, resulting in resistance to normal actions of insulin. Phosphor. of THREONINE residues also has similar effects. CATHECOLAMINES, GLUCOCORTICOIDS, & GLUCAGON can also induce insulin resistance by same mech.
53 yo man w/ 7-8mo of SOB. Several coworkers have same symptoms. Has HTN & DMType2. Pulm exam- diffuse crackles. CXray-Nodular densities both lungs at apical region. Calcification of hilar lymph nodes. Biopsy of node= birefringent particles surrounded by dense collagen fibers. Exposure to what?
A. Silica. Frequently asymptomatic but can have dyspnea on exertion & productive cough. Symptoms after 10-20 y after exposure. Has calcificatons of rim of hilar nodes (eggshell calc.) & birefringent silica particles surrounded by fibrous tissue. Also think of Silica TB.Asbestosis= Interstitial pattern on CXR. Pleural plaques also noted (looks like lines at diaphragm). Histo-Ferruginous bodies, fusiform rods w/ translucent absbestos & iron coating.Berylliosis= Dyspnea, ill defined nodular or irregular opacities on CXR. histo- non caseating epitheloid granulomas w/out obvious particlesCoal workers= exertional dypnea, nodular interstitial opacities CXR. histo- coal dust laden macrophages/ coal macules
Hirschprung disease. Where do you take biopsy to confirm diagnosis?
A. Submucosa of narrow part. Normally neuralcrest cells migrate to intestinal wall and form ganglion cells in Submucosal (meissner) & myenteric (Auerbach) plexus of bowel wall. These cells migrate caudally, the rectum is always involved. The submucosa is narrowed, and it should be biopsied.The dilated portion is usually histologically unremarkable. Ganglionic cells never occur in mucosa.
53 yo dude has rt shoulder pain. helped his kid move to college & lifted stuff a week ago. Localized tenderness below acromion. Abduct arms at 90 degrees to side & flex 30 degrees forward with thumbs pointing at floor. Doc then applies downward force. Dude gets pain on rt shoulder & weakness. Which tendon is injured?
A. Supraspinatus tendon. It is most commonly effected in rotator cuff syndrome. Its vulnerable to chronic trauma from impingement b/w head of humerus & acromion during abduction. The test described in question is aka empty can test.
46yo M w/ 30 pack yr smoking history develops rt. leg pain & swelling after returning from long trip. Diagnosed w/ DVT & started on IV Heparin. Develops rt sided weakness & face droop. CT head reveals MCA stroke. What finding most likely present?
A. Wide splitting of S2 that does not change w/ respiration. Pt has paradoxical embolus, they originate in Systemic vnous circulation (upper or lower) & enter systemic arterial circulation via an intracardiac or intrapulmonary shunt. Seen in patients w/ Patent foram oale, ASD, VSD, Large pulm. AV malformations.Atrial L-R shunts cause wide and fixed splitting of S2 and can facilitate paradoxica embolism due to periods of transient shunt reversal (straining , coughing etc)
Acute decompensated heart failure
ADHF can be due to lt vent. systolic or diastolic dysfunction.Increased atrial & vent. filling pressures are transmitted to pulm vasculature, causing fluid transudation into pulm. interstitial and alveolar spaces aka cardiogenic pulm. edema. precipitating factors include- MI or ischemia, HTN severe, Valvular heart disease, A.fib (arrhythmias), drugs (cocaine)
Amyl nitrate in Cyanide toxicity
AN oxidizes Ferrous (fe2+) in Hb to ferric (Fe3+), generating methemoglobin, this diminishes cyanide's toxic effect. Methemoglobin binds & sequesters cyanide in blood freeing it from Cyt C oxidase.
ANP/ BNP & their relation NO
ANP/ BNP are polypeptide hormoes that exert effect by binding to ANP receptors. These transmembrane recptors are linke to GUANYLYL CYCLASE that converts guanosine 5'-triphosphate to cyclic guanosine 3',5'-monophosphate aka cGMP. cGMP activates a downstream cGMP dependent protein kinase leading to relaxation of vascular smooth muscle and subsequent vasodilation. NO activates same cGMP 2nd messenger system by binding a cytosolic guanylyl cyclase.
Odds Ratio
Greater than 1 indicates increased Odds/ risk likelihood. If 95% CI doesn't include 1 then the difference is significant (though not necessarily clinically significant)
Maple syrup urine disease
AR disorder, defective breakdown of branched chain amino acids (leucine, isoleucine, valine). Degradation of these first involves transamination to their respective alpha-ketoacids, which are constantly metabolized by several enzymes referred to as branched chain a-ketoacid dehydrogenase complex.BCKD complex (in addition to PDH & alpha ketoglutarate dehydrogensae) requires 5 co factors: Thiamine, Lipoate, Co-A, FAD, NAD.Some pts improve w high dose Thiamine rx, but most require lifelong diet restrictions of leucine, isoleucine, valine.
Aortic stenosis pressure tracing
AS causes pressure gradient bw LV & aortic peak systolic pressures. LVEDP & PCWP can be elevated kn pts w AS, however both these values remain in approx same range.
Pathogenesis of Cholesterol gallstones
Absence of normal enteral stimulation in pts recieving total paraenteral nutrition leads to decreased CCK release, biliary stasis & increased risk of gallstones. Resection of ileum can also increase risk of gallstones due to disruption of normal enterohepatic circulation of bile acids.
Criggler Najjar syndrome
Absent liver conjugation enzymes. Autosomal recessive (Type I) genetic lack of Uridine diphosphate glucoronyltransferase/ UGT needed to catalyze bile glucuronidation. Non hemolytic jaundice, high levels of unconjugated bilirubin often leads to brain damage in infants.
Mesolimbic pathway
Anti schizophrenic drugs block this pathway. They relieve positive symptoms of schizophrenia, by blocking this pathway.
Arcuate v Central scotoma
Arcuate- occur due to damage to a particular region of the optic nerve head. Resulting visual field defect follows arcuate shape of nerve fiber pattern.Central- lesions of macula, such as macular degeneration. MD is characterized by progressive loss of central vision due to deposition of fatty tissue aka drusen behind the retina (dry MD), & neovascularization of retina (wet MD)
PArt of kidney impermeable to water, regardless of vasopressin levels
Ascending limb of loop of henle.
Sudden cardiac death in young males.
Asymmetric septal hypertrophy suggestive of Hypertrophic cardiomyopathy. AD disorder of cardiac myocytes caused by mutations in one of several sarcomere genes encoding myocardial contractile proteins. Common mutations include single point missense mutations for Beta myosin heavy chain and myosin binding protein C
MRSA/ SA
Asymptomatic colonization of nasopharynx is most common. Not hands.
Topography of the lungs
At lower border of pleura (1), Midclavicular line (2), Midaxillary line (3), Paravertebral line (4)1. Lungs (&visceral pleura), 2. 6th rib, 3. 8th rib, 4. 10th rib1.parietal pleura, 2.8th rib, 3.10th rib, Rt-upper border, Lt-lower border, 4. 12th rib
Blood smear of Inf. mono pt.
Atypical lymphocytes are observed, they represent CD8+ cytotoxic T-lymphocytes. When activated they destroy virally infected B lymphocytes.CD 21 us receptor for C3d complement component & is found on surface of mature B lymphocytes. B lymphocytes also proliferate during ACUTE phase of EBV, but they represent ~5% of atypical lymphocytes seen on peripheral smear.
Methylmalonic acidemia
Autosomal Recessive. Organic acidemia due to complete or partial def of Methylmalonyl-CoA mutase. Complete def classically presents w lethargy, hypotonia, vomiting, & tachypnea (resp distress) in a newborn. Labs show hyperammonemia, ketotic hypoglycemia & anion gap metabolic acidosis. Diagnosis is confirmed by elevated urine methylmalonic acid & propionic acid.Propionic acidemia, a def in propionyl-CoA carboxylase also results in hyperammonemia, hypoglycemia, & met acidosis,although it does not display elevated levels of urine methylmalonic acid.
Azoles & CYP450
Azoles are antifungal meds that inhibit the demethylation of lanosterol into ergosterol in fingal cells. They exert antifungal effects by supressing synthesi of ergosterol, an essential component of fungal cell membrane. They also INHIBIT CYP450.Azole increase serum conc. of drugs metabolized by liver CYP450 enzymes. This means when used concomitantly w/ azoles drugs metabolized by liver P450 system may have increased toxicity. For this reaason Warfarin, Cyclosporine, Tacrolimus, & oral hypoglycemics should be avoided or be carefully monitored.Cyt. oxidase induceers increase azole metabolism therby lowering azole conc. in serum.
Fertilization and implantation
B-HCG produced by synctiotrophoblast after implantation (6-7d) after fertilization. It is typically detectable in maternal serum approx 8 d after fertilization whereas it is detectable in urine 14 d after fertilization. Therefore a serum pregnancy test will be +ve before urine preg test.
Cell cycle phases
Interphase- 90% of cell cycle, in this stage cell prepares for division. It is further subdivided into----G1 = synthesis of RNA, protein, lipid & carbohydrates)-S = DNA replication-G2 = ATp synthesis
Endogenous natriuretic peptides
BNP & ANP. Promote vasodilation & natriuresis & provide beneficial counter regulatory mech. in pts w heart failure. They are metabolized by enzyme Neprilysin, & inhibition of neprilysin improves outcomes in pts w chronic systolic heart failure.Neprilysin is a mettaloprotease that cleaves & inactivates endogenous peptides including ANP & BNP, glucagon, oxytocin, bradykinin. Inhibiton ofneprilysin leads to increased levels of endogenous natriuretic peptides.
Alcohol withdrawal-BZPs
BZPs w/out activemetabolites are preferred. eg: Lorazepam, oxazepam, temazepam in advanced liver disease. Alcohol, Barbiturates, & BZPs have similar effects on GABA receptors & act by enhancing GABA inhibitory action.
GERD histo findings
Basal zone hyperplasiaElongation of lamina propria papillaeScattered eosinophils & neutrophils
Glycerol pathway changes in alcoholics.
Because NADH levels are high and NAD+ levels are low in alcoholics, Glycerol-3-phosphate cant be converted to DHAP, bc Glycerol-3-phosphate dehydrogenase enzyme is lacking. This causes buildup of Glycerol-3-P.Glycerol-3-P combines w/ Fatty acids, and this causes formation of triglycerides in heaptocytes.This is why alcoholics have high levels of TG's
Menopause
Before 35y is premature FSH levels increased, due to resistant ovarian follicles & lack of feedback from inhibin. Hyperestrogenic symptoms.
Medically intreatable Parkinsons.
Benefit form high frequency deep brain stimulation of GP internus or Subthalamic nucleus. This inhibits firing of these nuclei. This increases activity of downstream nuclei resulting in Thalamo-cortical disinhibition, with improved mobility.
Amphotericin B
Binds to ergosterol in fungal cell membranes to form holes. Resultant changes in membrane permeability lead to cell death. Renal toxicity is most notorious side effect. Also causes vasoconstriction & reduction in GFR. May also act as direct toxin on renal epi cells, leading to ATN, renal tubular acidosis & electrolyte disturbances. Severe hypokalemia & hypomagnesimia (likely reflecting increased distal tubular memrane permeability) can occur, w most pts requiring supplementation. Rena; injury may also lead to decreased EPO production & produce a normochromic normocytic anemia.
biotin as a cofactor
Biotin def- excess ingestion of Avidin (found in egg whites). Presents w/ mental status changes, myalgias, anorexia, macular dermatitis, & lactic acidosis.
