Uworld notes

nonmaleficence

"Do no harm." Must be balanced against beneficence; if the benefits outweigh the risks, a patient may make an informed decision to proceed (most surgeries and medications fall into this category)

MOA inhibitors - drugs

"MAO Takes Pride In Shanghai" -Trancylcypromine -Phenelezine -Isocarboxacid -Selegiline

SIrolimus (Rapamycin) Mechanism

"SIR-vives" mTOR inhibitor which blocks T cell activation and B cell differentiation by preventing IL-2 Signal transduction. Differs from Tacrolimus and Cyclosporine bc those drugs inhibited the TRANSCRIPTION of Il-2. Rapamycin inhibits signal transduction of IL2

Frohlich syndrome

"adiposogenital dystrophy" caused by secondary hypogonadism originating from decreased GnRH. Low levels of GnRH have been associated with defects of hypothalamic nuclei (growth extends and first effects ventromedial nuclei - thus pts will show increased calorie intake). Also find growth retardation, retarded sexual development, and hypoplasia/atrophy of the gonads. (due to impingement on pituitary and decreased GnRH) can present with vision problems from compression of optic nerve (from pituitary)

ulcerative colitis

"backwash ileitis"

hemochromatosis clinical findings

"bronze diabetes" d/t generalized darkening of the skin from hemosiderin deposition. will see palmar erythemia, gynecomastia, and spider telangiectasias.

cyclosporine toxicity

#1 is nephrotoxicity, gingival hyperplasia, HYPERtension, lipidemia, and glycemia, hirsutism

Wilson's pathogenesis

(hepatolenticular degeneration) lentiform nucleus (globus pallidus and putamen) --> involves excess of non-ceruloplasmin bound serum copper (total body copper is decreased) leading to injurious accumulation in liver, CNS, cornea and lenticular nucleus. Tx with chelation therapy --> Penicillamine. Gene is ATPB7

Benzodiazepine - A/E

*CONFUSION*, impairment of consciousness, orientation, thought, and attention, paradoxical agitation/aggression, *anterograde amnesia*, psychomotor retardation, ataxia, weakness, vertigo, and syncope. *falls and traumatic injuries are serious risks.* If toxic levels reached can precipitate respiratory depression and coma. Just remember that alcohol and barbituates have a greater chance to produce toxicity.

Bence jone proteins

*EOSINOPHILIC* (PINK) casts NOT made of eosinophils (do not get confused). Casts are glassy in appearance

uses of loop diuretics

*acute pulmonary edema*, heart failure, hypertension (vasodilate through increase prostaglandins - dilate kidney vasculature).

Nafcillin (methicillin) resistance

*altered penicillin binding protein in peptidoglycan* -mediated by alterations in the penicillin binding protein structure. PBP are the enzymes involved in cell wall synthesis and altered PBPs particularly PB2a have greatly reduced affinity for all beta lactam antimicrobial agents.

Tuberous sclerosis

*angiomyolipomas* are most common association - can be present in any organ - most common is renal angiomyolipomas. *Autosomal Dominant* will see cortical tubers and subependymal hamartomas (periventricular calcification) in brain with consequent seizures and mental retardation. Cardiac rhabdomyomas and facial angiofibromas, and ash leaf shaped skin patches.

pinnealoma's (location for what tumor?)

*brain germinoma* 1. precocious puberty = elevated bHCG 2. Aqueductal compression = obstructive hydrocephalus 3. Parinaud syndrome = *paralysis of upward gaze and of convergence - compression of tectal area of midbrain*

A/E of lithium

*has a very narrow therapeutic index* ebstein anomaly as teratogenic effects ataxia, tremor, sedation

how does multiple myeloma result in hypercalcemia

*increases osteoblastic production of RANKL (via macrophage inflammatory protein1a MIPa) - which upregulates osteoclast activation and inactivates osteoblasts. - thus precipitating increase bone reabsorption and elevated calcium levels. Osteoblasts have RANKL, osteoclasts have RANK

congenital syphillis

*keratitis* - white thickening (differ from conjunctivits from chlamydia) stillbirth nerve VIII - deafness saddle nose and mulberry molars notched teeth (hutchinson teeth) desquamating rash

Ventromedial and lateral hypothalamic nuclei

*lesion to lateral = skinny* *lesion to ventromedial = fat* Lateral nucleus stimulates hunger, when leptin is present --> will inhibit lateral nuclei Ventromedial nucleus when stimulated by leptin will decrease feeding. Thus --> leptin has a positive effect on ventromedial and negative effect on lateral

how to differentiate hemophilia from coagulation factor inhibitor?

*mixing study* - when mixing normal blood with patients who have hemophilia - the blood thats added will have sufficient factor 8 thus patients symptoms will no longer present, however in patients with coagulation factor inhibitor - the autoab present will still bind the factor 8 from the blood that was added - thus patients with this pathology will still present with symptoms even after mixing study. *high yeild*

syphillis stages

*primary stage* - painless chancre *ischemic necrosis* - have highest chance for false negative, best test for first stage is *darkfield testing* *secondary stage* - copper colored rash (palms and sole), alopecia, condyloma lata (flat wart) - 2 stage have highest chance of being positive for BOTH VDRL and FTA-ABs *tertiary stage* - gummas = granulomas, CNS (tabes dorsalis and argyll robertson pupils, and large vessel damage --> obliterative endarteritis of vaso vasorum (destruction of vaso vasorum - which supplies tunica media) --> complication aortic arch aneurysm of aortic ring leading to aortic regurgitation and CHF. specific tests are positive and non specific are typically negative.

scarring and traction of esophagus result in...

*true diverticula* seen in mid portion of the esophagus and result from tuberculosis or other fungal infections.

Mild 21 hydroxylase deficiency

*young woman can present with acne, hirsutism and menstrual irregularity* - early puberty *men also present with early puberty*

alpha 2 mediated effects

-CNS mediated decrease in blood pressure (central acting - clonidine and methyldopa) -decrease aqueous humor fluid production from ciliary body -inhibition of lipolysis in fat cells -inhibition of adrenergic and cholinergic nt release -increased platelet aggregation

carney triad

-GIST (gastrointestinal stromal tumor) - from interstitial cells of cajal (ckit 117), pacemaker for peristalsis (autonomic cells of GI). -pulmonary chondroma -paraganglioma

Metabolism of some benzodiazepines

-Hepatic oxidative reduction = diazepam and midazolam -Hepatic glucoronide conjugation = lorazepam, oxazepam, temazepam *these enzymes are metabolized directly and do not undergo any metabolism with CYP450 enzymes*

Gemfibrozil (fibrates) MoA

-Induction of LPL via activation of PPAR (transcription factors to mediate effects of insulin --> thus body will have mediated effects of insulin by adiponectin. This will result in the storage of fats, however this is better than having FFA floating around in blood plasma). Will cause weight gain but will treat hypertriacyglyceridemia (hyper TAGs) -Results in decreased VLDL and IDL with a modest decrease in LDL and increase in HDL.

lung abscess formation - typically contain peptostreptococcus and fusobaterium

-MC = aspiration of oropharyngeal contents risk factors = Seizures, Alcoholism, Prolonged anesthesia, found in right lung. -lung abscess from necrotizing pneumonia (predisposed pts are immunosuppressed, old age -> factors include S. Aureus, E.Coli, Klebsiella Pneumonia, S. Pneumonia -lung absecess from patients with septicemia or infectious endocarditis

causes of xanthelasma's

-Primary biliary cirrhosis -Hyperlipidemias ( familial hypercholesterolemia) -Hypothyroidism --> as a cause of hyperlipidemias -Menopause -Diabetes

first order elimination

-a constant FRACTION of the drug is eliminated per unit time. half life is constant. -the amount will change per unit time but fraction is the same.

what is the clinical presentation of a patient with wernicke encephalopathy

-anterograde amnesia -horizontal nystagmus -confabulation -bilateral abducens nerve palsy -*Note ocular irregularities are first to respond to thiamine infusion*

clinical findings of PCOD

-bilateral enlargement and smooth thickened capsules -subcapsular follicles in different stages of atresia -hyperplastic theca stromal cells rim the arrested follicles. -anovulation, oligomenorrhea --> amenorrhea, hirsutism, obesity, infertility and dylipidemia -type 2 diabetes -increased risk for endometrial adenocarcinoma

what are the drugs used to treat SVT

-class II and class IV anti-arrhythmics -Adenosine -Esmolol

Alpha 1 mediated effects

-contraction of vascular smooth muscle (both arterial and venous) resulting in increased systolic and diastolic BP. The resulting increase in systemic blood pressure stimulates baroreceptors in the carotid sinus and aortic arch with subsequent increase of vagal tone influence on heart. The increased vagal tone then causes decreased heart rate, contractility and conductance by inhibiting SA nodes pacemaker activity and by decreasing the conduction velocity in the AV node. Although A1 agonist act directly upon the heart to increase contractility, indirect vagal influence overwhelms their direct cardiac effects. -contraction of pupillary dilator muscle causing mydriasis -increased cardiac contractility (explained above) -increased internal urethral sphincter tone -pilomotor smooth muscle contraction

leber hereditary optic

-defect in NADH dehydrogenase (ETC) -mitochondrially inherited (transmitted from mother to offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; this affects predominantly young adult males

Noninvasive types of breast growths

-ductal carcinoma in situ = arises from ductal atypia, often will find early microcalcifications on mammography, fills ductal lumen, malignant without basement membrane penetration. -comedocarcinoma = pleomorphic cells surround central area of necrosis - pressure can extrude necrotic material (think crest tooth paste) -pagets = eczemous patches on nipple - paget cells (pas +ve) = large cells in epidermis with clear halo, can also be seen on vulva however does not suggest underlying malignancy. *eczema without a palpable mass (mass may or may not be present)

Type IV acquired - causes

-excess alcohol intake - MC cause = increased production of VLDL and decreased activity of LPL -OCPs - estrogen increases synthesis of VLDL -Diabetes mellitus - decreased adipose and muscle LPL - decreased effect of insulin renders less LPL -Chronic renal failure - increased synthesis of VLDL -Drugs = thiazides, beta blockers - inhibit LPL

H1 first generation

-hydra, -zines, -amines

H2 antagonist

-idines "to I's in name" • Cimetidine • Ranitidine • Famotidine • Nizatidine

Drug strategy for angina

-increase oxygen supply -decreasing vasospasm -decrease o2 myocardial requirements by decreasing peripheral vascular resistance or by reducing cardiac output.

watershed areas in GI

-inferior mesenteric and hypogastric (sigmoid to rectum) -SMA and IMA at splenic flexure

PCOD - clinical signs

-menstrual irregularity (most often oligomenorrhea) and infertility due to anovulation -hormonal dysregulation (progesterone deficiency, acyclic estrogen production, and elevated LH level - elevated LH/FSH ratio). The effects of abnormally high levels of unopposed estrogen on the endometrium increase the long term risk of endometrial hyperplasia and endometrial adenocarcinoma. -Increased insulin resistance (leads to obesity) and INCREASED RISK OF TYPE 2 (NOT 1) diabetes. -Hirsutism (d/t inc androgen levels) -changes in lipid metabolism - increase risk for atherosclerosis -Bilateral ovarian enlargement.

malignant breast tumors

-more common post menopause -common = overexpression of estrogen/progesterone receptors or c-erbB2 (HER2 which is a EGF receptor) -triple negative (ER-ve, PR -ve, HER2/Neu -ve) is very aggressive -mostly located in upper outer quadrant of breast -BRCA1 and BRCA2 mutations (increase risk for triple -ve breast cancer) -remember BRCA2 associated with male breast cancer

psoas abscess vs appendicitis

-psoas abscess- fever right flank pain, difficulty walking, dysuria - prevents in patients with DM, HIV, IVDA -appendicitis - fever, RLQ pain *both will have a positive psoas test*

Orlistat

...

lung cancer chart

...

pathogenesis of atheroma

...

pathological features of acute tubular necrosis

...

Long term use of systemic steroids is thought to promote osteoporosis by what mechanisms? (name 3)

1 decreased synthesis of bone matrix 2 inhibits vitamin D 3 increased PTH level.

what is statistical power?

1-beta. It is the probability of rejecting the null hypothesis (no association exists) when it is truly false. Thus, that implies that the study will be able to find a true relationship (fail to reject alternative) when its present.

What occurs when urachus (derivative of allantoin) fails to develop?

1. *Patent urachus* = connects umbilicus to bladder. Patients present with urine discharge from umbilicus 2. Failure to close the part of urachus adjacent to bladder results in a *vesicourachal diverticulum* an outpouching of the apex of the bladder which is commonly asymptomatic --> can also cause *urachal adenocarcinoma* --> cancer later in life. 3. *Urachal sinus* = failure to close the distal part of urachus which is adjacent to umbilicus. Presents with periumbilical tenderness and purulent discharge from the umbilicus due to recurrent infections 4. Urachal cyst = failure of central portion of urachus to obliterate. Results in a fluid filled structure between the two obliterated ends of the urachus - asymptomatic.

early onset alzheimer's (give 3 risk factors)

1. APP gene on chromosome 21 2. presenilin 1 gene on chromosome 14 3. presenilin 2 gene on chromosome 1

what factors are decreased in acute inflammation

1. Albumin (decreases to conserve amino acids for production of acute phase reactants) 2. Transferrin (sequestered by macrophages)

Early onset alzheimer mutations (name 3 with associated chromosomes)

1. Amyloid precursor protein on chromosome 21 2. Presenilin 1 on chromosome 14 3. Presenilin 2 on chromosome 1

three most common causes of male pattern baldnes

1. Androgenic alopecia (due to 5a reductase inhibitors in scalp - tx with finasteride) --> polygenic or autosomal dominant 2. tinea capitis (ringworm) --> tx with terbinafine 3. telogen effluvium

What are some associations with Guillian barre syndrome

1. CMV 2. Influenza 3. Campylobacter 4. Mycoplasma

what is the treatment for Torsades de point

1. Correct HYPOKALEMIA 2. Correct HYPOMAGNESEMIA 3. Discontinue drug that prolongs QT interval 4. Attempt to shorten AP with drugs like isoproterenol (b1 and B2 agonist) - reintroduce steady rhythm.

causes of nasal polyps

1. Cystic fibrosis 2. kartagener 3. Asthma 4. Aspirin induced asthma 5. Churg strauss/ Wegener's

treatment for thyrotoxicosis *3 stages*

1. Decrease thyroid hormone synthesis and released (give iodine) 2. Decrease peripheral conversion of t4 to t3 (give PTU or propranolol or amiodarone or glucocorticoids) 3. decrease sympathetic outlow

what are the histopathological changes of axonal reaction (4)

1. Enlargement of cell body 2. eccentric nucleus 3. Enlargement of nucleus 4. Dispersion of the nissl substance *consequence of neuronal enlargement*

what are the stages of RDS (3 stages)

1. Exudative stage - intraalveolar hyaline membrane formation occurs 2. Proliferative - type II pneumocytes and fibroblasts proliferate 3. Fibrotic stage - lung remodeling and fibrosis

Steps of indirect ELISA

1. Known antigen is fixed to a well 2. patients serum is added --> if present then specific antigen antibodies bind and remain fixed to the well. The plate is then washed to remove unbound patient antibodies. 3. *anti-human immunoglobulin antibody coupled to a substrate modifying enzyme ("enzyme linked") is added. This antibody binds to antigen bound antibodies in the wells. The plate is again washed. 4. A substrate or chromogen is added which is modified by the enzyme to elicit a detectable signal.

Virulence factors for S. Pyogenes

1. M protein 2. Hyaluronate - present in capsule (external to cell wall) and has antiphagocytic activity *note that this cannot be distinguished from GROUND SUBSTANCE* in human connective tissue and therefore cannot be immunogenic. 3. Streptolysin O - lyses RBCs - anti ASO used in dx of rheumatic fever NOT PSGN 4. DNase - allows strep to move more freely in tissue 5. streptokinase - catalyzes plasminogen to plasmin resulting in fibrin digestion and spread of strep in infected tissue.

Angelman's syndrome (2 causes)

1. Maternal microdeletion of 15q11 - child will inherit paternal gene with imprinted angelman gene thus expression of paternal SNRP. 2. Paternal disomy

causes of prader willi (2 causes)

1. Most common = paternal microdeletion of chrom 15q11 - child will inherit maternal gene with imprinted PW gene - thus expression of maternal UBE3. WILL BE DETECTED ON FISH. 2. Maternal disomy - will have NORMAL FISH

liquifaction necrosis

1. Necrotic tissue that becomes liquefied; enzymatic lysis of cells and protein results in liquefaction. 2. Characteristic of i. Brain inlarclion—Proteolytic enzymes from microglial cells liquefy the brain. ii. Abscess—Proteolytic enzymes from neutrophils liquefy tissue. iii. Pancreatitis—Proteolytic enzymes from pancreas liquefy parenchyma.

what are the 5 P's for acute peripheral artery vessel occlusion

1. Pain - shooting pain followed by numbness 2. Pallor - pale to cyanotic 3. Pulselessness - below occlusion 4. paresthesias 5. paralysis = weakness of distal extremities beyond occlusion - ischemia will also find that extremities are cold distal to occlusion

drugs that can decrease peripheral conversion of T4 to T3

1. Propylthiouracil 2. Propranolol (only Beta blocker that can do this). 3. Amiodarone 4. Glucocorticoids 5. Lithium

what are some complications of prematurity (6 causes)

1. RDS (difference between ARDS and RDS is in ARDS theres neutrophils) 2. Patent ductus arteriosus (from RDS) 3. Bronchopulmonary dysplasia 4. Intraventricular hemorrhage - germinal matrix hemorrhage 5. Necrotizing enterocolitis 6. Retinopathy of prematurity (hypoxic state - thus increase VEGF - vessel proliferation)

what are 5 acute phase reactants that are increased from stimulation by IL-1, IL-6, TNF, and IFNgamma

1. Serum amyloid A 2. C-reactive protein 3. Ferritin 4. Hepcidin 5. Fibrinogen

what layers will be cut through during a cricothyrotomy? (4 layers)

1. Skin 2. superficial cervical fascia (including subcutaneous fat and platysma muscle) 3. deep cervical fascia 4. *cricothyroid membrane* *note to find location palpate the laryngeal prominence "adams apple" on thyroid cartilage, then move inferior to cricothyroid membrane. You do not cut into cricothyroid cartilage (border of cricothyroid membrane). furthermore, if you cut to inferior to cricothyroid membrane - you risk cutting the thyroid gland)

thiamine (vitamin B1) is a cofactor for what enzymatic reactions

1. Transketolase in HMP shunt 2. alpha - ketogluturate DH in TCA cycle 3. pyruvate DH going from glycolysis to TCA 4. Branched amino chain DH *deficient in alcoholism --> resulting in Wernicke Korsakoff syndrome

Type IV hyperlipoproteinemia - acquired causes

1. alcohol consumption - increased VLDL, decreased activity of LPL 2. OCPs - increase synthesis of VLDL 3. Diabetes mellitus - decreased LPL, thus decreased clearance of VLDL (increased VLDL), and increased LDL 4. chronic renal failure - increased synthesis of VLDL 5. Genetic --> familial --> increased VLDL production

what are three clinical uses of benzodiazepines

1. anxiety 2. seizures associated with alcohol withdrawal 3. hypnotic (to treat insomnia)

Clinical effects of diazepam

1. anxiolytic 2. sedative - hypnotic 3. muscle relaxant 4. anticonvulsant

causes of increase pulse pressure

1. aortic regurgitation 2. sleep apnea 3. hyperthyroidism 4. exercise (transient)

causes of decrease pulse pressure

1. aortic stenosis 2. cardiogenic shock 3. cardiac tamponade 4. CHF

what are 3 motions that are associated with injury to supraspinatus tendon?

1. arm abduction 2. flexion of arm at the shoulder 3. fall laterally on an outstreched hand

medications causing hyperkalemia

1. beta blockers 2. ACEi 3. Angiotensin II blockers 4. K+ sparring diuretics 5. Digoxin 6. NSAIDS

What are the different methods by which a nonenveloped virus can be inactivated? (5 methods)

1. boiling (85 celcius) 2. bleach 3. ultraviolet radiation 4. chlorination 5. formalin (formaldehyde)

what are adverse effects of carbamazepine? (3 a/e)

1. bone marrow suppression - anemia, agranulocytosis, thrombocytopenia --> *must monitor blood counts* 2. hepatoxicity --> Must monitor *LFTs* 3. SIADH

Drugs to treat pulmonary hypertension

1. bosentan --> competitive inhibitor endothelin 2. Epoprostenol --> prostaglandin analogue (PGI) 3. Sildenafil 4. Nifedipine

Fluoroquinolone resistance

1. chromosomal mutations that effect DNA gyrase and topoisomerase IV (regulate sister chromatid separation in g2) 2. regulate expression of efflux pumps

what are the signs of peripheral arterial disease?

1. claudication with rest 2. loss of hair on extremities 3. thickened toenails 4. cold to touch 5. shiny color to skin

what are infants at risk of developing from infection with rubella? (3 pathologies)

1. deafness 2. patent ductus arteriosus 3. cataracts

morphology of a changing heart

1. decreased left ventricular cavity size (decreased apex to base dimension) = this decrease in chamber size causes the basal ventricular septum to bulge into left ventricle. 2. sigmoid shaped ventricular septum 3. increase collagenized connective tissue 4. increase in lipofuscin

decrease in SBP caused by (3 causes)

1. decreased preload 2. decreased contractility 3. increased afterload

what are adverse effects of MAOi (6 a/e) - antimuscarinic like

1. drowsiness 2. orthostatic hypotension 3. blurred vision 4. dry mouth 5. dysuria 6. constipation

PCOD - complications

1. endometrial hyperplasia 2. endometrial adenocarcinoma 3. type II diabetes 4. atherosclerosis (coronary)

tissue repair - consists of granulation tissue (what are the three components of granulation tissue)

1. fibroblasts (deposit type III collagen) 2. capillaries (provide nutrients) 3. myofibroblasts (contract wound --> Matrix metalloproteinases) - important that its the myofibroblasts that result in contraction of wound with secondary intention healing.

Potter facies (5 findings)

1. flattened nose and facial features 2. micrognathia 3. dysplastic displaced ears 4. compression of skull vault 5. club feet (talipes equinovarus)

what is antidote for methanol or ethylene glycol poisoning

1. fomepizole (inhibitor of alcohol dehydrogenase) 2. ethanol

what is the triad of a rupture of abdominal aortic aneurysm

1. hypotension from blood loss 2. pulsatile mass 3. acute onset of left flank pain

Primary amenorrhea in a patient with fully developed secondary sexual characteristics suggests the presence of an anatomic defect in the genital tract -->what are the two most common causes of amenorrhea with normal ovarian and pituitary function (remember that most common cause of amenorrhea is anovulation)

1. incomplete canalization of vaginal plate (imperforate hymen or vaginal agenesis) 2. mullerian duct anomalies

what are the acute effects of corticoisteroids on CBC?

1. increased neutrophil count 2. decreased lymphocyte, monocyte, basophil and eosinophil

increases in SBP are due to (3 causes)

1. increased preload 2. increased contractility 3. decreased aortic compliance

what are 4 causes of delayed wound healing?

1. inflammation 2. vitamin C deficiency (hydroxylation), copper def. (lysyl oxidase), zinc def. 3. foreign body, ischema 4. malnutrition, diabetes

how does leptin decrease food intake? (2 mechanisms)

1. leptin decreases the production of *neuropeptide Y* a potent appetite stimulant in the *arcuate nucleus of the hypothalamus* 2. Leptin stimulates the production of *POMC* (proopiomelanocortin) in the *arcuate nucleus* Alpha MSH is produced by cleavage of POMC and *inhibits food intake*

Features of anaplasia

1. loss of cell polarity with complete disruption of normal tissue architecture 2. significant variation in shape and size of cells (cellular pleomorphism) and nuclear pleomorphism 3. large N to C ratio, hyperchromatic 4. Mitotic figures (cells seen undergoing mitosis) 5. GIANT MULTINUCLEATED TUMOR CELLS. or GIANT CELS.

What are the histopathological changes of neuronal atrophy (2)

1. loss of neurons 2. reactive gliosis

bells palsy involves what cranial nerve deficits

1. motor output to facial muscles 2. parasympathetic innervation to the lacrimal, submandibular, and sublingual salivary glands (remember nerves 3,7,9,10 carry parasympathetics) 3. Special afferents to 2/3 of tongue for taste 4. somatic afferent from pinna and external auditory canal.

what are 4 DNA repair mechanisms

1. nucleotide excision repair 2. mismatch repair 3. base excision repair 4. nonhomologous end joining 5. homologous repair

what are four common tumor suppressors

1. p53 2. Rb 3. BRCA 1 4. APC

what are some complications of pagets disease of bone?

1. pathological fractures of hip, femur, skull 2. RISK FOR OSTEOSARCOMA 3. *risk for developing HIGH-OUTPUT-HEART FAILURE* (due to arteriovenous connections in vascular bone)

what are three causes of ACQUIRED type II hyperlipoproteinemia

1. primary hypothyroidism - decreased synthesis of LDL receptors 2. blockage of bile flow 3. nephrotic syndrome

what are the most vulnerable areas affected first in ischemia?

1. pyramidal cells of hippocampus (sommers sector) 2. perkinje cells of cerebellum *if ischemia is profound* then look for necrosis of the watershed areas - areas supplied by distal branches of MCA and ACA and PCA --> CORTICAL watershed infarcs appear as bilateral wedge shaped bands of necrosis over cerebral convexity.

what are histopathological changes in Red neurons (4)

1. shrinkage of cell body 2. Pyknosis of nucleus 3. loss of nissl substance 4. eosinophilic cytoplasm

what conditions are associated with papillary necrosis

1. sickle cell disease or trait 2. Analgesic nephropathy (aspirin + acetaminophen --> aspirin inhibits PGE resulting in afferent arteriole constriction thus decreasing RBF and GFR and acetaminophen generates free radicals) 3. diabetes mellitus 4. Acute pyelonephritis and Urinary tract obstruction - results in edematous interstitium of the pyelonephritic kidney and compresses the medullary vasculature thus predisposing the patient to ischemia.

what are the clinical presentation of patient with parinaud syndrome

1. upward gaze palsy 2. wide based gait 3. absent pupillary light reflex 4. failure of convergence

diastolic BP increased due to 3 causes Remember that diastolic BP correlates to volume of blood in aorta during diastolie.

1. vasoconstriction of pulmonary vasculature (greater volume of blood is present in artery while heart is filling) 2. increased in blood viscosity 3. increased HR (decreased filling of coronary vessels, thus more blood in aorta)

decrease DBP (3 causes)

1. vasodilation of pulmonary vasculature 2. severe anemia (decreased viscosity) 3. decrease the heart rate

Dilated cardiomyopathy (name 6)

1. viral myocarditis 2. peripartum cardiomyopathy 3. Alcohol abuse 4. Chronic supraventricular tachycardias 5. Cardiotoxic drugs (daunorubicin, doxorubicin) 6. Thiamine deficiency (wet berberi)

drugs that are safer in pregnancy

1. water soluble 2. large 3. protein bound

6L of Cr CL is what in ml/min for GFR

100ml/min

regional anatomy - rib levels

12th rib - damage kidney on left side 9th, 10th, 11th rib - damage to spleen 8th, 9th, 10th, 11th rib on right - liver at rest inferior margin of left lung lies at level of 10th rib in midscapular line, during maximal inhalation, lung descends to level of 12th rib, however note that fracture of first 6 ribs have highest chance of damaging visceral pleura.

1.44L in 1 day volume excretion

1ml/min

Each aortic arch is associated with a pharyngeal arch

1st pharyngeal arch --> 1st aortic arch ect.

gastric adenocarcinoma morphology

2 types of gastric adenocarcinoma - signet ring carcinomas and instestinal type adenocarcinomas.

loss of heterogeneity/zygosity

2nd hit is LOH - part of Knudsen two hit hypothesis.

how many calories are in one gram of protein?

4 calories to 1 gram protein

what is the karyotype to a complete mole?

46 XX (more common) than 46 XY; because there are just more "X" chromosomes

isochromosome - turner accounts for 15%

46 chromosomes with turners - must be due to isochromosome One X chromosome inherited from a parent has two long arms X's --> will be nonfunctional.

Pronephros

4th week develops, non functional - earliest sign of kidney growth is formation of pronephric duct and tubules.

Azathioprine contrandications

6-MP which is metabolite of azathioprine is degraded by xanthine oxidase, thus if XO is inhibited then 6-MP levels increase and can result in toxicity. THUS dose must be decreased if given in conjunction with Allopurinol a xanthine oxidase inhibitor.

FIlgrastim is used as an antidote to which drugs?

6MP and 5FU --> filgrastim is a granulocyte colony stimulating factor - stimulates proliferation and differentiation of granulocyes in patients with neutropenia. - do not use for methotrexate --> use folic acid (leucovorin instead)

Alcohol and acetaminophen toxicity

95% of acetaminophen is detoxified by the phase II enzymes and excreted in urine as glucoronate or sulfate conjugates, about 5% is metabolized by CYP2E in NAPQ1 which is highly reactive substance. NAPQ1 is detoxified by GSH. Alcohol will induce (chronic alcoholism, whereas acute alcoholism is inhibition of cyps) CYP2E and increase the fraction of acetaminophen metabolized in NAPQ1, this in turn will decrease the level of GSH making the cells more susceptible to ROS injury, also NAPQ1 can damage cellular components.

renal failure - whats urine osmolarity

<350mOsm

Extralobar sequestration

A pulmonary sequestration (also known as a bronchopulmonary sequestration or cystic lung lesion), is a medical condition wherein a piece of tissue that ultimately develops into lung tissue is not attached to the pulmonary arterial blood supply, as is the case in normally developing lung. As a result, this sequestered tissue is not connected to the normal bronchial airway architecture, and as a result, fails to function in, and contribute to, respiration of the organism. This condition is usually diagnosed in children and is generally thought to be congenital in nature. More and more, these lesions are diagnosed in utero by prenatal ultrasound.

what is the role of A1 receptors

A1 is a Gi and is activated to reduce heart rate

What is the role of A2 receptors

A2 = Gs Coronary artery vasodilation, decrease dopaminergic activity in CNS, inhibition of central neuron excitation, and bronchospasm

what is the role of A3 receptors?

A3 = Gi cardiac muscle relaxation smooth muscle contraction cardioprotective in cardiac ischemia

What antihypertensive drugs should be used in diabetic patients?

ACE inhibitors

first dose hypotension can be seen with...

ACE inhibitors - ensure patient is not taking a thiazide diuretic. Reason being = Bezold Jarish reflex which is vagally mediated hypotension and bradycardia (first dose of ACEi). If patient is already on thiazide diuretic then massive hypotension would result

HCOM

AD mutations in beta myosin heavy chain protein loud S1 Systolic murmur - similar in appearance to aortic stenosis - radiates to suprasternal notch haphazard arrangement of myocytes decreased LV volume LV outflow obstruction thereby increasing afterload

Familial hypercholesterolemia

AD disorder chrom 19 defective LDL receptor

Osler weber rendu syndrome - hereditary hemorrhagic telangiectasia

AD, marked by presence of telangiectasias in the skin as well as the mucous membranes of the lips, oronasopharynx, respiratory tract, gastrointestinal tract, and urinary tract. Rupture of these telangiectasis may causes epistaxis, gastrointestinal bleeding or hematuria.

ticlopidine and clopidogrel - MoA

ADP antagonist - used to treat and prevent ischemic strokes, acute coronary syndrome and peripheral vascular disease.

colonic adenocarcinoma sequence

AK53 1. APC (normal epithelium to early adenoma) - on chromosome 5 "remember 5 letters in POLYP" 2. KRAS (early adenoma to late adenoma) - will increase size of polyps 3. P53 (late adenoma to adenocarcinoma)

Alkaptonuria

AR def of homogenistic acid oxidase (enzyme involved with degradation pathway of phe and tyrosine) homogenistic acid --> reason for dark urine dark pigment changes (onchronotic pigment) - dark blue/grey discoloration visible on the sclera and ear cartilage "onchronosis" - 3rd and 4th decade

Type 1 hypercholesterolemia

AR, childhood disease deficiency in ApoCII or LPL presents with acute pancreatitis (chylomicrons blocks the circulation and cause rupture of pancreatic vessels Elevated TAG *TURBID SUPRANATE*

what antibodies is positive for crohns and UC

ASCA = Anti Saccharomyces Cervesia (bacterial product)

what are signs of reversible cellular damage?

ATP depletion Cellular/mitochondrial swelling (decrease ATP --> decrease activity of Na+/K+ pumps) Nuclear chromatin clumping decrease glycogen Fatty change Ribosomal/polysomal detachment (decrease protein synthesis) Membrane blebbing

what is regulating ventricular heart rate in a 3rd degree heart block?

AV node

what is the mechanism of action of fibrates?

Activates PPARalpha --> results in increased synthesis of ApoCII and increased LPL activity, thus decreasing plasma TAG levels. Also increases HDL.

after receiving a blood transfusion, patient rapidly develops symptoms of breathing difficulty, chills, pain in the chest - whats most likely diagnosis?

Acute hemolytic reaction to blood transfusion due to ABO incompatibility

acute inflammation whats increased?

Acute phase reactants

junctional diversity

Additional DNA nucleotides may be deleted, or inserted at V, D, or J gene segment junctions in order to maintain (downstream) an open reading frame, thus generating junctional diversity. Incorporation of nucleotides at junctions is mediated by a template independent DNA polymerase, terminal deoxynucleotidyl transferase (Tdt). Random association/assortment of any light chain with any heavy chain allows for another level of diversity in creating unique antigen binding sites.

quinidine adverse effects

Adverse effects: cinchonism ( GI, tinnitus, ocular dysfunction, CNS excitation), hypotension, prolongation of QRS and increase QT interval associated with syncope ( torsades) --> torsade a muscarinic effect.

ACEinhibitors effect on afferent and efferent arteriole

Afferent --> ACEi increase bradykinin via inhibition of Angiotensin Converting Enzyme in the lungs and in doing so decrease levels of Angiotensin II. Bradykinin that is produced will vasodilate afferent arteriole. (will also constrict veins) Efferent --> Decrease levels of angiotensin II will result in vasodialation of efferent arteriole thus decreasing GFR --> thus serum levels of creatinine will increase due to decreased filtration pressure.

EPS weeks to 2 months

Akathsia which is due to increased sensitization (decreasing Km) *compelling need to move* restless leg Tx with CNS depressant - benzodiazepine's

Patient presents with vomiting irritability, and lethargy days after birth. Diaper smells like burned sugar. The defective enzyme responsible for this patients condition normally catalyzes a reaction involving which of the following substances?

All cofactors of dehydrogenase complex - thus will require Thiamine (B1), Lipoic Acid, CoA (pantothenate B5), FAD (B2), NAD (B3).

AllantoiN will eventually form what in the infant?

Allantois --> forms urachus --> later will develop into the median umbilical ligament in infants

a 23 yr old asymptomatic male is homozygous for ApoE4 - whats he likely to develop?

Alzheimer's disease. specifically late onset familial alzheimer's disease. Mechanism unknown - it is thought that ApoE4 may be involved in formation of senile plaques.

cyclophosphamide MoA

An alkylating agent adds an alkyl group to DNA. It attaches the alkyl group to the guanine base of DNA, at the number 7 nitrogen atom of the imidazole ring. This interferes with DNA replication by forming intrastrand and interstrand DNA crosslinks. It is used to treat cancers and autoimmune disorders. As a prodrug, it is converted in the liver to active forms that have chemotherapeutic activity. Note: Give IL-2 to stimulate T lymphocytes DO NOT CONFUSE WITH CYCLOSPORINE

Quinidine side effect

An increase in AV conduction is characteristic of quinidine which exerts marked blocking actions on muscarinic receptors in the heart. Thus, an atrial rate of 2:1 ratio may be transmitted in a 1:1 ratio after quinidine. This effect of quinidine can be offset by the prior administration of an antiarrhythmic drug that decreases AV nodal conduction such as *digoxin or verapamil*

patient presents with normal 2nd sex characteristics and normal blood testosterone levels, but testosterone concentration in his seminiferous tubules and epididymis is abnormally low. What is the causes of this specifically? (we know its sertoli cells - but what is problem)

Androgen binding protein - maintain high levels of testosterone within seminiferous tubules. - if deficient, spermatogenesis will not occur bc testosterone levels will be insufficient.

Swayback's disease - lumbar lordosis

Anterior pelvic tilting secondary to excessive contracture of hip flexors (iliacus and psoas major) Pain with movement *etiology = obesity, pregnancy, osteoporosis, discitis, kyphosis, spondylolisthesis, and achondroplasia)*

immunology - acute hemolytic reaction

Anti-ABO ab in recipient bind to corresponding antigens on donor RBCs. The antigen-antibody complement then has an exposed Fc receptor which binds complement --> results in production of free anaphylatoxins (C3a and C5a) as well as MAC complex which results in hemolysis. The free anaphylatoxins will cause symptoms of shock.

primary biliary cirrhosis

Anti-mitochondrial antibodies it is a chronic liver disease characterized by autoimmune destruction of the INTRAHEPATIC bile ducts and cholestasis. *presents in middle aged women* will see pruritis, fatigue, hepatosplenomegaly and evidence of cholestasis (xanthelesma and pale stools) - can progress to jaundice, steatorrhea, portal hypertension and osteopenia.

treatment for EPS for 1 day to 1 month

Antimuscarinics to block indirect pathway -benztropine, triphenhexidyl

where is the most common site of aortic rupture from trauma?

Aortic isthmus which is the connection between the ascending and descending aorta distal to left subclavian artery.

what finding is associated with late onset alzheimers

ApoE4 --> formation of senile plaques *note that Apo E2 is protective.*

metachromatic leukodystrophy - deficient enzyme

Arylsulfatase A...

what is a common pathogen seen in patients with chronic asthma --> hint: if eosinophilia is seen - then this is what question is going after.

Aspergillus --> Allergic bronchopulmonary aspergillosis (ABPA) seen in immunocompromised OR patients on corticosteroids for asthma treatment. Patients have high serum IgE levels, Eosinophilia, and IgG ab against aspergillus. *can lead to bronchiectasis*

Samter's triad

Asthma, aspirin hypersensitivity (facial flushing and bronchospasm) and nasal polyposis that occurs in 10% of asthmatics treated with aspirin. --> symptoms occur due to overproduction of leukotrienes.

Ataxia Telangiectasia - clinical findings

Ataxia, Spider Angiomas, defect ATM gene, AGE deficiency (IgA, IgG, IgE), and increased AFP. will find lymphopenia and cerebellar atrophy.

familial combined hypercholesterolemia (type IIb)

Autosomal Dominant occurs around puberty associated with metabolic syndrome X elevated cholesterol, LDL, AND TAGs

criteria for diagnoses of LiFraumeni syndrome

Autosomal dominant -Sarcoma at <45 years age -1st degree relative with sarcoma <45 -sarcoma at any age in 2nd degree -chrom 17 -p53 binds and inactivates cdk4 - thus not allowing it to bind to cyclin D - which then cannot phosphorylate Rb - thus prohibiting G1/S phase *breast, brain, adrenal cortex, sarcomas and leukemias* *look for osteosarcoma or rhabdomyosarcoma*

Familial hypercholesterolemia (type IIa)

Autosomal dominant def of LDL receptors Xanthoma (cholesterol) - achilles, dorsum hand, patellar tendon Xanthelasma (LDL) Premature coronary artery disease Stroke Labs: increase in cholesterol, LDL, not tag's remember thats type IIb.

Peutz Jeghers poyposis

Autosomal dominant hamartomatous polyps predominant in small bowel mucosal pigmentation and buccal mucosa, *lips* increased risk for cancers - colorectal, breast, gynecologic cancers *colorectal cancer* is associated with inactivation of *serine/thronine kinase* tumor suppressor gene Differential - addisons (hyperpigmentation of buccal mucosa) Increased risk for intussusception (causes gastro bleeding) *pathognomonic = hyperpigmentation lips, buccal mucosa, hands, and feet* median age onset is 11 yrs large pedunculated polyp, arborizing and presence of smooth muscle intermixed with lamina propria

Familial dysbetalipoproteinemia (type III)

Autosomal recessive deficiency of ApoE (required for uptake of IDL and Chylomicrons) - chromosome 19 Palmar xanothams in flexor crease increase risk of coronary atherosclerosis and peripheral vascular disease increased cholesterol and TAGs, NO increase in LDL

Friedrich Ataxia

Autosomal recessive hypermethylation of GAA repeat in intron Frataxin --> normall role --> binds iron, thus decreased frataxin will increase iron toxicity in mitochondria (because mitochondria contain iron in ETC) will find ataxia, decrease reflexes (due to lesion of DCML), decrease touch, vibration, proprioception Effects: dorsal column, spinocerebellar (reason for ataxia), and lateral corticospinal Cause of death = hypertrophic cardiomyopathy

difference in presentation of B-ALL and T-ALL

B-ALL = fever, bone pain, bleeding, and hepatosplenomegaly - not associated with symptoms of mediastinal mass T-ALL = fever, fatigue, petechiae, *MEDIASTINAL* MASS - lymphadenopathy, hepatosplenomegaly, bone pain. The mediastinal mass can compress esophagus causing dysphagia, while compression of trachea may lead to dyspnea and stridor.

which enzyme can add to formation of gallstones?

