5.8.2015 Uworld Notes Flashcards
Opioid analgesic in ER–>Severe abdominal pain. Tender RUQ. Which is responsible for current condition?
Mu opioid analgesics like morphine cause contraction of smooth muscle cells in sphincter of Oddi=spasm; severe pain and cramping in RUQ.
Use NSAIDs like diclofenac or ketorolac for pain control.
New ACE inhibitor in 65 yo woman. Concerned about side effect with initial dose. Which is important to do before starting treatment?
First dose hypotension can be limiting factor when starting ACE inhibitors. They reduce venous return to heart secondary to decrease in angiotensin II levels. Can activate reflex causing vagally mediated hypotension and bradycardia.
Hypovolemic secondary to diuretic therapy, low bp, high renin, hyponatremia, high aldosterone, renal impairment, heart failure=PREDISPOSING FACTORS
Check for thiazide or loop diuretics (hypovolemic and hyponatremic).
ACE inhibitor plus beta blocker (suppresses renin)=No additional antihypertensive effect since both work on RAAS. Nonselective beta blockers in combo with ACE inhibitors increase risk of HYPERKALEMIA
15 yo: 3 mo of periodic sudden onset jerking of arms. Aggravated by sleep deprivation. What medication should he take?
Valproic acid
Has myoclonic seizures, form of generalized epilepsy. Jerking movements but preserved consciousness.
Broad spectrum anticonvulsants: Lamotrigine, levetiracetam, topiramate, valproic acid) treat most seizure types.
Narrow spectrum anticonvulsants: Carbamazepine, gabapentin, phenobarbital, phenytoin) are for focal onset seizures and avoided in generalized epilepsy.
Turner syndrome patients can become pregnant?
Lack of X chromosome–>Ovaries of connective tissue and no follicles or few atretic follicles (streak gonads).
Puberty: Normal pubic hair but no breast development or menarche due to ovarian failure. Elevated levels of gonadotrophins (LH and FSH).
Can become pregnant using donor oocytes and require estrogen and progesterone supplements.
Possibility of aortic dissection or rupture in pregnant Turner syn women. All must undergo med eval.
Half life of drug after single dose?
T1/2=(VdX ln2)/CL
Vd=Volume in distribution
CL=clearance
Ln=natural log of 2 (0.693=approx 0.7)
One half life: 50% of drug remains
Two half lives: 75% of dose is eliminated (50% plus half of 50%)
IL2 stimulates what cells?
IL2 made by helper T cells and growth factor of antigen specific CD4 and CD8 T cells AND B cells AND activates natural killer cells and monocytes.
Anti-tumor effects of IL2: T cells and NK cells
Diabetic ketoacidosis: Serum pH HCO3 and pCO2
Decreased serum pH, decreased serum HCO3, decrease in pCO2. Kidneys try to correct metabolic acidosis via:
- Increased HCO3 reabsorption from urine to buffer extracellular pH.
- Increased H+ secretion: Acidosis increases H+ secretion throughout nephron.
- Increased acid buffer excretion: Kidney uses acid buffers to trap H+ and allow excretion of more acid without lowering urinary pH by a lot. Two most important acid buffers are HPO4 and NH3 (best) which go into urine to buffer excess H+ ions.
H. H influenzae grows around streak of S. aureus why?
H. influenzae requires X factor (exogenous hematin) and V factor (NAD+) to grow. Sheep blood agar plates lack sufficient nutrients and are missing NAD+. Enzymes of beta hemolytic s. aureus lyse RBC then X factor is released and V factor is secreted by staphylococci into growth medium.
Catalase=enzyme in staphylococci but not in streptococi.
Lactose fermentation=E coli
Potter syndrome
Pulmonary hypoplasia, limb deformities, characteristic facies (suborbital creases, depressed nasal tip, low set ears, retrognathia) as a result of oligohydramnios. Bilateral renal agenesis=no fetal urine. Amniotic fluid required for proper lung development.
Maternal megaloblastic anemia: Deficiency of Vit B12 or folate.
Incontinence: Stress, urge, overflow?
Stress: Loss of urethral support and intrabdominal pressure exceeds urethral sphincter pressure. (Urethral sphincter=smooth muscle activity; symp.-contraction; parasymp.-relaxation). 2x as common in women because EUS trauma or pudendal nerve injury in vaginal child birth.Postmenopausal women=low E->Laxity and weakness of pelvic floor support.
Urge: Detrusor overactivity
Overflow: Impaired detrusor contractility; bladder outlet obstruction.
Peroxisomal diseases
Rare errors of metabolism where peroxisomes are absent or nonfunctional. Very long chain and some branches chain fatty acids cannot undergo mitochondrial beta oxidation. Fatty acids metabolized by special beta oxidation (VLC FA) or alpha oxidation (branched FA like phytanic acid) in peroxisomes. VLC FA and branched FA cannot undergo beta oxidation in mitochondria.
Zellweger syndrome: Infants can’t form myelin in CNS: Hypotonia, seizures, hepatomegaly, MR, early death. Defect in peroxisomal alpha oxidation. Treat: Avoidance of chlorophyll in diet.
Mucopolysaccharidoses=Lysosomal dysfunction
Pharyngeal arches
Muscular elements=mesoderm
Bony elements=neural crest cells
First arch: CN 5, maxilla, zygoma, mandible, vomer, palatine, incus and malleus. Muscles of mastication, ant belly of digastricm, mylohyoid, tensor tympani, tensor veli palatini.
Second arch: CN 7. Muscles of facial expression, stylohyoid, stapedius, posterior belly of digastric.