Fibroadenoma
Histo= typically appear cellular or myxoid stroma that encircles epithelium lined glandular & cystic spaces. Lesions have well defined border but may compress & distort surrounding glandular epi. As women age epi atrophies & stroma becomes more hyalinized
Glaucoma medications
CAIs = Carbonic anhydrase inhibitorsAlpha-2 AR = alpha-2 adrenergic receptor
fusion inhibitor, CCR5 antagonist
CCR5 antagonist = maraviroc
Cauda Equina Syndrome
CE- results from massive rupture of an intervertebral disc that is capable of causing compression of two or more of the 18 spinal nerve roots of the cauda equina. It can also occur dueto any trauma or space occupying lesion of the lower vertebral column. CE nerve roots provide th sensory & motor innervation of most lower extremeties, the pelvic floor and sphincters.classic symptoms- include low back pain radiating to one or both legs, saddle anesthesia, loss of anocutaneous reflex, bowel & bladder dysfunction (S3-S5) and loss of ankle jerk reflex w/ plantar flexion weakness of feet.
Pituitary Adenomas
CELL TYPE & CLINICAL FEATURES OF TUMOR.-Lactotroph (prolactin)--> Hypogonadism, infertility (males). Galactorrhea, amenorrhea (females)-Corticotroph (ACTH)--> Cushings disease-Somatotroph (GH)--> Acromegaly & gigantism-Thyrotroph (TSH)--> Thyrotoxicosis-Gonadotroph (LH, FSH)--> Nonfunctioning (hypopitutitarism), mass effect.
Superior orbital fissure
CN III, V1, IV, VI & sup ophthalmic vein enter orbit via sup orbital fissure
Inf orbital fissure
CN V2, infraorbital vessels, branches from sphenopalatine ganglion pass through Inf orbital fissure but do not enter orbit.
Weber Syndrome
CN3, corticobulbar & corticopinal tract.oculomotor palsy. Contralateral hemiparesis, Pseudobulbar palsy- UMN CN motor weakness, exaggerated gag reflex, spastiv tongue (no wasting), spastic dysarthria
Indications for anticholinergic medications
CNS- Effect= sedation. in toxic doses psychosis. Use= motion sickness (scopolamine) Parkinsons (benztropine)Eye- effect= mydriasis, cyclopegia (paralysis of accomadation) Use= ophth exam, rxof uveitis, CONTRAINDICATED IN GLAUCOMA`Heart- effect= tachycardia. use= sinus bradycardia, heart block (atropine)Secretions- effect=decrease lacrimation/ sweating/ salivation/ GI & bronchial secretions. Use= premedicate before anaesthesia (atropine, scopalamine)Bladder- effect= detrusor relaxation, delays voiding. use= neurogenic (spastic) bladder (oxybutynin)Bronchi- effect= bronchodilation. use= asthma & COPD (ipratropium)
INO
COnvergence & pupillary light reflex usually preserved
Congenital heart defects
CYANOTIC - Ebsteins, TOF, Tricuspid atresia, Transposition of great vessels. Truncus arteriosus, TAPVRNON CYANOTIC - ASD, VSD, PDA, Coarctation of Aorta
Drugs that affect Warfarin Metabolism
CYP450 Inhibitors (Increase warfarin effect)- Acetaminophin, NSAIDs, Antibiotics/fungals, Amiodarone, Cimetidine, Cranberry, Gingko, Vit E, Omeprazole, Thyroid hormone, SSRIsCYP450 Inducers (Decrease W effect)- Carbamazepine, Phenytoin, Ginseng, St.Jons wort, OCPs, Phenobarbitol, Rifampin.
Stop codons
Call for termination of protein synthesis. UAG, UAA, UGA do not code for amino acids or bind tRNA. Instead when ribosome encounters a stop codon, releasing factor proteins bind to ribosome & stimulate release of formed polypeptide chain & dissolution of ribosome-mRNA complex.
AV fistulas
Can be congenital or acquired. Acquired forms can rsult from medical interventions or penetrating injuries. AV shunts increase preload and decrease afterload by routing blood directly from the arterial system to venous system, bypassing the arterioles. High volume AV shunts can eventually result in high output cardiac failure.
SGLT 2 (sodium glucose co-transporter 2) inhibitors
Canagliflozin, DapagliflozinMOA- increases renal glucose excretions/e- UTI, hypotension
Medicare v Medicaid
Care= federal socialized med. insurance prog. that covers ppl older than 65 who have work history. And disabled ppl.Aid= state run med. insurance prog that covers homeless, undocumented immigrants, preg women, low income fams
baroreceptors & peripheral chemoreceptors
Carotid body receptors = Glossopharyngeal nerveAortic arch receptors = Vagus nerve
Lactulose
Catabolized by intestinal bacterial flora to the Short Chain fatty acids, lowering in Colonic pH & increased conversion of ammonia to ammonium (NH4)
Unbalanced Robertsonian translocations
Cause a minority of Down syndrome cases. Karyotyping shows 46 chromosomes w/ a translocation bw 2 acrocentric nonhomologous chromosomes eg: 46XX t(14,21)Whenan ovum containing translocated chromosome & a normal Chr21 is fertilized w a sperm containing normal set of chromosomes, the fetus has unbalanced robertsonian translocation. Has 3 effective copies of chr21. Another possible maternal gamte includes 0 copies of Chr 21, which increases rate of miscarriages in balanced Robertsonian translocation carriers.
Staphylococcal Scalded skin syndrome
Caused by some strains of Staph. that produce exfoliatin exotoxin. Exfoliative toxins show pathologic specificity in blistering only superficial epidermis. They act as proteases & cleave desmoglein in desmosomes. Bullous impetigo is more localized form of SSSS w/ bulla formation being another effect of exfoliative toxin.ENDOTOXIN mediated inflam. response is frequently the cause of septic shock during -ve as well as some gram +ve infections (listeria). not a cause of SSSS.
Il-6
Causes fever & stimulates production of acute phase proteins.Secreted by macrophages.
Il-1
Causes fever, acute inflammation. Activavtes endothelium to express adhesion molecules. Induces chemokine secretion to recruit WBCs.Secreted by macrophages
Gaucher disease
Cell looks like wrinkled paper/ silk. They are lipid laden macrophages. FOund throughout body, like liver bone marrow & lymphatic tissue
Painful genital lesions
Chancroid (H. ducreyi)- multiple deep ulcers. Basemay have grey/ yellow exudate. Organisms often clump inlong parallel strands (school of fish)Genital herpes (HSV 1 &2)- Multiple, small grouped ulcers. Shallow w erythamatous base. Multinucleated giant cells & intranuclear inclusions. (Cowdry Type A)
Chronic Glucocorticoid Usage
Characterized by low CRH, ACTH and Cortisol levels that cannot rise in response to stressful stimuli. This lack of stress repsonse can result in relative glucocorticoid deficiency even when patients baseline glucocorticoid regimen is maintained.
Bisphosphonates
Chemical structure is similar to pyrophosphate and disrupt osteoclast function by attaching to hydroxyapatite binding sites on bony surfaces.
Cardiac action potential
Class I antiarrhythmics-> inhibit initial depolarization, & prolong QRS duration. IA= prolong QRS & QT interval due to moderate K channel blocking activity. IB= no sig effect on QRS or QT during normal sinus rhythm due to rapid dissociation from receptor. IC= prolong QRS w minimal effect on QT interval due to lack of K channel blocking.Class III-> predominantly block K channels & inhibit outward repolarizing currents during Phase 3 of AP. This increases AP duration & QT interval prolongation.Ca channel blockers-> inhibit L-type Ca channels during Phase 2 of depolarization of AP. Slow sinus rate & prolong conduction through AV node & depress Heart contractility.Phase 1 & 4 of AP not significantly affected by anti arrhythmics.
Coarctation of Aorta
Classified into Preductal & postductal. Symptoms depend on age pf presentation & severity of stenosis.Severe- usually in infancy w/ differential cyanosis affecting lower limbs as long as ductus arteriosus is patent. on ductal closure neonates can dvelop signs of heart failure & shockmoderate- presents in childhood or teenage w/ symptoms of lower extremity claudication (pain & cramping w exercise), BP discrepency bw upper & lower limbs, and delayed or diminished femoral pulses. Continuous murmurs & pulsatile intercostal collaterals can also develop seconday to restricted circulation.
Insulin synthesis & secretion
Cleavage of proinsulin in pancreatic B-cells secretory granules yields insulin & C-peptide, which are stored in granules until they are secreted in equimolar amounts.
Treatment resistant Schizophrenia
Clozapine is drug of choice.
Cerebral amyloid angiopathy
Commonly presents as ELDERLY pt w recurrent LOBAR HEMORRHAGE. most common cause lobar hem. in adults >60yo. Usually involves occipital & parietal lobes.Amyoid angiopathy is consequence of B-amyloid deposition in walls of small-medium size cerbral arteries, resulting in vessel wall weakening & predisposition to rupture. NOT assoc w systemic amyloidosis, but more similar to alzheimers.
Rx of Myasthenia Gravis
Cholinesterase inhibitors, immunosuppresents, thymectomy. CHolinesterase inhibitors may cause adverse effects related to muscarinic overstimulation, which can be ameliorated by use of antimuscarinic agent such as Hyoscyamine, Scopalamine. They don't affect the action of cholinesterase inhibitors on SKM (bc they use nicotinic recpetors).
Adrenal medulla-chromaffin cells
Chr cells are modified post ganglionic sympathetic neurons derived from neurall crest that recieve symp. input (neuroendocrine cells). Stimulayed by Ach released by symp preganglionic neurons & secrete catecholamines-80% Epi 20% norepi, directly into bloodstream to amplify symp nervous system activity
Person what anxiety. treat with what?
Citalopram. Anxiety is treated with CBT or medication. Meds= SSRIs and SNRIs are first line. BZPs less preferred in chronic anxiety. they are 2nd line drugs bc of risk of dependence and tolerance, potential for rebound and withdrawal.
thoracic outlet syndrome
Compression of lower trunk of brachial plexus in scalene tirangle, the space bordered by ant. & middle scalene muscles & 1st rib. Symptoms include upper extremity numbness, tingling & weakness.In addition compression of subclavian vein can cause upper extremity swelling whereas compression subclavian artery can cause ext. arm pain.
Risk factors for Cervical ca
Consistent use of barrier methods to prevent STDs esp. HPV
Chronic Myelogenous Leukemia
Constitutional symptoms (eg: fatigue, weight loss, excessive sweating), splenomegaly & leukocytosis w marked left shift. (eg: myelocytes, metamyelocytes, band forms)Mutation- Philadelphia chromosome. t(9;22) BCR-ABL fusion protein
Supinator canal
Contains Radial nerve. Injury causes "finger drop"- weakness & thumb extension. Caused by repetitive supination & pronation. No sensory defects. DO NOT confuse w/ carpal tunnel/median nerve injury.
pathogenesis of crescent formation in rapidly progressive glomerulonephritis
Crescents in RPGN consist of proliferated glomerular parietal cells, monocytes, & macropohages that have migrated into Bowman's space as well as abundant fibrin bw the cellular layers of the crescents. As disease progresses crescents become sclerotic & obliterate Bowman's space, thus impeding glomerular function.