B-glucoronidase (from neutrophils, hepatocytes, and bacteria) -brown pigmented stones typically arise secondary to infection in biliary tract --> results in release of b-glucoronidase. This enzyme contributes to the hydrolysis of bilirubin glucoronides and increases the amount of *unconjugated bilirubin in bile* Biliary infections --> e.coli, ascaris lumbricoides, and *liver fluke clonorchis sinesis*

Procainamide A/E

Because its metabolized by N-acetyltransferase --> pts with genetic variation (slow acetylator) have a high risk of developing SLE like syndrome. -Other A/E = Hematotoxicity (check CBC, look for agranulocytosis and thrombocytopenia) and CV effects (Torsades)

Neuro fibrillary tangles

Beta amyloid abnormally phosphorylated tau

class II drugs

Beta blockers act at SA and AV nodes to decrease nodal activity. Used for SUPRAventricular tachycardias. (arrhythmias that arise above ventricles.)

BATS Drink Blood

Beta waves = awake Alpha waves = awake (eyes closed) Theta waves = STAGE 1 = light sleep Sleep spindles and K complexes = STAGE 2 = deeper sleep when bruxism (grinding teeth) Delta waves = STAGE 3 = *lowest frequency, highest amplitude* deepest NONREM sleep (slow wave sleep) when sleepwalking, night terrors, and bedwetting occur* Beta waves = REM sleep

Maple syrup urine disease MSUD

Blocked degradation of branched amino acids (Ile, Leu, Val) due to *decreased α-ketoacid dehydrogenase (B1).*

esophageal blood supply

Blood supply The cervical portion is supplied by the inferior thyroid artery The thoracic portion is supplied by bronchial and esophageal branches of the thoracic aorta The abdominal portion is supplied by ascending branches of the left phrenic and left gastric arteries

Atrial natriuretic peptide (ANP) and Nitric Oxide) - similarities

Both bind to Gq - increasing levels of cGMP. Another drug that increases cGMP is phosphodiesterase inhibitors - but this is through a different mechanism!

difference between unfractionated and LMWheparin

Both heparin's can bind to antithrombin to increase its activity against factor Xa. Only unfractionated heparin is able to bind BOTH antithrombin and thrombin to allow antithrombin to inactivate thrombin. Reason being that unfractionated heparin is much larger. So, unfractionated has euqal activity against thrombin and factor Xa whereas LMWH has greater activity against factor Xa than thrombin.

Pt has bilateral renal masses composed of fat, smooth muscle and blood vessels. What is an additional finding?

Brain hamartomas and ash leaf skin patches.

Tense bulla, multiple locations, separation of basement membrane from epidermis

Bullous pemphigoid - antibodies against hemidesmosomal proteins

chemokines for PMNs

C5a, IL-8, LTB4, FMet (bacterial product to initiate translation)

chemokines for Macrophages

C5a, PDGF, TGFb, MCP (macrophage chemokine protein)

CAAT box and TATA box - promoting regions

CAAT box is located 60 to 80 bp upstream of 5' coding region and TATA box is 25 bp upstream from beginning of the coding region. *gene transcription begins when RNA poly II attaches to one of these promoter sites in a process facilitated by transcription factors.* RNA poly II is unable to recognize the TATA box alone.

Right shift on oxygen hemoglobin curve

CADET C= C02 increase A= Acidosis (increase H+ ions) A= Altitude increase D= 2,3, DPG increase E= Exercise T= Temperature increase

what is the cellular receptor for EBV?

CD21 or CR2 --> present on B lymphocytes

what is the cellular receptor for HIV

CD4 and CXCR4/CCR5 CCR5 is on macrophages

CNS calcifications - TORCH

CMV, HIV, Toxoplasmosis

periventricular calcifications

CMV, toxoplasmosis (will also see chorioretinitis, and hydrocephaly - with toxo).

what is the MoA of anesthetics

CNS depression is achieved by influencing GABA receptors and increasing the inhibitory action of GABA.

caridac output equations

CO = HR x SV CO = HR x (EDV-ESV) CO = 02 consumption/(Arterial 02 content-venous 02 content) MAP = CO x TPR; CO = MAP/TPR

COX 1 inhibitors and COX 2 inhibitor risks

COX 1 = GI damage COX 2 = CVS damage (due to decreased PGI2 relative to TXA 2 --> which leads to vasoconstriction)

anti centromere

CREST

Clearance of drugs

CV: hepatic encephalopathy --> can give lactulose which when converted to lactic acid in the gut will effectively trap ammonia and form ammonium - thus decreasing absorption

A researcher treats an epithelial cell line with substance X which lyses intercellular adhesions but leaves cell adhesions to the basement membrane intact. Removing calcium from the cells environment causes the same effect. Substance X most likely effects which of following? (another way this question can be phrased is --> what intercellular junction requires calcium?

Cadherins, previously known as "calcium dependent adhesion proteins" subclassed into zonula adherins and desmosomes.

CREST syndrome

Calcinosis/anti-centromere Raynaud Esophageal dysmotility Sclerodactyly (tapered, claw like fingers) Telengiectasia (multiple punctate hemorrhages)

Carney complex

Carney complex and its subsets LAMB syndrome[1] and NAME syndrome[1] are autosomal dominant conditions comprising myxomas of the heart and skin, hyperpigmentation of the skin (lentiginosis), and endocrine overactivity.[2][3] It is distinct from Carney's triad. Approximately 7% of all cardiac myxomas are associated with Carney complex.

ARDS pathogenesis

Caused by injury to the *endothelial cells lining the pulmonary capillaries adjacent to the alveoli* due to cytokines and neutrophils. Damage to the endothelial cells allows fluid to enter the alveoli leading to respiratory compromise during the initial exudative stage. This is followed by proliferative stage where pulmonary edema resolves and there is proliferation of type II pneumocytes. There can be a fibrotic stage in where there is diffuse pulmonary fibrosis and cyst formation.

MSUD clinical features

Causes severe CNS defects, intellectual disability, and death, sweet smelling urine

what cells are responding in a patient with leprosy (tuberculoid type)

Cd4+ T cells (th1 cell response) -Th1 cells activate macrophages to kill the M. Leprae organisms

what are the COX 2 selective inhibitors? (2 drugs)

CeleCOXib and melOXicam

Germline mosacism

Cells in the body contain different genes, occurs when the GERM cells contain a different genetic makeup than somatic cells. CONSIDER when there is a mutation present in the offspring but not present in the parents or grandparents.

What is the cellular receptor for CMV?

Cellular integrins

*Recurrent* hemorrhagic stroke, (lacunar stroke = hemorrhagic stroke) different areas of the brain - older individual.

Cerebral amyloid angiopathy -beta amyloid is deposited into the arterial wall resulting in weakening of the wall and predisposition to rupture. Related to advanced age "senile amyloidosis" - not associated with systemic amyloidosis.

An otherwise healthy 23-year-old woman comes to the physician because she has not had a menstrual period for 2 months. Menarche occurred at the age of 14 years, and menses had occurred at regular 28-day intervals. Pelvic examination shows blue-tinged vaginal mucosa. The uterus is somewhat soft in the lower segment and is about the size of an orange. The adnexa are nontenderwith normal-sized ovaries

Chadwick = blue tinged vaginal mucosa indication of pregnancy.

follicular conjunctivitis, blindness

Chlamydia trachomatis A-C

as the airways continue distally, the epithelium changes. Which of the following features is last to disappear as the epithelium changes along the respiratory tube?

Cilia. -at *terminal bronchioles* the epithelium changes from pseudostratified ciliated columnar to ciliated simble cuboidal. Cilia are present through the respiratory bronchioles - but are not present in alveolar ducts. *bronchioles (including terminal and respiratory) lack goblet cells, glands, and cartilage, BUT contain cilia which can persist up to the end of resp. bronchioles.

What immune response would be effective against c. diptheria?

Circulating IgG against exotoxin

drugs that bind to 23rRNA - inhibits peptidyltransferase

Clindamycin Macrolides Chloramphenicol linezolid

Praziquantel A/E and MoA

Contraindicated in pregnancy Contraindicated for treatment of ocular cysticercosis (from cystercericosis "pig tapeworm") - destruction of organism may damage eye. will also see dizziness, malaise, anorexia and has CYP450 interactions.

Permissive actions

Cortisol on Growth hormone and Norepinephrine Thyroid hormone on alpha adrenergic on cardiac muscle

ACEi

Cough Angioedema Teratogen (fetal renal malformations, and bone) Creatinine Hyperkalemia (decrease effectiveness of Digoxin) Hypotension

detection of elevated 14-3-3 protein in CSF

Creutzfeldt Jakob disease - PRIONS

crossing over of homologous chromosomes

Crossing over occurs during meiosis I, and is the process where homologous chromosomes pair up with each other and exchange different segments of their genetic material to form recombinant chromosomes. Crossing over is essential for the normal segregation of chromosomes during meiosis. Crossing over also accounts for genetic variation, because due to the swapping of genetic material during crossing over, the chromatids held together by the centromere are no longer identical. So, when the chromosomes go on to meiosis II and separate, some of the daughter cells receive daughter chromosomes with recombined alleles. Due to this genetic recombination, the offspring have a different set of alleles and genes than their parents do. In the diagram, genes B and b are crossed over with each other, making the resulting recombinants after meiosis Ab, AB, ab, and aB.

type II pneumocytes

Cuboidal cells interspered within walls of the alveoli.

what is a patient with neurosyphillis is resistant to penicillin - whats first step?

DESENSITIZATION

what is the only sign of hypoglycemia that beta blockers do not mask?

DIAPHORESIS

shifts K+ out of cell

DO Insulin LAB Digitalis hyperOsmolarity Insulin deficiency Lysis of cells Acidosis Beta blockers

diethyl ether, or chloroform, or 50% trichlorofluoroethane treatment - sanitize

DOES not work on viruses that lack a envelope, these chemicals disrupt the lipid soluble envelope.

in a patient with liver cirrhosis - gynecomastia annd spider angiomas result from hyper estrogen secondary to liver damage.

Damage to liver results in inability to metabolize circulating estrogens specifically androstenedione - resulting in increased estradiol levels. Furthermore, concentration of sex hormone binding increases which results in higher binding of testosterone - thus decreasing the ratio of free testosterone to estrogen. --> thus creating a state of estrogen excess.

Rubella - TORCH (transplacental)

Deafness Cataracts *Patent ductus arteriosus* thrombocytopenia "blueberry muffin rash" Hepatomegaly

Whats the reason for rhabdomyolysis with the use of statin drugs?

Decreased levels of Farnesyl pyrophosphate (PPi) which is an intermediate in cholesterol synthesis (after mevolonate) which is required for production of dolichol CoQ (Coenzyme Q) which is REQUIRED in ETC to accept electrons from complex II and complex I. Thus, muscle undergoes breakdown. -decrease ATP, thus decrease ATP for Na/K ATPase, thus increase intracellular sodium, cell myocytes swell and rupture.

what is the most common defect in homocystinuria?

Defect in cystathionine synthetase --> converts homocysteine into cystathionine.

what is the enzyme deficiency in MSUD?

Dehydrogenase complex (also used in pyruvate to acetyl coa and alpha ketogluturate to succinyl coa.

what enzymes require thymine?

Dehydrogenase complexes Transketolase

What are requirements of diagnosis concerning dysthymic disorder?

Depressed mood occurring most days for at least 2 years. and presence of at LEAST 2 of following: 1. poor appetite or overeating 2. insomnia or hypersomnia 3. low energy or fatigue 4. low self esteem 5. poor concentration or difficulty making decisions 6. feelings of hopelessness

thyroid gland - embryology

Develops between the first and second pharyngeal arches. Normally, the thyroid descends forming thyroglossal duct which extends from foramen cecum to superior border of thyroid. Defective migration of thyroid gland can result in the gland presenting anywhere along its migratory path to normal location which is in lower portion of neck anterior to trachea and larynx.

Patient presents with fatigue, blurry vision, nausea and vomiting, and confusion- what drug where they given?

Digoxin - other a/e are changes in color perception, diarrhea, anorexia, abdominal pain, delirium, and bradycardia.

Splice site donor (1st)

Donor = AG

why can a HIV patient on medication for CMV retinitis develop seizures?

Drug being given is Foscarnet - bc its drug commonly used to treat CMV retinitis in immunocompromised or when gangciclovir fails. Now, foscarnet is associated with nephrotoxicity and is a analog of pyrophosphate which chelates calcium. Thus, patients will develop a state of hypocalcemia. Also, due to nephrotoxicity - patients will experience loss of magnesium - the state of hypomagnesemia will lead to decreased production of parathyroid hormone. Thus further putting patient into state of hypocalcemia. Both hypocalcemia and hypomagnesemia can result in precipitation of seizures. *note: magnesium decreases release of calcium from sarcoplasmic reticulum, thus decreased magnesium results in higher intracellular levels of calcium - thus decreasing PTH.* Remember that seizures and spams occur in hypocalcemia because its easier for action potentials to fire - lowers threshold for depolarization.

diethylcarbamazine

Drug choice for of lymphatic filariasis, loiasis & tropical eosinophilia. MOA • Immobilizes microfilariae & renders them susceptible to host defense mechanisms

You have a pt that presents with fatigue, unhappiness, decreased energy, hopelessness over last four years. neg toxicology. Dx?

Dysthymic disorder

contraction

E = increase calcium in cytosol, low concentration in SR, lower calcium uptake into SR A = greatest calcium sequestration in SR and lowest calcium concentration in cytosol.

ONLY LOOP DIURETIC THAT CAN BE USED IN PATIENT THAT IS ALLERGIC TO SULFA DRUGS IS>

ETHYCRINIC ACID - does not have a sulfa group.

Fatty streaks

Earliest lesion of atherosclerosis and are present in all individuals after age 10. They are composed of intimal, lipid filled foam cells derived from macrophages and smooth muscle cells that have engulfed lipoproteins (oxLDL). Although some fatty streaks progress to full fledged atherosclerosis later in life, *in general their occurrence and location in a child do not predict the occurrence or location of atheromatous plaques later in life*

Meckels diverticulum - finding of tissue outside of organ system is characterized by what?

Ectopic tissue - reason being that meckels is a remnant of the vitelline duct or "omphalomesenteric duct" --> its a true diverticulum with three tissue layers. Now, this outgrowth will contain ectopic tissue from stomach or pancreas. This is not metaplasia (because its not replacing a tissue) or dysplasia (no pleomorphism, increase N to C ratio, or loss of original tissue)

Giardia is a parasite thus main immune response is...

Eosinophils and Secretory IgA

New drug of spironolactone

Eplerenone - less side effects, used in Conn syndrome and as anti hypertensive drug.

Respiratory Distress Syndrome

Examination = shows cyanosis and lower rib retractions with respiration. Chest x-rays show fine densities with a reticulogranular appearance bilaterally; elevated respirations, respiratory distress

specific test for syphillis

FTA-ABS the screening test is VDRL

Factor V leiden deficiency

Factor V leiden is the most common cause of inherited thrombophilia.- Factor Va becomes resistant to cleavage by protein C. This results in increased thrombin production thus inducing a state of hyper coagulability. Patients will have recurrent VENOUS thrombosis resulting in thromboembolism. The patient will NOT have recurrent petechia or ecchymoses simply because those are problems of platelet quality or quantity - and not with anticoagulation.

what is drug used in hypertensive emergencies that protects kidney

Fenoldopam.

Neuroleptic malignant syndrome

Fever Elevated enzymes (creatine phosphokinase) Vitals unstable (metabolic acidosis) Encephalopathy (delirium) RIGIDITY (blockade of D2)

female pt 45 yrs, persistent back pain, easy fatigability, pain worse after exercise, point tenderness is elicited in periphery

Fibromyalgia

treatment for panic disorder, social phobia, GAD and OCD?

Fluoxetine (a SSRI) - a/e is sexual dysfunction.

What are adenosine receptors

G coupled receptors A1 = Gi A2 = Gs A3 = Gi

Perkinje cell

GABAergic and only output from cerebellum

renal elimination

GFR + active secretion-reabsorption

what are the symptoms of Henoch Shonlein purpura (GI tract - what is patient at risk of developing) (Renal) (skin) and (joints)

GI tract = hematemesis and bloody diarrhea, increased risk for intussusception Kidneys = IgA leukocytoclastic vasculitis - causes mesangial proliferation and crescent formation. Skin = acute inflammation leads to formation of palpable purpura on buttocks and lower extremities Joints = SELF LIMITED MIGRATORY ARTHRALGIAS seen in lower joints.

Bile acid binding resins A/E

GI upset, hypertriglyceridemia, and malabsorption

carney triad - MEN like syndrome

GIST - gastrointestinal stromal tumor - pediatric pulmonary chondroma paraganglioma

Tay Sach's disease - accumulated substrate

GM2 ganglioside

Krabbe disease - deficient enzyme

Galactocerebrosidase...

fibrates A/E

Gallstones Myopathy (will be exacerbated when given with a statin)

whats increased in a patient with autoimmune gastritis

Gastrin - reason being that antibodies against parietal cells are destroying fundus of stomach - patient will develop hypochlorhydia and decreased levels of intrinsic factor thus precipitating megaloblastic anemia and atrophic glossitis and possibly subacute combined degeneration, now gastrin will be elevated to try and compensate for the loss of parietal cell mass.

Pts develops sudden onset of focal numbness and tingling that fully resolved within minutes - this patient had TIA - whats side effect of drug thats most commonly administered to these patients.

Gastrointestinal bleeding from aspirin use.

what are absolute drug contraindications for Statins?

Gemfibrozil (fibrates) - will decrease clearance of statin - thus exacerbate *rhabdomyolysis* CYP450 inhibitors - enhance state of toxicity

genetic recombination (RAG1, RAG2)

Gene rearrangement of the variable light chain region involves the selection and ligation of one "J", and one "V" to form a VJ segment. For the heavy chain, one "D" and one "J" are randomly selected, to form a DJ gene segment, which then combines with a randomly selected "V" gene segment to form the variable region (VDJ) of that particular heavy chain.

a 30 yrs old female has two kids with *osteogenesis imperfecta*. She and her husband are free of symptoms and have unremarkable family histories. Whats the reason?

Germline mosaicism --> DEFINED as the presence of two or more genetically different cell lines within the body. Mosaicism results from a mutation early on in mitosis --> the earlier the mutation, the more daughter cells that will be affected. Mosaicism can be germline, somatic or both, however note that if its somatic moscaism then the mutations WILL NOT BE PASSED TO OFFSPRING.

adenosine acts via what G coupled receptor

Gi - thus decreases cAMP, and is similar to M2 receptors.

Moderate 21 hydroxylase deficiency

Girls present with ambiguous genitalia *BOYS present at 2-4 years with early signs of virilization*

A 32 yr old female complains of a lump in her throat. Hx significant for migraines. No abnormalities on barium swallow. Whats diagnosis?

Globus hystericus --> also called globus sensation or lump in the throat is a common occurrence in up to 45% of general population. Emotions commonly trigger globus hystericus.

whats the effect of glucocorticoids on peripheral lymphocyte counts?

Glucocorticoids will rapidly decrease lymphocyte count - the response occurs as a result of the redistribution of lymphocytes from the intravascular compartment to the spleen, lymph nodes, and bone marrow. Also, there are direct effects on T and B lymphocytes including *inhibition of immunoglobulin synthesis and stimulation of lymphocyte apoptosis*

niacin, hydrochlorothiazide, pyrazinamide, and cyclosporine - can precipitate attacks of what?

Gout - due to effects of increasing serum uric acid.

Gout - interesting fact

Gout under polarized light is negatively birefringent and composed of uric acid. Now, under normal situations without any pathological event - urate crystals are protected from recognition by IgG via a protective layer on urate crystal. Apo E or Apo B coat urate crystals and prevent IgG recognition, however in times of fluctuating uric acid levels of trauma, "bare" urate crystals are made and thus can be recognized by circulating IgG antibodies. Once these IgG's bind, the Fc portion will bind to Cd16 on neutrophils thus initiating a inflammatory cascade which results in symptoms of gout.

H1 receptors - which G coupled?

Gq

M1 receptors - (g protein type) and location

Gq target organ = brain and ONLY GI secretions effect of stimulation = memory formation and cognitive functioning effect of inhibition (as seen with atropine) - results in confusion (thus avoid atropine with elderly)

Smooth muscle relaxation via Gq

Gq coupled receptors (M3, bradykinin, H1 receptors on endothelium) will result in activation of guanyl cyclase and thus result in increasing concentrations of cGMP. This activates protein kinase G and phosphorylates myosin light chain PHOSPHATASE which will dephosphorylate myosin light chain - which results in inactivation and thus smooth muscle relaxation. drugs that activate guanyl cyclase = nitroprusside, hydralazing, nitroglycerin, isosorbide dinatrate and mononitrate, and nesiritide (recombinant form of ANF).

Angiotensin 2 type 1 receptor (activated by by AgII) - what kind g protein

Gq receptor

all cells of cerebellum are GABAergic except

Granule cells which are glutaminergic cells that are GABAergic are *perkinje, golgi, stellate and basket* - thus are inhibitory and only granular is glutaminergic

Thayer Martin Agar (VPN)

Grows neisseria V = Vancomycin, P = Polymyxin or Colistin (same thing) N = Nystatin + can add trimethoprim to stop growth of proteus.

H2 receptors - which G coupled?

Gs

GvHD - patient had a liver transplantation and developed SYSTEMIC signs a week later.

GvHD typically occurs following a bone marrow transplant or transplantation of organs RICH in lymphocytes (such as liver). The immunocompetent T cells in liver attach the immunosuppressed host. Both CD4 and CD8 cells involved. Any organ may be target of GvHD but the skin, liver and GI tract are GENERALLY affect most. Why isnt this chronic rejection? Reason is, no vasculitis was seen - and reaction was not at liver alone. If reaction is systemic consider GvHD (if transplanted organs make sense - such as liver or bone marrow).

why shouldnt first generation antihistamines (h1 receptor blockers) be used in the eldery?

H1 receptor antagonists also block muscarinic receptors - never great to give antimuscarinics to elderly due to cycloplegia, confusion, urinary retention ect.

culture negative endocarditis

HACEK (haemophilus, actinobacillus, cardiobacterium, eikenella, kingella) Bartonella quintana, Coxiella, Mycoplasma, Histoplasma, Chlamydia

HBV vs HCV which one has a greater chance of leading to hepatocellular carcinoma?

HBV; mechanisms of two virus are different though. HBV will actually incorporate into host cell genome whereas HCV can induce HCC from prolonged chronic inflammation

whats elevated in a seminoma?

HCG (acts like LH) and estrogen In a seminoma the increased levels of bHCG will act on thecal cells to increase testosterone which leads to increase peripheral conversion of testosterone to estrogen via aromatase. (check)

valsalva maneuver increases sound of what murmurs?

HCOM and MVP

Amyl Nitrite injection would increase the sound of what murmurs?

HCOM and MVP -amyl nitrite causes vasodilation (veins) and decreased venous return. It would have same effect as straining phase of the valsalva maneuver on murmurs. as well as patient standing up quickly.

what is the main cause of death in a patient with friedrich's ataxia?

HCOM which leads to cardiac arrhythmias and congestive heart failure

Most common hepatitis in IVDA

HCV

Maraviroc is what type of antiviral?

HIV CCR5 receptor inhibitor

saquinavir and ritonavir are what type of antiviral?

HIV protease inhibitors

efavirenz, tenofovir, lamivudine are what type of antiviral?

HIV reverse transcriptase inhibitor

Hairy cell leukoplakia

HIV with coinfection of EBV lateral border of tongue no malignant potential

What is the most common cause of genital herpes?

HSV 2

Preeclampsia

HTN >140/90 proteinuria (AFTER 20th wk) if prior think MOLAR pregnancy Increase AST/ALT *caused by abnormal spiral arteries* results in maternal endothelial dysfunction

What does hepatitis D require from hepatitis B to be infective

Hep D requires HBV's surface antigen "viral coat" HBsAg.

Syphillis - TORCH Transplacental

Hepatitis saddle nose hutchinson teeth blindness

Hepatitis associated with HCC

Hepatitis B

Neuropsychiatric findings in Wilson's disase (name 5)

Hepatolenticular degeneration - thus degeneration is seen of lenticulate nucleus which is putamen and globus pallidus. -Parkinosian like tremor -Rigidity -Ataxia -Slurred speech -Personality changes -Depression or paranoia

cystinuria

Hereditary defect of renal tubular amino acid transporter for *COAL* cysteine, ornithine, Arginine, lysine in the PCT of the kidneys.

what is the only family of viruses that attain envelope from the host nuclear membrane rather than from plasma membrane?

Herpesviruses which contain cytomegalovirus --> phospholipid composition from nuclear membrane.

crystal formation - cystine

Hexagonal *cause* - Cystinuria (unable to absorb neutral amino acids) COAL (cystine, ornithine, arginine, lysine)

Tay Sach's disease - deficient enzyme

Hexominidase A

normal individual - lung physiology - radial traction

High lung volume --> increased radial traction (outward pulling) --> decreased airway resistance Low lung volume --> decreased radial traction --> high airway resistance

Typical antipsychotics A/E - High vs Low potency

High potency antipsychotics are more likely to cause EPR than low potency antipsychotics but less likely to cause anticholinergic and antihistamine side effects (sedation and postural hypotension)

Sign of DVT

Homan's sign = tenderness of the calf muscle on dorsiflexion of the foot. Tx with heparin if pt is pregnant - Warfarin *coumadin* is teratogenic.

Thiazide A/E

HyperGLUC hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia. sulfonamide hypersensitivity, hypokalemia and alkalosis

Azotemia is associated with nephritic

Hypercellular glomeruli "clog" filtration - decrease filtration of electrolytes and nutrients - leads to intrinsic parenchymal damage

What is the effect of hyperventilation on a patient with cerebral edema?

Hyperventilation will result in decrease levels of C02, this can decrease cerebral blood flow and result in decrease of intracranial pressure.

structures that pass through diaphragm

I8 10E at 12 IVC and Rt phrenic N. - T8 Esophagus, Esophageal branches of left gastric vein, and 2 trunks of VAGUS nerve T12 - "red white and blue" (red = aorta, white = thoracic duct, blue = Azygous vein)

infliximab and adalimumab clinical use

IBD, rheumatoid arthritis, ankylosing spondylitis, psoriasis

What is the cellular receptor for Rhinovirus

ICAM1 (CD54) - glycoprotein

what are the two anti-inflammatory cytokines?

IL-10 and TGFb

what cytokine is produced exclusively by lymphocytes?

IL-2 (other choices were IL-1, TNFa, IFNa, GMCSF) IL-2 is produced exclusively by Th1 cells. IL-2 will stimulate the growth and differentiation of *T cells, B cells, NK cells and macrophages*. When IL-2 binds to T cell IL-2 receptors in an autocrine fashion the stimulated T cells proliferate. *if Il-2 is present for a long period, it can promote Fas-mediated apoptosis (CD95 --> extrinsic apoptosis)

Glucagon like peptide 1 - drugs are Exenatide and Liraglutide

INCRETIN (produced by gut - will increase and augment insulin release) -will only work following a meal A/E liraglutide = pancreatitis, and contrandicated in MEN 2a and 2b (can increase risk of Medullary carcinoma of thyroid)

What is the fastest route of ABSORPTION

INHALATION *NOT IV* drugs that are administered by IV are not absorbed. 100% bioavailability.

quantitative platelet disorders

ITP, TTP/HUS

HSV 2 - TORCH

IUGR vesicular lesions keratoconjunctivitis microcephaly

whats the order of medication use in status epilepticus?

IV lorazepam (intermediate) or diazepam --> IV phenytoin --> IV phenobarbital --> General anesthetia (propofol, barbituates, etomidate, ketamine)

treatment of status epilepticus

IV lorazepam or diazepam --> IV phenytoin --> IV phenobarbital --> IV anesthetics (haloperidol ext)

what are drugs that act directly of factor Xa? (inhibitors)

Idraparinux Rivaroxaban Apixaban Low molecular weight heparin (enoxaparin)

bulla at dermal epidermal junction

IgG against keratin 5 and 14

RhoGAM

IgG, given to mother thats Rh- and child is Rh+ve, RhoGAM binds fetal erythrocyte surface Rh antigens within the maternal circulation preventing their interaction with the maternal immune system and THUS preventing sensitization. -IgG is used because Fc receptors on phagocytic cells have greatest affinity for Fc fragments of IgG antibodies. the quantitiy of anti-D IgG injected is very small, thus preventing transplacental transfer into fetus.

Diffuse esophageal spasm (DES)

In DES several segments of the esophagus contract at the same time which prevents the propagation of food bolus towards the stomach. Additionally, these involuntary muscle contractions can be *painful*. Esophageal manometry studies show disorganized non-peristaltic contractions of the body of esophagus. Simultaneous contractions cause a *corkscrew* esophagus seen on barium swallow. *MIMICS UNSTABLE AGINA IN INTENSITY AND LOCATION* thus must run cardiac tests for CKMB, cTnI.

self selection bias

In statistics, self-selection bias arises in any situation in which individuals select themselves into a group, causing a biased sample with nonprobability sampling. It is commonly used to describe situations where the characteristics of the people which cause them to select themselves in the group create abnormal or undesirable conditions in the group.

blocked randomization

In the statistical theory of the design of experiments, blocking is the arranging of experimental units in groups (blocks) that are similar to one another. Typically, a blocking factor is a source of variability that is not of primary interest to the experimenter. An example of a blocking factor might be the sex of a patient; by blocking on sex, this source of variability is controlled for, thus leading to greater accuracy.

How to increase statistical power

Increase sample size

PCOD (stein-leventhal disease)

Increased LH: FSH ratio --> LH increases and FSH decreases. Will find elevated levels of androstenedione and testosterone.

Grunting - seen in children

Indicative of pneumonia or RDS -Noise caused by glottic closure in an attempt to keep airways open

What is the drug used to treat acute gout and its the drug of choice for closure of the ductus arteriosus

Indomethacin - a nonselective COX inhibitor

Niclosamide MoA

Inhibition of the parasite's mitochondrial phosphorylation of ADP. Anaerobic metabolism may also be inhibited.

What occurs after posttranscriptional modification in the cytosol.

Interaction with P bodies (storage of mRNA) mRNA that does not undergo translation are found in P bodies. These are involved with mRNA regulation and turnover and play a fundamental role in translation repression and mRNA decay, and contain numerous proteins including RNA exonucleases, mRNA decapping enzymes, and microRNA induced silencing.

where is the location of AV node?

Interarterial septum near the right AV orifice

earliest lesion in abdominal aortic aneurysm

Intimal (fatty) streaks are the earliest lesion of atherosclerosis. They are composed of intimal lipid filled foam cells which are derived from macrophages and smooth muscle cells that have engulfed lipoproteins -->predominantly oxidized LDL. These complexes then insudate into the intima through an injured leaky endothelium

what is an emergency treatment for hypoglycemia - besides IV glucose?

Intramuscular or subcutaneous glucagon *do not give cortisol or epinephrine.*

pt that is exposed to TB but has a negative X ray what drug do you give?

Isoniazid and vitamin B6 for up to 6 months will prevent infection in 90% of patients.

what is tumor lysis syndrome?

It is an oncologic emergency that can develop during chemotherapy for high grade lymphomas, leukemias, and other cancers with rapid cell turnover. When large numbers of tumor cells are destroyed during short interval, intracellular ions such as potassium and phosphorous are released into the serum along with nucleic acids (which are catabolized to uric acid).

what is transference and provide an example.

It is the unconscious shifting of emotions or desires associated with one person to another person (typically a physician or therapist). Often, arises from parent-child relationships. Ex. Adult was treated as a child by their parent, and adult now overreacts when he/she feels as if they are being treated like a child by physician.

What is dysthymic disorder?

Its a chronic disorder characterized by low intensity mood disorder that responds well to antidepressants. This does NOT meet the criteria of Major depressive (require 5 of 9 symptoms for at least two weeks).

Thiopental is used for induction of anesthesia, why?

Its a short acting barbituate that affects GABA receptors (increases duration of opened GABA channel - vs benzo's that increase frequency). Accumulation of thiopental in the brain is followed by its rapid "redistribution" into skeletal muscles and adipose tissue (within 5-10min of admin). Its a very lipophillic drug! Awakening during surgery was found to be due to rapid plasma decay of the drug - but it wasnt due to metabolism, it was due to REDISTRIBUTION to other tissues.

Histology - Renal

JGA cells produce Renin *mechanisms of renin release --> decreased tubular NaCl sensed by macula densa, decreased pressure in the afferent arteriole and sympathetic stimulation* Tamm-Horsfall glycoprotein can accumulate in the tubular lumen to form hyaline casts --> secreted from ascending limb of loop of henle.

ruxolitnib - is what kind of inhibitor?

Jak2 inhibitor thus can be used for treatment in JAK 2 leukemias = essential thrombocytosis, polycythemia vera, and primary myelofibrosis.

Polycythemia vera

Jak2 mutation --> rendering hematopoietic stem cells more sensitive to growth factors.

Efficacy

Just like Vmax.

Causes of diarrhea in HIV patients

Kaposi sarcoma (HHV 8) - bloody diarrhea Entamoeba histolytica - bloody diarrhea cryptosporidium - watery diarrhea

Isoniazid - activation

KatG --> requires oxidation to become active

hurler syndrome

L-iduronidase, corneal clouding, developmental delay, gargoylism, airway obstruction, hepatosplenomegaly, its autosomal recessive

at what spinal level do we find the renal arteries branching from abdominal aorta?

L1

Leukocyte alkaline phosphatase (levels in PCV, myelofibrosis, and CML)

LAP In polycythemia vera --> elevated LAP In primary myelofibrosis --> normal to increase LAP in CML --> always decreased

what are the inputs for cholesterol for aldosterone synthesis

LDL via LDL-receptor and HDL via SRB1 receptor (remember that HDL delivers cholesterol to liver and to glomerulosa for steroidgenesis)

Blood concentration of what bacterial structure would show a correlation between morbidity and mortality?

LOS (also seen in N, B, C --> Neisseria, Bordetella pertussis, and campylobacter) similar in structure to LPS except that it lacks the repeating O-antigen. -growth and lysis of meningococci causes the release of outer membrane vesicles with membrane attached LOS into the bloodstream. *severity of infection correlates to increasing concentrations of LOS) -LOS causes sepsis just like LPS, induces systemic inflammatory response --> produces TNFa, IL-1, IL-6, IL-8. (*formed from interaction with Toll Like Receptor 4 (TLR4)* -LOS causes cutaneous petechiae and hemorrhagic bullae -Waterhouse friderichsen syndrome -LOS present in all neisseria species

Lambert Eaton vs Myasthenia Gravis

Lamber Eaton - problem with initiation of movement Myasthenia Gravis - problem with maintaining movement

apple peal atresia

Large segment of small bowel with the distal ileum seen winding around a thin vascular stalk. Proximal jejunum ends in a pouch - no connection between jejunum and ileum. Will see bilous vomiting after first 24 hours and failure to pass meconium. THis occurs because the superior mesenteric artery is occluded or never develops.

what is the ratio used to determine maturity of fetal lung tissue?

Lecithin (aka "phosphatidylcholine") to sphingomyelin ratio. component of surfactant >2:1 ratio = fetal lung maturity starts at 32 weeks.

female pt presents with heavy menses and passing occasional clots. She also complains of heaviness and a palpable mass in the lower abdomen.

Leiomyoma --> uterine Fibroids --> differ from endometriosis (will have NORMAL SIZED UTERUS) whereas with leiomyoma UTERUS will be enlarged.

What is the best indicator for severity of mitral stenosis?

Length of the interval between A2 (of S2) and the opening snap. The shorter the interval the more severe the stenosis. The OS occurs due to tensing of the mitral valve leaflets after the valve cusps have completed their opening excursion. The more thickened and fibrotic the MV the earlier this tensing occurs. The A2-OS interval is also inversely correlated with mean diastolic left atrial pressure (shorter interval = increased pressure). Increased fibrosis and thickening of mitral valvue results in decreased blood passing into ventricle and elevate atrial pressures.

only cell in testes with desmolase

Leydig cell

Varicella - TORCH Transplacental

Limb defects Mental retardation blindness cataracts *differ from rubella --> look for PDA*

what tests need to be performed following drug administration with statins?

Liver function test

Lepromatous type - leprosy - clinical findings

Look for peripheral involvement, bacteria prefers cold areas (tips of ears, face, testes). Testes are a common site - thus pt will typically be infertile. Peripheral neuropathy with autoamputation, bacilli will invade microglia and *schwann cells.* Biopsy --> look for lipid laden macrophages with bacilli. *note that there will be a negative PPD test - because pt's cell mediated immunity is compromised.*

intermediate acting benzodiazepines

Lorazepam Estazolam Temazepam

factors effecting volume of distribution

Low Vd = drugs that have large molecular weights, are bound to plasma proteins (albumin), are highly charged (hydrophillic) Vd = 3 to 5 liters. Med Vd = large MW, but hydrophilic - drug can distribute to interstitial fluid. Vd = 14 to 16 liters. High Vd = small MW, hydrophobic, lipophillic - wide dispersion of drug across many tissues. Vd >41liters.

Serotonin syndrome - due to what drug interaction

MAO inhibitor + SSRI, SNRI, TCA or meperidine (breakdown product normeperidine a SSRI) *due to receptor overstimulation of 5HT1 and 5HT2*

Tyramine reaction

MAO inhibitor +chocolate, cheese, wine, pickled fish also can be due to OTC cold meds (phenylephrine) and other sympathomimetics

tyramine cheese reaction is seen with

MAOi Tranylcypromine Phenelezine Isocarboxacid Selegiline

subarachnoid hemorrhage (berry aneurysm) "saccular" - complications

MOST COMMON = Arterial Vasospasm (4 to 12 days) --> occurs in vessels surrounding the ruptured aneurysm. mechanism is related to impaired brain autoregulation.

Gaucher disease - deficient enzyme

MOST common glucocerebrosidase

Myeloperoxidase

MPO is found in azurophilic granules of neutrophils. In the presence of halides such as Cl- will convert hydrogen peroxide to hypochlorite which is a very potent antimicrobial agent

diethylstilbestrol and ethinylestradiol (estrogens)

Mechanism of action: binds to cytoplasmic receptor, the receptor-drug complex then moves to nucleus to modulate protein expression -can be used in prostate cancer - contraindicated in breast and endometrial cancers -A/e - Clotting

medroxyprogesterone

Medroxyprogesterone is used to treat abnormal menstruation (periods) or irregular vaginal bleeding. Medroxyprogesterone is also used to bring on a normal menstrual cycle in women who menstruated normally in the past but have not menstruated for at least 6 months and who are not pregnant or undergoing menopause (change of life). Medroxyprogesterone is also used to prevent overgrowth of the lining of the uterus (womb) and may decrease the risk of cancer of the uterus in patients who are taking estrogen. Medroxyprogesterone is in a class of medications called progestins. It works by stopping the growth of the lining of the uterus and by causing the uterus to produce certain hormones.

only dopamine pathway thats not fully effected by 5HT2A blockers

Mesolimbic pathway - which allows our drugs to still fight psychosis - reason being there are more 5HT2A > DA receptors.

what is the treatment of gastric damage induced by NSAIDs

Misoprostol - PGE2 analogue Proton pump inhibitors H2 blockers

Soft S1 (4 causes)

Mitral regurgitation, long PR, heart failure, aortic and pulmonary regurgitation

flutamide - MoA, Use

MoA = non steroid antiandrogen, competes with testosterone and DHT for receptors on target cells. Prevention of androgen-receptor binding blocks stimulatory effect of androgens on primary tumor and thus reduces the size. If used as *monotherapy, it causes a gradual increase in blood testosterone lvls due to negative feedback mechanism. This effect is reduced by the simultaneous administration of GnRH agonists* A/E hot flashes, gynecomastia, and impotence Use = prostate cancer

Chronic rejection

Months to years -Host B cell sensitization against graft MHC as well as host T cell sensitization to graft MHC.

DVTs will RARELY occur from superficial vessels of venous system. Thus dont expect thromboembolism to be answer when question is talking about varicose veins.

Most common complication of varicose veins "tortuous veins" are venous stasis ulcers over medial malleolus, and superficial venous THROMBOSIS - NOT THROMBOEMBOLISM.

what is the pathogenesis of spontaneous pneumothorax

Most commonly due to rupture of *apical subpleural bleb*

imperforate hymen due to incomplete canalization of vaginal plate.

Most girls go undiagnosed until teenage years and present with cyclic abdominal pain or pelvic pain and physical exam will show hematocolpos. hematocolpos = accumulation of blood in vaginal canal --> distends vagina, presents as a bulge or mass that can be palpated anterior to rectum.

What Ig respond to foreign AntiBODIES!

Mostly IgE which will be responsible for anaphylaxis. Also IgG and IgM.

HHV 6 and Influenza A are implicated in causing

Multiple sclerosis

24 yr old male with fever, malaise, anorexia, bilateral parotid swelling and a swollen tender scrotum. Never received MMR. whats cause of low testosterone?

Mumps - *paramyxovirus (PaRaMyxo = parainfluenza, RSV, Ribavirin as tx, Mumps, and Measles (rubeola))* More severe in adults than children This patient developed orchitis which is why he is presenting with swollen tender scrotum Leydig cell atrophy (results in decreased testosterone) Results in

Phenylketonuria deficiency - test

Must test infants twice, tested using mass spectrometer, and a guthrie test (involves heel pinprick test)

Pagets bone - pathogenesis

Mutation in RANK signaling, early phase of osteoclastic resorption of bone causing shaggy appearing lytic lesions. Late phase of increased osteoblastic bone formation --> markedly increased serum alkaline phosphatase (ALP) (increased osteoblast activity) and production of THICK but WEAKENED BONE.

osteomyelitis in patient with Potts disease

Mycobacterium tuberculosis hematogenous seeding from LUNGS effects vertebra (lumbar)

10 year old patient presents to you with painful swallowing, weight loss, pruritis. Upon examination, you note a plaque along the lingual papillae which is easily scraped off. You prescribe Nystatin. A few weeks later the patient returns with similar symptoms and the mother is worried. Upon further questioning you note that the boys sister has similar symptoms. The mother is clearly worried and says "I hope he doesnt have what my father had." You decide to run a NBT test that turns up positive. What does this boy MOST likely have?

Myeloperoxidase deficiency - Autosomal Recessive, will have a positive NBT test. Pt will be able to generate H202, however will not be able to form HOCL due to lack of MPO.

Adverse effects of fibrates

Myositis when used with statin *Gallstones*

what drug do you give for acetominophen overdose

N-acetylcystein - resupplies substrate for glutathione

Difference between MP and CGD

NADPH oxidase is resent, MPO is absent, respiratory burst, and H202 (product of NADPH ox) are present. IN CGD - pts only have MPO - but its useless against catalase positive organisms because they cannot form the substrate! (H202) for MPO which forms HOCL.

What is rational for NMDA antagonists in preventing tolerance to opioids?

NMDA antagonists will decrease levels of glutamate and therein reduce number of phosphorylated opioid receptors.

what is a serious adverse effect to the use of haloperidol?

NMS or neuroleptic malignant syndrome. will see hyperthermia, fever, generalized rigidity, autonomic instability and altered mental status.

Endothelial damage - factors released that inhibit platelet aggregation

NO adenosine diphosphatase (apyrase) PGI2 tPA

Crohns and Ulcerative colitis

NOD 2 upregulates receptor for muramyl (type of PAMP) (bacterial products) and increases nf-kb transcription which leads to a pro inflammatory state furthermore, absence or damage to tight junctions exacerbate inflammatory response. pg. pg 809

reciprocal translocation

NON homologous translocation - because if it is homologous then its just crossing over.

NSAIDs with loop diuretics

NSAIDs decrease production of prostaglandins which are responsible for vasodilatory effects of Loop diuretics, thus when given together - no vasodilatory effects are seen.

clinical presentation of prader willi

Neonatal hypotonia and genital hypoplasia are present at birth. b. Other findings include short stature (due to growth hormone deficiency) and hyperphagia (insatiable appetite) leading to obesity. • The satiety defect is due to increased levels of gherlin, a polypeptide hormone produced by the stomach and arcuate nucleus in the hypothalamus that increases food intake.

charcot joint mechanism

Neurotrauma: Loss of peripheral sensation and proprioception leads to repetitive microtrauma to the joint in question; this damage goes unnoticed by the neuropathic patient, and the resultant inflammatory resorption of traumatized bone renders that region weak and susceptible to further trauma. In addition, poor fine motor control generates unnatural pressure on certain joints, leading to additional microtrauma.

what blood count increases following glucocorticoid administration?

Neutrophils

bedaquiline

New TB medication *treat multidrug resistant TB* ATP synthase inhibitor in TB A/E - prolonged QT, increased death in participants, arrhythmias

what drug can precipitate gout that is used to treat hyperlipidemia?

Niacin

Niacin - if patient is on meds for diabetes and antihypertensives

Niacin potentiates the effects of some antihypertensive medications such as vasodilators and ganglion blocking agents because of its vasodilatory effects (prostaglandin mediated). *postural hypotension can ensue* Thus, dose adjustment is required in most patients who are also taking vasodilators (decrease dose) - Niacin also induces insulin resistance thus, if a patient is taking an anti diabetic med the concentration of that drug must be increased.

what are drugs that can increase serum uric acid levels?

Niacin, hydrochlorothiazide, cyclosporine, and pyrazinamide, allopurinol, uricosuric agents

what drug increases HDL the most

Niacin, then fibrates

What is the cellular receptor for Rabies?

Nicotinic acetylcholine receptors

observer bias

No blinding in the study - can creat an observer bias = variability in outcome assessment. In this q. testing effectiveness of vitamin C at preventing common colds in children. Pts were randomly assigned, HOWEVER it was not a blind study - creates observer bias.

NOD 2 (nucleotide binding oligomerization domain)

Normally - acts as an intracellular microbial receptor that triggers the Nf-Kb pathway but a NOD 2 mutation has been linked to crohns disease - increases activity of Nf-Kb protein thereby allowing the inflammation inducing intracellular microbes to persist. Note that crohns disease is associated with increased activity of nf-kb which is responsible for cytokine production. The appropriate immune response to intracellular microbes is blunted the microbes persist and induce chronic inflammation with GI tract.

Pathophysiology of graves opthalmopathy

Not reversible Anti TSH binds to TSHreceptors on orbit (stimulatory effect) lymphocytes (T cells) infiltrate the orbital tissues and secrete cytokines that stimulate fibroblasts to secrete increasing amounts of glycoaminoglycan ground substance such as hyaluronic acid. This increased hyaluronic acid draws water into the orbit resulting in extraocular muscle edema.

noncompetitive drugs

Not too many so memorize list Phenoxybenzamine, digoxin, allopurinol, PPis, Aspirin

what are signs of irreversible cellular damage?

Nuclear pyknosis, karyorrhexis, karyolysis Plasma membrane damage (degradation of membrane phospholipid) Lysosomal rupture Mitochondrial permeability/vacuolization; phospholipid-containing amorphous densities within mitochondria (swelling alone is reversible)

breast cancer risk

OCP's thus elevated estrogen (worse to have high amounts of estrogen after age of 35) family history alcohol use obesity premenopause can be protective on breast cancer because obesity can often result in anovulatory cycles. early menarche and late menopause (due to longer exposure to estrogen)

Loop diuretics A/E

OH DANG - ototoxicity, hypokalemia, dehydration, allergy (sulfa), nephritis (interstitial), gout

Side effects of Loop diuretics

OH, DANG Ototoxicity Hyperkalemia Dehydration Allergy (sulfa) Nephritis (interstitial) Gout (hyperuricemia) HYPOCALCEMIA, HYPOMAGNESEMIA (decreased positive potential in lumen of TALH - thus decrease reabsorption) hypokalemia and alkalosis.

what are the factors that determine the time required to reach steady state?

ONLY the half life; it is INDEPENDENT of dise size and frequency of administration. Rule: 4-5 half lives = Steady state.

Heparin A/E (rare)

OSTEOPOROSIS !!!!! Hyperkalemia (via inhibition of aldosterone synthesis)

allelic exclusion

Occurs after successful production of membrane immunoglobulin from one chromosome - process will inhibit production of other chromosome pair to ensure the that the membrane immunoglobulin on B cell will have same heavy chain variable region as other b cells.

Lidocaine PK

Only used IV because of extensive first pass metabolism, oral preparations are mexiletine.

female reproduction

Oocytes are arrested in prophase I until puberty. At puberty, ovulatory cycles begin. FSH stimulation during cycle (follicular stage) causes some oocytes to complete meiosis I forming secondary oocytes and polar bodies (extruded). The secondary oocyte begins meiosis II but HALTS at metaphase II. At ovulation (LH surge-->increase estrogen) the secondary oocyte frozen in metaphase II awaits fertilization --> formation of mature oocyte and second polar body. if fertilization does not occur it is extruded as secondary oocyte frozen in metaphase II.

Multiple telangiectasias of skin and mucosa, recurrent epistaxis or gastrointestinal bleeding (melena)

Osler Rendu Weber syndrome

whats contained in WP bodies

P selectin vWF

Urine samples in amino acid deficiencies

PKU (def in phe hydroxylase or dihydropterin reductase) = mousy odor to urine Alkaptonuria (deficiency of homogenistic acid oxidase which prevents conversion of tyrosine to fumarate) = darkening of urine within minutes to hours (color change is due to homogenistic acid) --> will also find a blue-black pigment "onchronosis" that is MOST evident in the ears, nose and cheeks (due to homogenistic acid that binds to collagen)

phenylketonuria deficiency

PKU I = Classic = deficiency in phenylalanine hydroxylase PKU II = more serious = defect in dihydropterin synthesis or reductase (which is cofactor for phenylalanine hydroxylase)

Medulloblastoma is what type of tumor?

PNET chromosome 11p

drug treatment for H.pylori

PPi + Clarithromycin + Amoxicillin or metronidazole

How will a patient respond to heparin if they have a congenital deficiency of AT3?

PTT will NOT RISE; normally heparin's activity on coagulation cascade is measured by PTT --> if no At3 is present then heparin will not exert any clinically significant effects. High dose heparin can activate the limited At3 - thus can be used for induction of warfarin therapy (to prevent warfarin skin necrosis)

Essential amino acids are

PVT TIM HALL Phenylalanine valine tryptophan threonine isoleucine methionine histidine arginine* conditional (kids) lysine leucine

Lambert Eaton

Paraneoplastic syndrome of small cell lung carcinoma. LE is a disorder of neuromuscular jxn (antibodies against V-G Ca channels) - manifests as proximal muscle weakness (decreased deep tendon reflexes) and weakness with gait, difficulty raising from a chair or trouble climbing stairs. Treatment - is 4aminopyridine (potassium channel blocker).

Fastest to slowest conduction through heart

Park At Ventura Avenue = Perkinje fibers, Atrial fibers, Ventricular fibers, AV node. *reason perkinje fibers are fastest = rapid transmission is essential to ensure contraction of ventricles rom apex of heart toward the base. This allows blood to propel upwards towards pulmonary artery and aorta.

Selective destruction of type II pneumocytes would result in what?

Patchy Atelectasis

Tuberculoid type - leprosy - clinical findings

Patients will present with many granulomas over the body however few bacilli will be present. There will be asymmetric peripheral neuropathy, and increased risk of trauma and ulcer due to local anesthesia. *note that PPD will be positive in this type vs lepromatous*

Diverticulitis

Perforation usually occurs into the pericolic fat, leading to fibrinous exudate, abscess formation, local adhesions, or peritonitis. Tx: High fiber diet and antibiotics Most common cause of fistula formation in GI On barium enema DO NOT CONFUSE WITH colonic polyps ---> remember if barium forms the pouch then we know it must be an outpouching (barium fills pouch). Clinical Findings a. Diverticulitis is the most common complication. (1) Caused by stool impacted (fecalith) in diverticulum sac (see Fig. 18-21B) • Produces ulceration and ischemia (2) Clinical Findings (a) Fever (b) Diarrhea initially followed by constipation (c) Leftlower quadrant pain ("left-sided appendicitis") (d) Tender mass is palpated in some cases (3) Best diagnosed with CT scan or water-soluble barium study (4) Increased risk for perforation and abscess formation (5) Most common cause of Fistula formation (connection between hollow structures) b. Diverticulosis (1) Painless bleeding, o!en massive (hematochezia), is characteristic. • Usually caused by erosion of juxtaposed vessel by a fecalith (2) Bleeding stops spontaneously in 60% of cases. (3) Sigmoid diverticulosis is the most common cause of hematochezia. • Scarring of the juxtaposed vessel in recurrent attacks of diverticulitis prevents bleeding.

EPS months to years

Peri-oral tremors "Rabbit syndrome" Tardive dyskinesia - sensitization, also *UPREGULATION* of DA receptors (will see chorea and athetosis - similar to huntingtons) *ATYPICAL ANTIPSYCHOTICS ARE LESS LIKELY TO CAUSE T.D.*

fabry disease - clinical features

Peripheral neuropathy of hands/feet, skin rash with bathing suit distribution, angiokeratomas, cardiovascular/renal disease

syphillis morphology

Perivascular inflammation with plasma cells --> Syphilitic chancres occur in the primary stage of syphilis and are characterized by lymphoplasmacytic infiltrates and by an obliterative endarteritis (small /medium vessels). Similar lesions also may appear with secondary syphilitic mucocutaneous lesions. Reason its painless is due to syphillitic infiltration of arteries and nerves --> can also infect vaso vasorum of aorta.

Phase I and II metabolism

Phase I metabolism - CYP450 (redox) in mitochondria and ER Phase II metabolism - glucronidation, acetylation, sulfation

what are the drugs that treat seizures that act on voltage gated sodium channels?

Phenytoin Lamotrigine Zonisamide Carbamazepine Valproate Phenobarbital Topiramate

beneficience

Physicians have a special ethical (fiduciary) duty to act in the patient's best interest. May conflict with autonomy (an informed patient has the right to decide) or what is best for society (traditionally patient interest supersedes) - Autonomy > beneficence

Refsum (autosomal recessive) - info

Phytanic acid is a dietary branched chain fatty acid, predominant in dairy products • -Oxidation of phytanic acid takes place in the peroxisomes • Refsum disease is a disorder characterized by deficiency of the peroxisomal phytanyl CoA -hydroxylase (defect in -Oxidation) • In this disorder, phytanate accumulates in tissues, especially the neurologic tissues • Characterized by visual defects, ataxia and polyneuropathy and skeletal manifestations • Management includes dietary restriction of branched chain fatty acids

rosenthal fibers is a buzzword for which tumor and/or state?

Pilocytic astrocytoma or longstanding gliosis. rosenthal fibers are just elongated eosinophilic structures within astrocytes.

what artery is of primary concern with both a posterior and anterior dislocation of the knee joint? Q: hockey player sustains a blow to right knee and is brought to ER - posterior displacement of tibia relative to femur.

Popliteal artery - it is rigidly fixed proximal and distal to the knee joint by the adductor magnus and soleus muslces, respectively --> making it highly susceptible to tearing by traction forces. Popliteal A. more commonly injured than Popliteal V. because the artery is 1) deeper within popliteal fossa and 2) is tightly fixed within the fossa. Note that tibial nerve also passes through popliteal fossa but it is not subject to same traction forces as popliteal artery.

How will glucocorticoids alter metabolism? This is basically asking what the role of cortisol on metabolism is.

Potent stimulators of gluconeogenesis increase glycogenolysis antagonize actions of insulin other effects of glucocorticoids = muscle weakness, skin thinning, impaired wound healing, osteoporosis, immunosuppression.

Endometriosis (also whats histology)

Presence of ectopic endometrial tissue outside of uterus - MC seen in ovaries. Responds to estrogen - during menstrual period these ectopic sites will collect blood. With time, blood undergoes hemolysis and induces inflammation around ectopic endometrium. Local inflammation is followed by formation of adhesions (fibrosis) and distortion of organ structure. In the ovaries blood may form chocolate cysts. *will find nodularity of the uterosacral ligament and fixed retroversion of the uterus* are common. Shedding of ectopic tissue causes pain during menstrual period (dysmenorrhea) and painful intercourse (dyspareunia) is due to retroversion of uterus and endometrial implants on uterosacral ligaments.) -Patients are infertile - likely due to organ fibrosis and distortion -Histology is simple columnar - why? --> bc its secretory.

Major depressive episode - clinical requirements to make diagnosis

Present for at least 2 weeks - and requires 5 of 9 following symptoms - SIGECAPS Sleep - increased or decreased Interest is decreased Guilt - feelings of worthlessness Energy deficit Consciousness or concentration deficit Appetitie Psychomotor retardation and agitaition Suicidal

Thionamides

Propylthiouracil and methimazole - decrease formation of thyroid hormones by inhibiting thyroid peroxidase. (inhibits organification within the thyroid)

Sjogren syndrome - question

Pts with sjogrens have bilaterally enlarged parotids, however if patient presents with one parotid thats growing more than other - think of *B cell lymphoma*

African american patient presents with hemolytic anemia - findings are jaundice, elevated LDH 1, and anemia. Upon history it is noted that the patients sister also suffers from similar symptoms. Furthermore, family history revealed that his maternal grandmother also suffered from the disease. What does this patient have?

Pyruvate Kinase deficiency, appears like G6PD but thats X linked - thus sister would not have. Pyruvate Kinase deficiency is second most common cause of hemolytic anemia and is AUTOSOMAL RECESSIVE!

hemolytic anemia in a autosomal dominant fashion (no heinz bodies present) young female

Pyruvate kinase deficiency, NOT G6PD --> THATS X linked - brilliant question

congenital QT syndromes

QT prolongation due to decreased outward K current. These syndromes result from mutations in a K+ channel protein that contributes to the delayed rectifier current. QT prolongation predisposes patients to syncopal episodes and the possibility of sudden cardiac death associated with polymorphic ventricular tachycardia including torsades de pointes.

Palivizumab clinical use

RSV prophylaxis in infants because its an antibody against RSV F protein.

Benzodiazepines effect on seizures

Raise the threshold for seizure's thus can be used in status epilepticus for anticonvulsant properties. Note that *abrupt* diazepam withdrawal in an epileptic patient can provoke a seizure.

Crescent formation - diagnostic of what kidney pathology

Rapidly Progressive glomerulonephritis (Type 1, 2, and 3) type 1 RPGN = characterized by anti-glomerular basement membrane antibodies. Anti-GBM antibodies cross-react with pulmonary alveolar basement membranes producing pulmonary hemorrhages (hemoptysis). Type 1 RPGN is found in association with Goodpasture syndrome. type 2 RPGN = immune complex mediated = "lumpy bumpy" granular pattern of staining Ex. SLE, PSGN, IgA nephropathy, Henoch Shoein Purpura type 3 RPGN = pauci immune - because there are *no immunoglobulins thus NEGATIVE IMMUNOFLOURESCENCE. associated with microscopic polyangiitis, wegeners, and churg strauss.

Growth factor binds to tyrosine kinase - activates Ras/Map pathway

Ras-MAP kinase pathway starts with a *growth factor ligand* binding to the receptor tyrosine kinase causing autophosphorylation of the receptor. *phosphotyrosine* produced in this reaction interacts with a number of proteins (such as SH2 domain proteins and SOS protein which is part of the binding complex) --> leads to *Ras activation*. Ras is a G protein that exists in active and inactive forms. Inactive Ras contains GDP Active Ras contains GTP Activated Ras beings a phosphorylation cascade starting with activation of Raf Kinase. *This results in activation of MAP (mitogen activated protein) kinase which enters nulceus to influence gene transcription* Ras is inactivated by a GTPase activating protein

osteosarcoma and retinoblastoma similarities

Rb gene

reactive lymphoid hyperplasia vs malignant lymphoid hyperplasia

Reactive hyperplasia of lymph node refers to enlargement of LN secondary to antigenic stimulus. There are 3 main types of reactive hyperplasia = follicular, sinus, and diffuse. Follicular hyperplasia = follicles increase in size and number Sinus hyperplasia = sinuses enlarge and fill with histiocytes Diffuse hyperplasia = nodal architecture is diffusely effaced by sheets of lymphocytes, immunoblasts, and macrophages. Note that in malignant transformation the number of lymphocytes will be much greater *malignancy associated lymphoid hyperplasia is classified as either follicular or diffuse* -the main difference between reactive hyperplasia and malignant is that reactive is polyclonal expansion of many different cell types, whereas malignant transformation is just monoclonal.

endothelial dysfunction is early manifestation of Scleroderma

Reason for raynauds phenomenon--> decreased nitric oxide and increase endothelin (vasoconstrictor) Damage to endothelial cells release PDGF and TGFb --> which attracts fibroblasts and causes *perivascular fibrosis* - narrowing of vessel precludes to increased ischemic injury.

interviewing techniques

Reflection --> physician repeats what he has just been told. Summarizing --> physician encapsulates several ideas into one or two statements Empathy --> expression of vicarious understanding of patients feelings and emotions "I can understand how difficult it must have been for you to face all those stressors..." Support --> expression of concern for patients experiences and well being. "this sounds like it has been very hard for you..." Confrontation --> draw patients attention to discrepancies in his/her statements. Facilitation --> encourage the patient to talk more about his/her experience. *help physician establish rapport with the patient*

Chlamydia and campylobacter can cause

Reiter syndrome

xeroderma pigmentosum (AR)

Repair mechanism = nucleotide excision repair cells exposed to UV radiation --> adjacent pyrimidine residues become covalently linked thereby forming cyclobutane pyrimidine dimers. Most commonly occurs with adjacent thymine residues. *pyrimidine dimers are recognized by UV specific endoneucleases which creates a break in the affected DNA strand on 5' side of the dimer* Exonuclease then removes damaged DNA segment (this is defective in xeroderma pigmentosum)

cause of "grunting" in newborns

Respiratory distress syndrome

Graves - exapthalamos

Retro-orbital fibroblasts are stimulated by cytokines released from infiltrating Th1 cells to produce excessive amounts of glycosamingoglycans. The resulting inflammation and accumulation of GAGs increased the volume of retro orbital tissues. --> eyes appear as popping out. TO treat give glucocorticoids (will have anti-inflammatory effects which decrease the opthalmopathy, also the drug will decrease peripheral conversion of T4 to T3). *ANTITHYROID DRUGS DON'T EFFECT OPTHALMOPATHY*

X linked dominant disorders

Rett syndrome Alports Fragile X syndrome

Posttranslational processing

Ribosomes facilitate the translation of mRNA into protein. This process begins in the cytosol when mRNA binds to a ribosome (in eukaryotic remember that the 18s of 40s binds to 7methylguanosine cap) and initiates translation. Proteins destined for the endoplasmic reticulum (rough) possess N-terminal peptide signaling sequences that identify them as such, once these N-terminal sequences are translated they are immediately recognized by signal recognition particles (SRPs) which *halt* translation and target the ribosome to protein pores in the RER. Once the ribosome is bound to the RER, the signal peptidase cleaves the signal peptide region from the elongating polypeptide within the RER. Within the RER proteins undergo folding, glycosylation (w/ Asparginine) and coupling with other subunits required for function. Note that the Signal sequences (N-terminal peptide once translated) are composed fo 15 to 20 amino acids (MOST OF WHICH ARE HYDROPHOBIC).

why is the right main bronchus more prone to foreign body aspiration then left main bronchus?

Right bronchus has a larger diameter, is shorter, straighter, and orientated more vertically.

Most cases of down syndrome are due to maternal nondisjunction meiosis I (trisomy - 47xxy)- however 4% are due to...

Robertsonian translocation.

STURGE mnemonic

S = Seizures T = Trigeminal port wine stain U = Unilateral weakness (opposite side of stain) R = Retardation G = Glaucoma E = Eye problems ie bupthalmos

Methionine is part of this cofactor

S-adenosylmethionine, which acts as a methyl donor

canagliflozin

SGLT2 inhibitor blocks renal reabsorption of glucose useful for diabetics

reason for short stature in turners

SHOX gene is critical for regulation and growth and remains activated on both X chromosomes (unique feature because most genes are inactivated), hence a deletion of one of the two results in short stature.

A pt is found to have a pulmonary lesion that contains peptostreptococcus and fusobacterium species. what is a predisposing factor to this finding?

Seizures --> peptostrep and fusobacterium are normal flora of the *mouth* pts that experience decreased consciousness (ie seizure disorder) may aspirate oropharyngeal contents causing a lung abscess. Remember that seizure meds - in this case cabamazepine (acts to block V-G Na channels on glutaminergic neurons) --> A/E aplastic anemia, agranulocytosis, p450 inducer, Steven johnson syndrome.

DNA laddering

Sensitive indicator of apoptosis. Laddering occurs during karyorrhexis when endonucleases break up DNA resulting in intervals of 180 base pairs.

Embryology - diaphragm --> Several Parts Build Diaphragm

Septum transversum Pleuroperitoneal fluids Body wall Dorsal mesentery of the esophagus

drug induced asthma

Several pharmacologic agents provoke asthma. Aspirin-sensitive asthma is an uncommon yet fascinating type, occurring in individuals with recurrent rhinitis and nasal polyps. These individuals are exquisitely sensitive to small doses of aspirin as well as other nonsteroidal anti-infl ammatory medications, and they experience not only asthmatic attacks but also urticaria. It is probable that aspirin triggers asthma in these patients by inhibiting the cyclooxygenase pathway of arachidonic acid metabolism without affecting the lipoxygenase route, thus tipping the balance toward elaboration of the bronchoconstrictor leukotrienes

pt with HUS has non-lactose fermenting gram negative rods on MacConakeys agar. The organisms do not produce gas on fermentation of glucose and do not produce H2S on triple sugar iron agar. whats the bacteria?

Shigella

Loud S1 (3 causes)

Shortened PR, anemia, Mitral stenosis

AntiRo (SSa) Anti La (SSb)

Sjogrens ---> keratoconjunctivitis sicca (dry eyes) and xerostoma (dry mouth). Parotid gland enlargement and increased risk of non-hodgkins lymphomas (MALToma). Can be positive for rheumatoid factor. Patients will present with xerostomia (making swallowing difficult) and keratoconjunctivits (affecting vision). Extraglandular involvement is due to B cell hyperactivity --> hypergammaglobinuria (lead to immune complex deposition, glomerulonephritis, palpable purpura, and peripheral neuropathy - (ab against myelin) synovitis and pulmonary fibrosis. 40 fold increase in B cell lymphoma.

SARCOID mnemonic

Skin - erythema nodosum Arthritis - hands and feet Respiratory - bilateral hilar lymphadenopathy, pulmonary infiltrates Cardiac - heart block, Ventricular tachy, heart failure Ocular - anterior uveitis --> blindness Intracranial - chronic meningitis, seizures, neuropathy Derangement of liver and renal function - hepatic granuloma, hypercalcemia (bone pain, kidney stones, psychosis, arrhythmias, confusion)

Nitrosamines

Smoked foods, Japan Base Excision Repair (nitrosamines cause cytosine deamination) --> Base-specific glycosylase recognizes altered base and creates AP site (apurinic/apyrimidinic). One or more nucleotides are removed by AP-endonuclease, which cleaves the 5′ end. Lyasecleaves the 3′ end. DNA polymerase-β fills the gap and DNA ligase seals it.

causes of increased tactile fremitus

Sounds will travel best through consolidations thus leading cause is lobar pneumonia

Staph aureus TSS (superantigen)

Superantigen because it activates large numbers of helper T cells. These toxins interact with MHC on APC AND the variable region of T cell receptors to cause a widespread activation of T lymphocytes. SO the TSS can actually BIND to the MHC AND to the APC!!! no wonder its super. this causes release of IL-2 from T cells and IL-1 and TNF from macrophages.

what quadrant contains the superior gluteal nerve when giving a gluteal injection

Superiomedial quadrant --> superior gluteal nerve supplies gluteus medius and gluteus minimus

Herpes simplex 2 treatments - Valcyclovir, Acyclovir, Famciclovir

Suppressive therapy - each of these drugs are purine/pryimidine analogues. For these drugs to prevent recurrent infections they must be given "DAILY" because the drugs only work when the virus is replicating! A one time dose will not help with recurrent infections.

CMV is implicated in causing

Systemic sclerosis

DES - was given to reduce pregnancy complications

T shaped uterus cervical cell carcinoma paramesonephric duct abnormalities

caseation necrosis

TB, fungi (systemic fungi)

a 24 year old female presents to your office with loss of energy, decreased appetite, and insomnia. She was given a "treatment" but then is brought BACK to ER with agitation and grandiose thoughts. Which of following agents was most likely used for this patients INITIAL treatment.

TCA's --> antidepressants when used in the depressive phase of bipolar disorder without an antipsychotic or mood stabilizer can PRECIPITATE a mania.

TCA heart effects

TCA's have a quinidine (1a) like depressant effect (blockade of fast Na channels in heart = slowed conduction and depressed cardiac contractility --> Antidote = SODIUM BICARBONATE - increase sodium availability to overcome sodium blockade.

SRY gene on Y chromosome secretes

TDF = testes differentiation factor which leads to development of testes from indifferent gonads

Erythropoietin receptors and other cytokine receptors - have no intrinsic tyrosine kinase activity and must interact with intracellular janus kinase for signal transduction.

THUS, JAK 2 mutations "primary myeloproliferative disorders" result in mutations to *non-receptor tyrosine kinases*

what should be monitored prior to taking amiodarone?

TSH levels

what are two pathological states when we would find microangiopathic hemolytic anemia?

TTP and HUS

Test for transplantation compatibility

Test for compatibility of the recipient and donor class II antigens - pts are compatible if lymphocytes DO NOT undergo mitosis whereas pts are INcompatible if lymphocytes DO undergo mitosis.

when is TOTAL pulmonary vascular resistance lowest?

The PVR is at a minimum at the FRC because there are two vessels you need to be concerned about: 1) the alveolar vessels (i.e. capillaries) and 2) the extraalveolar vessels (arterioles). In order to maximize flow (and minimize PVR) you need these two to have a certain amount of flow. At low lung volumes, the alveolar vessels are not compressed because there is no pressure on them. So flow is high through number 1. But the extraalveolar vessels run with the small airways, and since the lung volume is low there is decreased radial traction on number 2. So the diameter is smaller, and flow is minimal. At high lung volumes, the alveolar vessels ARE compressed because of the pressure within the alveoli. So flow is low through them, even though the arterioles are pulled open by radial traction. Thus, maximum flow is achieved at FRC, because that is where both capillaries and arterioles permit high flow, even though neither one is maximal.

wolf chaikoff effect - detailed

The Wolff-Chaikoff effect is an autoregulatory phenomenon that inhibits organification in the thyroid gland, the formation of thyroid hormones inside the thyroid follicle, and the release of thyroid hormones into the bloodstream.[6] This becomes evident secondary to elevated levels of circulating iodide. The Wolff-Chaikoff effect lasts several days (around 10 days), after which it is followed by an "escape phenomenon",[7] which is described by resumption of normal organification of iodine and normal thyroid peroxidase function. "Escape phenomenon" is believed to occur because of decreased inorganic iodine concentration secondary to down-regulation of sodium-iodide symporter (NIS) on the basolateral membrane of the thyroid follicular cell.

Intestinal influences in downregulating gastric acid secretion

The ileum and colon release *peptide YY* which binds to receptors on the endocrine, histamine-containing cells described as Enterochromaffin like cells (ECLs). Such binding counteracts the cephalic and gastric phases of acid secretion *by inhibiting gastrin stimulated histamine release* *somatostatin* and *prostaglandins* also decrease gastrin release

How to differ major depression from atypical depression?

The main distinguishing factor is *mood reactivity* - the person with atypical depression will have an improvement in mood with response to something positive, whereas this will NOT occur in major depression.

occipital myotome

The occipital myotomes (4, light green) mainly form the pharynx (throat) and upper or anterior neck musculature, including the tongue muscles. They are also responsible for the musculature in the occipital head region.

phospholambin

The overall effect of phospholamban is to decrease contractility and the rate of muscle relaxation, thereby decreasing stroke volume and heart rate, respectively. Beta blockers = phospholambin will be unphosphorylated therefore will be regulating calcium release or uptake -When phospholambin is phosphorylated - there will be greater relaxation or lusitropy (faster relaxation) due to greater SR sequestration of calcium, thus on next contraction - contractility will be greater due to more calcium release.

non-atopic asthma

The second group of individuals with asthma does not have evidence of allergen sensitization, and skin test results are usually negative. A positive family history of asthma is less common in these patients. Respiratory infections due to viruses (e.g., rhinovirus, parainfluenza virus) are common triggers in non-atopic asthma.It is thought that virus-induced inflammation of the respiratory mucosa lowers the threshold of the subepithelial vagal receptors to irritants.

Persistent yolk stalk (vitelline duct) - what occurs if incomplete obliteration occurs?

The vitelline duct connects the small intestine with the skin at the umbilicus. It presents with meconium discharge from the umbilicus. Incomplete obliteration of the vitelline duct (omphalomesenteric duct) results in a *meckel diverticulum*

why are abdominal aneurysms more likely to occur below the renal artery?

There is also a reduced amount of vasa vasorum in the abdominal aorta (compared to the thoracic aorta); consequently, the tunica media must rely mostly on diffusion for nutrition which makes it more susceptible to damage

What cofactors are needed for the dehydrogenase complex?

Thiamine, Lipoic acid, CoA, FAD, NAD reactions that use this complex are 1. Pyruvate to acetyl CoA 2. A-Ketogluturate to Succinyl CoA 3. Branched chain a-keto acid DH

40 year old woman develops symptoms of parkinsons. For many years she has been treated for bipolar disorder with lithium, and recently a hypertensive medication was added. Whats the medication that precipitated her onset of parkisonian like symptoms?

Thiazide diuretics, ACEi, or NSAIDs (all have ability of inducing lithium toxicity).

What is the effect of thiazide diuretics on lithium?

Thiazides work in DCT to decrease sodium resorption, therefore the PCT compensates by increasing sodium resorption and therefore lithium.

Menke's disease

This infant has Menkes disease, which is also known as Ehlers-Danlos syndrome type IX (kinky hair syndrome). It is an X-linked recessive disease that has an incidence of 1/100,000 newborns. Common with Ehlers-Danlos diseases, Menkes disease has a symptomology due, in part, to weak collagen. The disease is caused by mutations in the gene ATP7A, which encodes an ATPdependent copper efflux protein in the intestine. Copper can be absorbed into the mucosal cell, but it cannot be transported into the bloodstream. Consequently, an affected individual will have severe copper deficiency and all copper-requiring enzymes will be adversely affected. Lysyl oxidase requires copper and plays a direct role in collagen formation by catalyzing the cross-linking of collagen fibrils. A deficiency in the activity of this enzyme and other copper-dependent enzymes would be directly responsible for the described symptoms in this infant

Pt just placed on antipsychotic medication develops muscle spasms, tongue protrusions, opisthotonous, and oculogyric crisis (forced sustained elevation of the eyes in upward position).

This patient developed *ACUTE DYSTONIA* Treat with *antihistamines (diphenhydramine -end in amine, -zine, or -hydra-) or anticholinergics (trihexyphenidyl or benztropine)

What is a cause of foul vaginal discharge and tender uterus following a pregnancy.

This patient has endometritis most likely due to bacteroides species - seen in both vaginal and cesarian sections. Chlamydia can also cause this however it is extremely rare compared to bacteroides following a pregnancy. This is the only time when we find a vaginal pathology due to bacteroides and not chalmydia, neisseria, gardenella ect.

15 yr old male pt presents with gait instability, kyphoscoliosis, pes cavus, and lower extremity ataxia. Position and joint sensation are impaired. Whats complication?

This pt has friedrich's ataxia (trinucleotide repeat, GAA - present in first intron of frataxin gene - loss of function). MAIN complication of Friedrich ataxia is Hypertrophic cardiomyopathy (HCOM). Presentation is similar to *subacute combined degeneration* seen in deficiency of vitamin B12, vitamin E deficiency, or Nitrous oxide toxicity.

Thyroid gland pathway

Thyroid gland takes up inorganic iodine in an energy dependent manner with sodium via the Na/I co transporter (iodine uptake is upregulated by TSH) Once the inorganic iodine is taken up it is first converted to organic iodine via oxidation reaction by peroxidase. Once in the organic form the iodine binds to a tyrosine residue in the thyroglobulin to form monoiodotyrosine. Once in this form, there a couple different reactions that can occur. 2 monoiodotyrosines can combine to form a diiodotyrosine - which can bind with another diiodotyrosine to form t4 or a diiodotyrosine can combine with a monoiodotyrosine to form T3. - Note that the peroxidase is only responsible for oxidation of iodine. -Note that thyroglobulin synthesis is upregulated by TSH (increases gene transcription)

Justice

To treat persons fairly and equitably. This does not always imply equally (e.g., triage).

SERMS and Bisphosphonates

Treatment of osteoporosis and pagets disease. include bisphosphonates, calcitonin, and PTH. Bisphosphonates are most commonly used and are analogues of pyrophosphate (component of hydroxyapatite.)

short acting benzodiazepines

Triazolam Alprazolam Oxazepam

Tuberous sclerosis - facts

Tu = tuber calcification (cortical) of periventricular area (subependymal hamartoma) and Tumor (malignant astrocytoma) B = blood in urine (hematuria) E = Eye --> retinal mulberry R = Rhabdomyosarcoma O = Off white skin (ash lead skin patches) U = sub Ungual fibromas S = shagreen and sebaceous adenoma

Way to remember tuberculoid and lepromatous

Tuberculoid leprosy is associated witha strong cell mediated immune response --> recall that tuberculosis itself involves a strong cell mediated response (thus resulting in caseous necrosis). On the other hand, lepromatous leprosy causes patients to look like a "leper" (leonine facies) or have loss of fingers and toes because of the weak cell mediated immune response.

Homing - tumor metastasis

Tumor cells embolize in the bloodstream as self-aggregates and by adhering to circulating leukocytes and platelets; this may confer some protection from host anti-tumor effector mechanisms. Exactly where tumor cell emboli eventually lodge and begin growing is influenced by: • Vascular and lymphatic drainage from the site of the primary tumor • Interaction with specific receptors; certain tumor cells express CD44 adhesion molecules that avidly bind high endothelial venules in lymph nodes; other tumors exhibit specific chemokine receptors that interact with ligands uniquely expressed in certain vascular beds (e.g., CXCR4 and CCR7 in breast cancer) • The microenvironment of the organ or site (e.g., a tissue rich in protease inhibitors might be resistant to penetration by tumor cells)

Anesthetics - order of nerve blockade

Type B and Type C > Type Ad > Type Ab and Agamma > Type Aa order of loss = 1. pain 2. temperature 3. touch 4. pressure (pacinian corpuscle - actually transmitted on large myelinated fibers - type A)

SLE - hypersensitivity

Type II and III HS

why would selective destruction of type II pneumocytes result in atelectasis?

Type II pneumocytes are responsible for secreting surfactant which decreases the work load on the lungs required for respiration. (note that if type I pneumocytes are damaged, type II pneumocytes would differentiate into type I pneumocytes.) Insufficient surfactant (as seen in neonatal respiratory distress syndrome) results in atelectasis of alveoli due to increased surface tension. This would cause significant physiological vasoconstriciton in pulmonary arterioles (hypoxic vasoconstriction) HOWEVER the increase in pulmonary vascular resistance would NOT be sufficient to cause hypertension.

hepatitis E

UNENVELOPED RNA VIRUS, that spreads via the fecal oral route "vowels in the bowels" thus Hep A is also unenveloped (reason being that unenveloped makes virus resistant from acid degradation in the stomach). High incidence of fulminant hepatitis in pregnant women.

compression sleeves

USE for lymphedema - used for initial management of lymphedema.

malar rash formation in SLE

UV radiation induces apoptosis of keratinocytes releasing sequestered intracellular nuclear antigens --> this leads to formation of autoantibodies that combine with nuclear antigens to form immunocomplexes --> this results in a vasculitis which is responsible for the "erythematous" rash

What is the major source of sunburns? what Ultraviolet light?

UV-B radiation. Remember --> PABA containing sunscreens should be avoided in patients with a sulfa allergy.

when a ACEi is given - why would a patient have decreased levels of aldosterone?

Under normal situations without ACEi, angiotensin II (in times of hypotension) will increase aldosterone secretion, however when a ACEi is given, levels of angiotensin II decrease thereby lowering Aldosterone secretion.

stones that precipitate in acidic

Uric Calcium Oxolate Cysteine Xanthine

Cidofovir A/E and Use

Use - CMV retinitis in immunocompromised pts and acyclovir resistant HSV (just like foscarnet- however this drug has a longer half life). Also does not require phosphorylation by viral kinase. --> inhibits viral DNA polymerase A/E - nephrotoxicity - *coadminister with probenacid and IV saline to decrease toxicity)

Ganciclovir (use and A/E)

Use - CMV, note that valganciclovir is prodrug of gangciclovir with better oral bioavail. --> 5' monophosphate formed by a CMV viral kinase - inhibits DNA polymerase via chain termination. A/E = Leukopenia, neutropenia, thrombocytopenia, nephrotoxicity, more toxic than acyclovir.

methotrexate - facts

Use - Rheumatoid arthritis, anticancer (leukemia,lymphoma), IBD, psoriasis MoA - inhibits dihydrofolate reductase which reduces dihydropterin which is a cofactor for thymidylate synthase (forms dTMP). A/E = myelosuppression, mucositis (ulcers of digestive tract), macrovesicular fatty change of liver, teratogenic. *painful mouth ulcers, hepatotoxicity (hepatitis, fibrosis, cirrhosis). myelosuppression, increased risk for opportunistic infections, B cell lymphomas, and pulmonary fibrosis*

clomiphene (SERM)

Use - used in treatment of infertility MoA - acts as estrogen antagonist in hypothalamus and anterior pituitary Estrogen antagonist --> prevents feedback inhibition of GnRH release by hypothalamus --> continued release of GnRH --> LH and FSH release from pituitary --> Ovulation side effects = ovarian hyper-stimulation syndrome, ovarian enlargement, multiple pregnancy, visual disturbances

Foscarnet Use and A/e

Use = CMV retinitis in immunocompromised when gangciclovir fails and for ACYCLOVIR RESISTANT HSV!!! --> great because it does not require any phosphorylation to become active. A/E Nephrotoxicity, because this drug is a pyrophosphate analog - can *chelate* calcium also renal wasting of magnesium occurs which may lead to hypomagnesemia and a reduction in the release of parathyroid hormone thus adding to hypocalcemic state. This state can promote seizures.

AcycloVIR, famcicloVIR, valacycloVIR

Use = HSV and VZV. No activity against CMV. *Valacyclovir has highest oral bioavailibility.* --> becomes activated once phosphorylated by thymidine kinase and results in chain termination. A/E = Acute renal failure and nephropathy - TO PREVENT MUST HYDRATE

VACTERL association

V = Vertebral anomalies A = Anal atresia C = Cardiac anomalies TE = Tracheoesophageal fistula R = Renal and or radial anomalies L = Limb defects *can be seen in children with diabetic mothers or trisomy 18*, however this is not a syndrome because the findings are only associations and do not stem from one problem.

what will you find in the stool of a patient infected with vibrio cholera?