Cryptogenic stroke
Crypt. stroke is evaluated w/ echo w/ a bubble study to identify R-L intracardiac shunts. Study is performed by injecting agitated normal saline IV & observing for microbubbles in Lt heart. Shunt detection is improvedby having pt. release a sustained valsalva maneuver, which increases Rt atrial pressure. Commonly assoc w/ patent foramen ovale(more common) & ASD
Vas deferens
Cystic fibrosis- absence of vas deferens. That is cause of MALE infertilityKartegeners- No absence of vas. Male & Female infertility.
What happens during Inspiration in newborn?
Decreased intrathoracic pressure-->decreased resistance in pulm vasc-->moreblood entering pulm artery, more blood returning to LA. Increased LA pressure-->leads to closure of Foramen ovale. leads to highly oxygenated aortic blood-->closure of ductus arteriosus
Internuclear ophthalmoplegia
Disorder of conjugate horizontal gaze in which the affected eye (ipsilalteral to lesion) is unable to adduct & the contralateral eye abducts w/ nystagmus. COnvergence & pupillary light reflex preserved. Typically occurs w/ damage to heavily myelinated fibers of MLF. MLF is paired neural tract that mediates communication between CNIII & VI nuclei allowing for coordinated horizontal eye movements. conjugated horizontal eye movement is initiated w/ activation of frontal eye fields in cerebral cortex. Frontal eye field projects to contralateral paramedian pontine reticular formation, which then sends effernts to the ipsilateral CN VI nucleus at level of facial colliculus in dorsal pons. subsequent;y CN VI nucleus projects to ipsilateral lat. rectus muscle & contralateral medial rectus subnucleus of CN III via MLF.
Pulmonary artery catheter waveforms
During Pulm artery catheterization, the balloon at distal tip of catheter is inflated, and catheter is advanced forward through Rt. atrium, Rt. ventricle, & pulm artery andfinally into a branch of Pulm artery. Once lodged in a pulm artery branch, inflated ballon obstructs forward blood flow, creating a continuous static column of blood bw catheter tip & Lt. atrium. Pressure emasured at catheter tip is called Pulmonary artery occlusion pressure or PCWP and closely reflects Lt atrial & Lt ventricular end diastolic pressures.
Orotic aciduria
Excess orotic acid also found in citrullinemia & OTC def. these have hyperammonemia.
Pt has tremor which improves w alcohol consumption
Essential tremor. Most commonly diagnosed movement disorder. Aka familial tremor, it AD inheritance. It worsens while maintaining a particular posture (eg; when holding an object). Propranolol is 1st line rx , this nonselective B-adrenergic antagonist is thought to lessen the tremor via CNS effects.Benztropine can be used to treat Parkinsons tremor & extrapyramidal s/e of neuroleptic meds.
Inactivity of viral particles after exposure to ETHER
Ether & other organic solvents can inactivate "enveloped" viruses. Which by defenition have an outer lipid bilayer coat acquired from host cell plasma ornuclear membranes. Solvent induced disruption or dissolution of envelope lipid results in a loss of viral infectivity. Non enveloped viruses are generally resistant!
Lithium toxicity
Etiology: Overdose, Volume depletion (decreased GFR), Drug interactions- thiazides, NSAIDs, ACE inhibitors, Tetracyclines, MetronidazoleFeatures: ACUTE Toxicity- GI (nausea, vomiting, diarrhea), Late neuro sequelae. CHRONIC Toxicity (neurologic)- Confusion, agitation, ataxia, tremors/fasciculationsManagement: Hemodialysis for severe cases.
32yo white F has 3 eps of dvt in 6yrs. Also has pulm embolism. PTT is within limits, and unchanged after activated protein C is added to plasma.
Factor V leiden mutation. inherited. factor Va is resistant to onactivation by activated protein C. Approx 2-15% Caucasians carry it.Other casue of hypercoagulability is anti-Phospholipid Ab syndrome. Pt has antiphospholipid ab's (lupus anticoagulant and/or anticardiolipin antibodies. Frequent fetal loss is seen. But pts have prolonged baseline aPTT.
Neural tube defects
Failure of fusion of neural plate edges around 4th week. If opening persists b/w neural tube & amniotic cavity, it allows leakage of Alpha-fetoprotein & AchE into amniotic fluid.
Reddit pearl- Fibrates
Fibrates activate PPAR-a--causes upregulation of LPL ----results in descreased TGs. PPAR-a also upregulates production of Apo A-I & A-II and downregulates ApoC-III. Apo A-I activates LCAT, helps form mature HDL, resulting in increased hdl.relationship- Fibrate > PPAR-a > Apo A1 > LCAT > HDLFibrate > PPAR-a > LPL > Clearance of Tgs.if hdl goes up VLDL goes down bc hdl is made from vldl.
Antihyperlipidemic agents
Fibrates activate PPAR-alpha which decreases hepatic VLDL production and increased LPL activity. Fish oil supplements contain high omega-3 fatty acids, also decrease vldl production and inhibit synthesis of apolipoprotein B.
Folate & nucleotide synthesis
Folate def inhibits synthesis of nucleic acids, particularly formation of deoxythymidine monophosp (dTMP). This leads o defective DNA synthesis that characteristically causes increaed apoptosis of hematopoietic cells & megaloblastic anemia. Thymidine supplementation bypasses this enzyme and can reduce erythroid cell apoptosis.
anti Alcohol drugs
Fomepizole- inhibits Alcohol dehydrogenase. Usually given in treatment of methanol & ethylene glycol toxicityDisulfram- inhibits aldehyde dehydrogenase. It increases levels of Acetaldehyde. This causes sweating flushing palpitations, nausea & vomiting. Usually given in chronic alcoholics, to cause aversion.
Zinc fingers
Found in larger portion of other proteins. Zinc finger or motifs bind to other proteins, RNA or DNA.Often bind to other DNA sequences, they influence or modify the gene and genes activity.
Gs protein coupled receptors
Found on cell membrane. PTH & glucagon act here, by binding their respective ligands subsequently activates adenylyl cyclase & increases cAMP conc.
Fructokinase deficiency
Fruc. is converted by Hexokinase to Fru-6-Phosphate. Which then enters Glycolysis.This pathway not active in normal inducviduals.
Some drug s/e
Ganciclovir- interferes w/ human host cell DNA (more than acyclovir). Major s/e are neutropenia, anemia, thrombocytopenia, & impaired renal functionTMP-SMX- inhibit THF which contributes to purine & pyrimidine synthesis. As a result assoc w/ bone marrow supression.Zidovudine- inhibits some mammalian DNA polymerases, also assoc w/ bone marrow supression (anemia, thrombocytopenia etc)Didanosine- antiretroviral. pancreatitisFoscarnet- assoc w/ numerous electrolyte abnormalities, including hypocalcemia, hypokalemia, hypomagnesemia, & hypophosphatemiaAmiodarone- hypothyroidism, hyperthyroidism or thyroiditis.
Cell connections
Gap junctions- Specialized intercellular connection b/w multitude of cells. They directly connect the cytoplasm of 2 cells which allows various molecules, ions & electrical impulses to pass directly. Present in osteocytes,epithelia, cardiac muscles, smooth muscle, nerves . Tight junctions/zonua occludens- apices of glandular cells & consist of 2 closely adherent cytoplasmic membranes w/out intervening space. They are first component of junctional complex.Intermediate junctions/ zona adherens- delicate network of cytoplasmic filaments that radiate from cell membrane to hold adjacent cells together.
Clue cells
Gardnerella Vaginalis. Clue cells are squamous cells covered w/ rods to obscure normal epithelial margins
Roux-en-Y gastric bypass
Gastric bypass can cause small intestinal bacterial overgrowth (SIBO) due to excessive bacterial proliferation in the blind ended gastroduodenal segment. SIBO results in def of most vitamins (B12, A, D, E) & Iron. But there increased production of Folic acid & Vit K
Splenic vein thrombosis
Gastric varices can be seen w splenic vein thrombosis, due to chronic pancreatitis, pancreatic cancer, & abd tumors.
Reassortment.
Genetic shift in fluA virus involves reassortment of genomic segments of human strain w/ segments of animal strain, typically when both strains co infect birds or pigs. REsulting new strain can cause new flu pandemic or epidemic, if it has dramatically altered viral surface gylcoproteins (hemagglutinin) The key structural feature that enables flu virus to undergo such relatively rapid genetic shifts through reassortment is SEGMENTED nature of their genomes. Members of other virus group w/ segmented genome can also undergo such reasortment- as opposed to less radical slower genetic drift that occurs via POINT MUTATIONS. Segmented viruses include- rotavirus, orthomyxovirus, reovirus, bunyavirus, arenaviruses.
Monosaccharides
Glucose, Fructose, Galactose
Hep B markers
HBsAg- detectable during acute inf. persistence after 6 mo indicates chronic inf.Anti-HBs- confers long term immunity, indicates resolution of acute inf. or vaccinationAnti HBc IgM- Present during WINDOW PHASE when both HBsAg & anti HBs are asbentAnti HBc IgG- present in acute & chronic inf. not present after vaccinationHBeAg- marker of high viral replication activity in chronic inf.Anti HBe- presence in chronic inf indicates low viral replication & infectivity.
Hypospadias vs Epispadias
HYPO- Incomplete fusion of urethral/ urogenital folds results in hypospadias. abnormal opening of urethra proximal to glans penis along ventral shaft of penis.EPI- Genital tubercle becomes penis & clit. Epispadias is abnormal opening of urethra on dorsal surface of penile shaft, results from faulty positioning of genital tubercle in 5th wk gestation.
Edrophonium test
Helps differentiate 2 conditions. Clinical improvement after admins. indicates that the pt is under treated (myasthenic crisis)If temp improvement after initial admins. seen, it indicates ot hs Myasthenia Gr.
Blood filled vascular spaces in liver biopsy
Hemangioma
SLE blood changes
Hemolytic anemia (decreased erythrocyte count), leukopenia, thrombocytopenia, hypocomplementemia (decreased C3 & C4)SLE isType 2 hypersensitivity, after immune complex deposition it changes to T 3 hypersensitivity.
Hep B assists which of the following life cycle aspects of Hep D virus.
HepD Ag is considered replication defective as it must be COATED by the external coat HBsAg of Hep B virus to penetrate the hepatocyte. HDvirus can arise either as an acute co infctin with hep b or a superinfection of a chronic hep b carrier.HBsAg of hbv must coat HDAg of hep d virus before it can infect hepatocytes and multiply.
reyes syndrome
Hepatic findings= characteristic microvesicular steatosis, light micro. shows small fat vacuoles in cytoplasm of hepatocytes. Electron micro. shows swelling, decreased number of mitochondria & glycogen depletion. AST & ALT increased, Ammonia & bilirubin increased. Prolonged Pt & PTT.