V. Cholera is a gram negative, comma shaped, oxidase positive bacterium that grows in alkaline media. DOES NOT INVADE therefore will not find leukocytes or neutrophils in the stool - will find mucous and epithelial cells. "watery diarrhea" Note that this also applies to ETEC. both have similar exotoxin (ETEC; heat labile and V. CHolera) --> activate Gs and increase cAMP levels inducing secretion of Cl-

Treponema Pallidum - VDRL

VDRL detects nonspecific antibody that reacts with beef cardiolipin. Used for diagnosis of syphilis, but many false positives, including viral infection (mononucleosis, hepatitis), some drugs, rheumatic fever, SLE, and leprosy.

what amino acids can be used to form succinyl CoA?

Valine, odd carbon fatty acids, methionine, isoleucine, and threonine VOMIT to made Succinyl Coa

what drug competes with nicotine at the nicotinic receptor?

Varenicline - a partial agonist that competes with nicotine and prevents its binding. This drug helps reduce the symptoms of nicotine withdrawal by mildly stimulating the receptor.

Drugs that increase risk to develop Digoxin toxicity

Verapamil, Quinidine, Amiodarone

what are 2 causes of a high state of homocysteine which can lead to increase risk for thrombus formation? (homocysteine causes endothelial damage)

Vitamin B12 or folate deficiency Cystathione synthetase deficiency

What other pathological states can lead to lithium toxicity?

Volume depletion from GI loss (diarrhea) Decompensated CHF Cirrhosis *all cause increase in proximal tubular resorption of sodium and lithium*

glycogen storage diseases

Von Gierke Pompei Cori Anderson McArdle Hers

autosomal dominant, cerebellar hemangioblastomas, retinal hemangiomas, liver cysts, increase risk for bilateral renal cell carcinomas

Von Hippel Lindau disease chromosome 3 *problem with hypoxic inducing factor* - tissues believe they are under hypoxic conditions - thus increase in VEGF, PDGF, EGF.

a 12 yr old female is found to have multiple brownish spots on her body during physical exam. Number has recently increased. She also has two soft flesh colored non tender papules on upper chest that she describes as acne. whats diagnosis

Von Reckinghausen disease - AD (this is NF1 - chromosome 17) - diagnosis requires 2 or more of following --> cafe au lait spots, intertriginous freckling, two or more cutaneous neurofibromas (flesh colored benign growths of schwann cells), optic nerve glioma, bony lesions, iris LISH NODULES

churg strauss - clinical presentation

WILL see WRIST DROP/FOOT DROP, palpable purpura, peripheral neuropathy, SINUSITIS, eosinophilia, ASTHMA - can also involve heart, GI, and kidneys.

Pax 3 mutation

Waardenburg syndrome = dystopia canthorum (lateral displacement of the inner corner of the eye) pigmentary abnormalities (frontal white blaze of hair, patchy hypopigmentation of skin, heterochromia irides), congenital deafness, limb abnormalities.

45 year old pt presents to the emergency room with fever, and dyspnea on exertion. He is HIV positive and his CD4 count is <100. The patient is already on warfarin for previous exacerbation of hyper coagulable state. You administer TMP-SMX. What is a potential adverse effect of this administration?

Warfarin +sulfonamide - both compete for albumin binding site. Thus administration will displace warfarin, and toxic levels may be reached. Look for bleeding from different sites.

Best drugs for pregnancy

Water solubility > high protein binding.

Lepromatous type - Leprosy

Weak Th1 cell response and *ineffective* Th2 cell response, prominent humoral mediated immunity.

Atrial septal defect

Wide fixed splitting of S2 -hard to develop audible murmur because blood flow across the ASD is low velocity and minimally turbulent. however, ASD is associated with other murmurs --> midsystolic pulmonary flow or ejection murmur (secondary to increased flow across the pulmonic valve) a diastolic rumble (secondary to increased flow across tricuspid valve) and a low pitched diastolic murmur (secondary to pulmonary regurgitation).

Alports inheritance

X linked Dominant Col4A5 Most common type of Alport other types COL4a3 and a4 = AR, AD deafness and blindness

Fragile X syndrome

X linked Dominant hypermethylation of CGG in 5' UTR FMR1 (familial mental retardation) = normally helps transport mRNA to nucleus --> dendrites Second most common cause of mental retardation large everted ears, macroorchadism prognathism (large jaw) mitral valve prolapse autism

duchenne muscular dystrophy is what kind of inheritance

X linked rececessive

Acute respiratory distress syndrome - x ray

X ray - look for DIFFUSE symmetric pulmonary opacities. "white out"

Zwelleger - info

Zellweger syndrome is characterized by defective peroxisomal biogenesis mainly affecting the liver and brain • Levels of C26 fatty acids in circulation are increased in Zellweger syndrome • Neurological manifestations (mental retardation) and hepatomegaly are most commonly associated • Usually fatal in infancy

serum ANA = fluorescent antibody test

a "rim pattern" correlates with anti-dsDNA antibodies and presence of renal disease in SLE.

Normal complement in kidney pathology

a 125 year old sholein monk named alport had benign hematuria -Alport -Henoch Shoein Purpura -Benign hematuria -SLE 1, 2, 5

cariodlipin (diphosphatidylglycerol)

a phospholipid found in the inner mitochondrial membrane and in the bacterial cell membrane.

MSUD is deficient in this enzyme

a-ketoacid dehdrogenase

most common presentation of hyperchylomicronemia (hypertriglyceridemia)

abdominal pain due to acute pancreatitis (chylomicrons block the circulation and cause rupture of pancreatic vessels) these patients do not have increased risk for premature coronary artery disease

what are the adverse effects of theophyllines? (7 total) - what happens to potassium and glucose levels?

abdominal pain, vomiting *seizures*, *cardiac arrhythmias*, hypokalemia, hyperglycemia, insomnia

imperforate anus - embryology

abnormal development of anorectal structures --> absence of anal opening is most often associated with *urorectal, urovesical or urovaginal fistulas* when the fistula is present, meconium may discharge from urethra or the vagina. -*most commonly associated with GENITOURINARY TRACT MALFORMATIONS* which include renal agenesis, hypospadia, epispadia and bladder extrophy. will not see abnormalities of GI from areas of foregut, midgut or even hindgut.

annular pancreas

abnormal migration of ventral pancreatic bud presents with early billous vomiting

what is dykaratosis?

abnormal, premature keratinization. Dyskeratotic cells are strongly eosinophilic and may have a small basophillic nuclear remnant. Dyskeratosis can be found in squamous cell carcinoma

plasma concentration v time

above MEC - drug has an effect. changing pH will effect amount of drug thats absorbed. For instance, giving an antacid will increase pH of stomach and decrease absorption of weak acids (aspirin, penicillins, cephalosporins, loops and thaizides). Whereas, decreasing pH of stomach will increase absorption of WA.

decorticate is a lesion where

above the red nucleus (midbrain)

Placental pathologies that can result in IUGR

abruptio placenta placental infarction due to vessel thrombosis *single umbilical artery* results in asymmetric growth retardation

most common cause of stillbirth?

abruptio placentae - in placental abruption there is premature separation of the placenta because of a retroplacental blood clot. *present as: abrupt, PAINFUL bleeding in the 3rd trimester --> increase risk for DIC* life threatening for mother and fetus. Risks = trauma, accident, cocaine abuse

sarcoidosis - noncaseating granuloma

absence of surrounding lymphocytes = naked granuloma

in healthy individuals, whats the role of CFTR in sweat glands?

absorption of chloride

microscopy of psoriasis

acanthosis (epidermal hyperplasia) thinned stratum granulosum with overlying parakeratosis (retention of nuclei in stratum corneum) *auspitz sign* - pinpoint hemorrhages due to dilated vessels in dermal papillae *munro abscesses* epidermal neutrophils

bergers

accelerated immune response to virus, bacteria or food products --> IgA that deposits in kidney (mesangial deposition) is abnormally glycosylated *predisposition = celiacs disease*

Splice site acceptor (2nd)

acceptor = GU

whats deficiency and accumulated substrate in tay sachs

accumulate GM2 gangliosided def. is hexominidase A

whats accumulated substrate and def in krabbe

accumulated substrate = galactocerebroside, psychosine def enzyme = galactocerebroside

fetal alcohol syndrome - mechanism

acetaldehyde (breakdown product of ethanol metabolism) disrupts retinoic acid and hedgehog signaling pathways - inhibits cell migration, and DNA/protein synthesis

chloramphenicol

acetyltransferase of enzymatic mediators

filamentous hemagluttin in bordetella pertussis

aceullular pertussis vaccination hemagluttin is used for attachment to respiratory epithelium

uric acid stones will precipitate at what pH?

acidic pH

what is the regulation of PFK

activated by AMP and fructose 2,6 bisphosphate inactivated by ATP and *citrate!!!*

Glucokinase enzyme glycolysis

activated by insulin, only present in liver and pancrease B cells, responds to high glucose concentrations (10mmol) has a higher Km than hexokinase

TNFa produced by

activated macrophages

Antithyroid drug - potassium perchlorate or pertechnetate) --Type of anion inhibitor

acts as a competitive antagonist to iodine for transport into thyroid.

Aldosterone promotes

acts at principal cells to increase gene expression of carbonic anhydrase and increasing number of ENaC channels (note no direct effect on alpha intercalated but by increasing CA II - somehow passes into alpha intercalated increasing levels of the enzyme) potassium excretion hypervolemia (at alpha intercalated will see H+ excretion and HCO3 production) metabolic alkalosis

Epleronone is similar to spironolactone

acts at same receptor --> EXCEPT NO GYNECOMASTIA.

spasmodic torticollis

acute dystonic reaction most likely due to antipsychotic use. develops abruptly, disease characterized by muscle spasms or stiffness, tongue protrusions, or forced sustained elevation of eyes in upward position. Symptoms are due to inhibition of dopaminergic receptors. --> in the straitum, the inhibitory effects of dopaminergic neurons are normally balanced by the excitatory actions of cholinergic neurons. Strong blockade of dopaminergic neurons cause an excess of cholinergic influence, resulting in EPR. (acute dystonic reactions, akathisia, and parkinsoniansim). Typically caused by traditional high potency antipsychotics = haloperidol and fluphenazine. TREAT with benztropine or diphenhydramine (central antimuscarinic agonist and diphenhydramine is a antihistamine with antimuscarinic activity).

only form of hypersensitivity thats reversible

acute hypersensitivity give cyclosporine - IL-2 inhibitor antibody = CD3 ab

side effect of mannitol

acute hypovolemia

Guanosine analogues

acyclovir, famciclovir, valacyclovir and gangciclovir.

What are the nucleoside analogues that require phosphorylation via thymidine kinase

acyclovir, valacyclovir, famciclovir, ganciclovir.

what is the most comon lung carcinoma

adenocarcinoma

palpable but nontender gallbladder (courvoiser sign), weight loss, and obstructive jaundice (associated with pruritis, dark urine and pale stools) are indicative of what pathology?

adenocarcinoma at the head of the pancreas compressing the bile duct.

CA 19-9

adenocarcinoma of pancreas

35 yr female presents with lower abdominal pain, uterus is enlarged, and biopsy reveals normal endometrial glands within the myometrium - whats diagnosis

adenomyosis - presence of endometrial glands in myometrium with an enlarged uterus, - also patients will often develop painful periods (dysmenorrhea) and heavy periods (menorrhagia) --> can develop into adenomyoma (polyp).

what are the effects of giving adenosine to a patient for SVT

adenosine will 1. cause cardiac muscle relaxation 2. decrease cardiac heart rate 3. dilate coronary vasculature thus will increase coronary blood flow and relax the heart = cardioprotective

H. Pylori adheres to what cells in GI

adheres to foveolar cells (note that the foveolar cells increase in menetieres)

oxidase bacteria are what kind of bacteria

aerobes

what nerve mediates the cough reflex?

afferent limb = branch of vagus nerve which is the internal laryngeal nerve - this nerve is susceptible to damage when food is caught in the piriform recess which is a small cavity that lies on either side of the laryngeal orifice.

what are the risk factors for adenocarcinoma?

age smoking (doubles risk) diabetes mellitus chronic pancreatitis genetic predisposition

Clozapine and quetiapine - A/E

agents are LEAST likely to produce EPR

Low 5 hydroxyindole acetic acid associated with

aggression, suicide, violence

clozapine A/E

agranulocytosis

False diverticulum

aka "pulsion" diverticulum. Only consists of mucosa vs a traction diverticulum which consists of all layers of organ wall.

a young male has short stautre, short fingers, and a round face --> serum calcium level is low and his PTH is high. Whats the cause?

albright hereditary osteodystrophy

macrovesicular steatosis

alcohol

the recurrent laryngeal nerve supplies..

all laryngeal muscles EXCEPT cricothyroid muscle. In addiotion the recurrent laryngeal supplies sensory below vocal cords.

why is LOS a better measure of morbidity in a N.meningitis infection then capsular polysaccharide

all strains of neisseria have LOS whereas NOT all strains have a capsule (ex. group B serotype). The capsule is anti-phagocytic.

Omalizumab clinical use

allergic asthma by preventing IgE from binding to FceR1 on mast cells or basophils.

Measles virus (rubeola) - paramyxovirus is implicated in causing

allergic encephalitis

treatment for lesch nyan

allopurinol fuboxistat (also used in gout --> also a allopurinol inhibitor)

treatment for tumor lysis syndrome

allopurinol and rasburicase (remember that rasburicase forms allotoin which is very soluble)

what are treatments for tumor lysis syndrome?

allopurinol or rasburicase

what is the reason that the action potential is delayed at the AV node?

allow ventricular filling during diastole.

what is an adverse effect of all anesthetics?

almost all volatile anesthetics increase cerebral blood flow which is undesirable as it results in increased ICP. Other effects of inhalation anesthetics are myocardial depression, hypotension, respiratory depression and decreased renal function. MOST COMMON is increased cerebral blood flow.

Etoposide unique A/E

alopecia

What are lewy bodies

alpha synuclein fibrils in neurons

Fabry disease - deficient enzyme

alpha-glucosidase A

splitting of GBM

alports MPGN

Acetazolamide MoA for altitude sickness

altitude (decrease Patm --> decrease Pa02) --> results in hypoxemia. Thus, in order to ascertain more 02, body will begin to hyperventilate and in doing so kick off more c02, thus develop respiratory alkalosis. Also, hypoemia causes hypoxic vasoconstriction - which will increase hydrostatic pressure and result in pulmonary edema. TO combat this, acetazolamide induces a state of metabolic acidosis and increases excretion of Na and HC03 which will treat state of edema.

bronchioalvelar carcinoma arises from what cell?

alveolar epithelium (type 1 pneumocytes)

hypoxemia with normal A-a gradient

alveolar hypoventilation (high altitude)

Bronchial breath sounds

always abnormal sound - will be loud, high pitched

neurofibrillary tangles seen in what disease?

alzheimers

what is antidote for tPA, streptokinase - fibrinolytics

aminocaproic acid

whats often added with cephalosporins to increase effect?

aminoglycosides

Drug interactions with loop diuretics

aminoglycosides (enhance ototoxicity - loss of hearing --> ethycrinic acid is MOST severe). lithium (chronic loop administration, decreases clearance) digoxin (increase toxicity due to electrolyte disturbances)

Drugs that can result in autoimmune destruction of thryoid (drug acts as hapten)

amiodarone interleukin alpha and IL 2 lithium *all can induce hypothyroid state*

Drugs that inhibit conversion of T4 to T3

amiodarone propranolol corticosteroids lithium propylthiouraciol (thioamide)

Class III antiarrhythmics - drugs

amiodarone, sotalol

phentermine

amphetamine, appetite suppressant --> short term use for obese patients

Cryptococcus treatment

amphotericin B

a p02 <50mmHg results in what change in cerebral blood flow?

an arterial oxygen tension of below 50 results in rapid increase in cerebral blood flow and intracranial pressure.

dystrophin function when present

anchors muscle fibers, present in skeletal and cardiac muscle.

danazol

androgen that suppresses FSH and LH used in endometriosis, hemophilia, immune thrombocytopenic purpura

steroid use and reason for elevate hematocrit

androgens stimulate red blood cell production which accounts for the higher hematocrit in normal males compared to normal females. This effect is exaggerated in exogenous steroid abuse. Steroids decrease gonadotropin secretion which results in a small testicular size, decreased sperm production and decreased endogenous testosterone secretion.

Pa02 is normal in these lung pathologies

anemia, CO poisoning, methemoglobinemia, polycythemia

Sirolimus (Rapamycin) Adverse effects

anemia, thrombocytopenia, leukopenia, insulin resistance , hyperlipidemia *NON-NEPHROTOXIC* - reason kidney "SIR-vives"

klebsiella and shigella are implicated in causing

ankylosing spondylitis

Fenfluramine MoA

anorectic medication increases CNS serotonin levels

kinesin is involved with..

anterograde transport towards positive end of microtubule - note that positive end will be far from nucleus.

anti histidine tRNA ligase

anti JO for dermatomyositis/polymyositis

polymyositis facts

anti Jo = anti transfer RNA synthetase. Damage is mediated mainly by Cd8 cells, but also Cd4 Th1 cells activate macrophages to damage myocyte fibers in skeletal muscle. Trigger is either coxsackie B or HIV/HTVL1 - result in altered class I and II MHC. will find dysphagia (upper esophagus has skeletal muscle), morning stiffness all over, and labs will show elevated creatine kinase and aldolase.

sjogrens

anti SSa(ro) and anti SSb (la)

Graves

anti TSH

SLE

anti dsDNA and anti smith (anti-snRNA)

drug induced SLE

anti histone

SLE drug induced

anti histone ab will present in 30% with ITP (immune thrombocytopenic purpura)

a test is designed for diagnosing a viral infection. The test used the viral antigen attached to wells along with a chromogen for a peroxidase enzyme. What else should be added to make the test complete?

anti human immunoglobuline - this is an indirect ELISA - and we know that because ta viral antigen is being used - thus we are looking to identify whether the patient has serum antibodies.

pernicious anemia

anti intrinsic factor, anti parietal cell

primary biliary cirrhosis

anti mitochondrial

what are the antibodies to celiacs?

anti tissue transglutaminase anti gliadin anti endomysial anti reticulin

Systemic sclerosis

anti topoisomerase (anti-Sci70 is old term) and anti centromere

auto antibodies in CREST and diffuse systemic sclerosis

anti topoisomerase is more specific for diffuse systemic sclerosis and anti centromere is more specific for CREST.

Myasthenia gravis

anti- ach

whats the antibody for mixed connective tissue disease?

anti-U1RNP (ribonuclear protein) note will also see anti ribonuclear proteins in sjogrens

goodpastures

anti-basement membrane

CREST

anti-centromere, anti-mitochondrial Calcinosis, Raynauds, esophageal dysfunction, sclerodactyly, telangiectasia

mixed connective tissue disease

anti-ribonucleooprotein (anti-URP)

hashimotos

anti-thyroglobulin, anti-microsomial

whats the antibody for scleroderma?

anti-topoisomerase I (anti-scl-70)

flutamide

antiandrogen inhibits uptake or binding of androgen in tissue ---> used leuprolide

myasthenia gravis

antibodies bind more to open state of nicotinic receptors - thus MG will become worse with movement because as more nicotinic receptors are in open state (ligand gated) then more antibodies bind. Normally as ligand gated nicotinic receptors open - result in opening of V-G Na channels.

Denosumab mechanism

antibody against RANKL

infliximab and adalimumab mechanism

antibody against TNFa

Natalizumab mechanism

antibody against a4-integrin - which is for leukocyte adhesion

Abciximab mechanism

antibody against glycoprotein IIb/IIIa --> remember this way (IIb times IIIa equals abSIXmab)

what class of drugs is contraindicated with used of benzodiazepines?

antihistamines due to sedation effects

Azathioprine mechanism

antimetabolite of precursor of 6-MP, inhibits lymphocyte proliferation by blocking nt synthesis

abcixmab clinical use

antiplatelet agent for prevention of ischemic complications in patients undergoing coronary intervention.

Benzodiazepine use

anxiety disorders, alcohol withdrawal, and active seizures (status epilepticus)

medical uses of benzodiazepines

anxiety, insomnia, acute seizures, and alcohol withdrawal

Painless mass in groin, several palpable lymph nodes in right inguinal area --> where did the malignant cells originate from?

any structure that drains to superficial inguinal lymph nodes (drains external genitalia, and structures from lower extremities) *location - present in region bounded by the inguinal ligament, sartorius muscle and adductor longus muscle, overlie the femoral artery, nerve, and vein)*

Soft S2

aortic or pulmonary regurgitation

lesion to pons - breathing

apneustic - inspiratory cramps

band keratopathy

appearance of band across the central cornea formed by precipitation of calcium salts on the corneal surface directly under epithelium. associated with states of hypercalcemia.

yersinia enterocolitica will appear like what in a child

appendicitis

Marfan's syndrome - clinical

arachodactyly, scoliosis, aortic root dialation - defect in fibrillin 1 which wraps around elastase --> increase risk for aortic dissection

olivocerebellar cells

are modulatory and are part of motor planning can stimulate perkinje cell via glutamate and stimulate deep cerebellar nuclei (which receive gaba from perkinje) to modulate planning. *receives input from all cortical layers*

meningiomas

arise from cells of arachnoid villi. Slow growing. Symptoms of compression. Look for *new onset seizures*

round ligament of the uterus contains

artery of sampson this is a derivative of the GUBERNACULUM

complications of IBD

arthritis - HLA B27 (ankylosing spondylitis and enteric arthritis) Primary sclerosing cholangitis (UC>CD) --> P ANCA more associated with UC. Also remember that ASCA is pos for both Pyoderman gangernosum/ Erythema nodosum Both carry risk of colorectal cancer (but UC has a greater risk)

Smooth muscle relaxation via Gs

as seen with albuterol (B2 agonist) or theophylline (PDE inhibitor). Adenyl cyclase is activated, resulting in increased levels of cAMP - this activates protein kinase A which will phosphorylate myosin light chain kinase - rendering it inactive.

drugs that are weak acids

aspirin, penicillin, cephalosporin, loop diuretics, and thiazide diuretics

Androgen insensitivity syndrome

at birth testicles are present in inguinal canal or abdominal cavity. Paramesonephric duct structures are absent because MIF initiated apoptosis. Male accessory structures (SEED --> seminal vesicle, epididymis, vas deferens, prostate gland) are absent becaue testosterone had NO EFFECT on development of mesonephric duct (wolffian) due to defective androgen receptors! No effect of DHT. - Vagina ends in blind pouch reason being that its not derived from paramesopnephric duct. (lower 1/3)

Lower pons upper medulla lesion

ataxic breathing

causes of absent vocal tactile fremitus

atelectasis (collapse of airways), effusion (fluid) and air (pneumothorax) in the pleural space.

ITP

autoimmune IgG against GpIIb/IIIa - most common cause of thrombocytopenia in children and adults --> autoab are made in plasma cells in the spleen. (spleen is producing ab and consuming ab via splenic macrophages.) 2 forms acute and chronic. Acute - presents weeks after infection or immunization. Chronic - typically seen in women of child bearing age.and can be primary or secondary (SLE)

Primary Biliary Cirrhosis

autoimmune destruction of intrahepatic bile ducts and cholestasis. *granulomatous destruction of bile ducts in portal triads --> results in florid duct lesion associated with sjogren syndrome and occurs in women 40-50 yrs increased risk or HCC pathogenesis - environmental insult affecting mitochondrial proteins triggers CD* T cell destruction of intralobular bile duct epithelium. Autoantiboides --> antimitochondrial antibodies clinical findings = pruritis, painful hepatosplenomegaly, jaundice, inflammatory arthropathy, xanthelasma, kayser fleisher ring (most commonly associated with wilsons, but seen in PBC). Treatment = Budesonide (glucocorticoid) and ursodeoxycholic acid liver transplant

what is the pathogenesis of psoriasis

autoimmune/genetic, aggravating factors = strep pharyngitis, HIV, drugs (lithium, beta blockers, NSAIDs) sensitized CD4 TH1 and TH17 cells and activated CTL accumulate in epidermis and drive *keratinocyte proliferation* by elaborating cytokines (IL-12), IFNgamma, and TNF

VHL (chromosome 3)

autosomal dominant cysts in liver kidney pancreas Hypoxia inducing factor (HIF) bilateral renal cysts of bilateral renal cell carcinoma hemangioblastomas of retina, cerebellum, and medulla

Cowden syndrome

autosomal dominant hamartomatous polyp syndrome - PTEN mutation (tumor suppressor) *encodes lipid phosphatase that inhibits PI3K pathway* --> in cowden this is defective thus no inhibition of PI3K pathway. macrocephaly, intestinal hamartomatous polyps, papules, acral keratoses. polyps from all three germ layers (subq lipomas, leiomyomas, hemangiomas) -increase risk for breast carcinoma, follicular carcinoma of thyroid, and endometrial carcinoma.

Gaucher disease - inheritance

autosomal recessive

PKU inheritance

autosomal recessive

Tay Sach's disease - inheritance

autosomal recessive

PKU diet

avoid proteins (thus avoid eggs, meat, and artificial sweeteners)

what tumor are patients with sjogrens at an increased risk of developing

b cell lymphoma

causes of subacute combined degeneration

b12 def vit E nitrous oxide toxicity Metformin! HIV

How can b6 be a treatment of seizures in wilsons?

b6 will increase aminotransferase activity thus increasing levels of glutamate --> the increased formation of glutamate will act as substrate in CNS for glutamate decarboxylase forming GABA - which is helpful in seizures (decrease incidence).

gram positive rod that resembles medusa head

bacillus anthracis - in q gave "wool processing center" as hint -bacillus anthracis - D glutamate antiphagocytic capsule - unique feature.

Pores of Kahn

bacteria use this to travel from alveoli to alveoli.

blind loop syndrome

bacterial overgrowth --> decrease nutrient absorption because bacteria metabolize it first.

what are 3 bacteria that invade vessel walls

bacteroides fragilis pseudomonas aeruginosa salmonella

robertsonian translocation

balanced translocation between two acrocentric chromosomes (centromere is near end of chromosome) - thus long arm of one chromosome is translocated for short arm of another. occurs with chromosomes 14 and 21.

CYP450 inducers

barbituates, griseofulvin, carbamazepine, rifampin, st. john wart, chronic alcoholism, phenytoin

Inhaled corticosteroids

beclomethASONE flunisolide triamcinOLONE fluticaSONE budesSONide hydrocortiSONE prednisoLONE dexamethaSONE *Note that IV hydrocorticosone and prednisolone are life saving steroids in status asthmaticus*

decerebrate is a lesion where?

below red nucleus in midbrain

desmoid tumor

benign growths composed of broad fascicles of rounded fibroblasts with abundant cytoplasm and a significant surrounding collagenous matrix that infiltrates adjacent soft tissue.

what drugs are used to treat theophylline induced seizures?

benzodiazepines and barbituates

what drugs should be used to treat EPR?

benztropine = muscarinic antagonist amantidine = ion channel blocker trihexyphendyl = muscarinic antagonist diphenhydramine = H1 antagonist

What is treatment for drug induced parkinsons

benztropine, triphenhexidyl (central acting antimuscarinics) or amantidine or diphenhydramine

qualitative platelet disorders

bernard soulier glanzman Aspirin (decrease TXA2 from COX1)

drugs that decrease cardiac remodelling in CHF

beta blockers, ACEi, ARBs

Sibutramine (SERT and NERT)

beta phenylethylamine that inhibits the reuptake of serotonin and NE for weight loss --> a/e heart attack

Myoglobin is what type of subunit

beta subunit

side effects of acetazolamide

bicarbonaturia and acidosis hypokalemia hyperchloremia paresthesias (fluid loss induces) renal stones (can increase pH of urine - calcium oxolate which is less soluble in higher pH's) sulfonamide hypersensitivity *hydronephrosis* can cause ischemic damage by compression of renal vasculature. hydronephrosis results from a diuretic that is being used when a patient also has a renal stone.

metformin class

biguanides bypassing the desensitized insulin receptor and directly controls gene expression of insulin responsive genes - acts like insulin.

neurofibromatosis 2 - clinical presentation

bilateral acoustic schwanoma, meningiomas, ependymomas, juvenile cataracts, chromosome 22

pendred syndrome - congenital

bilateral hearing loss hypothyroidism autosomal recessive pendrin functions as iodide/chloride transporter --> this leads to reduced organification of iodine.

neuromyelitis optic

bilateral optic neuritis spinal cord demyelination antidobdies against aquaporins destroying BBB targets astrocyte foot processes

adjuncts to cholesterol therapy

bile acid resins and ezetimibe.

gallbladder hypomotility most commonly results in...

biliary sludge - results from bile precipitation. Contains cholesterol monohydrate crystals, calcium bilirubinate and mucous.

what are adverse effects of octreotide?

biliary sludge and bradycardia, along with abdominal pain, nausea and bulky bowel movements

Brown pigment stones result from -

biliary tract infection

Integrins - role

bind to ECM proteins such as fibronectin and laminin providing a connection between cells and ECM.

What is the role of plasma fibronectin

binds to fibrin, thus helping to stabilize blood clot and serves as a scaffold for ECM deposition and formation of matrix tissue during wound healing.

Fibronectin - role

binds to many molecules such as collagen, fibrin, and proteoglycans. Important --> fibronectin messenger RNA has two splice forms giving rise to tissue fibronectin and plasma fibronectin.

what is the mechanism of action of chloramphenicol?

binds to ribosomal 50s subunit - bacteriostatic - inhibits peptidyl transferase enzyme.

HSV 2 is only TORCH thats ONLY transmitted via

birth canal

treatment of paget's bone

bisphosphonates and calcitonin

what is a apical subpleural bleb

blebs are continuous distended airspaces that are up to 2 cm and can form cyst like sacs. These blebs may arise due to distal acinar (paraseptal) emphysema.

drugs that can cause pulmonary fibrosis

bleomycin amiodarone busulfan methotrexate procarbazine (alkylating agents)

Toxoplasmosis - TORCH Transplacental

blindness (chorioretinitis) hydrocephalus periventricular calcifications (basal ganglia) IUGR deafness hepatosplenomegaly

class III antiarrhythmics

block K+ efflux via delayed rectifier channels thus slowing phase 3 of repolarization. -prolongs ADP and ERP in all cardiac tissues

thiazide MoA

block NCCT channel --> blocking this channel - cell will have lower concentrations of sodium thus increasing the drive for sodium entry on the basolateral membrane which will increase calcium absorption into the blood Also ATPdependent K+ channel open can exacerbate a diabetic situation.

class 1 antiarrhythmics

block fast sodium channels in the active or open state. Will increase action potential duration and effective refractory period. Thus, will slow conduction of heart.

intracellular evasion - salmonella and mycobacterium tuberculosis

blocking fusion of phagosomes with lysosomes

Aspirin MoA

blocks (irreversible) Cox 1 and Cox 2 - at low doses predominantly inhibits COX 1 whereas in higher doses inhibits both cox1 and 2. Vascular endothelial cells express COX 1 and COX 2 whereas platelets only expresses COX 1.

What is the mechanism of action of niacin

blocks hormone sensitive lipase - thus decreasing plasma FFA. Decrease FA synthesis and decrease TAG synthesis. Niacin upregulates Lipoprotein lipase (LPL)

Sotalol

blocks potassium channels and B1 selective blockade thus decreasing HR and AV conduction. - used for life threatening VENTRICULAR arrhythmias.

miglitol and acarbose

blocks sodium glucose transport in GI tract by blocking alpha glucosidase in brush border of gut potential hepatotoxicity

acarbose MoA

blocks sodium transport alpha glucosidase inhibitor potential hepatotoxicity decreases postprandial glucose levels in type 1 and 2 DM Drug does not cause weight loss

How is pulsus paradoxus measured?

blood pressure cuff --> ex. bp cuff is inflated to 130mmHg and the pressure is decreased. At 100mmHg, intermittent korotkoff sounds are ONLY heart during expiration. At 80 mmHg korotkoff sounds are heard throughout the respiratory cycle.

renal transplantation - blood supply

blood supply to the donor organ is established by anastomosing the donor renal artery with the recipients external iliac artery. Similarly, the donor renal vein is connected to recipients external iliac vein. *renal artery supplies top 1/3 of ureter* *superior vesical artery supplies blood supply to distal segment of ureter*

negative symptoms - schizophrenia (lessened effect of normal fxn)

blunted affect (mood) poverty of speech social withdrawal diminished motivation

hypercalcemia (bones, stones, groans, and psychic overtones)

bone pain, abdominal pain, pyschosis (depression) CNS sx = weakness, confusion, coma Renal sx = polyuria, nocturia, dehydration, renal stones Gastrointestinal sx = constipation, pancreatitis, gastric ulcers Heart = arrhythmias (short QT) Acidosis will decrease affinity of albumin - thus free up calcium thats bound to albumin (whereas alkalosis will make albumin bind tighter thus decreasing free calcium levels).

Clinical findings of Pagets

bone pain, and facial bone coarsening (producing lion-like facies) headaches and hearing loss (note that this can also occur with osteopetrosis) *look for clinical hint = increase in hat size*

hydrocele and indirect inguinal hernia are formed by a similar mechanism.

both conditions are caused by incomplete obliteration of the processus vaginalis. Hydrocele occurs when there is a connection between the scrotum and abdominal cavity that only allows for the leakage of fluid; whereas a hernia occurs when the opening allows the protrusion of abdominal organs along the inguinal canal.

Why dont loop diuretics have same effects on lithium as thiazide diuretics?

both decrease Na absorption, however bc loops act at LoH the DCT will compensate and increase Na reabsorption - PCT will not have to compensate. So, because absorption is not increased at PCT 0 effects of lithium toxicity are not observed

Ewing sarcoma and retinoblastoma similarities

both have "small round blue cell" morphology BUT genes are different Retinoblastoma is Rb mutation on chrom 13 and ewings is on chrom 11 (mostly sporadic)

at glomerulus - clearance

both ionized and nonionized forms of drugs are filtered. Only nonionized forms undergo active secretion and active or passive reabsorption. Ionized forms of drugs are trapped in the filtrate.

mycoplasma and chlamydia - what do these lack

both lack muramic acid

genitourinary abnormalities in turner syndrome

both ovaries are replaced by fibrous stroma (called streak ovaries) and carry an increase risk for developing ovarian dysgerminoma. *elevated androgens (LH and FSH) but decreased estrogen and progesterone (d/t lack of ovaries) *increased risk of HORSESHOE kindey* caught on IMA.

difference between aromatase deficiency and 21 hydroxylase deficiency in a female

both will present with ambiguous genitalia, however 21 hydroxylase deficiency will also present with salt wasting, hypotension, hyponatremia, metabolic acidosis, hyperkalemia

a 52 year old smoker develops right sided face and right arm swelling and engorgement of subcutaneous veins on right side of neck - whats most likely obstructed?

brachiocephalic vein via an apical lung tumor (can also occur when a central catheter has been in place for an extended period of time. *the right external jugular vein is formed by the union of right subclavian vein and the right internal jugular vein* Furthermore, the right brachiocephalic vein also drains the right lymphatic duct which drains lymph from the right upper extremity, the right face and neck, the right hemothorax and right upper quadrant of the abdomen.

what other structures develop from the neural tube?

brain, spinal cord, posterior pituitary, pineal gland, retina.

subdural hematoma - damaged vasculature

bridging cortical veins

imipenem clinical use

broad spectrum -->gram positive, gram negative, aerobes and anerobes DOC for enterobacteriacea

what lung cancer stains with chromogranin?

bronchial carcinoid tumor (will find nests of neuroendocrine cells and chromogranin A +ve)

patchy inflammation of lung

bronchopneumonia

klinefelters

buccal barr body

first line treatment for Generalized anxiety disorder?

buspirone -> takes 2 weeks to show effect, its a selective agonist of 5HT1a receptor. well tolerated

how could some antipsychotic drugs influence levels of prolactin>?

by blocking dopamine receptors in tuberoinfundibular pathway will lead to hyperprolactinemia which will decrease levels of GnRH - women will show with amenorrhea and galactorrhea.

tocolytics

caclium channel blockers = nifedipine magnesium sulfate terbutaline = b2 agonist atosiban

cyclosporine mechanism

calcineurin inhibitor, blocks T cell activation by preventing IL -2 transcription

Tacrolimus mechanism

calcineurin inhibitor, but via binding of FK506

what causes amyloidosis in medullary carcinoma of thyroid?

calcitonin

treatment of variant angina

calcium channel blockers (class IV antiarrhythmics) and Nitrates

What are cadherins?

calcium dependent adhesion proteins that help muscle and epithelial cells stay bound together. They are transmembrane proteins that bind within the cytoplasm to intermediate filaments like keratin. Extracellularly, bind to other cadherins forming desomosomes and adherens junctions. *All interactions are calcium dependent, thus removing calcium will cause dissociated of cadherin mediated junctions = loss of cell adhesion*.

stones that precipitate in alkaline urine

calcium phosphate struvite

norwalk virus is in what family of viruses

calcivirus

hydralazine

can act as hapten --> A/E SLE (anti-histone) preferentially used for ER HTN because has high protein binding and does not cross placenta. Direct vasodilator - effects arterials

cluster headache

can also have horner like symptoms, treated with sumitriptan and oxygen, oftern occurs at night

motile and H2S production

can be grouped together salmonella and proteus

Migraine

can be hormonally responsive --> clinical hint look for women around menopause

Turner syndrome - ovaries

can be streak ovaries which are fibrosed ovaries or have a complete absence of ovaries.

polyyxin - can bind LPS

can be used for a patient with septic shock Toxic a/e

Amiodarone

can be used to treat all cardiac arrhythmias, however limiting factor is its onset --> half life is 80 days thus can take 15 months for it to reach steady state concentration

Niacin facts

can block Apo B100 expression -suppression of LDL production -Increase HDL

How can proline's presence effect proteins

can disrupt normal secondary structure due to substituted amino group

Pseudomonas

can form biofilms Strains of P. aeruginosa isolated from CF patients produce in high amounts *alginate* (an exopolysaccharide) which provides the matrix for these bacteria to live in a biofilm (an aggregate of bacteria). Biofilm act as a diffusion barrier, but also some of the bacteria within the biofilm show markedly high resistance to the antimicrobial agents, that's why it's difficult to treat these patients.

women with ITP (chronic form)

can have short lived thrombocytopenia in newborn thats short lived - because IgG autoab will be phagocytized

Fibrates

can inhibit CYP450

Lyme disease

can result in heart block --> type III heart block atrial and ventricular asynchrony tx - doxycyline (oral) or ceftriaxone

what fungi forms germ tubes at 37 c which are true hyphae?

candida albicans

opportunistic mycoses

candida, aspergillus, mucrorhizopus

what are 3 examples of fungi that invade vessel walls?

candida, mucor, aspergillus

amiodarone is used to treat

cardiac arrhythmias - it is a class III anti-arrhythmic

Cardiac hypertrophy

cardiac myocytes are terminally differentiated and thus CAN NO LONGER DIVIDE. Thus, chronic intensification of the hearts mechanical load results in increased dimension and mass of the individual cardiomyocyte (hypertrophy). The hypertrophic state is established through increases in the rate of protein synthesis, the quantity of protein, and the quantity of sarcomeres and mitochondria within each cardiomyocyte. Gene expression is altered with the genes responsible for *fetal cardiac development upregulated*. As heart makes larger quantities of growth factors -> *myosin mRNA is synthesized at a faster rate*.

pulsus paradoxus is associated with what heart pathology

cardiac tamponade

SLE - false positive tests

cardiolipin --> FP syphillis test and rheumatoid arthritis lupus anticoagulant --> falsely elevated PTT

pompes disease - clinical findings clinical hint --> Infant with heart findings, thats not due to congenital defect

cardiomyopathy (infantile hypertrophic cardiomyopathy) *only glycogen storage disease that shows with early clinical findings in heart* exercise intolerance hypotonia, macroglossia very early death deficiency of lysosomal a1,4 glucosidase (acid maltase, acid alpha-glucosidase). glycogen storage disease *muscle biopsy reveals abundant PAS positive intracellular granules*

pt presents at 5 months with coarse facial features, gingival hyperplasia, macroglossia, hepatosplenomegaly, joint immobility, clubfoot, scoliosis, growth and mental retardation, bone fractures and deformitis, mitral valve defect - what will this patient most likely die of?

cardiorespiratory failure. I cell disease

what is the term for episodic loss of motor tone triggered by emotion

cataplexy

phe and tyr are precursors to..

catecholamines

what makes up the straitum

caudate nucleus + putamen

HUS (hemolytic uremic syndrome) - will see microangiopathic hemolytic anemia

caused by EHEC or shigella. seen in children will also see decrease in ADAMS T13 due to endothelial damage.

narcolepsy with cataplexy - findings

caused by lack of HYPOCRETIN 1 (orexin A) and HYPOCRETIN 2 (orexin B) which are produced in LATERAL hypothalamus. -Promote wakefullness

beta thalassemia - pathogenesis

caused by mutations that result from defective mRNA processing (MC defective splicing). This leads to deficiency of beta globin chains required for normal hemoglobin synthesis. Patients who are heterozygous = beta minor and homozygous = beta major.

Ecthyma gangrenosum

caused by pseudomonas in immunocompromised patients, presents with multiple skin lesions (papules) over the effected area. This is due to perivascular bacterial invasion of arteries in the dermis and subcutaneous tissue with release of exotoxins. Skin lesions become edematous and will necrose.

urge incontinence or "overactive bladder syndrome"

caused by uninhibited bladder contractions (detrusor instability). results in sense of urgency accompanied by an involuntary loss of urine. Treat with antimuscarinic M3 drugs. caution elderly patients about confusion and functional decline.

pulmonary edema

causes alveolar collapse and results in decreased ventilation which causes hypoxemia. Results in reactive vasoconstriction to shunt blood toward areas where ventilation is less compromised.

what are clinical features of tyramine reaction

causes release of catecholamines so just think HYPERsympathetic response tachycardia hypertension arrhythmias seizures stroke

disulfiram

ceftotetan, cefoperazone, cefmanidole, griseofulvin, procarboxacid.

IgA deficiency is associated with

celiacs disease

anti-endomysial, anti tissue transglutaminas IgA, anti gliadin IgA

celiacs disease

Anti tissue transglutaminase seen in which disease?

celiacs disease tissue transglutaminase is an enzyme that participates in metabolism of gluten will also find antibodies to gliadin anti-endomysial and anti-reticulin

Signet ring adenocarcinomas

cells contain abundance of mucin droplets that push the nucleus to one side and lead to the characteristic appearance of a signet ring. Presence of signet rings imply invasive adenocarcinoma and represent infiltrative growth within stomach wall. Gastric mucosa will appear as *linitis plastica* or *leather bottle stomach* -SIGNET RING CARCINOMAS consist of cells that will NOT form glands - differentiating factor when comparing to intestinal type adenocarcinomas.

Invasive medullary breast cancer

cellular, *lymphocytic infiltrate* solid sheets of pleomorphic cells, high mitotic rate good prognosis

benztropine and triphenhexidyl are what type of drugs

centrally acting antimuscarinics

stages of digestion

cephalic, gastric, and intestinal stages

fabry disease - accumulated substrate

ceramide trihexoside

4yr old boy evaluated for difficulty walking, frequent respiratory infections, cultured cells show high rate of radiation induced genetic mutation - pt is most likely to experience what?

cerebellar atrophy

Ataxia Telangiectasia - AR disorder --> abnormal dilatations of capillary vessels.

cerebellar atrophy occurs in first year of life severe immunodeficiency with repeated sinopulmonary infections -risk of cancer increased because of inefficient DNA repair (nonhomolgous end joining --> DNA ds break repair mechanism)

metachromatic leukodystrophy - substrate accumulation

cerebroside sulfate

digoxin toxicity

change in eye color (yellow), confusion, nausea, anorexia, halo around eyes treat with anti digoxin ab.

Dermmatomyositis

characteristic purple papules overlying the knuckles and proximal and distal interphalangeal joints (GOTTRON PATCHES)

Tuberculoid type - Leprosy

characterized as prominent Th1 cell response and weak Th2 cell response

systemic mastocytosis

characterized by the abnormal proliferation of mast cells and increased histamine secretion. Histamine increases the production of gastric acid by parietal cells. Gastric hypersecretion therefore is a common occurrence in systemic mastocytosis.

lesion to forebrain - breathing

cheyne stokes

kid comes in - given amoxicillin and develops morbilliform rash (pruritis) - appears like measles - what went wrong

child actually had a viral infection with EBV and amoxicillin precipitates rash. not an allergic reaction do not stop current regimen

conjunctivits, infant pneumonia

chlamydia D-K

intracellular bacteria

chlamydia, listeria, legionella, nocardia, neisseria menigitidis, rickettsia, mycobacterium, salmonella typhi

what antibiotic can cause aplastic anemia? (pancytopenia)

chloramphenicol

Most first generation antihistamines end in - amine or -zine or have hydra in name

chlorphenirAMINE dophenHYDRAMINE dimenHYDRinate doxylAMINE HYDRoxyZINE mecliZINE promethaZINE

Alzheimer's

choline acetyltransferase (ChAt) defect in basal nucleus of meynert

donepezil (what kind of drug)

cholinesterase inhibitor

Retinoblastoma (rb) gene is on what chromosome

chromosome 13

neurofibromatosis 1

chromosome 17 multiple neurofibromas multiple pigmented lesions cafe au lait spots Crowe's sign - axillary freckling Lish nodules - pigmented iris hamartomas

VHL - disease of 3

chromosome 3 - autosomal dominant paraneoplastic EPO from cerebellar hemangioblastoma *3 words* = hemi-angio-blastoma and pheo-chromo-cytoma, renal cell carcinoma, 3 letters =EPO increases RBC bilateral renal cell carcinoma (major cause of death)

Achondroplasia - clinical features

chromosome 4, point mutation (substitution of Arginine for glycine of fibroblast growth factor receptor 3 (FGFR3). Mutation causes a defect in paracrine signaling that leads to increased function of *FGFR3 which is responsible for inhibition of cartilage proliferation*.pts present with restricted chondrocyte proliferation, decreased endochondral ossification and reduced cellular hypertrophy. Will also find shortened extremities and frontal bossing.

Hemochromatosis - HFE gene

chromosome 6, AR, characterized by abnormally high iron gastrointestinal absorption. HFE expression is the basolateral surface of epithelial cells of the small intestine crypts where is complexes with b2 microglobulin and then binds to the transferrin receptor to regulate endocytosis of the transferrin/iron complex into cells. In patients with hemochromatosis - the HFE gene is mutated which results in inability to detect circulating iron levels - resulting in unregulated and excessive iron uptake. *liver cirrhosis and hepatocellular carcinoma are two of the more ominous potential complications of this disease.*

whats the most common cause of sideroblastic anemia?

chronic alcoholism! elevated AST/ALT uses up B6 which is required for ALA synthase.

perineal abscess = perianal abscess - what is clinical presentation in patient with crohns

chronic diarrhea, transmural inflammation, noncaseating granulomatous rxn, most commonly effects terminal ileum (but can be seen throughout WHOLE GI mouth to anus). Aphthous ulcers is early sign (in mouth or bowel) look for skip lesions and fistulas and deep ulcers = cobblestone appearance. Look for creeping fat around serosa. Extragastrointestinal signs are erythema nodosum, sacroilitis (HLAb27 positive), pyoderma gangrenosum, and iritis. On radiography will find string sign = terminal ileum narrowing by inflammation. Complications = perineal abscess and fistulas, calcium oxolate renal stones, megaloblastic anemia due to decrease b12 absorption. -symptoms of malabsorption of fat soluble vitamins A, D, E, K --> thus increased bleeding due to lack of gamma carboxylation of factors 2, 7, 9, 10 (vitamin K). Night blindness (vitamin A), increase bone fragility (rare d/t fact pts still receiving sunlight (UVB) converts 7dehydrocholesterol to pre-vitamin D3 (cholecalciferol). Hemolytic anemia or sx of subacute combined degen.

Chlamydia LGV (lymphogranulosum L1-L3)

chronic disease characterized by an initial painless small ulcer on genital mucosa that contains chlamydia. Painless ulcer helps differentiate it from H.Ducreyi and HSV. The ulcer is followed by painful inguinal lymph nodes that ulcerate and rupture "buboes" Histologically lesions of LGV contain areas of mixed granulomatous (bc its intracellular) and neutrophilic inflammation with chalmydial inclusion bodies. The lymph nodes develop *stellate abscesses* surrounded by histiocytes that eventually coalesce into large necrotic draining foci.

progressive mucosal atrophy in stomach

chronic gastritis

IFNgamma exogenous use

chronic granulomatous disease

Recombinant IFNa used for what pathologies?

chronic hepatitis B and C, kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, renal cell carcinoma, malignant melanoma.

psoriasis

chronic inflammatory skin disorder characterized by sharply demarcated, salmon colored rounded plaques covered with a loosely adherent silvery-white scale. Most common areas of eruption include elbow, knees, and scalp.

Imipenem - what drug needs to be given along with imipenem

cilastin which is a dehydropeptidase I which prevents rapid metabolism at the liver - thus decreases adverse effects

dome shaped nonciliated cells in the bronchioles

clara cells

origin of bronchogenic carcinoma

clara cells

what drugs work on atria and ventricles

class I, II and III

what are the agents used to treat wolf parkinson white syndrome (WPW)

class IA and III antiarrhythmics

what drugs work on SA/AV nodes - antiarrhythmics

class II and class IV

what drugs can increase risk of Torsades de Point? (cause a long QT interval)

class Ia and III antiarrhytmics

ATN - ischemia

classic pathology include: 1. detachment of tubular cells from BM 2. muddy brown casts occlude tubular lumen - composed of epithelial cells, proteins 3. cellular necrosis is LIMITED to OUTER MEDULLARY REGIONS because the renal medulla is susceptible to ischemic injury (low medullary blood flow).

types of angina

classic, stable and variant (vasospastic)

olivocerebellar access cerebellum via what fibers

climbing fibers - only olivo uses climbing fibers --> which will synapse on granule cells.

Kallman syndrome

clinical hint - look for delayed puberty plus anosmia -failure of GnRH secreting neurons to migrate from their origin in the olfactory placode to their normal anatomic location in the hypothalamus. -KAL-1 gene -patients will have central hypogonadism and anosmia, there may also be midline defects (cleft palate and cleft lip). remember that cleft lip is failure of the maxillary prominence to fuse with nasal prominence. Cleft palate can be d/t failure of lateral palatine processes to fuse. -Pt present with delayed puberty, small testes

marfan syndrome vs homocystinuria

clinically these two pathologies present similarly - ectopia lentis, tall stature, chest and spinal deformities, however differences are: generalized osteoporosis, arterial and venous thrombosis, premature atherosclerosis, changes in hair, disorders of mental development are ABSENT in marfans.

intestinal type adenocarcinomas

closely resemble colon cancers --> grow as nodular, polyploid and well demarcated masses that can become ulcerated. will find well formed glands that consist of columnar or cuboidal cells.

what drug should be used if patient has tardive dyskenisia and requires antipsychotic

clozapine (atypical)

what are cardiovascular manifestations of turners?

coarctation of aorta (preductal), bicuspid aortic valve (thus early calcification of aortic valve)

crystal formation - stagghorn

coffin lid

dermatomyositis have an increase risk for what cancer?

colon cancer, bladder cancer, bronchogenic (lung) and NHL

CEA carcinoembryonic antigen

colorectal cancer breast cancer pancreatic cancer

40 yr female presents with mass on right breast, lesion is composed of ducts distended by pleomorphic cells with prominent central necrosis. Lesion DOES NOT extend beyond the ductal basal membrane.

comedocarcinoma (subtype of DCIS - ductal carcinoma in situ) -precancerous -basal myoepithelial layer is preserved and not involved -neoplastic cells confined to duct -noninvasive

third arch

common carotid artery and proximal party of the internal carotid artery associated nerve = glossopharyngeal nerve

intraventricular hemorrhage aka Germinal matrix hemorrhage

common complication of prematurity - occurs in infants born before 32 wks gestation. Occurs withing first 5 postnatal days.

Isoniazide causing peripheral neurotoxicity

competes for B6 - which is needed for GABA decarboxylase to glutamate - t

diastolic HF

compliance = change in volume/change in pressure in diastolic heart failure - EF is normal, end diastolic pressure will increase, and end diastolic volume will be normal to decreased. note that decomposition occurs in heart failure when LVEDP raises enough to cause pulmonary edema.

Pseudocysts - complication of acute pancreatitis

complication of pancreatitis, its walls consist of granulation tissue and fibrosis - which are unlike TRUE cysts which are lined by epithelium.

Subthalamic nucleus - anatomy

component of basal ganglia and it is ventral to the thalamus and superior to the internal capsule. Remember that the subthalamic nucleus is part of the indirect pathway. refer to FA 453

B cells - light chain

composed of V and J (variable and joining)

B cells - heavy chain

composed of V, D, J (variable, diverse, joining)

Schwannoma

composed of cells with elongated cells with regular oval nuclei. *schwannomas are biphasic* Antoni A pattern - highly cellular areas "picket fence pattern" Antoni B pattern - low areas of cellularity S-100 positive (other S-100 positive are langherhans (dendritic) histiocytosis X, neural crest tumor, and melanomas)

Kaposi sarcoma

composed of spindle cells forming vascular channels with associated chronic inflammatory infiltrate (infected cd4 cells will release cytokines to induce mesenchymal cells - which results in proliferation). CD 31 and 34 positive.

SVC syndrome

compression by mediastinal mass - lung carcinoma that are central = squamous cell, and small cell. Mediastinal mass will compress superior vena cava leading to swelling of face, neck and upper extremities as well as headaches, dizziness, confusion, and *dilated collateral veins*

why would a pregnant women develop hypotension when lying supine?

compression of IVC - results in decrease venous return --> decrease preload --> decreased contractility --> decreased cardiac output --> hypotension.

Pka

concentration at which the molecule is 50% ionized and 50% nonionized ionized = water soluble nonionized - lipid soluble

IgM in fetus is a sign of...

congenital infection

lobar pneumonia stages

congestion, red hepatization, gray hepatization, resolution - refer to picture.

phase II metabolism

conjugation via transferases types of conjugation include glucuronidation and acetylation

whats histology of neurofibromas

consists of loose and disorganized proliferation of schwann cells (elongated wavy cells with spindly nuclei), fibroblasts, neurites.

zero order elimination

constant AMOUNT of drug is eliminated per unit time; no fixed half life. ex. ethanol, phenytoin, salicylates (aspirin)

what is one clinical finding that will not develop tolerance to opioids?

constipation

Verapamil A/E

constipation *note can give after subarachnoid hemorrhage to prevent vasoconstriction*

complete Hep B virion

contains Dane particle (42nm) --> do not confuse with the 22nm HBsAg. Note that hepatitis D virus (double shelled particle - resembles the dane particle) --> furthermore note that Hep D requires HBV external surface coat antigen to become infective.

neurovascular bundle superior to thyroid

contains superior thyroid artery, superior thyroid vein, and external branch of the superior laryngeal nerve

carbonic anhydrase inhibitor

contraction alkalosis Hypovolemia

Pramlintide (amylinomimetics) - amylin produced by parasympathetic stimulation in cephalic and intestinal phase of digestion

controls starch (complex carbohydrate) metabolism decrease gastric emptying decrease glucagon release regulated appetitie activator insulin - thus risk of hypoglycemia

aromatase activity

converts testosterone into estradiol (responsible for secondary sex characteristics) and adnrostenedione into estrone.

mnemonic "CATs go numb"

convulsions, arrhythmias, tetany, and numbness/paresthesias in hands, feets and mouth - seen with hypocalcemia.

kayser fleischer ring

copper deposits where cornea meets sclera in descemet's membrane (composed of collagen type IV because its a basement membrane)

Copper metabolism

copper is absorbed in the stomach and duodenum loosely bound to circulating albumin and then transported to liver. Within the liver copper is incorporated into an alpha 2 globulin to form ceruloplasmin. The ceruloplasmin is then resecreted into plasma where it accounts for 90 to 95% of curculating copper. *Note that UNABSORBED copper is secreted into bile and excreted in stool which is the primary route for copper elimination.*

chlorpromazine - eye A/E

corneal deposits

tuberous sclerosis - clinical findings

cortical tubers sub ependymal giant cell astrocytomas with periventricular calcifications, mental retardation, keratin angiomyolipomas, ash leaf spots, rhabdomyoma benign, ungual fibroma, mTOR pathway mutation Tubers - cortical tubers, sub ependymal hamartoma, giant cell astrocytomas Ungual fibromas (nail bed) Blood in urine - angiomyolipoma Eye - retinal mullbery (hamartoma) Rhabdomyoma and retardation Off white skin Ungual fibroma Sebaceous adenoma

tracts that access cerebellum via mossy fibers (release glutamate)

corticocerebellar pontocerebellar spinocerebellar vestibulocerebellar *only olivo cerebellar are climbing fibers*

whats the drug of choice in dermato and polymyositis?

corticosteroids.

How can coughing result in syncope?

coughing --> increased intrathoracic pressure during coughing episode decreases venous return to the heart thereby transiently decreasing cardiac output and cerebral perfusion.

HBV - liver morphology

councilman bodies - apoptotic bodies ballooning degeneration

NOD 2 gene

crohn disease --> allows intestinal bacteria to enter the bowel and produce chronic inflammation.

NOD 2 gene

crohn's disease allows intestinal bacteria to enter bowel and produce chronic inflammation

yersinia enterocolitica will appear like what disease in an adult

crohns

pyoderma gangernosum

crohns CML hairy cell leukemia Rheumatoid arthritis HLA B27

regional enteritis

crohns disease

HFE receptor for transferrin is located where?

crypt cells in duodenum

where are the stem cells of gastrointestinal tract located?

crypts of lieberkuhn

Acyclovir, famciclovir, valacyclovir A/E

crystalline nephropathy and acute renal failure

where are the stem cells in the small and large bowel (labile cells)?

crytps

Niacin A/E

cutaneous vasodilation hyperglycemia (acanthosis nigricans) Hyperuricemia/gout Hepatitis

what is antidote for serotonin syndrome - as caused by MAOi + SSRI

cyproheptadine

morphology of craniopharyngioma

cystic or partially cystic with solid areas (calcium). Cysts are lined by stratified squamous epithelium Keratin pearls Cysts are filled with cholesterol

bromocriptine

d2 agonist - can be adjuvant to levodopa a/e GI effects, cardiovascular effects *pulmonary infiltrates, pleural and retroperitoneal fibrosis, and erythromelagia*

what is treatment for neuroleptic malignant syndrome

dantrolene or bromocriptine

alkaptonuria clinical features

dark connective tissue, brown pigmented sclera, urine turns black on prolonged exposure to air (due to homogenistic acid). May have debilitating arthralgias (homogentisic acid toxic to cartilage).

CMV - TORCH (transplacental)

deafness, IUGR CNS calcifications periventricular hepatomegaly with jaundice thrombocytopenia petechiae *look for large cells with eosinophilic intranuclear inclusions*

lesion below red nucleus

decerebrate - arms extended

lesion above red nucleus

decorticate - flexed arms

beta blickers

decrease 02 demand, negative ionotrope.

Patient with sickle cell disease has a reticulocyte of 5% and a MCV of 115 whats reason?

decrease folic acid --> these patients are predisposed to folic acid deficiency due to increased erythrocyte turnover. Folic acid def is much more common in these patients. Note the reticulocyte count should be markedly elevated if it were to result in and elevated MCV.

resorption atelectasis

decrease in lung volume due to lung collapse caused by a obstruction (tumor, peanut) that blocks airflow thus airway collapses. Note that bronchus will not collapse d/t presence of cartilage. *most common cause is mucopurulent plug as seen in broncheictasis* *REVERSIBLE*

what is pulsus paradoxus

decrease in systolic blood pressure of greater than 10mmHg with inspiration

lab values in ITP

decrease platelet count increase megakaryocytes in bone marrow biopsy normal PT and PTT treat with corticosteroids, if severe and worried about intracranial bleeding - can give IVIG (IV immunoglobulins) so that spleen will also degrade administered immunoglobulin rather than ones that are bound to platelets, only used for symptomatic states. Last form of treatment is splenectomy (which is best treatment - however its invasive so use only with refractory cases)

Effects of fibrate and nicotinic acid therapy

decrease production of VLDL

type II RTA

decrease reclamation of HCO3 hypokalemia at proximal convoluted tubule urine is first alkaline then acidic

calcium oxolate stones will precipitate at what pH

decreased pH (acidic)

ezetimibe decreases what...

decreases serum LDL by decreasing intestinal absorption of cholesterol.

whats def and accumulated substrate in niemann pick

def in sphingomyelinase accumulated substrate = sphingomyelin

Porphyria cutanea tarda

def in uroporphyrinogen dehydratase most common disorder Autosomal Dominant Photosensitivity, blistering skin in sun exposed, dark colored urine can treat with hydrochloroquine, hemin or glucose load

whats deficiency and accumulated substrate in fabrys

def of a galactosidase accumulated substrate = ceramide trihexoside (glycosphingolipid)

what is def and accumulated substrate in gaucher

def of glucocerebrosidase accumulation of glucocerebroside

whats accumulated substrate and def. enzyme in metachromatic leukodystrophy

def. enzyme = aryslsulfatase A accumulated substrate = cerebroside sulfate

HNPCC

defect in MSH1 and MSH 2 defect in DNA mismatch repair colorectal adenocarcinomas at a young age before 50 proximal large bowel is most commonly affected

Mature Onset Diabetes of the young (MODY)

defect in gene coding for glucokinase -look for family history -pancreatic islet cells have high set point to glucose

Huntington defect

defect is secondary to a triple repeat disorder CAG in exon gain in function mutaiton the huntington protein causes hypermethylation 30-40 repeats, expressed as 30-40 glutamine repeats - very polar and will change conformation *degeneration of GABA interneurons of indirect pathway* thus only direct pathway is activated which is why we find hyperkinetic dyskenisias. -Will find atrophy of caudate nucleus -boxcar ventricles -hydrocephalus ex vacuo - not a true hydrocephalus -Tx is antipsychotics (target D1 to decrease dopamine)

Hartnup disease

defective *neutral amino* (cys,asn,gln,met,ser,thr) acid transporter on renal and intestinal epithelial cells.

iron poisoning - what drug to treat?

deferoxamine

what is antidote for iron?

deferoxamine

Alkaptonuria

deficiency in homogenistic acid oxidase

abetalipoproteinemia (decrease serum concentrations of ApoB (100 and 48)

deficiency in microsomal TAG proteins - which load apolipoproteins onto chylomicrons or lipoproteins (VLDL) symptoms = hemolytic anemia, acanthocytes, decreased vitamin E reabsorption, will see fat accumulation in enterocytes, retinitis pigmentosa, ataxia, and motor dysfunction. *reason for motor dysfunction is due to VITAMIN E deficiency (subacute combined degeneration) *acanthocytes --> after passing through spleen will become more exaggerated thus forming spurr cells* spicules are NOT evenly spaced vs evenly spaced spicules in eicanthocytes (which is seen in hyperuremia - associated with pyruvate kinase deficiency and renal failure.) patient will have chronic diarrhea (due to malabsorption of fat) patients will have normal villi will see retinitis pigmentosa (also caused by kerne-sayre mitochondrial disease - will see ragged red fibers, muscle ataxia)

Abetalipoproteinemia

deficiency in microsomal tag protein, autosomal recessive, loss of function mutation in *MTP* manifests during the first year of life with sx of malabsorption (abdominal distention, foul smelling stool). *Lab studies show very low plasma TAG and choelsterol levels and chylomicrons, VLDL and ApoB are entirely absent from the blood.* Poor lipid absorption causes deficiency of fat soluble vitamins (A, D, E, K) and essential fatty acids. This results in red blood cells with abnormal membranes and thorny projections called acanthocytes as well as multiple neurologic abnormalities (progressive ataxia, retinitis pigmentosa).

pathogenesis of type III dysbetalipoproteinemia

deficiency of ApoE - thus decreased liver uptake of IDL and CM remnants

pathogenesis of type I hyperchylomicronemia

deficiency of LPL or ApoCII

tarui glycogen storage disease

deficiency of PFK-1 severe myopathy early in childhood myoglobinuria, hemolytic anemia tons of glycogen

Osteogenesis imperfecta

deficiency or abnormality in type 1 collagen impaired bone matrix formation endochondrial ossification and intramembranous ossification are defective - but thaty are impaired due to primary defect which is bone matrix formation.

ovary, lung breast

degeneration of perkinje cells dysarthia limb ataxia truncal ataxia lack of coordination *cerebellar dysfunction* anti YO, anti P/Q (lung), anti HU (lung)

Alzheimers - degree of dementia is relative to what?

degree of neurofibrillary tangles which are hyperphosphorylated Tau proteins inside neurons - NOT amyloid plaques which are APP.

Duchenne muscular dystrophy - pathology

deletion of dystrophin gene results in calf muscle pseudohypertrophy via fibrofatty replacement of muscle tissue

glomerulonephritis - decreased C3

dense deposit disease (type II MPGN) and PSGN *will have normal C1 and C4 levels because it results from activation of alternative complement*

only a matter of time when prerenal azotemia will lead to renal azotemia

depends on degree of ischemia

what is atypical depression

depression characterized by *mood reactivity*, leaden fatigue (the patients arms and legs feel extremely heavy) *rejection sensitivity* (overly sensitive to slight criticism) and the reversed vegetative signs of *increased sleep and appetite*.

inflammatory breast cancer

dermal lymphatic invasion by breast carcinoma --> peau d orange, neoplastic cells block lymphatic drainage 50% survival rate at 5 years.

cutaneous mycoses

dermatophytosis and pityriasis versicolor (tinea versicolor caused by malassezia furfur)

Anti-cardiolipin (diphosphatidylglycerol) antibodies

detected in syphillis, and is a nonspecific marker for infection.

Transcription factor

determines cellular differentiation ex. differentiates progenitor cell into a dermal cell. *all nucleate cells in human body possess the entire genome; transcription factors specific for each individual tissue allow only those genes relevant to a cells specific type and function to be expressed.*

mesonephros

develops 4th week and becomes the mesonephric duc (wollfian duct) thus this will undergo atrophy in females, but persist in males to become GU tract in males.

Metanephros

develops 5th to 6th week, the mesonephric duct forms a diverticulum called the ureteric bud. Mesoderm around ureteric bud forms metanephric vesicles (blastema) which develops into collecting ducts, calices, renal pelvis and parenchyma. Remember then ureteric bud will form everything DISTAL to DCT thus CD, minor calyx and ureters whereas metanephros forms nephrons up to DCT.

PTPN 22 gene seen in what diseases?

diabetes and rheumatoid arthritis

what is another metabolic complication of patients with friedrich's ataxia. hint: this is one of the most high yield diseases of step 1.

diabetes mellitus

what is the most common cause of autonomic neuropathy in US

diabetes mellitus --> peripheral neuropathy

Anti-glutamate decarboxylase

diabetes type 1

what is the ergonovine test?

diagnostic test for coronary vasospasm

common adverse effect of colchicine

diarrhea - because GI tract sheds so often, administration of colchicine will

what are adverse effects of colchicine

diarrhea, abdominal pain, nausea

what is the mechanism of heart failure in restrictive cardiomyopathy?

diastolic HF - due to decreased compliance and decreased filling. Cardiac output will be decreased - Ejection fraction CAN BE normal - this is because its Stroke volume/End diastolic volume

hypothyroidism causes systolic or diastolic HTN?

diastolic HTN due to retention of sodium.

long acting benzodiazepines

diazepam flurazepam clorazepate chlordiazepoxide

what are three long acting benzodiazepines

diazepam, flurazepam, chlordiazepoxide

therapy to reduce serum uric acid levels

dietary changes (decrease in purine intake) weight loss abstinence from alcohol change in drug therapy (discontinue thiazides) Note that uricosuric agents (probenecid and sulfinpyrazone) can only be used in patients with good GFR

what is treatment of loa loa

diethylcarbamazine

what is treatment of wucheria bancrofti

diethylcarbamazine

Type II hypercholesterolemia

difference between type IIa and IIb = IIb has an increase in TAGs wherease type IIa does not

allelic heterogeneity

different mutations in the same genetic locus cause similar phenotype (ex. duchenne muscular dystrophy and becker's muscular dystrophy - DMD is a frameshift and beckers is a missense - however both are mutations in dystrophin gene.

drug interactions with thiazides

digoxin (increase toxicity - due to hypokalemia) and avoid in patients with diabetes mellitus. (can decrease insulin release (because it acts on ATP sensitive K+ channels).

Digoxin effects on heart rate

digoxin causes increased parasympathetic tone through its action on the vagus nerve which leads to decreased rate of AV conduction. Atria will continue to fibrilate, however the ventricles will have a slower more controlled contraction.

Phenylketonuria II is deficient in this enzyme

dihydropterin reductase

mammary duct ectasia

dilation of lactiferous ducts aka plasma cell mastitis or granulomatous mastitis inflammation, granular debris and leukocytes with foamy histiocytes, lymphomononuclear cells, plasma cells and granulomas produces *induration (hardening) and nipple retraction* mimics carcnioma

what is a varicocele

dilation of spermatic vein in pampiniform plexus that develop in left scrotum in 15-20% of adult males. Tend to be due to increased left renal vein pressure.

large volume transfusion

dilutes coagulation factors and results in a relative deficiency.

arsenic poisoning - treat with what?

dimercaprol

what is antidote for mercury

dimercaprol

what is antidote for lead?

dimercaprol, EDTA, succimer

why wouldnt IgA be effective against c. diptheria?

diptheria colonizes the pharynx and does that by expressing K antigen which inactivated IgA which allows for cellular adhesion

obstructive lung disease

diseases that cause high airflow resistance, patients breathe at a lower rate (slow, deep breaths) in order to minimize the work of breathing.

female athlete triad

disordered eating amenorrhea osteoporosis (d/t increased cortisol and decreased testosterone) pathophysiology = hypogonadotropic amenorrhea (decrease GnRH - imbalance between food consumption and energy output leads dysregulation and suppression of GnRH pulsatility)

retinoic acid mechanism - teratogen

disrupts hox gene function - which is important in determining the different structures that develop in the anterior-posterior axis. - can find visual and hearing imairment, facial dysmorphism, mental retardation, CNS defects and cardiovascular defects

Second generation antihistamines - why they are better to give with elderly

do not have antimuscarinic, antiserotonergic or anti alpha adrenergic properties, thus their side effects are minimal. They are LESS LIPOPHILIC thus do NOT cross BBB - thus NON SEDATING!

bromocriptine

dopamine agonist

the superior parathyroids develop from what pharyngeal pouch?

dorsal wing of fourth pharyngeal pouch.

inferior parathyroids develop from what pharyngeal pouch?

dorsal wings of third pharyngeal pouch

EPS 1 week to 1 month

drug induced parkinsons

etinyl estradiol

drug interaction - antibacterial and ethinyl estradiol used in OCPs other drug interaction with P450 --> Metabolism of estrogens relies on cytochrome P-‐450 system; they have enterohepatic circulation. Combination with p450 inducers can lead to decreased contraceptive efficacy.

Bithionol

drug of choice for fasciolosis (sheep liver fluke) inhibition of helminths electron transport chain

what is the dopamine hypothesis for schizophrenia

drugs that increase dopamine will produce positive symptoms and drugs that decrease dopamine will decrease positive symptoms but in doing so will increase negative symptoms. For treatment purposes its more desirable to rid patient of positive symptoms (hallucinations, delusions, incoherent thought, disorganized speech ect)

hyperestrogenemia in cirrhosis

due to decreased metabolism of estrogen by failing liver, decreased production of sex hormone binding globulin by liver (which causes increased free sex hormone levels) and decreased metabolism of androgens which are converted peripherally to estrogens by aromatase.

falsely elevated PTT in SLE

due to lupus anticoagulant

compression atelectasis

due to pleural effusion. Accumulation of fluid in pleural cavity most commonly caused by CHF and/or pneumothorax. *REVERSIBLE*

most susceptible time period for congenital malformations - malformation is defect in morphogenesis.

during 4-5th week when organs are being formed from the germ cell layers.

niacin is used to treat...

dysbetalipoproteinemia MoA - niacin decreases ApoB100 gene expression - thus decreasing VLDL

Niacin also used to treat

dyslipidemia lowers LDL and raises HDL

esophageal findings in scleroderma

dysphagia of solids and liquids because peristalsis is absent in lower 2/3 of esophagus because of collagen deposition (from fibroblasts which were stimulated by TGFb and PDGF) in the lamina propria and submucosa. --> the dysfunction leads to increased risk of developing *gastric reflux esophagitis* which leads to *barrets esophagus* and eventually *esophageal adenocarinoma*

EPS 1 to 5 days

dystonia - due to D2 blockade thus (downregulation of indirect pathway and upregulation of direct pathway - thus increase initiation of movement) *painful torticollis*

Multiple Myeloma - symptoms

easy fatigability constipation hypocalcemia (bones, groans, and moans) Rib bruising/ bone pain CRAB = hypercalcemia, renal insufficiency, anemia (normocytic normochromic), bone pain (vertebral, ribs, and skull --> look for punched out lesions on xray/back pain

Nifedipine A/E

edema

Basiliximab adverse

edema, hypertension, tremor

Aortic dissection complication

effusion into pericardial sac resulting in cardiac tamponade.

how to prevent reperfusion injury

either give antioxidants (vitamin E) or anti leukocyte adhesion antibody (this will decrease transmigration of neutrophils - thus limiting production of free radicals).

for minimal change disease - how to diagnose?

electrom microscopy --> podocyte foot effacement. associated with hodgkin lymphoma, mostly idiopathic

lab values in hemochromatosis

elevated LFTs elevated plasma iron >50% saturation of transferrin and elevated serum ferritin

effects of alcohol on metabolism

elevated NADH/NAD ratio leads to hepatic steatosis -decreased beta oxidation of fat -increased activity of lactate DH - increased lactic acid -decreased gluconeogenesis due to increased conversion of oxaloacetate to malate -decreased apolipoprotein synthesis -increased TAG synthesis

what are lab values like in tumor lysis syndrome?

elevated potassium - hyperkalemia --> can lead to arrhythmias elevated uric acid - hyperuricemia --> can precipitate in tubules causing obstructive uropathy and acute renal failure. -hyperphosphatemia -hypocalcemia --> tetany

Alpha fetoprotein (AFP) marker

embryonal carcinoma teratoma Yolk sac tumor Hepatocellylar carcinoma nonseminomatous germ cell tumors

Neuroleptic malignant syndrome - typically seen when receiving IV antipsychotics

emergency ---> stop treatment of antipsychotic --> *give bromocriptine to reverse block + DANTROLENE* (dantrolene causes decrease contractility by decrease calcium release from SR) -cause = low dopamine, increases rigidity, increase muscle tone, and increase cycling of actin and myosin. (Every muscle in body) - generates great amount of *heat* from ETC. --> leads to *hyperthermia* --> causing a MASSIVE increase in sympathetic autonomic system and develop hypertension, arrhythmias, and autonomic instability. *Life threatening* -all caused by dopamine antagonism.

what are causes of decreased vesicular breath sounds?

emphysema, asthma (increased AP diameter)

causes of decreased vocal tactile fremitus

emphysema, asthma --> obstructive lung diseases any increase of the AP diameter results in decreased vibration.

splitting defense mechanism - immature

employed by patients with borderline personality disorder where people, events, or actions are either all good or all bad. ex. women who thinks her boyfriend is the love of her life until they have first disagreement at which point the patient decides that her boyfriend is the worst human being on earth.

PTPN22 gene

encodes a defective tyrosine phosphatase *rheumatoid arthritis and Diabetes type 1*

PTPN 22 gene

encodes a defective tyrosine phosphatase that cannot control tyrosine kinase activity - which is important in normal lymphocyte responses

Protease inhibitors adverse effects (name 3)

end in -avir "adverse effects" - part of HAART therapy 1. lipodystrophy - leads to deposition of fat on the back and abdomen and decreased adipose tissue in extremities. Cushingoid habitus 2. Hyperglycemia - increased insulin resistance 3. Inhibition P450

Step 1. endothelial damage results FIRST in transient vasoconstriction via

endothelin released from endothelial cells and neurally triggered vasoconstriction --> all of this is immediate and transient.

Entacapone

entacapone can only work peripherally to decrease metabolism of levodopa (dopamine precursor) by COMT, thus increasing amount of levodopa that passes into CNS. Entacapone cannot cross BBB. Tolcapone can cross BBB, however. Tolcapone can decrease COMT in both periphery and CNS, but there is a risk of fulminant hepatitis with its use. Therefore entacapone is preferred.

amebiasis

entamoeba histolytics flask shaped ulcer filled with RBCs

yersinia

entercolitica = found in dogs pestis = fleas

pinworm is caused by what parasite?

enterobius

calcium stones - crystal formation

envelope/dumbbell shaped

ADAMS T13 --> seen in TTP

enzyme deficient in TTP -role of ADAMST13 - vWF formed as multimers and ADAMS T13 degrades multimers into monomers. If deficient multimers of vWF will lead to abnormal platelet adhesion resulting in microthrombi.

what is prinzmetals angina?

episodic, transient attacks of coronary vasospasm typically occurring at rest and during the night. These episodes produce temporary transmural myocardial ischemia with ST segment elevation.

PGI2 analogue

epoPROStol

what drug can induce transient ST segment elevations in a patient with prinzmetal angina?

ergonovine (ergot alkaloid)

how to diagnose variant angina

ergonovine - also used to induce labor.

intracellular evasion - listeria and shigella

escape from the phagosome into cytosol. Listeria is able to lyse the vacuolar membrane through the action of listeriolysin O a pore forming toxin that is selectively activated within acidified phagosomes.

achalasia

esophageal aperistalsis radiograph --> barium swallow --> look for birds beak sign pathogenesis --> due to reduced number of inhibitory ganglion cells thus favoring contraction of LES. clinical signs --> dysphagia with solids and liquids, chest pain, weight loss

Foregut derivatives

esophagus, stomach, liver, gallbladder, pancreas, and upper duodenum

Cricothyrotomy "tracheotomy"

establishes airway between the cricoid and thyroid cartilages

whats the cause of gallstone formation in females (most common cause)

estrogen and progesterone influences

oral contraceptives = hypercoagulable state

estrogen increases production of coagulation factors

loop diuretics

ethacrynic acid, furosemide, and torsemide.

turner syndrome - genetics

etiology = loss of parental X chromosome during mitosis (result 45XO) or meiotic nondisjunction. Mosaicism arises secondary to mitotic errors after fertilization has taken place.

keloid scar

excess granulation tissue, out of proportion to wound, genetic predisposition in african americans

what is hypergranulosis?

excessive granulation in stratum granulosum of epidermis - associated with lichen planus.

preeclampsia

excessive thickening of spiral artery -->increased deposition of maternal endothelial cells - possibly due to TGFbeta

Fractional excretion

excretion rate/filtered rate x 100

what are some virulence factors of pseudomonas

exotoxin A, elastase, phospholipase C, and pyocyanin (generates ROS)

diffuse crackles

expansion of alveoli due to fluid

physiologically whats longer expiration or inspiration

expiration is always longer. Interesting fact, over the lung fields on auscultation, whats longer? Inspiration, despite fact that expiration is physiologically longer, the time expiration can be heard over lung fields is only the early third of expiration - thus on auscultation it will be shorter. When auscultating the trachea however, expiration will be longer.

Volume of distribution

expressed in Liters, however if seen as L/kg must multiply patients weight to get in "Liters"

What is adenomyosis?

extension of endometrial tissue into myometrium.

what nerve supplies cricothyroid muscle? Remember that cricothyroid is responsible for pitch.

external branch of superior laryngeal nerve

superior thyroid artery is a branch of what artery

external carotid artery

superior thyroid artery is a branch of what artery?

external carotid artery

mycoplasma (intracellular or extracellular)

extracellular

hyperopia

eyeball is too short farsightedness point at which light crosses is beyond the retina

lysosomal storage disease

fabry gaucher niemann-pick tay-sach krabbe metachromatic leukodystrophy

Niacin side effects

facial flushing - which is due to prostaglandins and not histamine, thus this can be treated with aspirin. Hepatotoxicity can occur with HIGH doses of niacin, and attacks of gout (due to increase serum uric acid levels) Hyperglycemia (acanthosis nigricans)

what provides special sensation (taste) to anterior 2/3 of tongue?

facial nerve --> chorda tympani

factor 7 activates

factor 10 into 10a. and factor 9 into 9a.

what cleaves prekalikrien into kalikrien

factor 12a and factor 11a

pancreatic divisum

failure of fusion of dorsal and ventral pancreatic bud *single pancreatic duct is NOT formed*

myelomeningocele

failure of neuropores to fuse will find elevated AFP and AchE Valproate and methotrexate

SLE - antiphospholipid syndrome

falsely elevated PTT --> due to LUPUS anticoagulant (does not correct with mixing studies) others are anti cardiolipin (most sensitive and specific) and B2 glycoprotein (produces venous thrombi --> possible hypothesis is resistance to protein C).