5yo kid w/ jaundice and tiredness. Has recent URI. recovers spontaneously. Paplable splenomegaly, pallor and scleral icterus. Retic count-10.8%, Hb-9. Total bil-3.
Her. Spherocytosis. RBC Membrane cytoskeleton abnormality (Spectrin & Ankyrin). AD inheritance. In northern european ppl. MCHC increased. Spherocytes on smear ( no central pallor of RBCs). -ve Coombs test. Increased osmotic fragility on acidified Glycerol lysis test.Complications: Pigmented gallstones. Aplastic crises from parvovirus B19 inf.
MODY- Mature onset Diabetes of young
Heterozygous mutations of Glucokinase gene cause a decrease in beta cell metabolism of glucose, less ATP formation, and diminished insulin secretion. This produces MODY, which is characterized by mild, non progressive hyperglycemia that often worsens with PREGNANCY induced insulin resistance. Homozygous mutations lead to fetal growth retardation & severe hypoglycemia at birth.
Fructokinase deficiency
Hexokinase takes over role of fructose metabolism.
alcohol synthesis- accumulation of fatty acids
High NADH levels stall B-oxidation. there is less FA breakdown. And bc TCA cycle is slowed, FA synthesis increases.Rate limiting step of FA synthesiss is Acetyl CoA carboxylase, converts acetyl coA to Malonyl CoA.Increase in Malate levels also increases FA syn.
Graves ophthalmopathy
High dose glucocorticoids such as prednisone are useful for control. They are helpful in decreasing the severity of inflammation and decreasing extraocular volume. Conventional antithyroid drugs don't improve opthalmopathy
Permeability of nephron to water
High permeability= Glomerulus, PCT, descending limbNon permeable= Thick & thin ascending limb, Early DCTVariable= Late DCT, Collecting duct.
Tongue motor innervation
Hypoglossal nerve w exception of palatoglossus muscle which is innervated by Vagus nerve.
Eukaryotic Topoisomerase I & II inhibitors
I = Irinotecan / topotecanII = Etoposide / TeniposideFluoroquinolone inhibit PROKARYOTIC toposiomerase II(dna gyrase) & IV
Most imp. opsonins
IgG, Complement C3b, mannose binding lectin, C Reactive protein.
Rotor syndrome
Impaired canalicular bile transit. Autosomal recessive. Asymptomatic conjugated hyperbilirubinemia that results from numerous defects in hepatic uptake & excretion of bilirubin. Pts are often jaundiced but have normal life expectancy. No black liver.
Bohr haldane effect
In Lungs, binding of O2 to Hb drives releas of H+ & CO2 form Hb (haldane effect). In peripheral tissues high conc. of CO2 & H+ facilitate O2 unloading from Hb (Bohr effect)
Delirium treatment
In elders Low dose anti-psychotics (eg-Haloperidol) are medications of choice to treat behavioural & psychotic manifestations of delirium.
Cortisol mechanism of action
In inactivated state cortisol receptors are found within cytoplasm in assoc. w/ heat shock proteins. Binding of cortisol to carboxy terminal portion of receptor causes release of heat shock proteins & receptor dimerization. Activated heterodimers are then transported to nucleus where they control gene expression by binding to hormone responsive DNA elements in the promotor region of target genes.Cortisol increases transcription of enzymes involved in gluconeogenesis (formation of glucose from fat & protein substrates) as well as those involved in lipolysis & proteolysis
Parvovirus B19
In kids- Erythema infectiosum aka 5th disease aka Slapped cheekIn adults- Acute symmetric arthropathy. Self limiting & non destructive.
Cirrhosis indicators
Increased AST & ALT of hepatocellular damageIncreased ALP & GGT indicate biliary injurySerum albumin & bilirubin levels, Prothrombin time reflective of liver function & are of greatest PROGNOSTIC SIGNIFICANCE w/cirrhosis
DIC
Increased PT, PTT & D-dimers
Hashimotos thyroiditis
Increased TSH, Decreased T4, T3 levels variable bc of short 1/2 life, Normail until relatively late stage hypothyroidism.
Causes of Gout
Increased Urate production- Primary gout(idiopathic), Myeloprolifereative/ lymphoproliferative diseases, Tumor lysis syndrome, HGPRT def.Decreased urate clearance- Chronic kidney disease, Thiazide/ Loop diuretics
Optic disc in glaucoma
Increased cup:disc >0.6. THinning of disc rim. Pale disc (optic nerve atrophy)
Pneumothorax
Increased lucency on affected side. tension pneumo trachea deviates AWAY from affected lung. bc excess air pushes against mediatinal structures
Eccentric & Concentric hypertrophy
Increased wall thickness = ConcentricIncreased cavity size = Eccentric
CYP450
Inducers- carbamazepine, barbiturates, phenytoin, rifampin, griseofulvin, st johns wort, modafinil, cyclophosphamide.Inhibitors- amiodarone, cimetidine, fluorquinolones, clarithromycin, azoles, grapefruit, isoniazid, ritonavir (protease inhibitors)
IL-12
Induces diferentiation of T cells into Th1 cells. Activates NK cells.Secreted by macrophages.
IL-4
Induces differentiation of Tcells into Th2 cells. Promotes growth of B cells. Enhances class switching to IgE & IgG.from Th2 cells.
Thyroid Surgery
Inf thryoid artery (branch of subclavian)- supplies ant neck along w/ sup thyroid artery.----Inf thyr. artery close to RECURRENT laryngeal nerve. can be injured in surgery.Sup thyr artery---close proximity to sup laryngeal nerve.
Hyperglycemia
Infection, pain, sleep deprivation . these stressful situations increase glucose by decreasing pancreatic insulin secretion & by increasing glycogenolysis & gluconeogenesis.
orbital floor fracture
Infraorbital nerve, continuation of maxillary nerve is damaged in #. Damage can result in numbness & paraesthesia of upper cheek, upper lip, & upper gingiva. In addition Inf. rectus muscle may get trapped limiting vertical gaze.
GLUT-4
Insulin dependentIn fat, skeletal muscle. Take up glucose only when Insulin levels are high & store it as fat or glycogen. (exercise can also increase GLUT4expression)
GLUT 1
Insulin independent transporters (uptake when glucose is high)In Brain, cornea, placenta and RBCs
GLUT-2
Insulin independent. Bidirectional (gluconeogenesis)In liver & kidney. Intestine (glucose out of epi cells to portal vein). Pancreas ( β islet cells)
PI3K / Akt / mTOR pathway
Intracellular signaling pathway imp. for anti-apoptosis, cellular proliferation & angiogenesis. Mutations in groth factor receptors, Akt, mTOR or PTEN that enhance this pathways activity contribute to cancer pathogenesis.
Tibial nerve
Larger of 2 terminal branches of sciatic nerve. Damage may result in difficulty w foot plantar flexion & inversion, toe flexion., and decreased sensation over sole.
LR6 SO4
Lat rectus- innervated by CN VISup oblique- innervated by CN IVAll other extraocular muscles are innervated by CN III
HPV Strains
Low risk strains = 6 & 11. cause condyloma acuminatahigh risk= 16,18, 31. they arae integrated into human genome leading to overexpression of viral oncogenes E6 &E7. E6 binds to p53 gene & increases its degradation. E7 binds to RB1 and displaces transcription factors normally bound by pRB, the tumor suppressor protein product of RB
Selective Arteriolar vasodilators side effects
Lower BP by reducing SVR. However this effect is limited by stimulation of baroreceptors w/ resulting reflex sympathetic activation. This increases HR, Contractility, & CO. In addition symp. stimulation of RAAS axis results in Na2+ & fluid retention w peripheral edema. These effects offset much of the BP lowering effect of these druugs & limit their long term efficacy.Can be given w sympatholytics & diuretics to mitigate the side effects & provide synergistic BP lowering inpts w resistant HTN.
Postpartum ovarian vein thrombosis
Lt ovarian vein drains into lt renal vein, while the rt ovarian vein drains directly into IVC.
Descending colon cancer
Lt sided cancer usually at rectosigmoid colon, tend to be smaller. Often infiltrate wall of colon encircling it & narrowing the lumen. More likely to cause obstruction & pts generally have altered bowel habits, abd distension & nausea/ vomiting.
Sectional anatomy of spinal cord
Lumbar has Dorsal & Ventral nerve roots.Sacral only has dorsal nerve roots.
Transmembrane domain- Gprotein coupled recptors
Madde up of Non polar hydrophobic amino acids (Alanine, Valine, Leucine, Isoleucine, Phenylalanine, Tryptophan, Methionine, Proline, Glycine)These AA's ar arranged in alpha helical fashion & project their hydrophobic R groups outwardly anchoring the transmembrane domain may also play an important role in cellular signaling & transport.
Stages of acute tubular necrosis
Maintenance stage = Decreased urine output, fluid overload, increasing creatinine/ BUN, hyperkalemia. Anion gap met. acidosis, hyperphosphatemia.Recovery phase = Gradual increase in urine output leading to high volume diuresis. Electrolyte abnormalities include -decreased K, Mg, PO4, & Ca, due to slowly recovering tubular function. PT CAN BECOME DEHYDRATED
IL-8
Major chemotactic factor for neutrophils.Secreted by macrophages
Re infection w Influenza virus
Major mechanisms that prevent re infection include anti-hemagglutinin antibodies. neuraminidase antibodies are not as effective, though they may have some protective action (decrease extent of virus invasion & shedding).Innate immunity doesn't appear to prevent primary flu or reinfection. Best prevented by adaptive immunity.
Anterior nuclei
Mediates heat dissipation, destruction leads to hyperthermia
Ventromedial nuclei
Mediates satiety, destruction leads to hyperphagia
Biguanides
MetforminMOA- stimulates AMP-activated protein kinase, decreasing glucose production & insulin resistances/e- Lactic acidosis. esp. in older pts & those w hepatic or renal dysfunction. Renal function should be assessed by serum creatinine measurement prior to initiation of therapy. Metformin should be avoided in congestive heart failure or alcoholism due to increased risk of lactic acidosis.
Urea cycle/ Ornithine transcarbamylase (OTC) defeciency
Most common urea cycle disorder. It results in excesss carbamyl phosphate, which stimulates pyrimidine synthesis. A intermediate at this pathway orotic acid accumulates & iis increased in urine.Pts have hyperammonemia, due to impaired excretion, which is metabolic emergency. Metabolic decompensation is often triggered by illness, fasting or increased protein intake. Carbamoyl phos synthetase 1 & N-Acetylglutamate synthetase also result in hyperammonemia, levels of CArb,phos are LOW and orotic acid isn't elevated in piss.Uridine monophosphate synthetase (UMPS) defeciency leads to orotic acid build up but no hyperammonemia. Findings include megaloblastic anemia & delayed growth.
Unfractioned Heparin
Most effective inactivating thrombin. It can bind to both antithrombin & thrombin. Allows antithrombin to inactivate thrombin.
K filtration in kidney
Most of K+ filtered by glomeruli is resorbed in PCT & loop of henle. Late distal & cortical collecting tubules are primary sites for regulation of K+ conc. in urine. K+ depletion stimulates alpha-intercalated cells to reabsorb extra K, principal cells secrete K+ under normal conditions or increased K load.
Assessing severty of Mitral Regurg.
Mostly by Doppler &2D echo. On auscultation best indicator of SEVERE MR w/ lt. vent. volume overload is presence of S3 gallop. The intensity of holosystolici murmur does not correlate w regurgitant volume as larger regurgitent orifices often present w softer murmurs.
Length & time constant in MS
Multiple sclerosis. decrease in conduction velocity and increased time constant. Decreased length constant aka space constant
Op poisoning treatment w/ atropine. pt still at risk for what?
Muscle paralysis. b/c atropine only reverses muscarinic symptoms but has no effect on nicotinic receptors. Pralidoxime reverses both muscarinic and nicotinic effects.
Charcot-Marie-Tooth
Mutation in myelin protein gene.weakness of foot dorsiflexion due to involvement of common peroneal nerve.
Adverse effects of some HIV antiretrovirals
NRTIs- Lactic acidosis, Lipodystrophy, Hypersensitivity reaction (abacavir), Pancreatitis (didanosine), Bone marrow suppression (zidovudine)NNRTIs- Rash (SJS), Hepatotoxicity, neuropsych effects & teratogenicity(efavirenz)PI- Met complications (lipodystrophy, dyslipidemia, insulin resistance)II-myopathy
important respiratory tract infections in children
Nasopharyngitis (common cold) = rhinovirus inflienza virus, coronavirusLaryngotracheitis (croup) = parainfluenza virus. URI w hoarseness, barking cough, stridor & resp distressDiptheria = C. diptheriaeEpiglottitis = H. influenzae. Sore throat, dysphagia, drooling & resp distressBronchiolitis = Resp syncytial virus. wheezing, cough & resp distress
Prolonged PT & aPTT
PT-> indicates defect inExtrinsic pathway. most likely factor VII def.aPTT-> 1.Factor VIII def. in classic Xlinked Hemophilia A (Normal BT & PT).2. Factor XI def results in rare AR disorder called Hem.C. Prolonged aPTT & normal PT. spontanoeous bleeding rare, but increased risk following surgery or trauma.3. Factor XII (Hageman factor) def is AR, doesn't cause prolonged bleeding. aPTT prolongation
Scaphoid # - Avascular necrosis
Pain in anatomical snuffbox of hand indicates scaphoid #. Diagnosis made by MRI. Avascular necrosis of proximal 1/3 scaphoid is most common. Bc it derives blood from DORSAL BRANCHES OF RADIAL ARTERY. -Displacement of lunate results in median nerve damage. # is rare.-Injury to hook of hamate results in ulnar nerve injury.
Features of pituitary apoplexy
Patho-caused by acute intrapituitary hemorrhage, occurs most often in preexisting adenomaPresents as- Severe headache, Bitemp. hemianopsia, Ophthalmoplegia, Panhypopituitarism. Can develop rapid cardiovascular collapse due to ACTH DEF & subsequent adrenocortical insufficiencyDiagnosis- imaging shows pit. enlargement & signs of hemorrhageRx- Glucocorticoid replacement (critical to prevent life-threatening hypotension), Surgical decompression for persistent visual symptoms.
pacemaker action potential
Phase 4= spontaneous depolarization. begins after hyperpolarization triggers the opening of HCN channels that allow slow influx of Na ( funny current). T-type (transient) Ca channels then open once membrane potential becomes +ve, allowing Ca2+ influx to contribute to depolarization. As pacemaker cell approaches threshold L-type (long lasting) Ca channels begin to open, which further increases Ca influx & significantly decreases the time until threshold is reached.Phase 0= upstroke. characterized by continued opening of L type Ca channels. In cardiac slow response tissues the AP upstroke is much slower & transitions gradually from phase 4 due to relatively slow influx of Ca into cell.Phase 3= repolarization. opening of K channels & efflux of K from cell in conjunction w closure of L type Ca channels.
experimental rats undergo resection of pituitary gland, and controls undergo craniotomy w/out pituitary resection. Experimental animals are found subsequently to have decreased production of epinephrine by adrenal medulla compared w/ control animals. Decreased activity of which enzyme is responsible?
Phenylethanolamine-N-methyltransferase / PNMT. It converts Norepi to epinephrine in adrenal medulla. Expression of PNMT upregulated by cortisol. Following pit. gland resection ACTH secretion and subsequent cortisol production is low. this results in decreased PNMT activity. COMT & MAO are responsible for breakdown of catecholamines. COMT converts epi to metanephrine & norepi to normetanephrine. MAO converts metanephrine & normetanephrine to vanillylmandelic acid.
Power. Type I(α) & Type II (β) error
Power= the power of a study is to detect a difference b/w groups when such a diff. truly exists. Power is related to type II error, where probability of concluding there is no difference b/w groups when one truly exists. Power= 1 - βType I error is probability of seeing a difference when there is no difference in reality. The value of α is generally compared to probablity that the observed difference is due to chance alone (simplified explanation of p-value).
Reactive arthritis
Preceding Infection- GU infection (Chlamydia Trach.). Enteritis (Salmonella, Shigella, Yersinia, Campylobacter, C. Diff)Musculoskeletal- Asymmetric oligoarthritis, enthesitis, dactylitisExtrarticular symptoms- Ocular (Conjunctivitis,ant. uveitis), Genital (Urethritis, cervicitis, prostatitis), Dermal (keratoderma blennorrhagicum, circinate balanitis), Oral ulcers.
Cells rich in Rough ER
RER is site of protein synthesis. RER has membrane bound ribosomes (produce protein for secretion, protein hormones, digestive enzymes). Nissl bodies are RER in neurons, they secrete neurotransmitter.Cell types- Goblet cells of intestines (mucus), Plasma cells (antibodies), Pancreatic beta cells (insulin)
Tetralogy of Fallot
RV outflow tract obstr., RV hyoertrophy, VSD, Overriding aorta. RVOT causes Pulmonic stenosis.Boot shaped heart.
Von Hochstetter triangle
Safest place for dorsogluteal injections. However Gluteal & sciatic nerves can still be damaged from injections into this region.Safest place for inj is superolateral quadrant for intragluteal inj, although anterolateral gluteal region is preferred.
Aschoff body
Seen in Rheumatic fever. It is interstitial myocardial granuloma. Plump macrophages w abundant cytoplasm & central slender chromatin ribbons called Anitschkow (caterpillar cells) often present. Over years Aschoff bodies are replaced w fibrous scar tissue leading chronic MV stenosis & regurgitation.
Ulipristal
Selective progesterone receptor modulator. Used as emergency contraception.
DPP4 (dipeptidyl peptidase) inhibitors
Sitagliptin, SaxagliptinMOA- increases endogenous GLP-1 & GIP levelss/e- nasopharyngitis
Anatomy of basal ganglia & common brain deficits.
Subthalamic nucleus damage= hemiballism. commonly occurs during lacunar stroke (due to longstanding HTN & DM)Caudate nucleus= Atrophy occurs in Huntington disease.Internal capsule= Contralateral pure motor or combined sensorimotor deficits. Damage occurs w/ lacunar infarcts.Lentiform nucleus= Atrophy in Wilson's disease (hepatolenticular degeneration). Characterized by dysarthria, movement disordersSubstantia nigra= degeneration is seen in Parkinsons. Bradykinesia, rigidity, & resting tremorVPL & VPML of Thalamus= complete contralateral sensory loss. Can also result in thalamic syndrome (contralateral burning or stabbing pain on one side). Commonly casued by lacunar stroke.
Superior gluteal nerve lesion
Sup gluteal nerve derived from L4-S1 venteal rami & leaves pelvis through greater sciatic foramen above level of piriformis. Inj at superomdial quadrant of buttock have high probablity of injuring sup gluteal nerve.Inj at superomedial, inferomedial & inferolateral regions of buttocks risk sciatic nerve injury.
Common peroneal nerve injury, fracture of fibula, injury to lateral part of rt leg.
Superficial & deep branches. Super= innervates muscles of lat compartment of leg, function to evert foot. provides sensory innervation to dorsum of footDeep= innervates ant compartment of leg, function to act as dorsiflexors of foot & toes. provide sensory innervation to region b/w 1st & 2nd toes.Injury- loss of dorsal foot sensation, impaired dorsiflexion & eversion resulting in FOOT DROP.TIBIAL N= courses throufh pop. fossa, innervates skin of post. calf, lat foot & sole, tissues of knee joint & muscles providing plantar flexion & inversion. muscles= gastrocnemius, soleus, tibialis post.
IL-3
Supports growth & differentiation of bone marrow stem cells. Functions like GM-CSFSecreted by all T cells
Genital ulcer disease
Syphilis- single painless ulcer w/ heaped up borders & clean baseHSV- multiple PAINFUL superficial vesicles or ulcers w/ erythematous baseChancroid (hemophilus Ducreyi) - Deep purulent PAINFUL ulcers w/ matted/ suppurative lymphadenitisGranuloma inguinale (donavanosis) (klebsiella granulomatis)- PAINLESS, preogressive red serpiginous ulcers w/out lymphadenopathy
Factors influencing Cerebral circulation
Systemic BP & ABG levels. When systemic bp is 60-140 it has little effect on cerebral blood volume because autoregulation ( via cerebral blood vessel dilation & contraction) keeps blood flow constant. BP >150 increases cerebral vascular volume & blood flow causing a corresponding increase in ICP. In contrast BP <50 causes hypoperfusion & potential ischemia.CO2 is a potent vasodilator of cerebral vasculature. Tachypnea causes hypocapnia & cerebral vasoconstriction, thereby decreasing cerebral blood volume & ICP.
CD28
T cell specific surface protein that interacts w/ B7 on antigen preenting cells, providing a costimulatory signal necessary for T cella ctivation. Therefore antibodies blocking CD28 would inhibit T cell activation. CTLA-4 also binds to B7 but has an inhibitory function on activated T cells.
Systemic inflammatory response
TNF-alpha, IL-1, IL-6.
BActerial transposons
The location of a gene in the genome is imp. as it determines its proximity to promotor or suppressor regions.
Mitral stenosis pressure tracing
There is resistance to blood flow from LA to LV that increases LA pressure. This increase is transmitted back to pulm veins & is recorded as elevated PCWP during pulm artery catheterization. If LA pressure is sufficiently high to overcome resistance bw LA & LV, LV filling may not be significantly affected, resulting in normal LVEDP
Naive T helper cells
These cells possess T cell receptor as well as CD 3 & CD 4 on their cell surface. When an Ag MHC 2 complex is presented to a naive Th cell by an antigen-presenting cell, both the TCR and CD 4 proteins interact with the ag MHC2 complex, whileCd3 transmits the signal to the cells interior.The activated T-cell now differentiates into th1 or th2 subset. If the antigen is presented by a macrophage, the macrophage will produce IL12 that stimulates differentiation into th1 subset. IL4 reeased by other types of antigen presenting cells facilitates differentiation into the th2 subset.
Uric acid & lactate excretion location in nephron.