Melanoma - info

familial --> mutation of chromosome 9p21 (CDKN2A which encodes for cyclin dependent kinase inhibitor 2a (p16) which negatively regulates cell cycle progression at the checkpoint between G1 and S by binding to cyclin dependent kinase (CDK4). - P16 mutations interfere with its inhibition of CDK4 allowing the cell to advance through cell cycle. atypical cells - irregular nuclear contours, hyperchromasia and spindle shaped Tx can include hydroxyurea and aldisleukin and vemurafenib (inhibitor of B-Raf) Note that vemurafenib is for metastatic melanoma or unresectable. BRAF and CDKN2A positive. Marker S100

Familial type IV

familial hyperTAG Increased production of VLDL decreased clearance of VLDL increase risk for CAD and peripheral vascular disease *eruptive xanthomas* increase TAG and moderately increased cholesterol, and increase VLDL Turbid infranate looks like chronic renal failure

acetylation (type of conjugation reaction) phase II - genotype variation

fast and slow acetylators --> ex isoniazid or hydralazine --> can see drug induced SLE in patients that are slow acetylators taking hydralazine.

hemochromatosis - clinical findings (AR)

fatigability, dry mouth, impotence, *mild hepatomegaly* and atrophic testes. Blood glucose elevated. Urine will be positive for glucose. Bronze "tan" skin - due to dermal hemosiderin deposition. -Diabetes present secondary to pancreatic islet cell destruction via iron deposition -atrophic testes are due to iron deposition in pituitary thus decreasing levels of FSH and LH. -pts can also have cardiac enlargement

digoxin cardiotoxicity

fatigue, blurred vision, change in color vision (e.g. "yellow vision"), anorexia, nausea, vomiting, diarrhea, abdominal pain, headache, dizziness, confusion, delirium.

pt has intracellular lipid accumulation in aorta - and is 12 years old.

fatty streaks --> earliest lesion in progression to atherosclerosis. Streaks are not raised and thus do not disturb normal blood flow - can be seen in aortas of children less than 1 year old (all children over 10 will have fatty streaks) *NOT all fatty streaks progress to atherosclerosis*

Embryology of GU tract

fetal GU tract develops from pronephros, mesonephros, and metanephros. the adult kidney forms by the 5-6th week of gestation from the ureteric bud (which is a dorsal outgrowth from the mesonephric duct also known metanephric diverticulum) and the metanephric mesoderm that surrounds it. The mesoderm forms the renal parenchyma (nephron, PCT, LoH, DCT) while the uteric bud is the percursor to (CT, minor calyx, renal calyx, ureters). The ureteric bud is initially present as a solid cord but it is FULLY canalized by the 10th week of gestation. Occasionally the metanephros will begin producing urine before canalization of the ureteric bud is complete and this leads to development of a TRANSIENT hydropnephrosis. The uretopelvic junction (jxn between kidney and ureter, is the last segment of fetal ureter to canalize. It is also the most common site of obstruction.

true hermaphrodite

fetus has testis on one side and an ovary on the other side or fusion = ovotestes

clinical symptoms of temporal arteritis

fever jaw claudication headache scalp tenderness tongue claudication neck, shoulder, pelvic girdle pain morning stiffness weight loss blindness (severe complication)

What are some other symptoms of a acute hemolytic reaction?

fever, hypotension, DIC, renal failure, and hemoglobinurine

Second generation antihistamines typically end in -adine

fexofenADINE LoratADINE cetririzine* (exception) acrivastine

what are the two antihyperlipidemic drugs that can cause gallstone formation? Why?

fibrates and bile acid resins reason - increase biliary cholesterol excretion

Marfans

fibrillin 1 on chromosome 15

fibrosarcoma

fibroblast based malignancy characterized by anaplastic spindle cells that grow in an organized in herringbone pattern (cross hitch) - marked disarray, pleomorphism, mitotic activity, hemorrhage and necrosis.

sex cord stromal tumor

fibroma granulosa-theca sertoli-leydig

what are two causes of hyperplastic arteriosclerosis in the kidney?

fibromuscular dysplasia and systemic sclerosis. look for "onion skinning" of afferent and efferent arteriole

pain that improves with exercise, no auto ab, skeletal muscle pain, seen in individuals 25-50 yrs

fibromyalgia

masson bodies

fibrous tissue plugs seen in BOOP (bronchiolitis obliterans organizing pneumonia)

invasive ducta carcinoma of breast

firm and fibrous rock hard stellate infiltration on gross appearance most common and most invasive

whats the action of the supraspinatus?

first 15 degree abduction --> above 30 degree the deltoid becomes main propagator of further abduction while supraspinatus stabilizes the glenohumeral joint.

definition of neonate

first 4 weeks of life

Kluver Bucy syndrome

flat affect, inappropriate sexual behavior, hyperphagia -lesion to amygdala

VIPoma

flattened T waves shortened QRS achlorhydria (WDHA syndrome = watery diarrhea, hypokalemia, achlorhydria) *diarrhea did not improve with fasting*

whats clinical presentation of patient with decorticate posture

flexed arms, extended lower extremities

what drug do you give for benzodiazepine toxicity?

flumazenil - benz antagonist at subunit between alpha and gamma. on GABA receptors.

CYP 2d6 (homozygous slow = poor metabolizers; homozygous fast = fast metabolizers)

fluoxetine imipramine desipramine antiarrhytmics analgesics metoprolol haloperidol codeine (fast metabolizers at risk for morphine A/E) and dextromorphan

niacin side effects

flushing, pruritis, rashes treat with Aspirin The flushing is due to PROSTAGLANDINS not histamine! -hepatotoxicity

adenosine A/E

flushing, sedation, dyspnea (acts at Gq receptors thus acting like M3)

what lymphoma presents with "waxing and waning" lymphadenopathy?

follicular lymphoma

what separates anterior 2/3 from posterior 1/3 area of tongue

foramen cecum which is located along the terminal sulcus

gut rotation

foregut - 90degree rotation midgut - 270degree rotation (if failure will see cecum in RUQ --> bands attached to duodenum "LADs bands" *apple peal atresia* Intestinal malrotation occurs -> in this condition the cecum is found in the URQ fixed via fiberous bands aka LAdds bands to the second portion of the duodenum the midut is fixed to the superior mesenteric artery, the fiberous bands = intesteional obstruction = bilious vomiting during hte first few days of life. IF the SMA is twisted can cause gangrene

What is the allantois?

formed during 3rd wk gestation forms a duct between the *bladder* and *yolk sac* which is referred to as the *URACHUS* *failure of urachus to obliterate* leads to 4 different pathologies. -*The urachus will then form the mediaN umbilical ligament*

Inferior vena cava anatomy

formed from common iliac veins at L4-L5 drains into RA (right above diaphragm) at T8

how does a complete mole form?

forms when a sperm fertilizes an egg and replicates its own chromosomes while eliminating maternal chromosomes

viral DNA polymerase inhibitors

foscarnet and cidofovir

thymidine kinase deficient (resistant to acyclovir) varicella zoster virus isolates (often found in AIDS pts) need to be treated with

foscarnet or cidofovir foscarnet does not require phosphorylation cidofovir only requires cellular kinases.

mycobacterium scrofulaceum

found in water sources, causes scrofula which is cervical lymphadenitis typically sen in children

nephrotoxicity - what lab values to expect

fractional excretion of Na >2% will have normal BUN/Cr ratio increased BUN

common causes of peroneal nerve injury

fracture of the fibular neck blunt trauma to lateral leg below knee pressure on fibular neck from tight fitting cast or work boot

crook hyaline change

from ACTH secreting cells increase of intermediate filaments In *Cushing's syndrome*, irrespective of the cause, increased levels of cortisol produce feedback effects on the non-tumorous corticotrophs, resulting in aggregates of intermediate cytoferatin filaments in the cytoplasm, producing the Crooke's hyaline change seen microscopically.

tuberoinfundibular (function and associated disease)

function = controls prolactin secretion associated disease = hyperprolactinemia

Nigrostriatal (function and associated disease)

function = coordination of voluntary movements associated disease = parkinsonism

mesolimbic - mesocortical pathway (function and associated disease)

function = regulates behavior associated disease = schizophrenia

role of paclitaxel in coronary stents

functions by binding beta tubulin and preventing microtubule breakdown thus causing arrest of the cell cycle in the M phase. By inhibiting cellular division the presence of paclitaxel prevents stent restenosis by preventing intimal hyperplasia.

Role of DNA polymerase I in prokaryotes

functions to excise the RNA primers and replace them with DNA - then DNA ligase subsequently joins the segments of DNA formed by DNA polymerase III to those formed by DNA polymerase I

enfuviritide is what type of antiviral?

fusion inhibitor

otosclerosis - aging

fusion of ear ossicles producing conductive hearing loss

gag, pol, env

gag - encodes capsid protein p24 pol - reverse transcriptase, integrase, and protease env - envelope gp41 and gp 120

fat, fertile, female, and forty - cause for what pathology?

gallstone formation.

COX 1 inhibition in platelets results in an increased risk of what?

gastrointestinal bleeding --> inhibition of TXA2 (platelet aggregation) and impairment of PGE2 and PGI2 (which are protective of gastric mucosa).

Valproic acid - use

generalized tonic clonic seizures, absence seizures, myoclonic seizures, mood stabilizer (also used for mixed manic-depressive episodes), and acute episodes of mania).

bernard soulier syndrome

genetic deficiency in Gp1b; platelet adhesion is impaired. blood smear shows mild thrombocytopenia (gp1b not functioning well - platelets do not survive as long) with enlarged platelets --> get "Big Suckers in Bernard Soulier" = large platelets.

GFAP (stains positive for what tumors?)

glial fibrillary acidic protein - involved with cell to cell communication and blood brain barrier. Stains positive for tumors of astrocytes, oligodendrocytes and ependymal cells.

what provides general sensation of posterior 1/3 area of the tongue?

glossopharyngeal nerve

Gaucher disease - accumulated substrate

glucocerebroside

Glutamates role in opioid tolerance

glutamate is an excitatory nt that binds and activates NMDA receptors. This activation can cause increased phosphorylation of opioid receptors - thus tolerance development.

focal necrosis of alveolar walls and intra alveolar hemorrhages - seen in what pathology?

goodpasture syndrome, wegeners, churgs, SLE

what are the adverse effects of niacin?

gout, hepatotoxicity, and hyperglycemia Niacin flush - PGE mediated (flushing, warmth, pruritis)

what is the only clotting drug that binds to fibrinogen

gpIIb/IIIa inhibitors ABCIXMAB EPITIFIBATIDE TIROFIBAN

what pathology has similar histology as PBC

graft vs host disease - remember that in GvH disease patients will present with clay colored stools - this could have helped you discern what the similar pathology was from other answer choices.

Bartonella henselae

gram negative, cat scratch fever, immunocompromised develop bacillary angiomatosis which is characterized as development of red to purple patches along skin that resemble KAPOSI sarcoma.

only excitatory cell of cerebellum

granular cells (glutaminergic)

what is morphology of giant cell arteritis

granulomatous inflammation of tunica intima and 1/2 of media, and will see fragmentation of internal elastic lamina (IEL) -->(NOT TRANSMURAL)

female presents with abnormal uterine bleeding, shes 30 yrs, negative pregnancy test, and pelvic ultrasound revelas endometrial hyperplaspia and a unilateral adnexal mass. - whats diagnosis?

granulosa cell tumor - characterized by call exner bodies (which recapitulate glomerular capillaries) - tumor produces lots of estrogen which has been linked to precocious puberty, endometrial hyperplasia and endometrial carcinoma.

drugs that act on microtubules

griseofulvin - inhibits mitotic spindle and mitosis colchicine - binds tubulin and prevents formation of microtubles pacitaxel (taxanes) - stabilize mitotic spindle in polymerized state vincristine/vinblastine - prevents formation of mitotic spindle mebendazole/albendazole

Dermatitis herpetiformis

groups of small vesicles that occur on extensor surfaces. Knees, elbows, buttocks and back are most typical locations for the rash. The eruptions are symmetrically distributed and extremely pruritic. Skin biopsy will show neutrophils and fibrin at tips of dermal papilla forming microabscesses. Immunoflourescence reveals IgA deposits in tips of dermal papilla. At dermal pappilla will find microbascesses, neutrophils and IgA.

barth syndrome - absence of cardiolipin

growth delay increased risk of still birth cardiomyopathy (dilated) at birth (like pompe) learning disorders hypotonia of musculature can resolve after puberty - with growth acceleration and height can die later in life from cardiomyopathy *role of cardiolipin* helps maintain structure of complex III (bc1) and complex IV (a3) in blood - 3 methylglutaconic acid

examples of factors that activate JAK/STAT pathway - remember these are still tyrosine kinase receptors, but difference is that there is NO intrinsic effect (no autophosphorylation)

growth hormone, cytokines, prolactin

Mycoplasma pneumonia and campylobacter can cause

guillain barre syndrome

cimetidine may cause what side effect?

gynecomastia

positive symptoms - schizophrenia (excess of normal fxn)

hallucinations mood increased agitation incoherent thought

what are four classical antipsychotics

haloperidol, fluphenazine, chlorpromazine, Thioridazine High potent agents = haloperidol and fluphenazine low potent agents = chlorpromazine and thioridazine

Only benign mass of the lung is a...

hamartoma

thio or sulfa - sulfur containing drugs.

has a sulfa group - sulfa groups are lipid soluble and will increase tissue dispersion. Because its lipid soluble - in plasma will be bound to albumin thus it can act as a hapten when it becomes protein bound.

anti microsomial

hashimotos

Hypertensive encephalopathy - presentation

headache, vomiting, confusion brain edema and petechial hemorrhages will be found throughout the gray and white matter

where are stem cells of bone marrow? (labile cells)

hematopoietic cells - cant be seen thus MUST know that its CD34+ve

what drug must be given prior warfarin therapy?

heparin

EBV is implicated in causing

hepatitis B, SLE, and rheumatoid arthritis

statin A/E

hepatitis, and myopathy thus check LFT's and serum creatine kinase

HBsAg --> hepatic changes

hepatocellular cytoplasm becomes filled with spheres and tubules of HBsAg and cytoplasm takes on a *finely granular eosinophilic appearance = "ground glass"*

Gaucher disease - clinical features

hepatosplenomegaly, aseptic necrosis of femur, bone crises, osteoporosis. Adult form (most common) shows no neurological damage. Gaucher cells = Macrophages that look like crumpled tissue paper.

what are the side effects of statins

hepatotoxicity and myopathy

Ezetimibe adverse effects

hepatotoxicity when coadministered with statins.

what are the neurological effects seen in wilson's disase

heptolenticular degeneration - lenticulate nucleus = globus pallidus and putamen will find 1. parkinsonian like tremor 2. ataxia 3. slurred speech 4. rigidity

regulation of glucokinase

high levels of Fructose 6 phosphate will shuttle glucokinase into the nuclease and inactivate it whereas presence of glucose will activate glucokinase and remove the enzyme from the nuclease into cytosol. Activators are Insulin and glucose. Glucokinase is not inhibited by Glucose 6 phosphate whereas hexokinase is.

Iodide salts

high levels of iodide can inhibit thyroid hormone synthesis --> wolff chaikoff effect (lasts 10 days) followed by escape phenomenon where thyroid function returns. Remember that its the Na/I symporter that brings iodine into thyroid along with sodium.

what are some causes of inspiratory stridor and whats the sound characterized by

high pitched inspiratory sound - which is a sign of upper airway obstruction causes = epiglottitis (H. influenza and strep pneumo) and croup (parainfluenza)

Germinal matrix - what is it/

highly cellular and vascularized layer in the subventricular zone from which neurons and glial cells migrate out during brain development. The matrix contains numerous thin walled vessels lacking the glial fibers that support other blood vessels throughout the brain which contributes to the risk of hemorrhage.

Homeobox genes

highly conserved set of genes - code for TRANSCRIPTION FACTORS (determine differentiation of progenitor cells) known as homeodomain proteins. These homeodomain proteins modulate expression of other genes in the cell.

spironolactone can be used to treat

hirsutism (PCOD) acne, and used post MI to increase survival by decreasing effects of aldosterone.

clinical features of fetal alcohol syndrome

hirsutism forehead microcephaly short palpebral fissures thin upper lip wide spaced eyes small nose flat nasal bridge Mental retardation Congenital heart defects (VSD, ASD)

intracellular fungi

histoplasmosa, cyrptococcus, pneumocystis

systemic mycosis

histoplasmosis, coccidioidoses and blastomycosis

HoxA

homeobox gene that is mutated in hand-foot-genital syndrome = characterized by clinodactyly, shortened thumbs, small feet, short great toes and urinary tract abrnormalities. Genitourinary abnormalities include duplications of reproductive tract in women and hypospadias in men.

alkaptonuria results in buildup of what intermediate

homogenistic acid

Alkaptonuria is deficient in this enzyme

homogenistic acid oxidase

Alkaptonuria - info

homogenistic acid oxidase deficiency homogenistic acid accumulates in dermis, cartilage, and sclera excreted in sweat in urine urine will change color on standing (15 min)

atrophy of caudate nucleus is seen in what disease?

huntingtons

what pathology involves atrophy of caudate nucleus?

huntingtons --> will see chorea, dementia and behavioral abnormalities

mucopolysaccharidoses

hurler and hunters

hyperkalemia, metabolic acidosis - effects on contractility

hydrogen ions can compete with calcium for troponin C - thus decrease heart contractility.

thiazide diuretics A/E

hyperGLUC = hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia HYPOKALEMIA, *HYPONATREMIA* -inhibits Na-Cl cotransporter

OTC deficiency

hyperammonemia X linked recessive seizures/coma orange crystals (due to dehydrated orotic acid - not urate) no urea produced *decreased BUN/Cr ratio* when orotic acid dries out - results in orange crystals in diapers (xanthine also looks this way)

SIADH

hypercalcemia hypomagnesium lithium demeclocycline (used to treat bacterial infections, lyme disease, acne, and bronchitis, and off label treatment for hyponatremia due to SIADH - works by decreasing ADH sensitivity)

bile acid binding resins should not be used in patients with what disease?

hypercholesterolemia with hypertriglyceridemia. reason being that they can increase TAG's Note that these drugs will be drug of choice in pregnancy and children.

INR below normal

hypercoagulable state

Glucocorticoids adverse effect

hyperglycemia, osteoporosis, central obesity, muscle breakdown, psychosis, acne, hypertension, cataracts, peptic ulcers. THINK cushing's syndrome (exogenous glucocorticoids is #1 cause)

what are the electrolyte abnormalities in ATN stage 2

hyperkalemia, metabolic acidosis, hyponatremia, hypocalcemia, hyperphosphatemia, hypermagnesium

presentation for hyperchylomicronemia Type I

hyperlipidemia, pancreatitis, lipemia retinalis, eruptive skin xanthomas (not over tendons) and hepatosplenomegaly.

Myotonic dystrophy

hypermethylation of CTG repeat in 3' UTR of DMPK gene on chromosome 19 (dystrophia myotonic protein kinase) - normal job is to phosphorylate calcium channels (like L type calcium channels) associated with phospholambin in muscles - *phospholambin when unphosphorylated will prevent calcium release from sarcoplasmic reticulum*

what sort of stones do patients with crohns develop?

hyperoxaluria - decreased calcium uptake (from decreased absorption) results in more free oxolate --> precipitates

thiazide diuretic uses

hypertension, CHF Nephrolithiasis (calcium stones) Nephrogenic diabetes insipidus (by increasing aldosterone level - and allows free water to be retained in absence ADH.)

niacin and fibrates are used to treat

hypertriaclygeridemia (increased VLDL)

lesion to midbrain - breathing

hyperventilation

unique feature of pH with acetazolamide

hypokalemic metabolic acidosis. - typically we find hyperkalemia with metabolic acidosis and hypokalemia with metabolic alkalosis.

Shifts K+ into cells

hypoosmolarity insulin alkalosis beta adrenergic agonist

what problem with the thyroid can be produced with amiodarone?

hypothyroidism

what are some acuses of type II hyperlipoproteinemia

hypothyroidism (decreased synthesis of LDL receptors) blockage of bile nephrotic syndrome (increase liver synthesis of cholesterol) MOST common = genetic

a 45 yr old man - suffered from cardiogenic shock - autopsy findings = bilateral wedge shaped bands of necrosis seen over cerebral convexity - appear to follow interhemispheric fissure. Whats the cause

hypoxic encephalopathy - this is describing hypoxia and resultant watershed infarction of the brain.

what are some causes of restrictive cardiomyopathy

idiopathic, amyloidosis, sarcoidosis, metastatic cancer

hunter syndrome - deficient enzyme

iduronate sulfatase (think hunter X long bow --> longer name, no corneal clouding and its X linked) also aggressive behavior bc he's a hunter

Norepinephrine extravasation

if patient is receiving a drip of NE and develops cold hard, and pale skin surrounding IV site, then NE is leaking from catheter resulting in local vasoconstriction - to treat just provide a local injection of phentolamine (just to localized area)

When to consider globus hystericus

if physical examination, endoscopy or barium swallow is negative and patient presents with feeling of lump in throat then consider this as a diagnosis.

general rule for fungi treatment

if systemic - use amphotericin B

Heminephrectomy results in compensatory hyperfiltartion and hypertrophy of the nephrons in the remaining kidney. What is the GFR immediately after the surgery and 6 weeks later?

immediately = 50% 6 weeks = 80% --> will not reach 100% because comparative number of nephrons will not be replenished or equal to what the patient once had.

band test in SLE looks for what?

immune complex formation in a *band like distribution* along the dermal-epidermal junction

other A/E of diazepam

impair coordination and balance decreased memory and concentration confusion

difference between duchenne muscular dystrophy and myotonic dystrophy - morphology

in DMD will see fibrofatty replacement and muscular necrosis, whereas that will NOT be seen in myotonic dystrophy.

differ MCAD from von gierke or mcardles

in MCAD will not see elevated ketones wherease in VG and McArdle there will be elevated ketones. furthermore note in mcardles will not have systemic lactic acidosis to significant degree because liver is unaffected.

pseudocyst - pathogenesis

in acute pancreatitis, proteolytic enzymes (induced from inflammatory state) degrade pancreatic ducts, thus causing the secretion of pancreatic proteins and enzymes that induce inflammation in surrounding organs including the pancreas. This results in formation of granulation tissue and encapsulation of the fluid collecting --> forming a pseudocyst.

intracellular evasion - M. tuberculosis

in addition to phagolsysosomal inhibition, also inhibits the phaglysosome acidification

Umbilical arteries (fetus)

in fetus provide oxygenated blood to the neonates internal iliacs (which is why there are 2)

What are potassium levels in stage 2 and stage 3?

in stage 2 = hyperkalemia in stage 3 = hypokalemia

CFTR channel varies in function from tissue to tissue - displays tissue specific function

in sweat glands = reabsorbs luminal chloride ions and enhances sodium reabsorption --> mutated CFTR in contrants diminishes sodium chloride reabsorption and increases sweat tonicity. in respiratory and intestinal epithelium = normal CFTR allows for active luminal chloride secretion --> mutated CFTR in contrast reduces luminal chloride secretion and increases luminal sodium absorption. thus in sweat glands will find increased sodium and chloride whereas in bronchial and luminal secretion will find decreased sodium and chloride.

Differences between Multiple Myeloma and Waldenstrom (lymphoplasmocytic lymphoma)

in waldenstroms - no osteolytic bone lesions, and will find generalized lymphadenopathy with hepatosplenomegaly, IgM in waldenstroms, and in multiple myeloma its IgG (most) or IgA.

type 1 RTA

inability to regenerate HCO3 at Distal convulted tubule (alpha intercalated cells) damage to H/K ATPase --> cannot secrete H+ normal anion gap metabolic acidosis hypokalemia

alpha 2 antiplasmin

inactivates plasmin note: in cirrhosis of liver = decreased alpha 2 antiplasmin

risk is a measure of what in a population?

incidence of disease. to calculate risk divide number of diseased subjects by the overall number of subjects in the corresponding group

macrolides MoA

include erythromycin, streptomycin, clarithromycin, azithromycin -bind 50s subunit which stops initiation -16s rna of 30s rna binds shine delgarno sequence -23s rna of 50s rna required for peptidyl transferase activity -binding of the 30s ribosomal subunit to mRNA and an N formylated methionine tRNA forms the prokaryotic initiation complex facilitated by the initiation of factors IF1, IF 2, and IF3.

difference between incomplete penetrance and variable expressivity

incomplete penetrance = pt has the genotype but does not have phenotype variable expressivity = pt has genotype, and different degree (either mild or severe) of the phenotype.

what is the pathogenesis of Systemic sclerosis?

increase Cd4 Th2 cells reacting against unknown antigen. - the t cells release cytokines that activate inflammatory cells and *FIBROBLASTS* --> collagen deposition.

exercise

increase HR, increase respiratory rate, increased cardiac output - normal Pa02 and PaC02, changes occur in venous blood, elevated PVC02 and decreased PV02

what are the *urinary* electrolytes in acetazolamide?

increase Na --> body has hyponatremia Increase K ---> body has hypokalemia increase HC03 --> body will have decrease pH *acidosis*

Urinary electrolytes in ethycrynic acid, furosemide, torsemide

increase Na --> body is hyponatremic increase K+ --> body is hypokalemic *alkalosis* Increase Ca --> body is hypocalcemia Increase Mg --> body is hypomag. increase Cl --> body is hypochloremic

lab values in vWF

increase bleeding time, increase PTT (because vWF stabilizes factor 8) normal PT, abnormal ristocetin test

Type IIa hypercholestrolemia

increase in cholesterol, LDL familial hypercholesterolemia and polygenic hypercholesterolemia

why does neutrophil count increase from corticoidsteroid use?

increase in neutrophil count results from demargination of neutrophils previously attached to the vessel wall.

what is acanthosis?

increase in thickness of stratum spinosum.

Ammonium magnesium phosphate stones (struvite stones) precipitate at what pH

increase pH

tacrolimus adverse effects

increase risk of diabetes and neurotoxicity, no gingival hyperplasia, no hirsutism

what are lab values in hemophilia?

increased PTT normal platelets normal PT

Restrictive lung disease - reason for high expiratory flow rate

increased elastic recoil pressure and increased radial traction on the conducting airways by fibrotic pulmonary interstitium.

reason for erectile dysfunction in cirrhosis

increased estrogen from decreased metabolism of testosterone (in adipose), thus estrogen feeds back on to pituitary and decreases levels of GnRH, LH, FSH --> overall there's less testosterone and less libido.

findings in wilsons

increased liver copper low serum copper Elevated urinary copper defect in ATPB7 (note ATPA7 is menkes) Autosomal recessive chromosome 13 ATP*B*7 = Biliary, Blood, Body liver transplant is curative

calcium phosphate stones will precipitate at what pH

increased pH (alkaline)

sjogrens

increased risk for non hodgkin lymphoma (b cell)

maternal diabetes mellitus - congenital effects

increased risk neural tube defect fetal macrosomia - due to hyperinsulinemia in the fetus which increases muscle mass and stores of fat in adipose.

whats the effect of estrogen on gallstone formation

increases cholesterol synthesis by upregulating HMG-CoA reductase which causes *hypersecretion of bilirubin* (causes bile to become supersaturated with cholesterol)

Lung physiology - increasing radius or conducting airway will have what effect on expiratory flow rate?

increases the expiratory flow rate because increasing radius of conducting airway decreases the resistance

suffix - dronate

indicates a bisphosphonate

heparin effect on LPL

induces the release of lipoprotein lipase

chloramphenicol - gray baby syndrome

infants have absent levels of UDP glucoronosyl transferase

what quadrant contains the sciatic nerve when giving a gluteal injection?

inferiomedial quadrant

lichen sclerosis et atrophicus

inflammatory condition - autoimmune - antibodies against extracellular matrix. Affects males and females equally - but female genital and perineal region is most commonly affected.

Polymyositis

inflammatory myopathy bilateral proximal muscle weakness elevated creatinine kinase and electromyographic abnormalities. -Anti Jo-1, Anti SRP, Anti-mi2

typical antipsychotics "classical" - MoA

inhibit D2 receptors in mesolimbic pathway - thus decreasing positive symptoms

Niacins effects

inhibit hepatic VLDL production, suppresses free fatty acid release from peripheral tissues, also decreases VLDL to LDL. mainly used to increase HDL levels

albendazole

inhibit microtuble synthesis and glucose uptake

mechanism of ototoxicity of aminoglycosides

inhibition of NKCC2 symporter in inner ear

wolf chaikoff effect

inhibition of organification --> followed by escape phenomenon which is downregulation of Na/I cotransporter

Doxorubicin MoA (anthracyclines = doxorubicin, daunorubicin)

inhibition of topoisomerase II leading to DNA breaks -used to treat breast cancer, AML, lymphomas, sarcomas.

capsofungin - inhibits cell wall synthesis

inhibits beta 1,3 glucan synthesis

Lithium MoA

inhibits inositol polyphosphatase and monophosphatase thus blocking the regeneration of inositol. Free inositol is essential for the synthesis of PIP2, therefore lithium blocks the PIP signaling cascade in the brain *by blocking the regeneration of PIP2, lithium inhibits central adrenergic, muscarinic, and serotonergic neurotransmission*

ezetimibe MoA

inhibits intestinal absorption of cholesterol - inhibits enterohepatic circulation of bile acid (like the bile acid resins) and is used primarily with statins. reduces serum LDL by 20-30%

glucocorticoids mechanism

inhibits nf-kb - suppress both B and T cell function by decreased transcription of many pro inflammatory cytokines.

Osteoprotegrin

inhibits osteoclasts (normally *upregulated by estrogen* - thus when estrogen is absent in menopause then will have upregulated activity of osteoclasts - osteoporosis. -function = it blocks RANKL on osteoblasts --> by binding RANKL, inhibits nf-kb. Reduces production of osteoclasts by inhibiting the differentiation of osteoclast precursors (derived from monocytes) into osteoclasts. *blocks RANKL-RANK interaction*

role of nicotinic acid - hyperlipidemia

inhibits the synthesis of VLDL apoprotein and decreases VLDL production. Its use results in decrease of both cholesterol and triglycerides, so total cholesterol in the plasma decreases.

intestinal phase

initiated when food enters duodenum, plays minor role in stimulating gastric acid secretion.

extrafusal muscle fibers

innervated by gamma fibers

examples of factors that use tyrosine kinase

insulin and many growth factors (PDGF, EGF, VEGF)

Raltegravir is what type of antiviral?

integrase inhibitor

Down syndrome clinical findings

intellectual disability, flat facies, prominent epicanthal folds, single palmar crease, gap between 1st 2 toes, duodenal atresia, Hirschsprung disease, congenital heart disease (most commonly ostium primum-type atrial septal defect [ASD]), Brushfield spots (white/gray/brown spots on periphery of iris). Associated with increase risk of ALL, AML, and Alzheimer disease (> 35 years old).

superior laryngeal nerve - branches internal branch and external branch

internal branch - sensory innervation above the vocal cords external branch - circothyroid muscle

black pigment stones result from

intravascular hemolysis

Growth factors (PDGF, EGF, VEGF) use what receptor

intrinsic tyrosine kinases - just like insulin

a researcher is studying macrophage antigen presentation to CD4 T lymphocytes. Which of the following HLA class II components is digested by macrophages during antigen processing.

invariant chain --> MHC class II are on APCs. Each class II is a *heterodimer* composed of a alpha chain and a beta chain. During antigen processing, the *invariant chain* brings the alpha and beta chains together to form a stable complex in the RER. The MHC-invariant complex then leaves the RER passes through the golgi body and enters an endocytic compartment in which the invariant chain is *proteolytically degraded* and external protein (antigen) is inserted between the alpha and beta chains. Travels to surface for presentation to T cells.

Affinity

inverse to Kd, its similar to Km thus lower the Km = higher the affinity

antigen binding site

is between the light and heavy chain - referred to as hypervariable region

ischemic colitis vs colon obstruction on barium enema

ischemic colitis = thumbprint sign, and will see pain on eating step ladder sign appears like clouds = bowel obstruction

ATN - stage 1

ischemic injury to renal tubules - precipitated by hemorrhage, acute MI, sepsis, surgery

vitamin A analogues

isotretinoin acitretin tretinoin adapalene tazarotene

what is akathisia

it describes a range of symptoms from mild feeling of anxiety to intense physical restlessness. -typically presents days to weeks after initiation of treatment and patients complain of feeling tense or restlessness. *often manifests as restless leg syndrome (purposeless movements of legs). -treat by decreasing antipsychotic meds.

Sertraline - what type of drug and use

its a SSRI *drugs that end in -etine* (other SSRI's are paroxetine, fluoxetine, sertraline, and citalopram, Use = major depression, first line for anxiety disorders

Sumatriptan

its a serotonin postsynaptic receptor agonist of 5ht1b/5ht1d - inhibit release of vasoactive peptides, promotes vasoconstriction, and blocking pain in brain pathways. Used for migraines

what is oxidase in bacteria

its cyctochrome C oxygen acceptor

what happens in cooling stage of PCR

its not double strand DNA reannealing - its primers that were added (dNTP's) that bind to single strand of DNA (forming hydrogen bonds). Reason being because excess DNA primers are present in the reaction mixture thus have a greater chance to re-anneal with ssDNA.

what is treatment of strongyloides and onchocerca volvulus

ivermectin

rule - in disorders of secondary hemostasis

joint and muscle bleeding

where is the most common site for a saccular aneurysm (berry)?

junction of communicating branches with the ACA - reason being that the communicating branches lack a internal elastic lamina and smooth muscle.

what are activating mutations for adenocarcinoma

k-ras, EGFR, ALK

CYP 450 inhibitors

ketoconazole, macrolides (except azithromycin), grapefruit, acute alcohol, quinidine, ciprofloxacin, indinavir (protease inhibitors), cimetidine, sulfonureas *most will decrease metabolism of the drug thus increasing its active confirmation resulting in toxicity.

Sirolimus (Rapamycin) use

kidney transplant rejection PROPHYLAXIS

Basiliximab

kidney transplant rejection prophylaxis

pulmonary bacterial infections in alcoholics

klebsiella bacteroides prevotella fusobacterium peptostreptococcus *remember that lung abscesses are most frequently caused by a POLYMICROBIAL infection involving anaerobes*

wernicke encephalopathy - feature

korsakoff syndrome is associated with damage to anterior and dorsomedial thalamic nuclei. --> results in *confabulation* -anterograde amnesia -*foci of hemorrhage and necrosis in the mamillary bodies and periaqueductal gray matter are found on autopsy*

Enteroendocrine cells containing argentaffnic of argyrophilllic granules

kulchitsky cells - secrete serotonin, located in gastrointestinal tract and respiratory tree and have been implicated in the development of small cell carcinoma

Turner syndrome - mode of fertilization

lacks ovaries but has a uterus --> thus in vitro fertilization will work -main role of progesterone - maintain pregnancy

major adverse effect of metformin

lactic acidosis (increases lactate via increased anaerobic glycolysis) - metformin also inhibits gluconeogenesis. must monitor serum creatinine.

What pathology results in damage to the internal capsule

lacunar infarcts as seen with intraparenchymal stroke. --> lenticulostriate arteries "arteries of stroke" --> will find *pure motor or pure sensory deficits* rare to find hemibalismus - thats associated with subthalamic nucleus.

Piriformis muscle - anatomy

landmark muscle in the gluteal region. On the superior edge of the muscle is the location of the superior gluteal vessels. On the inferior aspect of the muscle is the location of the inferior gluteal (a+v) internal pudendal vessels (A+V), sciatic nerve, nerve to obturator internus and pudendal nerve.

Type Ad fibers

large myelinated sharp pain

differ condyloma lata from condyloma accuminata

lata = flat accuminata = warty

age related macular degeneration

leading cause of blindness in industrialized countries -degeneration of central retina -dry = subretinal drusen deposits or pigment changes -wet = abnormal blood vessels with subretinal fluid/hemorrhage, gray subretinal membrane or neovascularization. -Dry AMD (gradual vision loss in one or both eyes) will progress to wet AMD (more common, with acute vision loss over a period of days to weeks)

Lambert vs myasthenia - clinical symptoms

leg involvement is more severe and common in myasthenia gravis

all of the -ella's require cystine

legionELLA, francisELLA, brucELLA, pasturELLA

biofilms

legionella pseudomonas (otitis externa - malignant) staph epidermis cis2-decenoc acid (candida) strep mutans staph aureus (when Beta lactam is used) Proteus

what is the most common tumor in females

leiomyoma --> presents with multiple discrete tumors, increase incidence in black women. Benign smooth muscle tumor --> malignant transformtaion is RARE and does not progress to leiomyosarcoma. Look for a whorled pattern of smooth muscle bundles with well demarcated borders. Causes abnormal uterine bleeding (heavy during periods because responds to estrogen and will decrease in size with menopause). can lead to iron deficiency anemia.

Juvenile polyps

less than 3cm pedunculated present in rectum rectal bleeding red lesions with cystic spaces, filled with mucin and inflammatory debris

azathioprine adverse effects

leukopenia, anemia, thrombocytopenia

drugs that decrease FSH and LH via GnRH agonist - continuous

leuprolide, goserelin, nafarelin, and histrelin

catachol - o - methyltransferase inhibitors should only be used with what drugs to be effective?

levodopa

which drug should never be used to treat EPR

levodopa - because will exacerbate psychosis

what drugs are contraindicated in drug induced parkinsons?

levodopa/carbidopa and bromocriptine (D2 agonist - both will exacerbate.)

what is the treatment for amiodarone induced hypothyroidism?

levothyroxine

Class 1 b drugs

lidocaine and mexiletine

CMV esophagus

linear lesions

Failure of thyroid migration can result in what pathology?

lingual thyroid - can cause hypothyroidism (lethargy, dry skin, constipation, macroglossia, umbilical hernia, hypothermia and prolonged jaundice).

difference between lipoma and liposarcoma

liposarcoma are most common soft tissue sarcoma in adults, they present as painful masses and have many round cells with multiple mitosis. Cells have a round clear cytoplasmic vacuoles scalloping the nucleus. Nonmobile. Vs Lipomas - are mobile subcutaneous nodules, nontender, soft, mature fat cells without pleomorphism

How is lithium excreted by the body?

lithium is excreted by the kidneys and is handled like sodium with filtration and resorption (>60%) in the PCT. Thus drugs that change the GFR can lead to increased proximal tubular absorption of sodium and lithium --> leading to toxicity.

insertion of a needle below the 9th rib at the middle axillary line on the right may cause what injury?

liver injury.

pneumonia over whole lobe

lobar pneumonia

amylin

localized amyloid endocrinopathy (diabetes type 2)

hypertensive arteriolar sclerosis - presentation

long standing hypertension predisposes to occlusion of small perforating branches of major cerebral arteries --> lacunar infarcs occur in basal ganglia, internal capsule, and *thalamus* lenticulostriate arteries --> thalamus

clinical hint - tyramine reaction

look for depressed patient who has a hypertensive crisis after a wine party - or eats cheese. MAOi for depression and add the cheese and you have yourself a problem.

How can you determine whether a clot is post mortem or from a thrombus?

look for lines of zahn which are characteristic of a thrombus (RBCs interspersed between "lines" of fibrin and platelets)

Difference between measles (rubeola) and german measles (rubella)

look for postauricular lymphadenopathy which is strongly associated with rubella

what is a intermediate acting benzodiazepine

lorazepam

what is atelectasis

loss of lung volume secondary to alveolar collapse - leads to decreased oxygenation of blood and ventilation perfusion balance becomes 0 (d/t presence of perfusion without ventilation)

what are signs of liver failure?

low albumin levels prolonged PT note that high AST is a marker of hepatocellular injury. High transaminase levels do not reflect liver function and do not predict outcomes. *albumin level and prothrombin time are GREATEST indicators of prognostic significance in liver damage/failure.*

causes of pre renal failure

low perfusion d/t CHF, hypovolemia, shock *will decrease both urea and creatinine* BUN/Cr --> Increase BUN and Increase Cr BUT low velocity in tubule further allows more UREA to be reabsorbed - therefore increasing BUN further.

midgut derivatives

lower duodenum, small intestine, ascending colon, and proximal 2/3 of the transverse colon

whats the number one cause of appendicitis?

lumen obstruction - most common obstructing agents are fecaliths. other agents are hyperplastic lymphoid follicles, foreign bodies and tumors that may cause obstruction.

Bronchioalveolar carcinoma is a subtype of what cancer?

lung adenocarcinoma

digital clubbing

lung disease = lung cancer (large cell carcinoma), CF, TB, bronchiectasis, pulmonary hypertension heart diseases = cyanotic congenital heart diseases (5 T's = tetralogy of fallot, tricuspid atresia, truncus arteriosus, transposition of great arteries, total anomalous pulmonary venous connection.) Other = IBD (crohns, ulcerative colitis, hyperthyroidism

cancer paraneoplastic syndrome - *paraneoplastic cerebellar degeneration* is associated with what cancers?

lung, breast, ovary, uterus, and lymphoma this paraneoplastic syndrome results in a autoimmune process resulting in the production of antibodies = Anti-Yo (ovary and breast), anti-P/q (lung), and anti-Hu (lung). The antibodies result in cross reaction with neurons causing perkinje cell degeneration in cerebellum. Patients will present with limb ataxia and truncal ataxia, lack of coordination, dysarthria, and nystagmus.

Pt with radial masectomy and radiation is at risk of developing what 10 years later?

lymphangiosarcoma. persistent lymphedema with chronic dilation of lymphatic channels predisposes to the development of lymphangiosarcoma, which is a neoplasm of endothelial lining of lymphatic channels.

chlamydia - causing LGV

lymphogranuloma verum 2 and 3 --> inguinal bubo = painful enlarged inguinal masses

HCV

lymphoid aggregates within the portal tracts and focal areas of macrovesicular steatosis

enyzme deficiency in pompe's

lysosomal a1,4-glucosidase

Fragile X syndrome - clinical

macroorchidism (also seen in myotonic dystrophy), large jaw, mental retardation (second most common cause after downs), patients can develop diabetes, and autism

GMCSF is produced by

macrophages, T cells, NK cells, mast cells, endothelial cells, and fibroblasts

what is the most common cause of blindness in the elderly

macular degeneration.

osmotic diuretic - mannitol facts

main site of action is at the PCT - will increase osmolarity thus decreasing water reabsorption - thus increase fluid water loss. Will find increase in urine volume. Used for increased ocular pressure (glaucoma) decreased intracerebral pressure, and oliguric states (rhabdomyolysis). *Rhabdomyolysis is a adverse effect of STATINS, thus mannitol can be used in conjunction with statins to increase myoglobin clearance.*

ATN - stage 2

maintenance stage - oliguric stage --> last 1-3wks will find decreased urine output, fluid overload (weight gain and pulmonary vascular congestion) increasing BUN/Cr, hyperkalemia (peaked T waves, wide QRS, fatal arrhythmias) metabolic acidosis (high anion gap, due to retention of hydrogen ions and anions = sulfate, phosphate, and urate). will also see hyponatremia, hypocalcemia, hyperphosphatemia, and hypermagnesium *characteristic muddy brown casts* Urinalysis *low urine osmolarity <350, high urine sodium >30 and high urinary fractional sodium excretion FeNa>1)*

Protein M in strep pyogenes - ROLES (4 roles)

major virulence factor only for pyogenes. -Inhibits phagocytosis -Inhibits activation of complement -Is cytotoxic for neutrophils -Mediates bacterial attachment

a fetus with 46 XY with normal leydig cells but absence of sertoli cells - what will childs phenotype be? Why?

male internal and female internal genitalia and female external genitalia. Reason - Sertoli cells contain 5 alpha reductase which catalyzes the reaction of testosterone from leydig cells into dihydrotestosterone which is responsible for secondary sex characteristics. This explains the female external phenotype. The fetus will have both female and male internal genitalia because Mullerian inhibiting factor was never secreted from the sertoli cells (responsible for apoptosis of paramesonephric ducts). The fetus will also contain male internal genitalia because the presence of testosterone from the leydig cells will stimulate proliferation of mesonephric duct (wollfian duct).