They compete to be excreted by PCT.
thiazide diuretics on distal tubular calcium reabsorption
Thiazides effectively increase Ca reabsorption from nephron. They are indicated in pts w nephrolithiasis 2ndary to hypercalciuria & contraindicated in hypercalcemia.Loop diuretics block Na-K-Cl cotransporter & therefore increase urinary Ca excretion.
side effects of common antihypertensive medications
Thiazides-> acute kidney injury, electrolyte disturbances (hyponatremia, hypokalemia), Hyperuricemia, acute gout. Increased glucose & cholesterol.ACE inhibitors-> cough, angioedema, hyperkalemia.Ca channel blockers (amlo/nifedipine)-> peripheral edema, dizziness or lightheadedness.Beta blockers-> bronchospasm, bradycardia, fatigue, sexual dysfunction.
Other names for DiGeorge Syndrome
Thymic aplasia, Velocardiofacial syndrome, Shprintzen syndrome, Sedlackova syndrome, and conotruncal anomaly face syndrome. 22q11 deletion syndrome.
two-sample t test
To dtermine if means of 2 populations are equal. Basic requirements to perform this test are 2 mean values, the sample variances (eg; standard deviations), & sample sizes. The t statistic is then calculated from which p value can be determined. If p<0.05 the null hypothesis ( which assumes there is no diff bw 2 groups) is rejected & the 2 means are assumed to be statistically different.
C.difficile
Toxin A (enterotoxin) & Toxin B (cytotoxin). B is slightly more virulent. Both toxins inactivate Rho regulatory proteins involved in signal transduction & actin cytoskeletal structure maintenance. As a result toxins disrupt intercellular tight junctions leading to cell rounding/ retraction as well as increased/ paracellular intestinal fluid secretion.
Pleural effusion
Tracheal deviation AWAY from affected side. bc of excess fluid pushing against mediastinum
P-Glycoprotein
Transmembrane protein that functions as ATP dependent efflux pumps. Human tumor cells resist drugs by MDR1 gene, it is a product of P-glycoprotein.P-Glp normally expressed in Intestinal & Renal tubular epi cells. It functions to eliminate foreign compounds from body. Also + in capillary endothelium of vessels that form BBB.
True vs False Diverticulum
True: Contains all parts of Intestine. It is Mucosa, Submucosa, Muscular layers. eg- Normal appendix, Meckel's diverticulumFalse: Contains ONLY mucosa, submucosa, layers herniate through msucular layers. eh- Colonic & Zenker (upper esophageal) diverticula. They are examples of false/ pulsion diverticula.
Abacavir hypersensitivity
USed to treat HIV, it is NRTI. The negative test for allele has almost 100% negative predictive value.
Gastric Ulcer v Erosion
Ulcer-> extend to submucosal layers & muscularis propria. (inner circumferential & outer longitudnal smooth muscle layers)Erosion-> do not fully penetrate muscularis mucosa.
Urachal abnormalities
Urachus is a remnant ofallantois that connects bladder w the yolk sac during fetal development. Failure of urachus to obliterate at birth results in patent urachus, which can facilitate discharge of urine from umbilicus
Gout in alcoholics
Urate & lactate compete to be excreted by PCT in nephron. BC of elevated lactate in alcoholics, there is decreased excretion of urate.Uric acid builds up & causes gout.
Kidney development
Ureteric bud ultimately gives rise to collecting system of the kidney, including the collecting tubules & ducts, major & minor calyces, renal pelvis, & the ureters.The metanephric mesoderm (blastema) gives rise to glomeruli, Bowman's space, proximal tubules, the loop of Henle & DCT.
Osteomyelitis affects which part of bone?
Usually Metaphysis of long bones, as this region contains slow flowing, sinusoidal vasculature that is conducive to microbial passage. Adults less likely to develop hematogenous osteomyelitis in long bones due to changes assoc w epiphyseal closure.Epiphysis of long bone usually spared unless acute inf. is not treated
Isolated systolic HTN
Usually caused by increased arterial stiffness caused by endothelial dysfunction & change in extracellular matrix composition (eg:decreased Elastin, Increased collagen deposition) Increased arterial stiffness leads to decreased compliance of aorta & major peripheral arteries, causing elevated pressures during systole. ISH can also result from increase in CardiacOutput due to severe aortic regurgitation or systemuc causes (eg: anemia, hyperthyroidism)
Epstein BArr virus
Usually infects in B cells, stimulating them to enter cell cycle & proliferate continously ( transformation or immortalization) This is accomplshed when EBV encoded oncogenes activate proliferative & anti apoptotic signaling pathways within the infectted B cell. In immunocompetent host the b-cell proliferation is contained. Immortalized B cells maintain ability to secrete immunoglobulin & B cell activation products (CD23)
Primitive Neuroectodermal tumors (PNETs)
Usually occur in children. Peripheral PNET similar to Ewings sarcoma. CNS PNETs= Medulloblastoma, Pineoblastoma
Hypothalamic nuclei
Ventromedial, Lateral, Anterior, Posterior, Arcuate, Paraventricular, Supraoptic, Suprachiasmatic
Supplementation of breastfed infants
Vit D- bc of exclusive breastfeeding, lackof sunlight exposure, dark skinIron- preterm/ low birthweightVit K- immediately after birth to prevent hemmorhagic disease
Alcohol pathway
When excess alcohol is consumed, there is a build up of NADH, and that is what causes most of alcohols s/e.NADH inhibits isocitrate & a-ketoglutarate dehydrogenases.Also shunts Oxaloacetate to Malate (this drives TCA cycle backwards & slows down). This Increases Acetyl CoA levels, this favours ketones formation. This is because acetyl coA can't enter TCA cycle, so ketones are produced.MEOS is activated in extreme alcohol consumption
Sweat test in Cystic fibrosis
Whn eccrine sweat is first produced it is isotonic w extracellular fluid. Normally sweat travels through eccrine duct to skins surface Cl is reabsorbed via CFTR and Na & water follow. In normal ppl CFTR facilitates production of hypotonic sweat. zcf pts ate unable to reabsorb Cl & Na in eccrine ducts & therefore secrete sweat w high Na & high Cl.
JAK2 mutation
With exception of CML, Chronic myeloproliferative disorders (esp. Polycythemia vera) frequently harbor a mutation in the nonreceptor cytoplasmic tyrosine kinase, JAK2. This mutation results in constitutive Tyr Phosphorylation activity, & consequently in cytokine-independent activation of signal transducers & activators of transcription (STAT) pathway. Once activated, STAT proteins translocate to the nucleus & promote transcription. A JAK2 inhibitor (ruxolitinib) has been approved for treatment of primary myelofibrosis.
X linked Inheritance
XLD= ALL female kids of affected males will have disease. Both male & female kids of an affected female will have 50% chance of being affected. NO FATHER TO SON TRANSMISSION.XLR= Male kids of female carriers have 50% chance of disease, female kids have 50% of being carriers. Female childrens of affected fathers are carriers. Can skip generations. NO FATHER TO SON TRANSMISSION.
Internal hemmorhoids
above dentate line. covered in columnar epithelium. site of adenocarcinoma. derived from endoderm.NERVE- inf. hypogastric plexus. (not sensory)ARTERIES- sup. rectal artery, continuation of IMAVEINS- suprectal vein-->inf mesenteric vein-->portal systemLYMPH- mesorectal lymph nodes / int. iliac nodes
Acute Calculous cholecystitis
acute inflam of gallbladder initiated by gallstone obstruction of cystic duct. Pts typically have persistent Rt upper quadrant pain, fever & leukocytosis. Murphys sign +ve. Symptoms often preceded by transient episodes of abd pain & nausea after fatty meals due to temp cystic duct obliteration.
HUS some findings
acute kidney injury, microangiopathic hemolytic anemia & thrombocytopenia. Decreased Hb & platelets. Increased BT, LDH, bilirubin, BUN & creatinine.
Neuroblastoma findings
age on onset ~2yo. Microscopically- solid sheets of small cells w dark nuclei & scant cytoplasm (small blue round cells)Presentation- retroperitoneal mass, HTN, anorexia & wt loss. Metastases- invasion of epidural space "dumbbell tumor" (spinal cord compression). Pancytopenia, hepatomegaly, skin: palpable nodules. Periorbital: proptosis, ecchymoses. Paraneoplasm- opsoclonus, myoclonus, truncal ataxiaIncreased excretion of catecholamines in urine. N-myc amplification (increased number of gene copies)Prognosis- better if pt is <1yo. Worse if higher no of N-myc copies MAY CONFUSE W WILMS TUMOR AKA nEPHROBLASTOMA. occurs in 2-4yo. On micro resembles primitve metanephric tissue
Stewart-Treves Syndrome
aka Angiosarcoma/ Lymphangiosarcoma after lymph node dissection
Wallenberg syndrome
aka LAt. medullary syndrom. caused by injury to post. inf. cerebellar artery.
Asthma attack triggers
allergens- animal dander, dust mites, cockroaches, pollens & molds.resp. irritant- cig smoke, air pollutants, perfumesinfection- viral upper Resp infection, rhinosinusitispharm- aspirin, nsaid, non selective b-blockersother- exercise, cold dry air, gerd, emotions
SCID
also has thymic aplasia, due to severe T cell deficiency. low or absent CD3+ T cells & hypogammaglobulinemia.
anticholinergic s/e
also:-Blood vessels= vasoconstriction via musc. receptor blockade in endothelialcells results in decreased NO synthesis. Despite this atropine poisoning is assoc w cutaneous flushing, its pathogenesis is unknown-Resp= bronchodilation-eyes- cyclopegias as well
Interscalene nerve block
anaesthetizes the brachial plexus as it passes throughthe scalene triangle. It is used to provide anesthesia for the shoulder & upper arm. Nearly all pts develop transient ipsilateral diaphragmatic paralysis due to involvement of phrenic nerve roots as they pass through the interscalene sheath.
Characteristics of Antiemetic drugs
anticholinergics & antihistamines are recommended for Vestibular nausea.
Collapsed lung/ bronchial obstr
as air trapped in lung gradually gets absorbed, there is loss of lung volume due to alveolar collapse (atlectasis), trachea deviates TOWARD affected side. loss of radiolucent air combined w shifting organs into hemothorax appears as completely opacified hemithorax on CXR
Idiopathic membranous nephropathy
assoc w circulating IgG 4 antibodies to PhospholipaseA2 receptor (PLA2R). PLA2R not seen in secondary membranous nephropathy.
IL-10
attenuates inflammatory response. Decreases expression of MHC class II & Th1 cytokines. Inhibits activated macrophages & dendritic cells. Also secreted by reg T cells.TGF-Beta & IL-10 both attenuate the immune response.from Th2 cells.
CMV in utero illness
complications in neonates include- Chorioretinitis ( most common), Sensorineural deafness, seizures, jaundice, hepatomegaly, splenmegaly & microcephaly
Fun fact - Celiac disease
bcof defective mucosal absorption of vitamins & nutrients, malabsorption occurs. Vit D def occurs due to excess excretion in bulky, fatty stools.Rickets & osteomalacia seen.
External hemmorhoids
below dentate line, covered in modified squamous epithelium. site of squamous cell Ca. derived from ectoderm.NERVE-Inf. rectal nerve, branch of pudendal nerve.ARTERIES-mid & inf. rectal art, branch of in.t pudendal art. VEINS- mid & inf rectal vein-->int pudendal vein-->int iliac vein-->IVCLYMPH- superficial inguinal nodes.PAINFUL
G protein coupled receptors
bind Glycoprotein hormones (TSH, LH, FSH) contain 3 major domains.- extracellular domain for ligand binding- Transmembrane domain- Intracellular domain coupled w/ heterotrimeric G proteins.
Ticagrelor
binds to ADP P2Y12 receptor on platelets which prevent platelet aggregation by blocking ADP mediated activation of GP IIb/IIIa receptor complex.
Anterolateral/ medial humeral fracture
brachial artery, median nerve, & radial nerve all run ant to elbow & may be injured in supracondylar humeral fractures.Radial N injury w lat displacement of proximal fracture fragment.Median N & brachial artery injury w anteromedial displacement of proximal fracture fragment.
Ulnar nerve
bw olecronon & medial epicondyle of humerus, before entering forearm. There is lies bw flexor carpi ulnaris & flexor digitorum profundus.
Catalase positive bacteria
common= s.aureus, burkholderia cepacia, serratia marcescens, nocardia, aspergillus.
CNS lymphoma markers
commonly +ve for B cell markers CD20 & CD79a
Expanding space occupying lesion w/in temporal lobe
can cause elevated ICP w transtentorial herniation of uncus. Uncal herniation compresses the ipsilateral 3rd CN as it exits midbrain, resulting in oculomotor nerve palsy w a fixed dilated pupil (due to preganglionic parasympathetic fiber damage)
cofactor for Carboxylation enzymes
carboxylation adds 1 carbon group via CO2.-Pyruvate carboxylase- Acetyl-CoA carb.- Propionyl- CoA carb.
Idiopathic pulmonary hypertension
commonly presents as dyspnea & exercise intolerance in women 20-40yo. Usually caused by mutatins in pro-apoptotic MBPR2 gene. Lung transplant is definitive rx. But vasodilators can be used for symptomatic relief.
Genomic Imprinting
caused by DNA methylation, an epigenetic process by which genes can be silenced by attaching MEthyl groups to cytosine residues in the DNA molecule. Methyl groups added to nucleotide residues (often adenine & cytosine) by DNA METHYLTRANSFERASE enzyme that uses SAM (S-Adenosyl methionine) as methyl donor.
Diastolic heart failure
caused by decreased ventricular compliance & is characterized by normal LV ejection fraction, normal LV EDV, & elevated LV filling pressures. HTN, obesity & infiltrative disorders ( eg; transthyretin related amyloidosis, sarcoidosis) are imp causes of DHF.
HArtnups disease.
caused by inactivating mutations affecting neutral amino acid transporter. Results in impaired transport of neutral amino acids. particularly Tryptophan in small intestine & PCT of kidney.rx = high protein diet w daily niacin or nicotinamideneutral amino acids= alanine, serine, threonine, valine, leucine, isoleucine, phenylalanine, tyrosine, tryptophan
p27 protein
cell cycle inhibitor. It acts during G1 by inhibiting cyclin dependent kinases. Normal tissues contain high levels of p27, while malignant tissues contain very low levels of p27. Upregulation of p27 would stop cell cycle.
Hypertensive encephalopathy
characterized by progressive headache & nausea/ vomiting followed by non localizing neurologic symptoms. eg:confusion.
Suprachiasmatic nuclei
circadian rhythm regulation & pineal gland function
Nucleosomes
composed of DNA wrapped around a core of 8 histone proteins ( 2 molecules of H2A, H2B, H3, H4). H1 is only histone located outside of core. They bind linker segments of DNA that lie bw nucleosomes & facilitate packaging of nucleosomes into more compound structures
Gap junctions
composed of connexin proteins that create channels between cells, permitting free passage of small ions (eg: Ca) & molecules.Gap junctions facilitate communication & coordination bw cells & play an imp role in labor contractions.Connexins are proteins that assemble into gap junctions & their density increases in uterus before delivery in response to rising estrogen levels.
Median nerve
courses through flexorum digitorum profundus & superficialis muscles
Helicobacter pylori gastritis
curved or spiral bacilli. characterized by lymphocytes, lymphoid follicles & plasma cells.
Rifaximin (based on Rifamycin)
decreases intraluminal ammonia production. USES- Hepatic encephalopathy, Irritable bowel syndrome, travelers diarrhea.MOA- inhibits bac. RNA synthesis through binding w/ DNA dependent RNA polymerase. This results in blockage of translocation step that normally follows formation of 1st phosphodiester bond, which occurs in transcription process.Poorly absorbed orally
Dubin Johnson
def bilirubin excretion into bile canaliculi. Autosomal recessive. Caused by absence of biliary transport protein, MRP2 (multiple drug resistance protein 2) used in hepatocellular excretion of bilirubin glucoronides into bile canaliculi. Liver is darkly pigmented. Pts usually asymptomatic. Normal life expectancy.
Refsum disease
defect in peroxisomal alpha oxidation & leads to neurologic disturbances in response to accumulation of Phytanic Acid w/in the body. rx= strict avoidance of chlorophyll in the diet.
confounding vs effect modification
effect modification is not a bias.
Monoamine oxidase inhibitors
eg; phenelzine, trancypromine, selegiline. Due to severe adverse effects they are NOT 1st or 2nd line drugs. Useful in atypical depression & treatment resistant depression.
Enteropeptidase def.
enteropeptidase is a duodenal brush border enzyme, it activates trypsin from it's inactive precursor, Trypsinogen. Trypsin degrades complex polypeptides to dipeptides, tripeptides & amino acids while activating other pancreatic enzymes. Deficiency impairs both protein & fat malabsorption, leading to diarrhea, failure to thrive & hypoproteinemia (edema).
Medium chain Acyl-CoA dehydrogenase deficiency
fatty acid oxidation disorder. presents w hypoglycemia, hyperammonemia, met acidosis. but no ketosis.
Sickle cell trait
features- usually none. More prevalent in african, mid eastern & mediterranean countries. No change in life expectancy.Diagnosis- Normal Hb/ retic count/ RBC indices & morphology. Hb electrophoresis shows both HbA & HbSw amount of HbA more than HbS
Hemolytic uremic syndrome
features= antecedent diarrheal illness (often bloody), Hemolytic anemia w schistocytes, thrombocytopenia, acute kidney injury
Pulmonary edema
fluffy-patchy infiltrates. usually not unilateral
Superficial peroneal nerve
foot eversion (peroneus longus & brevis) & sensory loss over the lateral leg & dorsolateral foot.
Blood brain barriers Cell Junctions
formed by tight junctions bw non fenestrated capillary endothelial cells that prevent the paracellular passage of fluid & solutes. This barrier only permits the passage of substances from the blood to brain via transcellular movement across endothelial plasma membrane, which is limited by diffusion or carrier mediated transport.
Mixed Cryoglobulinemia
found in pts w Hep C & multiple myeloma, most likely due to IgM (directed againdt Fc portion of IgG) deposition in glomerulus that leads to basement membrane thickening & cellular proliferation.Symptoms include- joint pains & swelling, splenomegaly, skin vasculitis w purplish patches.
Hep C
has >6 genotypes & multiple subgenotypes. These strains vary primarily at hypervariable genomic regions, such as those found in sequences encoding its 2 envelope glycoproteins. There is NO proofreading 3'--->5' exonuclease activity in the virion encoded RNA polymerase.Basically antigenic variation
cavernous sinus thrombosis
headache, diplopia as well
RNA interference
imp mechanism by which short (20-30 bp) non coding RNA sequences induce post transcriptional gene silencing. Types of silencing RNA include small interfering RNA (siRNA) & microRNA (miRNA). Human genome encodes over 1000 miRNA genes each one capable of repressing 100s of target genes. Altered expression of even a few miRNA genes can lead to cellular dysregulation & has been implicated in the development of many diseases including hematologic & solid malignancies. In addition siRNA sequences can be introduced into cells to silence specific pathogenic genes (eg; c-MYC oncogene) & are being explored as possible therapeutic agents.Afer being transcribed miRNA undergoes processing in nucleus to form a double stranded precursor that is then exported into cytoplasm. There the precursor is cleaved into short RN helix by a ribonuclease protein called dicer. Induvidual strands are then seperated & incorporated into RNA induced silencing complex aka RISC. this multiprotein complex uses it's assoc miRNA as a template to bind complementary sequences found on target mRNAs. exact match generally results in mRNA degradation but a partial match also causes translational repression by preventing ribosome & transcription factor binding.
Smooth ER
important for lipid & steroid synthesis. Also for detox of drugs & toxins. Sarcoplasmic reticulum in muscle is equivalent to SER. Lots of SER found in: Hepatocytes. Organs such as adrenal glands (cortisol), gonads (testosterone & estradiol)
Primary active transport
in primary active transport, carrier molecules are enzymes that hydrolyze ATP (ATPases) & use energy released to transport ions & molecules against their concentration gradients. Examples pf such carriers= Na/K ATPase, H/K ATPase, & Ca ATPase
Direct factor Xa inhibitors (apixaban, rivaroxaban)
increase Prothrombin & activated partial thromboplastin times but do not affect thrombin time. Unfractioned heparin & direct thrombin inhibitors (dabigatran etc.) prolong thrombin time.
Sulfonylureas & meglitinides
increase secretion of insulin & C-peptide from pancreatic B-cells. C-peptide can be used as a merker of endogenous B-cell insulin secretion.
Anaplasia - features
increased N:C ratio, loss of cell polarity w disruption of normal tissue architecture. Cellular & nuclear polymorphism. Numerous & often abnormal mitotic figures, giant multinucleated cells.
Zellweger syndrome
infants unable to properly form myelin in CNS. Hypotonia, seizures & hepatomegaly, mental retardation and early death. This & refsums disease are peroxisomal disease,
pathogenesis of pigment stones
inhibition of 7a hydroxylase increases risk of cholesterol stones. Same for aromatase & HMG coA reductase.
Disulfiram like reaction
inhibition of Acetaldehyde dehydrogenase, causes increase in aldehyde.Drugs that cause this-> Metronidazole, procarbazine, cefotetan, cefamandole, cefoperazone
Protease inhibitor
inhibits HIV polyprotein cleavage.-Atazanavir, Darunavir, indinavir, ritonavir
Oculomotor nerve
innervates - Sup/ medial/ inf. rectus, Inf oblique, Levator palpebrae superiorisOculomotor functions - Adduction, Depression, Elevation, Ext rotationLesion findings - eye deviated downwards & laterally. Diagonal diplopia, Dilation of pupil & loss of accomodation, ptosis
Musculocutaneous nerve
innervates Biceps & coracobrachialis, before descending toward elbow bw biceps brachii & brachialis
Deep peroneal nerve
innervates ant. compartment muscles responsible for ankle dorsiflexion /foot dorsiflexion (tibialis anterior) toe extension (extensor digitorum longus, ext hallucis longus).