Osteogenic sarcoma - epi

males 10-25 years, however if seen in older patient then typically secondary to paget's disease of the bone.

bronchioalveolar carcinoma - morphology = columnar mucin-secreting cells that fill alveolar spaces without invading the stroma or vessels (is this benign or malignant)?

malignant

clinical features of serotonin syndrome

malignant hyperthermia muscle rigidity myoclonus due to overstimulation of 5ht1 and 5Ht2

what are patients with Ataxia telangiectasia at risk to develop

malignant lymphomas

Characteristics of osteosarcoma

malignant osteoid radiographic findings = "sunburst" appearance = spiculated pattern from calcified malignant osteoid) and "codman triangle" tumor that results in lifting of the periosteum (seen in adjacent soft tissue). Commonly metastizes to the lung (sarcoma --> hematogenous).

scurvy in the US is most likely seen in what demographic?

malnourished individuals (homeless, IV drug abusers, and alcoholics) Decreased vitamin C (required for proline hydroxylation)

what provides general sensation to anterior 2/3 of tongue?

mandibular branch of trigeminal nerve (V3)

Ultrasound vs radionuclide biliary scan

many asymptomatic individuals have gallstones inside gallbladder, thus a finding of gallstones in gallbladder with symptoms is only *suggestive* of acute cholecystitis. To make a definitive diagnosis of acute cholecytitis by ultrasound will need to look for distention of gallbladder wall, presence or pericholic fluid inside gallbladder or even positive murphy sign (ultrasound technician pressing on gallbladder with probe and eliciting pain). A Radionuclide biliary scan (HIDA) - pt ingests dye and views path to gallbladder --> if the gallbladder does NOT fill and an obstruction if seen in cystic duct or common bile duct then its indicative of acute or chronic cholecystitis.

Tryptase - released from both basophils and mast cells

measures degree of cell death that is occurring - marker for type 1 HS

what is the treatment of enterobias

mebendazole or albendazole

ezetimibe - facts

mechanism = prevents intestinal absorption of cholesterol, results in decrease LDL side effect = gastrointestinal distress *used with statin to decrease cholesterol* - synergistic activity

cephalic stage

mediated by cholinergic and vagal mechanism, is triggered by thought, sight, smell and taste of food. *stimulates release of HCL*

The gastric phase

mediated by presence of gastrin which is triggered by receptive relaxation of fundus of stomach.

if a young patient presents with fasting hypoglycemia and low blood ketones - look for pathology of beta oxidation or ketone synthesis - whats the most likely cause

medium chain acyl CoA dehydrogenase deficiency -->presents with symptoms of nausea, vomiting, and hypoglycemia.

nests of polygonal cells with congo red positive deposits - thyroid cancer

medullary carcinoma of the thyroid seen in MEN 2

MEN2b

medullary carcinoma of thyroid pheochromocytoma marfanoid habitus/mucosal neuromas

MEN 2a

medullary carcinoma of thyroid pheochromocytoma parathyroid

MEN2a

medullary carcinoma of thyroid pheochromocytoma pituitary

whats the diagnosis? tumor in child, cells are small and poorly differentiated, scant cytoplasm (increase N:C ratio) high mitotic index, classic homer wright rosettes, and tumor is midline in cerebellum.

medulloblastoma

barbituates, carbamazepine, and phenytoin lead to what kind of anemia?

megaloblastic - d/t folate deficiency - reason being --> these drugs inhibit GI conjugases which decreases folate absorption in jejunum.

TMP-SMX A/E

megaloblastic anemia, Steven Johnson syndrome and Toxic epidermal necrolysis

Psammoma bodies

meningioma, papillary carcinoma of thryoid, papillary renal cell carcinoma, papillary serous cystadenocarcinoma

associated tumors with neurofibromatosis I

meningiomas, astrocytomas, gliomas, pheochromocytomas

what are the symptoms of adenomyosis?

menorrhagia (heavy period), dysmenorrhea (painful period), large uterus (due to smooth muscle hypertrophy and hyperplasia in response to ectopic endometrial glandular tissue).

what are findings in PKU 1

mental retardation, low IQ, delay in developmental milestones, seizures (if Phe levels stay elevated), *mousy odor* to urine due to phenylalanine*, will also find decreased pigmentation (due to phe inhibiting tyrosinase - thus decreased melanin production - look for hypopigmentation of skin, hair, eyes, and brain nuclei (substantia nigra, locus ceruleus ect.)

homocystinuria clinical features

mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation, and atherosclerosis causing premature stroke and myocardial infarction. diagnosis is based on a positive nitroprusside cyanide test.

osteblasts are from what cell origin

mesenchymal bone cell Marker for activity = ALP produces angiopoietin will inhibit hematopoiesis (opposite to EPO)

negative symptoms are thought to be due to hypoactivity of (choose one: mesolimbic or mesocortical)

mesocortical

positive symptoms are due to overactivity of (choose one: mesolimbic or mesocortical)

mesolimbic

positive symptoms in schizophrenia are due to overstimulation of what dopamine pathway

mesolimbic

Dopaminergic pathways

mesolimbic-mesocortical nigrostriatal tuberoinfundibular

Osteosarcoma - location

metaphysis of distal femur and proximal tibia. Most common primary bone cacner.

what is the resistance mechanism of bacteria against macrolides

methylation of the 23s rRNA increased efflux of the drug production of esterases that hydrolyze drug

how does methyldopa (central A2 agonist) result in normocytic anemia?

methyldopa alters Rh antigens on surfaces of RBCs, IgG autoab develop against Rh antigens, and splenic macrophages end up phogocytosing and destroying RBCs. (Type II HS)

what class of drug is theophylline

methylxanthine PDE 3 inhibitor nonselective adenosine receptor antagonist

thiazide drugs

metolazone, hydrochlorothiazide, and indapamide

cocaine teratogenic

microcephaly low birth weight renal agenesis --> oligohydramnios intestinal atresia GU abnormalities

anti-myeloperoxidase

microscopic polyangiitis

Abetalipoproteinemia deficiency

microsomal TAG protein - thus no production of beta proteins - will find decreased ApoB100 and ApoB48

tramadol

mid to low potency mu agonist and SERI and NERI - can be DOC for neuropathic pain -if given with a mao can result in serotonin syndrome.

Thoracentesis

midclavicular - above 7th rib midaxillary - above 9th rib paravertebral - above 11th rib

epidural hematoma - damaged vessel

middle meningeal artery branch of maxillary artery

Juxtaglomerular apparatus - histology

modified smooth muscle

whats the role of thrombomodulin?

modulates thrombin so that it will activate protein C instead of converting fibrinogen to fibrin and stabilizing the clot via cross linking. remember that protein C inactivates factors 5 and 8.

what vessel pathology is characterized by medial band like calcification

monckeberg - benign finding

Basiliximab mechanism

monoclonal antibody blocks IL-2R

IFNa is produced by

monocytes, macrophages, B cells, and NK cells.

IL-1 produced by

mononuclear phagocytes

atypical antipsychotics MoA

more effective at decreasing negative symptoms - therefore act within mesocortical pathway

Loading dose

more rapidly achieve effective blood levels. -if doses are administered at each t1/2 of a drug and the minimum effective concentration is eq to CSS then the loading dose is TWICE the amount of the MAINTENANCE dose. LD= Cs x Vd

what are findings in PKU 2

more severe CNS symptoms, decreased production of *serotonin, dopamine, and catecholamines* will find same findings as PKU 1

nontypable H. Influenza

more than 90% of H.influenza stains isolated from middle ear aspirates of infected children are nontypable - meaning that this bacteria does not have a capsule - thus vaccine fails to protect.

weak bases

morphine, local anesthetics (-caines), amphetamines, and PCP

most cases of turner syndrome are due to

mosaicism

RTA 4

most common hyperkalemia normal anion gap metabolic acidosis *lack of responsiveness to aldosterone* decrease ammonia synthesis due to hyperkalemia (prevents formation - by altering intracellular pH (alkalosis)

fibroadenoma

most common benign tumor of breast responds to estrogen (thus increases in size during pregnancy) mobile and spherical

fibrocystic disease

most common cause of *palpable nodular* masses in the breast (just palpable is fibroadenoma), lesions are multiple and painful with tenderness maximal during the premenstrual phase of the cycle.

HSV 2

most infections are below waist occur due to reactivation of a latent infection within s2, s3, s4 DRG's.

pancoast tumor is typically what kind of tumor?

most likely adenocarcinoma

Turner syndrome

most likely due to nondisjunction during mitosis of early embryonic period.

Maternal PKU (findings)

mother lacks proper dietary therapy during pregnancy - findings in infant are microcephaly, mental retardation, growth retardation, and congenital heart defects.

whats the cause of pseudotumor peritonei?

mucinous cystadenocarcinoma

Coal workers pneumoconiosis

multiple discrete nodules prominent in upper lung zones

Cardiac embolism - presentation brain

multiple infarcts within different vascular territories

Natalizumab clinical use

multiple sclerosis and crohns

Cytomegalovirus colon

multiple ulcers and mucosal erosions cytomegalic cells (Owls eye - intranuclear basophilic)

systemic sclerosis (scleroderma)

multisystem disease that is characterized by vascular dysfunction, excessive production of COLLAGEN that primarily targets the skin and visceral organs. Two types Limited = CREST and diffuse systemic sclerosis.

before prescribing isoretinonin (accutane) to a female on OCP's WHAT must you check - this is very common!

must check b-HCG levels. Why? Reason being that vitamin A has severe teratogenic affects, and also reduces efficacy of OCP's. Thus patients must also be informed that they should use an additional form of birth control during this time.

genetic (locus) heterogeneity

mutations at different loci (genes) cause similar phenotypes (example is osteogenesis imperfecta - mutations in either chromosome 17 or 7 results in phenoytpe of OI)

side effects of statins

myalgia, myopathy (check creatine kinase) *rhabdomyolysis* hepatotoxicity (check LFTs) (AST/ALT) metabolized by CYP450 thus inhibitors will increase statin to toxic levels.

carbolfuchsin stain for what bacteria

mycobacterium tuberculosis Ziehl Neelsen acid fast stain

guillian barre

mycoplasm, campylobacter, influenza - etiology HLA DBQ1 look for clinical hint - prodrome of inflammatory diarrhea Hypersensitivity Type IV = T cell and B cell mediated Antibodies to GM1 gangliosides --> "molecular mimicry" (note GM1 gangliosides also seen in MS) Inflammation of endoneurium symmetrical ascending paralysis *albuminocytologic dissociation* (increase in protein without an increase in cells) = normal white blood cell count with an increase in protein Treatment Baclofen and IFNbeta, natalizumab (human monoclonal antibody)

what are the three bacteria that do not have peptidoglycan layer

mycoplasma, chlamydia

Pt presents with S. pneumonia, has a great deal of green sputum - whats cause for pigmented sputum?

myeloperoxidase (azurophilic) granule.

coxsackie is implicated in causing

myocarditis, and type 1 diabetes

Differ NMS and Serotonin syndrome

myoclonus in serotonin *rigidity* and bradykinesia in NMS

cataplexy and sleep paralysis are suggestive of what disease

narcolepsy

what are the adverse effects of bile acid sequestrants?

nausea, bloating, cramping, decreased absorption of digoxin, warfarin and fat soluble vitamins gallstone formation

myopia

nearsighted eyeball is longer point at which light crosses is shorter than retina improves with age - due to decrease with elastin

small cell carcinoma - histology

neoplasma of neuroendocrine cells, *kulchitsky cells* which are small dark blue cells (high nuclear to cytoplasm ratio)

Acyclovir A/E

nephrotoxicity - monitor BUN/Cr

Cafe au lait spots originate from what structures (neuroectoderm or neural crest?)

neural crest -->neurofibromas are tumors of schwann cells. *described as skin colored or pink nodules with a rubbery texture that exhibit pathognomonic "buttonholing"*

posterior pituitary develops from what embryological structure?

neural tube

Whats the diagnosis? most common extracranial solid tumor in children, small round blue cell, *neuropil* stains with NSE (neuron specific enolase), chromogranin, synaptophysin, and S100 POSITIVE. elevated urinary levels of HVA and/or VMA. Most important biologic marker is n-myc on chromosome 2.

neuroblastoma

neurofibromatosis I (von reckenhausen)

neurofibromas, cafe au lait spots, lisch nodules (eye), pseudoarthritis, scoliosis, chromosome 17

autosomal dominant disorder characterized by neurofibromas (plexiform and solitary), optic gliomas, pigmented nodules of iris (lisch nodules) and cutaneous hyperpigmented macules (cafe au lait spots)

neurofibromatosis type 1 chromosome 17

autosomal dominant, bilateral acoustic neuromas, multiple meningiomas, gliomas, ependymomas of spinal cord

neurofibromatosis type 2 chromosome 22

lish nodules

neurofibromatosis type I

what are derivatives of neuroectoderm?

neurohypophysis retina pinneal gland preganglionic autonomic fibers astrocytes ependymal cells choroid plexus

pt has an intracranial mass detected on CT scan. Biopsy reveals neoplastic cells that stain positive for synaptophysin and negative for GFAP. These neoplastic cells most likely originate from the same precursor tissue as which of the following?

neurons (other answer choices were astrocytes, oligodendrocytes, ependymal cells, and meningothelial cells)

Isoniazid A/E

neuropathy hepatoxicity inhibits CYP450 SLE-Like syndrome metabolized by N-Acetyltransferase (slow acetylators = high concentration of drug)

differ charcot joints in neurosyphillis and diabetes

neurosyphillis will be of KNEE and in diabetes will be of FOOT

charcot joints - seen in syphillis and diabetes, alcoholics (damage to nerve by thiamine)

neurotrama to joints neuropathies that prevent feeling of joint position - microtrauma, repeatedly, weight bearing joints --> infections --> necrotizing lesions --> amputation

Adverse effects of ticlopidine and clopidogrel

neutropenia, *mouth ulcers* and fever.

maternal hypothyroidism

newborn develop cretinism with severe MR this is bc thyroid hormone is necessary for normal development of the brain.

maternal SLE

newborn may develop heart block if mother has anti-Ro (SS-A)

whats treatment for type IV hyperlipoproteinemia

nicotinic acid or fibrates

whats the treatment following a SAH to prevent arterial vasospasm?

nifedipine

what is treatment of trypanosoma?

nifurtimox

difference between b12 def and folate

no subacute combined degeneration in folate due to NO increase in methylmalonic acid.

primary silicosis

nodular densities and eggshell calcifications of hilar nodes

Mosaicism

nondisjunction of chromosomes during mitosis in the early embryonic period.

cryptosporidium colon

nonulcerative inflammation - does not invade -basophilic clusters seen on surface of mucosal cells

lab findings in HUS and TTP

normal PT and PTT low platelets schistocytes increased megakaryocytes in bone marrow

what are clinical features of Xeroderma pigmentosum

normal at birth photosensitivity increased pigmentation increased risk for SCC, basal cell carcinoma, and melanoma

liver cirrhosis

normal lobular architecture of the liver is replaced with regenerative spherical nodules separated by bridging fibrous septae. These are composed of proliferating hepatocytes. What are mediators of cirrhosis -hepatocyte damage - results in proliferation and forms spherical nodules -stellate cells - will differentiate into myofibroblast upon injury to liver

lab values in androgen insensitivity

normal male levels of DHT and testosterone slight increase in LH slight increase in estradiol

huntington protein

normally inhibits apoptosis by inhibiting caspases interacts with CREB (TF thats a leucine zipper) - cAMP depdent increases BDNF interacts with tubules and clathrin for endocytosis

esmolol, propranolol, acebutolol

note esmolol is only used IV.

Entamoeba histolytica colon

numerous discrete, flask shaped ulcerative lesions -trophozoites containing red blood cells

Cystericosis

obtained from fecal oral route (ingestion of eggs) - aslo causes tape worm but thats due to ingestion of raw uncooked meat (scolex attaches to intestine) which results in tapeworm.

leptospirosis

occurs following exposure to infected animal urine, no cutaneous manifestations, however can lead to Weil syndrome (jaundice, renal dysfunction, thrombocytopenia, and bleeding)

Page'ts disease of bone (osteitis deformans) - EPI

occurs in men > 50 yrs associated with paramyxovirus infection of osteoclasts targets: pelvis, skull, and femur

Pre-mRNA to mRNA

occurs in nucleus --> involves 5' cap (methylguanosine), splicing of introns, and 3' PolyA tail.

Allergic contact dermatitis (type IV HS)

occurs when antigens at the epidermal surface are selected by langerhans cells (APC- dendritic cell) and carried into draining lymph nodes where they are presented by langerhans cells to naive CD4 T cells. These Cd4 T cells generate Th1 memory cells whereas others become effector CD8 T cells. Upon reexposure - Cd8 T cells will respond and release cytokines/perforins.

what are some causes of superior mesenteric artery syndrome?

occurs when aortomesenteric angle critically decreases secondary to diminished mesenteric fat (low body weight or rapid weight loss), pronounced lordosis, or surgical correction of scoliosis (later being due to decreased mobility of SMA)

Polyploidy

occurs when more than two complete sets of homologous chromosomes exist within an organism or cell. Ex. hydatiform mole

what are four atypical antipsychotics

olanzapine, clozapine, risperidone, quetiapine (Qthepine)

two cells that will release glutamate

olivocerebellar and granular cells. remember that olivocerebellar are entry tracts and granular cells are inherent to cerebellum.

fourth arch

on left = aortic arch on right = proximal party of subclavian artery associated nerve = superior laryngeal of vagus nerve

b2 microglobulin - Antigen presentation - part of MHC class 1 domain. Alpha 1, 2, and 3 + b2 microglobulin.

once inside the ER, the peptides assemble with transmembrane polypeptide and b2 microglobulin.

acute rejection

one week to four weeks -T cell mediated sensitization against graft MHC antigens -Prevent reaction with with calcineurin inhibitors such as cyclosporine or tacrolimus

thiazides cause hyperglycemia... how?

open ATP dependent K+ channels - thus decrease potential for insulin to be released.

Women taking pain meds develops RUQ pain --> what drug did she take?

opioid analgesics like morphine can cause contraction of smooth muscle cells in sphincter of oddi leading to biliary colic

What is the leading cause of injury related mortality in adults - exceeding that caused by motor vehicle collisions?

opioid pain relievers

Role fo C3b

opsonization and phagocytosis clearance of immune complexes

Leber hereditary optic neuropathy - eye

optic atrophy

HIV TORCH transplacental, birth canal, OR BREAST FEEDING

oral thrush recurrent bacterial infections intracranial calcification - periventricular failure to thrive

Tangiers disease (autosomal recessive)

orange tonsils low serum HDL early degradation of ApoA (required for LCAT) thrombocytopenia, anemia, and GI disorders hepatosplenomegaly, coronary artery disease defect in ATP binding cassette

denosumab use

osteoporosis via inhibition of osteoclast maturation --> thus decreased bone resorption.

intracranial bleeding can be a symptom of severe thrombocytopenia

other symptoms are petechiae, purpura (>3mm), ecchymoses (>1cm), easy bruising. Note petechiae is a sign of thrombocytopenia (quantitative disorder NOT qualitative)

RBC abnormalities in folate deficiency

ovalocytosis, macrocytosis - megaloblastic due to decreased synthesis of purines and thymidine. will also show hypersegmented neutrophils in blood smear.

suspensory ligament of the ovaries contains...

ovarian artery and vein. - during ligation of ovarian vessels during oophorectomy the ureters are at risk

CA-125 marker

ovarian cancer *surface epithelial ovarian tumors* (serous, mucinous, clear, brenner, endometriod)

broad ligament contains

ovaries, fallopian tubes, cardinal ligament, and round ligament of the uterus

phase I reactions

oxidation, reduction, or hydrolysis

ionization of drugs

pH < pka = acidic pH > pka = basic pH = pka --> 50% ionized, 50% nonionized *drugs are easily cleared when in ionized form*

patient develops pulmonary embolism - what is pH, PaC02, and Pa02

pH >7.4 (respiratory alkalosis), PaC02 = <40 (due to hyperventilation), and Pa02 around 70mmHg

HSV 2 characteristics

painful ulcer, presence of vesicles on the mucous membranes of genitals that develop into *shallow ulcers* Lesions are painful. *histologically, will find multinucleated giant cells and large INTRANUCLEAR (not intracytoplasmic) inclusion bodies that are eosinophilic.

methanol poisoning symptoms

paint thinner, photocopying fluid, windshield washing fluid, home brewing wood alcohol symptoms - *dilated pupils with hyperemia of optic disc and retinal edema* gastrointestinal distress and loss of consciousness, coma, and shortness of breath.

what is courvoiser sign?

palpable nontender gallbladder

MEN 1

pancreas pituitary parathyroid

Mammillary bodies are part of what brain structure?

papez circuit --> limbic system that is involved in the cortical control of emotion and memory. (structures of papez circuit)

repair of tissue is mediated by what type of communication?

paracrine signalling

what cancers in MEN 1

parathyroid pituitary pancreas

paracentric inversion

parent is normal, in mothers can lead to high rate of abortions.

First aortic arch

part of maxillary artery (branch of external carotid) associated nerve = trigeminal

Buspirone

partial agonist of 5HT1a receptor - treats generalized anxiety disorder - and is unique because it has minimal to no hypnotic, sedative, or euphoric effects. Thus, this drug is useful in patients with a history of abuse of anti-anxiety drugs.

Vitiligo path (name 5 associated dieases)

partial or complete loss of epidermal melanocytes lesions are flat well circumbscribed macules and patches of absent pigment. Autoimmune --> circulating melanocyte antibodies *associated with autoimmune disorders = tyoe I DM, pernicious anemia, autoimmune thyroiditis, graves disease, autoimmune hepatitis, addisions disease)

where are the chromosomes derived from in a complete mole?

paternally derived; karyotype is 46 XX (more common) or 46XY

bronchiectasis

pathophysiology = abnormal dilation of the medium and smaller airways due to mucous plug - infection will be distal to the plug.

sickle cell patient presents with acute bacterial infection, he is 35 years old, becomes hypotensive and dies. whats most likely infecting organism?

patient develops Asplenism during early life d/t recurrent vascular infarctions. This places the patient at risk to develop infections with encapsulated bacteria *most common are steptococcus pneumoniae and Haemophilus* -reason being - we all have some degree of strep pneumo in our lungs at one time or another - we are asymptomatic bc our immune system is constantly suppressing - however once we lose our spleen then we become more susceptible to these bacteria. Remember that staph aureus would be from a breach in the skin, or some invasive modality which would preclude a patient to an infection - otherwise go for step pneumo.

what is a "empty can supraspinatus test" - 90% specificity

patient is asked to abduct his arms to 90 degrees and flex them to 30 degrees with thumbs pointing to the floor - pressure then applied downwards on arm --> if pain elicited then strongly correlates to a supraspinatus injury.

50% (MC) of kidney stones are associated with idiopathic hypercalciuria

patient will have normal calcium levels, but with increase calcium in urine. *calcium oxolate*

displacement defense mechanism - immature

patient will redirect emotions from the person or object that is causing the negative emotions to a more acceptable but still inappropriate person or object.

Blood transfusion of packed RBCs

patients are at risk of paresthesias due to calcium chelation by citrate. Packed RBCs are stored with citrate for anticoagulation!

female pseudohermaphroditism

patients are genotypically female, but have ambiguous genitalia. most common cuase is adrenogenital syndrome due to 21 or 11 hydroxylase deficiency

male pseudohermaphroditism

patients are genotypically male (XY with testes) and phenotypically the external genitalia are ambiguous, or completely female (ex. androgen insensitivity syndrome) and 5a reductase def.

summary of achondroplasia

patients have a mutation on chromosome 4 that results in defective Fibroblast growth factor 3 which inhibits collagen type 2 (cartilage) proliferation. This results in short stature, frontal bossing, and shortened extremities.

what will jugular venous pulse look like for constrictive pericarditis

patients present with dyspnea, chronic edema, and ascites *rapid Y descent that becomes deeper and steeper during inspiration*

restrictive lung disease

patients with stiff lungs (d/t fibrosis) which is characterized by an increase in elastic resistance, the work of breathing is MINIMIZED when the respiratory rate is high and the tidal volume is low. Therefore, rapid and shallow breaths are favored in diseases that increase elastic resistance.

types of ECG changes in STEMI

peaked T during acute MI (either within an hour or during)

Hyperkalemia

peaked T waves wide QRS slow heart rate loss of P wave severe = sine wave pattern which manifests as ventricular fibrillation (peaked T waves fuse with wide QRS)

how does polymyalgia rheumatica present?

pelvic and shoulder girdle pain morning stiffness fatigue, fever, weight loss

anti desmogleins seen in what pathology

pemphis vulgaris

anti desmoglin

pemphis vulgaris

what is the antidote for copper, aresenic, and gold?

penicillamine

yersinia enterocolitica treatment

penicillin

treatment for syphillis

penicillin G - benzathine pencillin

what is the most common autopsy finding in SIDS

petechiae on the visceral and perietal pleura, epicardium, and thymus.

neisseria meningitidis - route of infection

pharynx --> blood --> choroid plexus --> meninges

h. influenza - route of infection for meningitis

pharynx --> lymphatics --> meninges

pseudohermaphrodite

phenotype (external appearance) and genotype (true genetic sex) do not match.

Phenylketonuria I is deficient in this enzyme

phenylalanine hydroxylase

MEN 2b

pheochromocytoma medullary carcinoma thyroid marfinoid habitus and oral gangliomas (mucosal)

RTA type II what happens to phosphate

phosphaturia -due to damage - vitamin D does not have an effect - thus patients develop vit D resistant rickets

Cilostazol and dipyradamole - MoA

phosphodiesterase inhibitors thus increase cAMP - decreases aggregation

glucagon, cortisol, catecholamines - how does it inhibit insulin effects

phosphorylates serine on IRS - inhibit insulin effects

nucleoside antiviral drugs require...

phosphorylation into nucleotides to become active. these include: acyclovir, valacyclovir, famciclovir, ganciclovir.

mechanisms of resistance of aminoglycosides

phosphorylation of hydroxyl group adenylation acetylation

what is the mechanism behind opioid tolerance?

phosphorylation of opioid receptors by protein kinase

Bloom syndrome clinical features

photosensitivity short stature erythema telangiectasia *defective DNA helicase* patients predisposed to lymphoproliferative and gastrointestinal malignancies

Whats the diagnosis? Cystic tumor in cerebellum, biopsy reveals neoplasm comprised of spindle cells that have hair like glial processes and are associated with microcysts. Cells are mixed with rosenthal fibers and granular eosinophilic bodies.

pilocytic astrocytoma

most common benign neural tumor in children

pilocytic astrocytoma

Parinaud syndrome

pinneal gland, midline structure located dorsal to the superior colliculus and between the thalamic bodies. Secretes melatonin in response to darkness or sympathetic stimulation. *patients experience upward gaze palsy, absent pupillary light reflex, failure of convergence and wide based gait* role of superior colliculi = *visual reflex center* upward gaze role of inferior colliculi = hearing Will also find compression of EW nucleus - which results in absent pupillary light reflex, movement disorders from occulomotor and trochlear.

Conjugation

plasmid transfer - direct contact (sex pilus) HFR plasmid will insert between highest expressed and lowest expressed with highest expressed being expressed first (its circular dna so origin of replication travels in one direction)

intracellular parasites

plasmodium and toxoplasma

stage 3. platelet aggregation

platelet aggregation at site of injury via gpiib/iiia using fibrinogen as linking molecule --> results in formation of weak platelet plug --> needs to be stabilized by weak platelet plug.

Step 3. platelet degranulation

platelets release ADP (dense core granules) and TXA2 (derivative of platelet cycloxygenase), will then express GPIIb/IIIa (ADP is essential for expression)

Dose - Response curve

plot percentage of population responding to a specified drug effect vs dose or log dose. can be used to measure the ED50 or (effective dose in 50% of the population)

spontaneous pneumothorax definition

pneumothorax in pt without pre-existing pulmonary disease and not caused by trauma or barotrauma (diving ext).

what vasculitis has a morphology of transmural inflammation with fibrinoid necrosis?

polyarteritis nodosa

What are adults likely to develop from infection by rubella?

polyarthritis and polyathralgia

budd chiari syndrome *hepatic vein thromboses* associated with

polycythemia vera SLE

Osteomyelitis in patient with diabetes mellitus

polymicrobial (often pseudomonas or serratia) continguous spread from infected food ulcer is most common (not hematogenous spread) effects bones of the feet most commonly

what pathology is associated with temporal arteritis?

polymyalgia rheumatica

neonate presents with hepatomegaly and cardiomegaly --> biopsy shows accumulation in lyososomes

pompe's disease

enterotoxin - staph aureus

pore forming toxin heat stabile 2-6 hrs pastries, butter, diary

lidocaine is most commonly used to treat

post MI and digoxin toxcicity.

serine and threonine are involved with this process in golgi apparatus

post translational modification; O-glycosylation

fibromyalgia possible etiology

postulated to be produced by a genetic predisposition to heightened pain sensitivity or pain misperception that results following a stressor such as an infection.

Pt has weakness, lower extremity cramps, increased rate of urination. what electrolyte is this patient deficient in?

potassium (hypokalemia)

Minimal alveolar concentration

potency is inversely related to MAC - the lower the MAC the more potent the anesthetic.

list 3 alpha blockers

praZOSIN, doxaZOSIN, teraZOSIN -alpha 1 blocker leads to relaxation of smooth muscle in arterial and venous walls leading to a decrease in peripheral vascular resistance. Also, induce relaxation of smooth muscle in the bladder neck and prostrate leading to decrease in urinary obstruction caused by BPH.

what is treatment for schistosoma, clonorchis sinesis and paragonimus westermani

praziquantel

Elevated beta HCG

pregnancy multiple pregnancy (down syndrome fetus) hydatidiform mole choriocarcinoma testicular cancer (embryonal carcinoma, teratoma)

how to differ drug induced SLE from autoimmune SLE

presence of antihistone antibodies, no antibodies against native DNA, no decrease in serum complement levels, and LOW incidence of renal and CNS involvement - and DISAPPEARANCE of symptoms and lab test results when drug is discontinued.

difference between pseudocyst and true cysts

presence of epithelial tissue surrounding the walls of the pancreas.

vesicular breath sounds - heard over lung fields (its tracheal sounds that are modified in alveoli)

present in normal lungs, chronic bronchitis, emphysema. heard over lung fields and central bronchi.

coagulation factor inhibitor - typically of factor 8

presents same as hemophilia

Zollinger Ellison syndrome

presents with gastric and duodenal ulcers (90% of patients) diarrhea due to inactivation of intestinal and pancreatic enzymes by excess gastric acid

morphines mechanism of action

presynaptically binds V-G calcium channels thus preventing exocytosis postsynaptically opens potassium channels thus hyperpolarizing the cell. Mu receptors are a type of G protein linked receptor.

class 1b

prevents return back to resting state of sodium channels - and prevents firing of new action potentials. *unique for tissues that are hypoxic which are "stuck" in depolarized state thus sodium channels are in inactive state (H gate closed, M gate open).* -Will decrease action potential duration due to BLOCK of the SLOW na window currents

zinc deficiency

problem with MMPs - wound healing poor hearing poor smell (anosmia) hypogonadism *decrease zinc finger reactions* - transcription factor perioral rash cirrhosis (increase risk) allopecia

difficulty rising from chair

problem with gluteus maximus supplied by inferior gluteal nerve

Ataxia telangiectasia

problem with nonhomologous end joining defect ATM gene particularly follows ionizing radiation decrease in IgA, IgG, IgE spider angiomas, ataxia, increase in AFP

drugs that can cause SLE like syndrome are...

procainamide, hydralazine, and isoniazed (all are metabolized by N-acetyltransferase). -will have positive ANA and anti histone.

classical complement activated without antibody = Lectin pathway

proceeds through activation of c4 and c2 forming C3 convertase - and activating classical complement. *activation of classical complement without antibody*

What is palmitolyation?

process in which fatty acids are covalently anchored to plasma membrane cysteine residues, thereby increasing the hydrophobicity of a protein. Many G protein coupled receptors have carboxyl tails palmitoylated on cysteine residues.

Isoniazid MoA

prodrug thats activated by *catalase peroxidase - KatG* and then targets enzymes involved in mycolic acid synthesis (inhA and KasA) InhA = enoyl acyl carrier protein reductase.

first step in pyrimidine cycle

production of carbamoyl phosphate from glutamine and carbon dioxide. Aspartate and phosphoribosyl pyrophosphate (PRPP) are additional substrates require.

Low level of melatonin in CSF

progression of Alzheimers

Tay Sach's disease - clinical features

progressive neurodegeneration, developmental delay (child not able to sit or stand), cherry red spot on macula--> blindness, lysosomes with onion skin appearance, *no hepatosplenomegaly* (vs Niemann-pick)

Niemann-pick disease - clinical features

progressive neurodegeneration, hepatosplenomegaly, cherry red spot on macula, foam cells (parenchymal and reticuloendothelial cells)

pathogenesis of torsades de point

prolonged QT interval due to prolonged depolarization - thus any drug that increases Action potential duration or decreases potassium efflux has the potential to cause Torsades.

Viagra (sildenafil) a PDE 5 inhibitor - action

promotimes erection through relaxation of venous smooth muscle within *corpora cavernosa*

Venlafaxine

prophylactic migrain meds - its a serotonin and norepinephrine reuptake inhibitor

Azathioprine uses

prophylaxis for transplant rheumatoid arthritis crohns

what is antidote for heparin?

protamine sulfate

Metaplasia

protective mechanism - replacement of one epithelial type for another - seen in the esophagus (barrets esophagus), and in the respiratory epithelium (smokers) to stratified squamous.

whats the reason for transient hypercoagulable state with onset of warfarin therapy

protein C, a natural anticoagulant, is inactivated first with warfarin therapy thus producing a transient hypercoagulable state prior to the inactivation of the other factors.

Adenocarcinoma colon

protuberant mass -dysplastic mucosal cells with variable degree of gland formation

sixth arch

proximal party of pulmonary arteries and ductus arteriosus associated nerve = recurrent laryngeal of vagus nerve

what is origin of renal cell carcinoma

proximal tubule cells. most common subtype is clear cell carcinoma which appears as cuboidal or polygonal cells with abundant clear cytoplasm On macroscopic examination appears as golden yellow due to high glycogen and lipid content.

what are the clinical signs of lichen sclerosis et atrophicus?

pruritis, dysuria, pain with defecation and dyspareunia. lesions being as white atrophic macules that develop into papules.

Albright hereditary osteodystrophy - clinical findings

pseudohypoparathyroidism, short stature, short 4th and 5th metacarpals. *end organ resistance to PTH* also resistant to TSH and LH/FSH (infertility). PTH resistance manifests with hypocalcemia, hyperphosphatemia and elevated PTH.

what disease is associated with acanthosis?

psoriasis (do not confuse with acantholysis which is seen in pemphigus vulgaris)

Age related changes - eye

pt with mild myopia (difficulty viewing objects in distance) all of her life - has improvement upon old age - and this is due to Presybyopia. Presbyopia - inability of the lens to focus on near objects - thus individuals hold objects at a farther distance to read them. Develops in near sighted individuals Remember that hyperopyia is difficulty seeing objects up close.

what kind of renal stones does a patient get in crohns?

pts develop hyperoxaluria - thus oxolate stones. This is because of decreased levels of calcium in blood to bind oxolate (decrease absorption in gut results in decreased calcium)

what muscle forms the perineal flexure (angle)?

puborectalis - attaches at pubic symphysis and wraps around rectum.

Amiodarone - Adverse effects

pulmonary fibrosis (drug acts as hapten and effects tissue that receives 100% of cardiac output). Other drug causing pulmonary fibrosis is bleomycin. (Normal to increase FEV1/FVC) -Smurf skin - blue pigmentation -thyroid dysfunction - can be either hypo or hyperthyroidism - this is because amIODarone can iodinate tissues - which lends to reason why it has such a high Vd. (binds extensively to tissues) -corneal deposites and phototoxicity and hepatic necrosis.

Loud S2 (2 causes)

pulmonary or systemic hypertension and ASD

HSV esophagus

punched out

secondary hemostasis - coagulation cascade

purpose is to use thrombin to convert fibrinogen into fibrin thus forming a stable clot

Flucytosine - MoA/ A;e

pyrimidine analog whose metabolites impair fungal DNA replication and RNA synthesis. Human cells are unable to synthesize the active metabolites. A/E include *colitis* and *bone marrow suppression* due to release of active metabolites by gut flora.

what drug needs to be administered prior to administration of quinidine? and why?

quinidine in addition to its effects at fast sodium channels also is a muscarinic blocker and alpha blocker - thus by pretreating with digoxin AV nodal conduction will be decreased so theres less of a chance to develop reflex tachycardia (not desired). *MUST MONITOR EKG* because quinidine also can enhance digoxin's effects leading to digoxin cardiotoxicity.

Class 1a drugs

quinidine, procainamide, disopyramide

Blocks guanine nucleotide synthesis

rabavirin

FCC - sclerosing adenosis (has atypical hyperplasia)

rare to present as palpable mass - instead detected by mammogram as denisty - must biopsy to rule out cancer

craniopharyngoma are a derivative of what?

rathke's pouch (ectoderm) --> develops into anterio lobe whereas neuroectoderm is responsible for posterior lobe

what are structures that develop from surface ectoderm

rathke's pouch (everything in anterior pituitary), lens, cornea, inner ear, olfactory epithelium, nasal and oral epithelial linings, epidermis, salivary, sweat, and mammary glands.

what is the Reid Index

ratio of submucosa thickness to epithelium thickness (DOES NOT INCLUDE CARTILAGE).

MCTD clinical findings

raynauds, athralgia, pulmonary hypertension (will see anti phospholipid), pericarditis in 40% and *trigeminal neuralgia* anti u1-RNP (ribonucleoprotein)

is urea actively reabsorbed or reabsorbed by diffusion?

reabsorbed by diffusion Urea follows water

what does activation require for coagulation cascade

reaction is taking place on the platelet - requires 1. exposure to activating substance, 2. phospholipid surface (comes from platelet surface) 3. calcium thats released from dense core granules

type 1 hypersensitivity

read page 199 - 200 in robbins

why is a patient with bruton's susceptible to infections with Giardia?

reason being that in bruton's the patient has very low to absent levels of secretory IgA. This immunoglobulin plays a role in defense against the parasite.

Nesiritide (recombinant BNP)

recombinant form of BNP, increases cGMP resulting in vasodilation used for decompensated CHF

rasburicase

recombinant urate oxidase - catalyzes conversion of uric acid to allantoin - which is more soluble than uric acid. Treats hyperuricemia.

Stage 3 ATN

recovery stage gradual increase in urine output leading to high volume diuresis. Will find decreased EVERYTHING = most serious complication is HYPOkalemia

what nerve runs with inferior thyroid artery

recurrent laryngeal nerve

Bechets disease

recurrent oral apthous ulcers genital ulcers uveitis can be due to cross reactive immune response --> from HSV, strep, staph or e.coli

Kaposi sarcoma colon

red to violet flat maculopapular lesions or hemorrhagic nodules *spindle shaped tumor cells with small vessel proliferation*

selinum and copper are required for glutathione peroxidase

reduce H202 to H20

whats the effect of progesterone on gallstone formation

reduces bile acid secretion and slows gallbladder emptying

action of Peptide YY

released from ileum and colon - acts to decrease gastrin stimulated histamine release by blocking the receptor for gastrin on ECLs.

whats the most common cause of death in Fabry's

renal failure

what tumor develops from the collecting tubule

renal oncocytomas - large well differentiated neoplastic cells that contain numerous mitochondria.

short 4th and 5th metacarpals

renal osteodystrophy (albrights)

whats the role for type II pneumocytes

repair of alveolar epithelium after destruction of type I pneumocytes and secretion of surfactant

copper cofactor

required for oxidation - most important is *cyctochrome oxidase A3* dopamine hydroxylase tyrosine oxidase lysl oxidase

Pygmalion effect

researcher's beliefs effect efficacy of treatment.

pulmonary berylliosis

resembles sarcoidosis (nodular infiltrates, enlarged lymph nodes, non-caseating granulomas) but is not strongly associated with pleural plaques or effusions.

enterococci

resistant to penicillins, penicillinase resistant penicillins, aminoglycosides, TMP-SMX, and Vancomycin ALL via different organisms. *for aminoglcycosides* --> enterococci produce aminoglycoside modifying enzymes that transfer different chemical groups (acetyl groups or phosphate groups) to aminoglycoside molecule and therefore impair antibiotic binding.

what are the types of atelectasis?

resorption compression contraction

bilateral lesion to medulla

respiratory depression

what is the most common cause of death in scleroderma?

respiratory failure --> due to interstitial fibrosis (produces restrictive lung disease - increased FEV1/FVC ratio and hypoxemia) - also produces Corr pulmonale.

amyloidosis of the heart results in what?

restrictive cardiomyopathy - which is characterized by a decrease in ventricular compliance. It is diastolic heart failure due to decreased ventricular filling - resulting from decreased compliance.