Trochlear(IV) nerve
innervates- Sup obliquefunctions- abduction, int. rotation, depression while adductedlesion- eye deviated upwards, vertical & torsional diplopia
Abducens (VI) nerve
innervates- lat rectusfunction- abductionlesion- eye deviated medially, horizontal diplopia
Dresslers Syndrome
late onset post myocardial infarction pericarditis. Dresslers typically begins 1 week to a few months after MI in fewer than 4% patients. Typical features include fever, pleuritis, lekuocytosis, pericardial friction rub, & chest radiograph evidence of new pericardial or pleural effusions.It is autoimmune polyserositis provoked by antigens exposed or created by infarction of cardiac muscle. Periacrdium is usually diffusely inflamed. Lung pleura maybe involved. Generally responds to Aspirin, NSAIDs, &/or glucocorticoids.Not to be confused w/ early onset pericarditis, which develops b/ days 2-4, following a transmural infarction. It represents an inflammatory reaction to ardiac muscle necrosis that occurs in adjacent visceral & parietal pericardium.
Ovarian tumors
leydig/ sertoli cells- make testosterone, can cause masculinizationGranulosa cell- produce estrogen.
Intermediate junctions (zonula adherens or belt desmosomes)
located below tight junctions & form a beltlike anchor between adjacent cells in assoc w actin microfilaments.
Loop diuretics & NSAIDs
loops work by inhibiting Na-K-Cl symporters in asc. limb of loop of henle. Increasese Na, Cl & fluid excretion b blocking Na& Cl transport. ADDITIONALLY loop diuretics also stimulate prostaglandin release. PGs have vasodilatory effects. So when PGs are stimulated loops also increase renal blood flow leading to increased GFR & enhanced drug delivery. COncurrent use of NSAIDs with Loop Diuretics can result in decreased diuretic response.
Cachexia mediators
main mediators of paraneoplastic chachexia are TNF-alpha aka cachectin, IL-1beta, IL-6
Thiazolidinedione mechanism of action
main side effects = fluid retention dueto increased Na absorption in renal collecting tubules. Leads to Weight gain, peripheral edema decompendation of underlying congestive heart failure. Fluid retention is exacerbated when given w/ insulin.Also cause weight gain, likely due to increased fat storage in adipocytes & an increased number of adipocytes in subcutaneous tissue. hepatic toxicity seen wth older drug TROGLITAZONE, it is now disc.
Sciatic nerve injury
may cause sensory loss over peroneal, tibial & sural nerve distributions w weakness in majority of lower leg muscles (including hamstrings)
VDJ (heavy chains) & VJ (light chains) recombination
occurs via DNA reaarangement. After undergoing immunoglobulin gene rearrangement, each B cell makes antibodies a single specificity. An enormous vaiety of diff IG molecules can potentially be produced through rearrangement. REcombination of these regions occurs during B cell maturation w/in bone marrow. Later on during primary immune response, affinity maturation occurs in germinal centers through process of somatic hypermutation.
Conjugation of bacteria aka bacterial sex
one-way DNA transfer persormed by carrying plasmid w/ the Fertility (F) factor. Begins w/ donating bacteirum producing sex pilus, which forms a direct connection w/ recieving bacterium. Next the donating bac, transfers a single DNA strand containing the F factor to the recipient organism, after which complementary DNA strands are synthesized.
Tadalafil
only PDE inhibitor used for BPH, NOT Sildenafil or Vardenafil.
OOgenesis & Spermatogenesis
oogen = Meiosis 1 is arrested in prophase. Meiosis 2 is arrested in metaphase
Paroxysmal supraventricular tachycardia
palpitations, feeling faint, sweating, SOB, chest pain. Start and end suddenly.risk factors- alcohol, caffeine, nicotine, psychological stress, Wolf-parkinson-white syndrome. rx- vagal stimulation (eg: carotid sinus massage or valsalva maneuver), if this fails then IV adenosine is recommended.Carotid sinus massage leads to increase in parasympathetic tone causing temp. inhibition of SA node activity, slowing of conduction through AV node, and prolongation of AV node refractory period. Useful for termination of PSVT.
Osteoprotegerin (OPG)
physiologic decoy protein that decreases binding of RANK-L to RANK. Inhibition of RANK-L to RANK receptor interaction reduces the differentiation & survival of osteoclasts, resulting in decreased bone resorption & increased bone density.OPG Loss of function mutations can cause Juvenile Paget's disease. A monoclonal Antibody (DEnosumab) inhibits RANK/ RANK-L interaction also leads to increased bone density and is commonly used for treatment of osteoporosis.
Niacin
precursor for NAD & NADP, 2 imp. cofactors for many dehydrogenase & reductase enzymes. NAD is key constituent for TCA cycle, serves as cofactor for isocitrate dehydrogenase, alpha ketoglutarate dehydrogenase, & malate dehydrogenase.
Lactose intolerance
presents w flatulence, crampy abd pain, watery diarrhea after dairy consumption. Can be acquired by inflammatory/ inf conditions that injure mucosal brush border of small intestine where lactase is expressed. Studies can show increased Breath H content, reduced stool pH, & elevated stool osmolality.
Persistent gallbladder outflow obstruction
prmotes hydrolysis of luminal lecithins to lysolecithins which disrupts protective mucus layer. Luminal epi is then exposed to the detergent action of bile salts, results in chemical irritation & PG release. Inflam of mucosa & deeper tissues cause gallbladder hypomotility.
Arginase defeciency
progr. development of spastic diplegia, abnormal moviements, growth delay in setting of elevated arginine levels indicate def. Pts have mild or no hyperammonemia Diagnosis based on elevated levels of arginine on plasma amino acid testing.Rx= low protein diet devoid of arginine. Admin. of synthetic protein made of essential amino acids usually results in dramatic decrease of arginine & improvement of neuro abnormalities.
IL-5
promotes growth & differentiation of B cells. Enhances class switching to IgA. Stimulates growth & diff of eosinophils.from Th2 cells.
Renal osteodystrophy
pts w CKD may develop renal osteodystrophy from 2ndary hyperPTH (caused by hyperphosphatemia & hypocalcemia)Pts can also develop Pth resistance resulting in low turnover adynamic bone disease & osteomalacia.Deranged signaling between renal cells & bone osteoblasts & osteoclasts (eg; FGF-23, Klotho) also contributes to skeletal changes that occur in CKD.
Recombination
refers to gene exchange that occurs through crossing over 2 dsDNA molecules w/in homologous origins. Progeny can have recombined genomes w traits from both parent viruses.
Statistical power
represents a study's ability to detect a diff. when one exists. It is probability of rejecting null hypothesis when it is truly false. That is the probability of finding a true relationship.Power= 1-Beta
Nucleolus
round, dense basophilic body. It is primary site of rRNA transcription, ribosomal subunit maturation & assembly.As cells become more differentiated, their growth slows & they require fewer no of ribosomes for protein production. In contrast malignant cells w high metabolic activity usually have an increase no of active rRNA & prominent nucleoli.
Arcuate nuclei
secretion of dopamine (inhibits prolactin), GHRH &GnRH
Antibody classification
see in notes
BZPs contraindications
shouldn't be used w Alcohol, BArbiturates, neuroleptics, or 1st gen antihistamines.
Phase 4 Cardiac pacemaker cells
slow depolarization occurs due to closing of repolarizing K+ channels, the slow influx of Na through funny channels, & opening of T-type Ca channels. Ach & Adenosine reduce rate of spontaneous depolarization in Cardiac pacmaker cells by prolonging Phase 4. This action results in transient slowing of sinus rate & an increase in AV nodal conduction delay. Adenosine is useful in termination of Paroxysmal supraventricular tachycardia.
HPV
small dsDNA virus. most common STD. Types 6, 11 can result in warts. It infects BAsal epithelial cells through small breaks in skin or mucosal surfaces. It has prediliction for STRATIFIED SQUAMOUS EPITHELIUM which is found in anal canal, vagina, & cervix
GFAP
stain for gliomas. Astrocytes, oligodendrocytes & ependymal cells.
Radial nerve
supinator muscle & head of radius
Macula densa & JG cells
tall, narrow cels located in distal tubule that monitor salt content & tubular flow rate. This info is transmitted by nearby JG cells that are located mainly in wall of afferent arteriole. JG cells are modified smooth muscle cells w renin containing zymogen granules.
Doxorubicin cause dilated cardiomyopathy
to prevent this Dexrazoxane is given. It is an iron chelating agent that decreases formation of O2 free radicals by doxorubicin & other anthracyclines.
Synaptophysin
transmembrane glycoprotein found in presynaptic vesicles of neurons, neuroectodermal & neuroendocrine cells.
Transformation
uptake of naked DNA by a prokaryotic or eukaryotic cell. In virology, transformation also describes incorporation of viral DNA into a host cell chromosome (lysogeny). Transformation alters the genetic composition of host cell but typically causes no genomic change in progeny virions.
Inulin Clearance
used for GFR calculation. Inulin is freely filtered at glomerulus & is neither reabsorbed not secreted by renal tubules.
PAH
used to calculate Renal plasma flow. It is freely filtered at glomerulus & also secreted into urine by an energy dependent organic acid transporter in the proximal tubule.
IFN-gamma release assays
used to test for latentTB, by measuring response of T lymphocytes when exposed to antigens unique to M.TB. Similar to Tuberculin skin tests, IGRA's measure cell mediated immunity.
Lac operon gene mutation
usually a single base deletion, it will casue a frameshift mutation if it occurs in coding region/exons of gene.
Ristocetin Test
vWF deficiency- decreased platelet aggregation on test. On adding normal plasma aggregation occurs.Bernard Soulier Syndrome- platelet aggregation is abnormal, but bc vWF levels are normal, adding normal plasma will not correct aggregation.
Disulfide bonds
very strong covalent bonds bw 2 cysteine residues w/in same polypeptide chain that enhance a proteins ability to withstand denaturation
Statins
w/ exception of pravastatin, they are metabolized in liver by CYP 3A4. Erthromycin & other macrolides inhibits CYP 3A4. Concurrent use increases statin levels. Other such drugs include Ketoconazole, cyclosporine, HIV potease inhibitors, grapefruit. Azithromycin doesn't have a strong affect.
zone of autoregulation
w/in zone of autoreg, increases in coronary blood flow are primarily mediated by relative myocardial hypoxia that ocur during times of increased work.
Phenotypic mixing
when host cell is coinfected w 2 viral strains & progeny virions contain parental genome from 1 strain & nucleocapsid (or envelope) proteins from other strain. May result in progeny acquiring additional traits.However as the genome is unchanged subsequent progeny would not retain these traits.
Macula
yellowish spot approx. 1.5 mm diameter located near center of retina. Histologically- densely packed cones, few overlying cells & no blood vessels. Each macular cone synapses to single bipolar cell, which in turn synapse to a single ganglion cell. Due to this arrangement the visual acuity in the macula, and particularly the fovea is greater than any area of retina. The neural fibers that serve macula transmit to an area of accipital visual cortex that is seperate from area of representation of peripheral field. Due to this peculiar cortical representation macular sparing is common in lesions of occipital cortex.
skewed Lyonization
• Females very rarely develop X linked RECESSIVE disease• Usually only occurs if homozygous for gene• Father must have disease and mother must be carrier• Females can develop disease with skewed lyonization• Results in inactivated X chromosome in females• One X chromosome undergoes "Lyonization"• Condensed into heterochromatin with methylated DNA• Creates a Barr body in female cellsLyonization• Randomprocess• Differentinactive X chromosomes in different cells• Occurs early in development(embryo<100 cells)• Results in X mosaicism in females• May cause symptoms in femalesX-recessive disorders• "Skewed lyonization"