Zenker diverticulum

results from cricophayngeal dysfunction - symptoms of "high dysphagia" (high up in esophagus) *can be palpated as a lateral neck mass*

thiamine deficiency

results in decrease glucose utilization in CNS --> if glucose infusion is given without thiamine administration prior then patient will develop *severe lactic acidosis* and acute cerebral damage. (foci of hemorrhage and necrosis in mamillary bodies and periaqueductal gray matter)

Defect in glucokinase

results in maturity onset diabetes type 2. results in less insulin secretion and decrease metabolism of glucose.

osteoclasts are from what cell origin

reticulocyte origin (monocyte) - Cd34+ve and CD14+ve Marker for activity = hydroxyproline Receptors on osteoclasts are *calcitonin* and *Receptor to RANKL*

thioridazine - eye A/E

retinal deposits

Refsum, Kerne Sayer, abetalipoproteinemia, usher syndrome and drug (thioridazine) - cause what eye disorder

retinitis pigmentosa

S. Pyogenes can causes

rheumatic fever and post strep glomerulonepritis

Infliximab and adalimumab

rheumatoid arthritis "INFLIX" pain in "DA LIMbs"

crystal formation - uric acid stone

rhomboid or rosette

RIPE - treatment for what

rifampin - binds to RNA polymerase isoniazid - targets drugs of mycolic acid pyrazinamide - acidifies lysosomes ethambutol - inhibits arabinotransferase (carbohydrate polymerization)

right recurrent laryngeal nerve courses around what vessel?

right subclavian artery.

how will a patient appear with decerebrate posture

rigid, extended upper and lower extremities

periductal mastitis

risk factor = smoking secondary due to low vitamin A levels

hepatic adenoma

risk increased with use of OCPs - can rupture and result in shock. associated with wieght lifters, OCP's.

young female has a child with down syndrome - what was mothers problem?

robertsonian translocation, she has 45 chromosomes, reason being that she did not have enough time to develop the trisomy (occurs after 35yrs)

invasive lobular breast cancer

row of cells "indian file" often BILATERAL with multiple lesions

neural crest origin marker

s-100

subarachnoid hemorrhage - damage vasculature

saccular aneurysm - circle of willis

caudal regression syndrome

sacral agenesis causing lower extremity paralysis and urinary incontinence --> Associated with *poorly controlled maternal diabetes* X ray will show poorly developed lumbar spine and sacrum.

osteomyelitis in patient with sickle cell

salmonella (mostly), sometimes staph A Hematogenous seeding to infarcted bone effects long bones

What are the different clinical phenotype of 21 hydroxylase deficiency? and degree of deficiency?

salt wasting (SEVERE), non-salt wasting (MODERATE) and delayed (non-classic) MILD

Severe 21 hydroxylase deficiency

salt wasting type - girls present at birth with ambiguous genitalia, and boys present at 1-2 wks (birth) with failure to thrive, dehyrdation, hyperkalemia, and hyponatremia. Girls will have same lab values

clinical presentation of patient with doxorubicin toxicity

same as that of CHF. dyspnea on exertion, orthopnea, and peripheral edema.

systems in series

same blood flow - as change in R increase deltaP will increase Q=dP/R

systems in parallel

same change in pressure dP = Q x R as Q increases then R decreases and vice versa.

contraction atelectasis

scarring of lung that hampers expansion and increases elastic recoil of lung during expiration. *irreversible*

haloperidol is used to treat what disorder?

schizophrenia

osteogenesis imperfecta - eye

sclera appear blue due to choriodal veins.

tubular necrosis ( 2 most common cause)

secondary to ischemia (damage to PCT and Loop - bc in medulla) secondary to drugs (PCT is damaged)

in healthy individuals whats the role of CFTR in respiratory and GI epithelial cells?

secretion of chloride

Whats the most common side effect of diazepam

sedation

tissues that lack regenerative capacity will develop a fibrous scar (type I collagen)

seen in neurons, skeletal muscle, cardiac muscle

uremia disrupts platelet function

seen in renal failure both adhesion and aggregation are impaired.

autosplenectomy is due to what?

seen in sickle cell patients (substitution for glutamic acid with valine) and the autosplenectomy is caused by recurrent splenic infarctions. will result in a shrunken, fibrotic spleen.

tubular/tendon xanthomas and xanthelasmas

seen with hypercholesterolemia

where is the site for normal airway resistance?

segmental bronchi

what is the major cause of morbidity and mortality in theophylline intoxication?

seizures (mechanism is not entirely clear - but believed to be due to PDE inhibition and reducing CNS inhibition through adenosine receptors)

What are the uses of carbamazepine?

seizures, bipolar disorder, and neuropathic pain --> trigeminal neuralgia DOC.

Imipenem adverse effects

seizures, rash, diarrhea

Berkson bias

selection bias created by selecting ONLY hospitalized patients as control group

what are two drugs that can decrease dopamine degradation in CNS?

selegiline = MAO-B inhibitor tolcapone = COMT inhibitor

Germ cell tumors - male

seminoma - no marker - fried egg embryonal carcinoma - inc AFP and HCG - large anaplastic cells with indistinct cell borders yolk sac tumor (endodermal sinus) - inc AFP - schiller duval bodies (recapitulate glomeruli) choriocarcinoma - inc bHCG - sheets of small cuboidal cells eosinophilic mature teratoma - multiple tissues - totipotent

Transthyretin

senile amyloidosis liver and heart

presbycusis - aging

sensorineural hearing loss, at high frequency

SSPE

sequelae of measles (rubeola), hypothesized to be due to absent M protein on measles virus. The missing antigen causes failure of the virus to be cleared by the immune system and allows persistence in the CNS. Note that there are No antibodies to the M component of the virus.

O glycosylation

serine, threonine, and hydroxylysine

Trp are precursors to..

serotonin and niacin

surface epithelial cell tumors

serous mucinous endometriod brenner cystadenofibroma

two causes of hirsutism

sertoli-leydig PCOD

best test for thyroid function?

serum TSH Note: T4 levels can be low, but within normal limits in early milk primary hypothyroidism, since TSH levels rise before T4 levels are low, TSH is a more sensitive test. Serum T3 is the last to decline in most patients with hypothryoidism.

Labs paget's disease of bone

serum alkaline phosphatase is increased but serum calcium and phosphate are normal.

Edward syndrome clinical findings

severe intellectual disability, rockerbottom feet, micrognathia (small jaw), *low-set Ears*, clenched hands , prominent occiput, congenital heart disease. ocular hypertelorism (eyes far apart) Death usually occurs within 1 year of birth.

retinitis pigmentosa - morphology and pathology

severe vision impairment - blindness (often) due to loss of photoreceptors patients may experience defective light to dark adaptation and vice versa as a result of degeneration of peripheral visual field (tunnel vision) *bone spicule shaped pigment deposits*

Transduction (specialized)

shigA - like toxin EHEC Botulinum Cholera Diptheria Erythrogenic Strep Pyogenes

what are the five bacteria that encode special phage transduction

shigA-like toxin EHEC Botulinum toxin Cholera toxin Diptheria toxin Erythrogenic toxin of S. pyogenes

what two bacteria can cause HUS

shigella and EHEC mucosal invasion is the essential pathogenic mechanism for shigella infection.

Leucine zipper

short alpha helix fragment with leucine residues at every seventh position is most likely part of a leucine zipper dimerization domain found in transcription factors. *these leucine zippers are short 30 amino acid alpha helical protein fragment with leucine residues at every seventh position* -transcription factors contain specific aa sequences (in this case a short strand of 30 aa) that bind to DNA (major groove) or to dimerize for DNA binding.

turner syndrome - clinical

short stature, broad chest, primary amenorrhea, 45 XO

Prader willi - clinical

short stature, obesity, hypotonia, microdeletion 15p, mental retardation, maternal imprinting, and defective paternal gene inherited.

two types adenocarcinoma stomach slide 444 goljan.

signet ring type = Diffuse type, infiltrate large areas of stomach wall causing leather bottle stomach (linitis plastica) - loss of E-cadherin, spread is hematogenous, *NOT ASSOCIATED WITH H.PYLORI* Autosomal dominant E cadherin mutation. intestinal type = resemble colon cancer, grow as nodular polypoid, well demarcated masses with well *formed glands* that consist of columnar or cuboidal cells. associated with nitrosamine (smoked cooked food --> highly present in Japan) - *ASSOCIATED WITH H.PYLORI* and menetieres disease.

all triplet repeats expect H.D (exon chrom 4) result in methylation of repeat - which leads to what?

silencing of the gene expression, thus diagnosis is via *lack of protein*

menkes - copper deficiency X linked recessive

similar to EDS type IX kinky, colorless, brittle hair tortuous weak vessels in CNS strokes hyperextensible skin/joints will find low blood copper/ceruloplasmin and *decreased urine copper* whereas in wilsons there is *elevated urine copper*

histology of thick ascending loop of henle

simple cuboidal with few microvilli

histology of DCT

simple cuboidal with short microvilli

histology of thin loop of henle descending

simple squamous epithelium

histology of proximal convoluted tubule

simple tall cuboidal with tall microvilli

cross sectional study

simultaneously measure exposure and outcome. limitation in this study design is that a temporal relationship between exposure and outcome is not always clear. ex. researchers are studying relationship between essential HTN and mutation in structure of sodium channel protein. Study population randomly selected. Blood samples are obtained for leukocyte genotyping and arterial blood pressure is measured. Researchers conclude that mutation in the structure of sodium channel protein is associated with hypertension.

Aspargine are involved with what cotranslational process

site for N-glycosylation in the endoplasmic reticulum

anti ribonucleoproteins

sjogren and mixed connective tissue diease anti ssa and ssb

anti-SSa and anti-SSb

sjogrens infants - with mothers who have sjogrens can develop heart block and will require pacemaker.

rule - in disorders of primary hemostasis

skin and mucosal bleeding

clinical features in TTP and HUS

skin and mucosal bleeding microangiopathic hemolytic anemia fever renal insufficiency (predominant problem in HUS) CNS abnormalities (predominant problem in TTP)

Nikolsky sign

skin slipping off with gentle pressure - as seen in scalded skin syndrome.

Wilson's disease - cheapest diagnostic tool

slit lamp examination - look for kayser fleischer rings

drug induced SLE more likely to occur in what kind of patients

slow acetylators

Type B fibers

small myelinated fibers preganglionic autonomics

Type C fibers

small unmyelinated postganglionic autonomics dull, burning pain

what drug can be used to treat carcinoid syndrome?

somatostatin analog = octreotide. -can also be used to treat VIPomas

Niemann-pick disease - accumulated substrate

sphingomyelin

Niemann-pick disease - deficient enzyme

sphingomyelinase

estrogen excess

spider angioma palmar erythema gynecomastia testicular atrophy dupuytrens contractures

K+ sparing agents (remember aldosterone receptors are zinc finger receptors)

spironolactone and eplerenone - act at aldosterone receptor amiloride and triamterene block sodium channel on luminal membrane.

what is the adenocarcioma sequence

sporadic mutation APC -> KRAS -> DCC -> p53

subcutaneous mycosis

sporothrix shenkii

what are long term sequelae of lichen sclerosis?

squamous cell carcinoma and genital disfigurement. Tx with corticosteroids.

what malignancies are alcoholics most likely to develop?

squamous cell of the esophagus, and signet ring stomach cancer

secondary hemostasis

stabilizes the primary platelet plug via coagulation cascade

Acute tubular necrosis

stage 2 = hyperkalemia, hyperphosphatemia, hypermagnesiumia, HYPOnatremia, HYPOcalcemia stage 3 = low everything; hypokalemia most serious PATCHY necrosis Low calcium d/t decreased vitamin D hyperuricemia --> lethargy, confusion, seizures, PERICARDIAL disease

Second arch

stapedial artery and hyoid artery associated nerve = facial never

cause of osteomyelitis in children

staph aureus -hematogenous seeding during an episode of bacteremia -typical site of infection = long bones

what is the most common cause of osteomyelitis

staph aureus (present on skin) - note that staph epidermis is rare and only associated with prosthetic devices or indwelling catheters.

what drug decreases LDL the most

statins

whats treatment for type II hyperlipoproteinemia

statins

tension headache

steady pain, no photophobia, band like pattern, can last 4 to 6 hours, stress induced, hypersensitivity to sound.

What is the mechanism of action of a drug can be used to treat both bipolar disorder and seizures?

stimulate GABA release and decrease its breakdown - thus enhancing the inhibitory action of GABA and blocking voltage gated sodium channels *drug = Valproic acid*

Growth factors

stimulate growth and differentiation of various cell lines usually by regulating synthesis of transcription factors Ex. GM CSF and PDGF

IL-3

stimulates growth and differentiation of bone marrow stem cells

bone growth

stops when the epiphysis fuses with the metaphysis --> sex steroids initially increase linear growth but they also encourage closure of the epiphyseal growth plate. (estrogen and testosterone)

histology of cornea

stratified columnar with goblet cells at base of cornea then becomes squamous

where are the stem cells in the epidermis? (labile cells)

stratum basale

whats fibroblast growth factor - role

strong initiator for angiogenesis

hawthorne effect

study population to affect an outcome due to knowledge of being studied. Results in change of behavior when knowing that they are being observed.

Congenital vascular disorders, facial port wine stain, leptomeningeal capillary venous malformation, seizures

sturge weber syndrome *mutation in GNAQ* which is a Gq (g coupled protein receptor)

what activated factor 12?

subendothelial collagen (SEC)

what activates factor XII

subendothelial collagen, platelets, basement membrane, HMWK, negative charge.

Polymyalgia rheumatica (what vasculitis is it associated with?)

sudded onset stiffness pain tenderness over the shoulders hips, neck and torso - elevated ESR associated with giant cell arteritis rapid response to corticosteroids

photosensitivity

sulfonamides amiodarone tetracyclines 5FU

Gluteal injections should be given where to avoid damaging superior gluteal nerve and sciatic nerve.

superiolateral quadrant of buttock

Why is supraspinatus most vulnerable in rotator cuff?

superior location - thus susceptible to chronic repeated trauma from impingement between head of humerus and the acromioclavicular joint.

fourth pharyngeal

superior parathyroids (dorsal wings)

inferior gluteal nerve

supplies gluteus maximus nerve

what is the most common injury in the rotator cuff?

supraspinatus

dystonia

sustained and involuntary muscle contractions that can force body parts into abnormal postures -spasmodic torticollis -blepharospasm *closure of eyelid* -writers cramp

treponema pallidum

syphillis, painless ulcer or chancre, condyloma lata seen in 2nd syphillis

Anti topoisomerase (Sci-70)

systemic sclerosis

graves disease results in systolic or diastolic hypertension?

systolic HTN from increased cardiac contraction

what tumor translocation results in upregulation in G1 to S phase.

t11;14 mantle cell carcinoma --> cyclin D1 on chromosome 11 --> mutation results in upregulation of cyclin D1 which is a promoter of G1 to S phase - remember that cyclin D1 will by cdk4 and phosphorylate Rb thus removing Rb from E2F which allows progression into S phase (allows transcription of replicative enzymes)

Follicular lymphoma

t14;18

what tumor translocation results in inhibition of apoptosis?

t14;18 = follicular lymphoma chrom 18 - near BCL2 which is antiapoptotic

what are some factors that endothelial cells release to protect against thrombus formation

tPA heparin like molecule - activate At3 Nitric oxide PGI2 Thrombomodulin

ARDS clinical findings

tachypnea, respiratory alkalosis, and hypoxia are early clinical findings, elevated A-a gradient.

aromatase deficiency in males

tall stature, osteoporosis, NO genital abnormalities

Pt with prolonged antipsychotic treatment develops involuntary perioral movements (biting, chewing, grimacing, and tongue protrusions). Irreversible.

tardive dyskinesia *best managed by replacing antipsychotic with atypical antipsychotic = Clozapine. B/c clozapine is associated with agranulocytosis - considered medication of last resort.

whats the target of anti-SSa and anti-SSb

target is ribonuclear proteins (anti-ribonuclear antibody)

Ribavirin A/E

teratogen and hemolytic anemia

germ cell tumor

teratoma dysgerminoma choriocarcinoma endodermal sinus tumor

How to determine whether a patient has cholinergic crisis.

test with edrophonium

trendelenburg sign

tests superior gluteal nerve (stabilize hip during walking) supplies gluteus medius and minimus

anal canal embryology

the anal canal extends from the perineal flexure (angle formed by puborectalis) to the perianal skin (anal verge "butthole"). It is divided into upper and lower anal canal. The upper anal canal which is above the pectinate line is formed by the hindgut, whereas the lower anal canal which is below the pectinate line is derived from *surface ectoderm* The junction between these canals is closed during embryonic life by an anal membrane that is located at level of pectinate line. Failure of surface ectoderm to canalize results in *imperforate anus* which presents as failure to pass meconium.

overall what is the effect of estrogen and progesterone on gallstone formation

the estrogen upregulates hmg coa reductase therein increasing cholesterol formation and bilirubin hypersecretion - this results in supersaturation of bile acids in the gallbladder - couple this finding with progesterone which reduces the motility of the gallbladder and a perfect environment is created for gallstone formation (cholesterol gallstones)

what structures can cause repeated injury or strain on the supraspinatus tendon

the head of the humerus and acromioclavicular joint

what is the methyl THF trap.

the reaction catalyzing N5-methyl-tetrahydrofolate is irreversible and thus requires B12 to become recycled into a usable intermediate for other reactions of pyrimidine synthesis. This reaction occurs via methionine synthetase which converts homocysteine into methionine. Thus, if a patient has b12 deficiency then N5THF will accumulate and the synthesis of methionine will be impaired. *this is why patients with B12 def. have megaloblastic anemia and homocystinuria*

Metastasis are found in liver from a cancer in rectum - whats venous drainage route

the rectum is supplied by 3 arteries (and veins) - superior rectal (branch of IMA), middle rectal artery (branch of internal iliac artery) and inferior rectal artery (branch of internal pudendal artery) -*venous drainage* - route for the metastasis to liver -->*superior rectal vein drains into PORTAL SYSTEM* via *IMA* and Inferior rectal and middle rectal vein drain to *systemic circulation*

what epidermal layer is thickened in a callus.

the stratum corneum is generally thickened in areas of the body commonly exposed to friction or trauma (soles of feet). A painless thickening of the stratum corneum "callus" may occur at locations of repeated external pressure or friction. Note that stratum corneum is composed of 20 layers of dead epithelial cells.

theophyline interaction with adenosine

theophylline will block the effects of adenosine.

Adenosine is antagonized by what other drugs?

theophylline, caffeine, and methylxanthines

Dose response curves can also be used to measure...

therapeutic index --> which compares the toxic dose (TD50) or lethal dose (LD50) to the effective dose (ED50) *low TI drugs = HIGH YEILD NOTE - desired to have a STEEP curve because it means that there is less variability in drug response among the population.

Doxorubicin toxicity

these anthracyclines *generate free radicals in the myocardium.* Will find *swelling of sarcoplasmic reticulum* which is followed by loss of cardiomyocytes *myofibrillar dropout*. Thus, patients develop DILATED CARDIOMYOPATHY (presents with signs of left and right heart failure).

Guanine and cytosines - role in silencing

these are nucleotides that are methylated

what are the effects of NSAIDs and ACEi on lithium toxicity

these drugs are thought to impair lithium clearance leading to increased lithium levels, mechanism is controversial.

do not give warfarin to a patient who is undergoing heparin induced thrombocytopenia. Why?

these patients are at a greater risk fo developing warfarin skin necrosis.

other findings of SIDS on autopsy

thickened pulmonary arteries brainstem changes - hypoxia (hypoplasia of the arcuate nucleus) Astrogliosis (hypertrophy and hyperplasia of astrocytes) in cerebellum and brainstem

In a case control study

think of 2 x 2 table Patients with disease and without and Pts with Risk factors and without Just look at the title - in a case control study - there is case (experiment - disease present, risk factor may or may not be present) and the control - disease NEVER present and risk factor may or may not be present)

granulation tissue - will eventually form type I collagen

this is performed via collagenases which require ZINC as a cofactor -->which will remove type III collagen

cricopharyngeal muscle

this muscle is used during swallowing - it is responsible for *initiating* the propulsion of food. Dysfunction occurs due to diminished relaxation of pharyngeal muscles during swallowing. More force is therefore required to move the food bolus downwards. This results in more intense contractions of the pharyngeal muscles which increase luminal pressure. With time, the mucosa in pharynx will actually *herniate* through the muscle fibers (from the increased luminal pressure) - zone of weakness is the posterior pharynx. Thus forming a zenker diverticulum which can be palpated as a lateral neck mass

a 72 year old male is brought to ER with involuntary, wild, flinging movements of his right arm. Which area has been injured in patient?

this patient has hemibalismus. It occurs due to damage of the contralateral *subthalamic nucleus* - most commonly from a lacunar stroke - which is a type of intraparenchymal stroke. *most common risk factor * = hypertension.

Gangciclovir A/E

thrombocytopenia, leukopenia, neutropenia, nephrotoxicity

inferior thyroid artery is a branch of what artery

thryocervical trunk

PBPs are proteins in CELL MEMBRANE

thus penicillin's site of action is in cytoplasmic membrane which CONTROLS the synthesis of peptidoglycans FOR cell wall

what develops from the ventral wings of third pharyngeal pouch?

thymus

the inferior thryoid artery is a branch of what artery?

thyrocervical trunk

what are some adverse effects of amiodarone?

thyroid dysfunction, corneal micro deposits, blue gray skin discoloration, drug related hepatitis, and pulmonary fibrosis

what muscles are supplied by common peroneal nerve

tibialis anterior peroneus longus peroneus brevis extensor digitorum longus extensor hallucis longus sensory to anterolateral leg and dorsal foot

Tissue ischemia - electrolyte changes

tissue ischemia increases the extracellular K concentration via reduced functionality of the membrane Na/K ATPase and subsequent K leakage from affected cells. Ischemia may reduce extracellular Na, Ca, HCO3. *cytoplasmic calcium is a hallmark ischemic injury*

what activates factor 7?

tissue thromboplastin (TT)

Magnesium use

torsades

Pimozide

traditional high potency anti-psychotic in addition to treating tourettes.

Growth factor receptors

transduce signals delivered by corresponding growth factors but DO NOT DIRECTLY regulate progenitor cell differentiation.

hindgut derivatives

transerve colon, descending and sigmoid colon

fMETHIONINE - only in bacteria

translocation of translation --> fMET is chemotactic for neutrophils Note P site initially binds to methionine, successive amino acids bind A site.

What is synaptophysin

transmembrane glycoprotein found in presynaptic vesicles of neurons, neuroectodermal (neural crest derivatives and neural tube derivatives - spinal cord, cortex, post pituitary, retina) and neuroendocrine cells. Make up <1% of CNS tumors.

cyclosporine use

transplant rejection PROPHYLAXIS, psoriasis, rheumatoid arthritis

tacrolimus use

transplant rejection prophylaxis

Cystinuria is deficient in

transporter for COAL (cystine, ornithine, asparginine, lysine)

Hartnup is deficient in

transporter for neutral amino acid in renal epithelial tubule

whats the pathology of the lung tissue following a acute myocardial infarction?

transudate accumulating in the alveolar lumen

scrotum tissue levels

transversalis fascia - becomes internal spermatic fascia internal oblique muscle - becomes cremasteric muscle external oblique muscle - becomes the external spermatic fascia

nevus of ota

trapped melanocyte in sclera - failure of neural crest cell migration. seen in sturge weber, leptomeningeal melanosis, and NF1

hip extensors

trauma to gluteal nerves slow walking speed weakness muscles = gluteus medius, gluteus maximus

aminocaproic acid

treat overdose of tissue fibrinolytics - do not confuse with protamine sulfate that is used for heparin overdose.

do not treat WPW with digoxin

treat with class Ia and class III

Foscarnet A/E

treats CMV in HIV patients. A/E = nephrotoxicity, hypocalcemia, hypomagnesemia, and hypokalemia

what is a short acting benzodiazepine?

triazolam

poor prognosis breast cancer

triple negative test PR+ve without ER+ve High cathepsin D in tumor - will degrade BM

hydatiform mole is what type of disease?

trophoblastic disease

only squamous cell carcinoma along respiratory tract is

true vocal cords - note that laryngeal carcinoma can be caused by HPV 6,11 which is very unique seeing that its typically HPV 16,18 which cause cancer.

Negative pressure room - quarantine

tuberculosis, measles, varicella, St. Louis encephalitis, coxiella burnetii. N95 gas mask

glioblastoma multiforme

tumor in subcortical white matter which is why it may cross over corpus callosum to other cerebral hemisphere thus presenting as a "butterfly glioma in appearance" (usually does not occur). These tumors are composed of pleomorphic astrocytic cells with a pseudopallisading appearance and marked mitotic activity. Necrosis is an essential diagnostic feature and there is prominent microvascular proliferation (recaptitualates arteries - which is why there is hemorrhage).

Best prognosis breast cancer

tumor less than 2cm, no LN involvement, ER+ve, lack aneuploidy, lack cathepsin D

lymphedema of hands, feet, and neck in infancy is associated with what pathology?

turner syndrome *webbed neck* is caused by *dilated lymphatic channels* (cystic hygroma) and persists into adult life.

Physiologic antagonism

two agonists with opposing action that antagonize each other

Muscle spindle

type 1 a fibers

Golgi tendon

type 1 b fibers

hypertrophic scar

type I collagen, not out of proportion to wound

flat, nonciliated epithelial cells

type I pneumocytes,

what type of hypersensitivity is acute hemolytic reaction?

type II hypersensitivity

what are stem cells of the lung? (labile cells)

type II pneumocytes

Pt presents with joint pain, pruritis, vasculitis and vessel wall fibrinoid necrosis with neutrophilic infiltration after taking sulfa drug (TMP-SMX) What type of hypersensitivity is this?

type III --> serum sickness reaction produces fever, urticaria, arthralgias, glomerulonephritis, and lymphadenopathy 5-10 days after exposure to antigen. --> type III HS reactions activate complement

hepatin induced thrombocytopenia

type III hypersensitivity - IgG ab against heparin - platelet factor 4 complex.

sjogren syndrome - hypersensitivity

type IV HS patients at increased risk of dental caries (decrease saliva = increase risk of infection)

antipsychotics are broken up into 2 categories

typical "classical" antipsychotics atypical antipsychotics

clinical signs of iron deficiency anemia

typical symptoms + glossal pain, atrophy of tongue papillae, alopecia, and pagophagia (craving for ice).

Alkaptonuria is due to an enzyme deficiency of homogenistic acid oxidase which is involved in the degradation of what amino acid?

tyrosine

what amino acid becomes essential in PKU?

tyrosine

BH4 (tetrahydrabioterin) helps form what amino acid

tyrosine --> Bh4 needed to form aromatic amino acids

Prolactin, Interleukins (cytokines) and Growth Hormone use what receptor?

tyrosine kinase --> activates JAK/STAT pathway

sublimation defense mechanism - mature

unacceptable drives are redirected toward completely acceptable targets

reaction formation defense mechanism - immature

unacceptable feelings are ignored and the opposite sentiment is adopted.

projection defense mechanism - immature

unacceptable or personally disagreeable impulses or drives are attributed to others

what type of inhibition does lithium show?

uncompetitive inhibition which means that it only acts on neurons that are active.

spinocerebellar tract

unconscious proprioception DO NOT CROSS this lesion results in ipsilateral deficiency

small cell carcinoma characteristics

undifferentiated, may produce ACTH, ADH, Lambert eaton, amplification of myc.

Mycoplasma pneumonia - attachment

unique attachment P1 adhesin

ALA synthetase

upregulated by alcohol, barbituates (CYP inducers) and hypoxia inhibited by heme, hemin, and glucose *ALA synthetase requires vitamin B6, succinyl coa glycine*

Roles of ApoE

uptake cholesterol into neurons made my macrophages lipid antigen presentation (cd1 is marker - and is mediated by Natural killer T CELLS - not to be confused with NK cells). uptake of IDL and Chylomicrons

a healthy women 18th week of pregnancy - fetal ultrasound shows unilateral fetal hydronephrosis - wheres the obstruction?

ureteropelvic junction

what is the only stone thats radiolucent?

uric acid

What sort of stones will a patient develop with myeloproliferative disorders, are undergoing chemotherapy, have gout, lesh-nyan or have high alcohol intake/high purine diets?

uric acid stone

what are the 3 stones that precipitate in acidic urine?

uric acid, calcium oxolate (MOST COMMON STONE) and cystine

ribavirin (use and A/E)

use = RSV, HCV --> inhibits synthesis of purine via inhibition of inosine monophosphate DH. A/E = hemolytic anemia and teratogenic

spironolactone - facts

use = hyperaldosteronic state and *adjunct to K+ wasting diuretics*, antiandrogenic uses, congestive heart failure A/E = *hyperkalemia, acidosis* and antiandrogen (gynecomastia) *can block other steroid receptors*

metoclopramide MoA

used as a prokinetic agent for gastroparesis (#1 cause is diabetes) 5HT 3 antagonist, 5HT 4 agonist D2 Antagonist

IFNBeta exogenous use

used for multiple sclerosis

large increase in glutamine

used to buffer increased ammonia levels.

MAO inhibitors - use

used to treat atypical depression, anxiety, and hypochondriasis

Procainamide use

used to treat cardiac arrhythmias has less muscarinic effects metabolized via N-Acetyltransferase

Metyrapone testing

used when theres a suspicion of an interruption in the hypothalamic-pituitary-adrenal feedback loop. -Metyrapone blocks cortisol synthesis by inhibiting 11-Beta hydroxylase (catalyzes reaction between 11Bdeoxycortisol to cortisol), thus serum cortisol levels are reduced thus stimulating secretion of ACTH. *note 11-deoxycortisol metabolites are measurable in urine as 17-hydroxycorticosteroids* This test basically determines whether HPA axis is functional or not.

bile acid binding resins are used with what drugs to increase LDL

used with niacin or statins.

cardinal ligament contains...

uterine vessels - ureter is at risk of injury during ligation of uterine artery "water under the bridge"

locations of b2 agonist

uterus, adipose, vasculature, bronchioles

Step 2. Platelet adhesion

vWF binds to subendothelial collagen (remember that vWF comes from platelet's alpha granules and weibel pallades body within endothelial cell). Then platelets bind vWF using *Gp1b*

symptoms of a complete mole

vaginal bleeding, enlarged uterus, hyperemesis, pre-eclampsia (proteinuria, hyperglycemia, elevated blood pressure), hyperthyroidism (bHCG cross reacts with TSH receptor). Imaging = honeycomb uterus or clusters of graps ---> snowstorm appearance on ultrasound.

what supplies that tongue root, larynx and upper esophagus

vagus nerve

Drugs that work in cell wall

vancomycin and telvanc

scrotal mass that is palpable when patient stands but disappears when patient lies down. Transillumination is negative

varicocele.

edema in brain

vasogenic edema --> disruption of BBB leads to increased vascular permeability and plasma filtration into cerebral interstitium producing this form of edema - Cytotoxic edema --> refers to increased intracellular fluid within neurons, glia and endothelial cells that occurs when cellular injury impairs the Na/K ATPase following an ischemic insult. will not result in elevated ICP because it represents a shift of fluid from the extracellular compartment to the intracellular compartment.

Metastatic carcinoid - symptoms

vasomotor instability - cutanous flushing, dizziness GI symptoms - secretory diarrhea, crampy abd pain bronchoconstriction - dyspnea with wheezing right sided (pulmonary, tricuspid) - valvular heart disease.

sickle cell presentation

vasoocclusive symptoms - hand and foot syndrome = dactylitis = involves small infarctions within the bone marrow, trabeculae and inner cortical layer of the bones (hand, foot, wrist) --> common in first years of life because the affected bones still contain hematopoietic bone marrow (cd34+ve) -later in life --> acute chest syndrome (cause of death), autosplenectomy (risk for infections by encapsulated bacteria), stroke -renal papillary necrosis (due to low 02 in papilla - microhematuria - will be only presentation in heterozygotes -*salmonella osteomyelitis*

Staph aureus endocarditis

vegetations on valves are associated with bacterial endocarditis that represents fibrin and platelet deposition (factor VII) at site of bacterial colonization.

Drugs that can increase toxicity of digoxin

verapamil, quinidine, amiodarone *hypokalemia will exacerbate digoxin and hyperkalemia will decrease effects*

A patient who's anemic should have what kind of reticulocyte count?

very high to account for the hemolysis.

Amiodarone differs from other drugs that cause long QT (can lead to Torsades). why?

very low risk of causing Torsades. - other drugs that can cause torsades are class IA and III antiarrhythmics.

causes of dilated cardiomyopathy = systolic dysfunction

viral myocarditis, alcohol toxicity, diptheria myocarditis, doxorubicin toxicity

posterior column degeneration is seen in what disease or states?

vit b12 deficiency, syphillis, vit E def. NO toxicity

type II nuclear receptors

vitamin A VItamin D Thyroid

bitot spots

vitamin A def conjunctiva characterized as squamous metaplasia producing localized keratin debris that deposits in conjunctiva

what cofactor is required for transamination reaction - as seen in formation of aspartate from oxaloacetate and glutamate?

vitamin B6 -required for transamination and decarboxylation of amino acids

patients taking levodopa/carbidopa should not take

vitamin B6 (over the counter medication) because it increases peripheral conversion of dopamine thus decrease effectiveness in CNS. Look for a patient that has peptic ulcers because there will typically be less absorption of vitamins and supplementation will be needed.

what are the cofarctors required for cystationine synthetase?

vitamin B6 and serine.

phytonadione

vitamin K analogue

phytonadione is a antidote in asymptomatic individuals with what overdose?

warfarin --> phyntonadione is vitamin K

Warfarin with a cyp 450 inhibitor

warfarins effects are increased due to decreased metabolism --> remember that warfarin is mainly metabolized by CYP 2C9 rendering the drug inactive --> if an inhibitor is given then the metabolism is delayed and the drug will be active for a longer period of time. Thus look for an increase in PT (factor 7). Adversely, if a CYP 450 inducer is given then warfarin will have LESS effects due to rapid metabolism (inactivation) and the PT will decrease (less anticoagulant effects).

Quinidine with antacids - absorption increased or decreased?

weak base thus not readily absorbed in stomach, however use of antacids will increase its absorption thus precipitating toxic effects.

primary hemostasis forms

weak platelet plug

what are the adverse effects of "-glitazones"

weight gain edema congestive heart failure

atypical A/E

weight gain, hypotension, antimuscarinic, blockage of autonomics (orthostatic hypotension)

orlistat

weight loss inhibits pancreatic lipase - thus decreases triglyceride breakdown in the intestine. - will cause diarrhea.

foci of hemorrhage and necrosis in the mamillary bodies and periaqueductal gray matter

wernicke encephalopathy

Reticulocyte count

when a patient has anemia - look for the corrected reticulocyte count to account for anemia - thus take Hct (which can be determined by multiplying the hemoglobin by 3) and divide by 45 then multiply by the present reticulocyte count - this will give you corrected reticulocyte count. Note ONLY extremely high reticulocyte counts will increase MCV.

Myocardial stunning

when ischemia lasts less than 30 minutes loss of contractile function is reversible. On restoration of blood flow, full myocardial contractility is not immediately restored. Instead, there is prolonged dysfunction of the myocardium = *myocardial stunning* with contractility gradually returning to normal over the next several hours to days. Increasing durations of ischemia prolong the time that the myocardium remains stunned.

where is the most common site for aortic aneurysm due to hypertension, syphillis or vasculitis?

where right brachiocephalic artery branches off ascending aorta.

Aortic dissection

widened mediastinum chronic hypertension and marfan syndrome

ARDS

widespread injury to pulmonary microvascular endothelium or alveolar epithelium - which results in the alveolarcapillary membrane to be leaky (resulting in fluid accumulation in alveolar spaces). *will find endothelial injury, pulmonary interstitial and intra alveolar edema, inflammation and alveolar hyaline membrane formation*

fibromyalgia characteristics

widespread musculoskeletal pain, more severe in morning, and exacerbated following exercise.

Rate of infusion will determine what at steady state?

will NOT influence time to SS, but will influence the concentration. Thus doubling oral doses can double the plasma levels of a drug

Sibutramine

will act like an amphetamine and increase levels of 5HT and NE --> thus will cause anorexia. Can also be used to increase memory.

Multiple myeloma and osteoporosis

will also see an increase in IL-1 which causes increased osteoclast activation resutling in increased bone breakdown and subsequent hypercalcemia - interesting that both a cancer and osteoporosis have similar pathogenesis. Note both IL1 and TNF increase RANKL (note RANKL is on osteoblasts --> furthermore, note that TNF has a direct effect on turning osteoblasts into osteoclasts is without RANKL-RANK signaling)

Noncompetitive inhibitor when spare receptors are present

will appear first like a competitive antagonist, then as drug concentration of noncomp increases will then appear like normal noncompetitive inhibition

class IV antiarrhythmics - Verapamil and diltiazem

will block L type calcium channels (phase 0 of SA and AV node) thus decreasing their activity. will also decrease phase 4 bc both L type and T type calcium channels are open, however these drugs only block L type.

what will kalikrein act on (natural anticoagulant)

will cleave HMWK into bradykinin and will activate plasminogen into plasmin

concept - action of 5HT2A

will decrease dopamine, therefore blocking 5HT2A will increase Dopamine. in mesocortical and nigrostriatal and tuberofundibular pathway - The increase in dopamine will be enough to displace dopamine antagonism

class 1b effects

will decrease duration of action potential due to block of the slow sodium window currents which will INCREASE DIASTOLE and EXTENDS recovery time - thus allowing more filling and increase oxygenation and increase cardiac output.

cocaine

will decrease uptake of dopamine - at nucleus accumbens of mesolimbic pathway

ischemia will result in patchy necrosis however

will eventually progress to diffuse then ATN (which is number one cause for acute renal failure)

FSGS

will find IgM

aromatase deficiency in females

will find high levels of testosterone and androstenedione, low estrogen levels. If female, will have ambiguous genitalia. this deficiency can also effect the mother during pregnancy because the increased levels of testosterone and androstenedione will cross the placenta. (can result in masculinization of mother during pregnancy)

what are lab values in diabetic ketoacidosis?

will find metabolic acidosis, ketonemia, ketonuria, hyperglycemia, glycosuria, hyponatremia, hypovolemia, and kyperkalemia. The serum sodium is decreased in DKA because of the osmotic activity of glucose (as glucose increases - serum sodium decreases).

CVID differential

will have low Igs low plasma cells, normal B cells -Nephrotic syndrome (patients would present same lab values but would be in hypercoagulable state due to urination of At3)

HBV causing HCC

will incorporate into host genome. -Causes chronic liver cell injury and regenerative hyperplasia - thus increasing the number of hepatocytes susceptible to genetic mutations -Encodes HBx protein which activates growth promoting genes, and *binds to p53* thus impeding growth suppression.

in patients with combined hyperlipidemias what will happen to LDL levels when a fibrate is given?

will increase levels of LDL.

amphetamines

will increase release of dopamine from mobile pool - non vesicular release - at nucleus accumbens of mesolimbic pathway

Platelet activating factor - uses what secondary messenger system

will induce platelet aggregation, vasoconstriction, and bronchoconstriction Gq coupled.

Allopurinal with azathioprine or mercaptopurine

will need to reduce the dose of azathioprine or mercaptopurine

germinal matrix hemorrhage - IVH

will see characteristic hemorrhage into a ventricle - typically lateral ventricle.

what pathology involves degeneration of lentiform nucleus (what makes up lentiform nucleus)

wilson's disease = heptolenticular degeneration - lentiform nucleus = putamen +globus pallidus

microvesicular steatosis

wilsons reye's

Kayser fleischer rings

wilsons primary biliary cirrhosis

would an antiapoptotic gene be upregulated or downregulated in cancer?

would be upregulated - no apoptosis, thus in follicular lymphoma the t14;18 results in overexpression of BCl-2 which is antiapoptotic.

clinical findings of churg strauss

wrist drop polyneuropathy nasal polyps *elevated eosinophil count* asthma mono/polyneuropathy pulmonary infiltrates P-ANCA = Anti myeloperoxidase

Duchenne muscular dystrophy - inheritance

x linked recessive

fabry disease - inheritance

x linked recessive

Two types of transcription factors

zinc fingers leucine zippers

rugal thickening with acid hypersecretion

zollinger-ellison syndrome

SERMs

• Selective Estrogen Receptors Modulators: They exhibit agonistic action in some tissue and antagonists in other tissues. • Tamoxifen: Antagonist effect on breast tissue but agonistic effect on endometrium & bone. Used in metastatic breast cancer • Raloxifene: Antagonist at breast & endometrium but agonist at bone