Fourth and sixth arches: Cartilaginous structures of larynx
Adult lead poisoning:
- Colicky abodminal pain, constipation, headaches, impaired concentration, short term memory
- Bluish pigmentation at gum-tooth line
- Wrist drop or foot drop due to perip. neuropathy
- Microcytic hypochromic anemia and basophilic stippling on peripheral smear.
Classic complement pathway
IgG and IgM trigger classical complement after binding C1 molecule. Cl binds to Fc portions of two different Ab. igM is more effective in starting complement cascade because IgM circulates in pentameric form.
Activatoin of complement by IgM is inhibited due to fact that C1 binding site on IgM is hidden while unbound IgM is circulating in planar form. Conformational change after Ag binding.
Von Hippel Lindau:
Rare AD condition: Capillary hemangioblastomas in retina and/or cerebellum and congenital cysts and/or neoplasms in kidney, liver, and pancreas. Pts increased risk for renal cell carcinoma. CLUE: Cerebellar hemangioblastoma in association with congential cysts of kidneys, liver, and/or pancreas.
NF1: neurofibromas and optic nerve gliomas. Lisch nodules: pigmented nodules of iris and cafe au lait spots (hyperpigmented cutaneous macules).
NF2: AD nervous system tumor syndrome in which patients develop bilateral cranial nerve 8 schwannomas and multiple meningiomas
Sturge-Weber: Neurocutaneous disorder: Facial angiomas and leptomeningeal angioams. Ophtalmic and maxiallary divisions of trigeminal nerve=skin involvement is over these two areas. Associated with MR, seizures, hemiplegia, skull radiopacities.
Tuberous sclerosis: kidney, liver, pancreatic cysts. Cortical and subependymal hamartomas. AD. Cutaneous angiofibromas, visceral cysts, renal angiomyolipomas and cardiac rhabdomyomas. Seizures.
Osler-Weber-Rendu syndrome: Hereditary hemorrhagic telangiectasia. AD inheritance of congenital telangiectasias. Rupture of these==>GI bleeding, hematuria, epistaxis. NO CYSTS.
Nonsense, missense, silent mutations, frameshift?
Nonsense: Mutations that introduce a stop codon.
Missense: Mutations that result in change of amino acid.
Silent: Mutations that result in same amino acid (single base substitutions that code for same aa).
Frameshift: Deletion or insertion of bases that are not a multiple of three.
Alter reading frame of genetic code.
Lentivirus subgropu of retroviruses: HIV has what type of genome?
Single stranded positive sense RNA diploid genome.
HIV 1 provirus contains three genes (gag, pol, env) and six regulatory genes (tat, rev, vif, vpr, nef, vpu).
Gag encodes Ag in virion core such as nucleocapsid proteins p24 and p7.
Pol encodes proteins like reverse transcriptase, integrase, and protease.
Env gene indirectly encodes envelop glycoproteins gp120 and gp41.
Rev encodes protein that facilitates transport of unspliced viral transcripts out of nucleus.
HIV tat gene encodes protein that transcriptionally activates other viral genes. Virulence of HIV.
Oxygen Hb dissociation curve
Left shift
Right shift
Left shift: Decreased H+ (increased pH) Decreased 2,3 DPG Decreased temperature Thing LUNGS=Left shift Hb has increased affinity for Hb (lower P50). O2 is less available to tissues.
Right shift: Increased H+ (decreased pH)
Increased 2,3 DPG (chronic lung disease, heart failure, exposure to high altitudes)
Increased temperature
Allows release of more O2 in peripheral tissues (elevated levels of DPG decrease Hb O2 affinity).
Hypoventilation=Respiratory acidosis
Strenuous exercise=decreased tissue pH
Angina pectoris: Nitroglycerin Why does it work?
NITRATES decrease cardiac preload (LV volume during diastole/LV filling volume) by VENODILATION. This decreases myocardial O2 demand and results in venodilation and retention of blood in venous system.
Nitrates have modest dilatory effect on coronary arterioles and can cause decrease in afterload through systemic arteriolar vasodilation. Significant systemic arteriolar dilation can REDUCE coronary blood flow so HIGH DOSES of nitrates are BAD for angina.
Coronary steal syndrome: Pharmacologic dilation of coronary vessels without decreasing cardiac work is BAD. Decrease in blood flow to area of ischemic myocardium because blood will flow though pharm dilated arteries of heart not obstructed by atherosclerotic coronary vessel narrowing (and these vessels are already maximally dilated by innate mechanisms).
Increase in coronary perfusion pressure would require increase in diastolic bp since leaflets of aortic valve are closed and aortic blood flows into coronary arteries. Increased diastolic bp would mean increased afterload against which LV must contract. This would increase cardiac work and myocardial oxygen demand.
ACE inhibitors, ARBs, CCB=Decrease arteriolar resistance and this decreases cardiac work due to decreased AL.
CCB and B-blockers decrease heart rate which is useful in ischemic heart. BUT nitrates actually increase HR due to decrease in arteriolar resistance induced by nitrates.
How does vasodilation work in vascular endothelial cells?
Ach, bradykinin, serotonin, substance P, shear forces stimulate specific membrane receptors to increase cytosolic Ca levels. This causes activation of endothelial NO synthase which synthesizes NO from ARGININE, NADPH, and O2.
NO diffuses into adjacent smooth muscle cells and activates guanylyl cyclase and increases cGMP which activates protein kinase G which causes reduction in cytosolic calcium levels and relaxation of vascular smooth muscle cells.
Minute ventilation: Lung elasticity vs. restriction
Work done against elastic resistance of lung is increased when tidal volume is increased. Work done against airflow resistance is increased when breathing frequency is increased.
Stiff lungs=Increased elastic resistance=Work of breathing is minimized when respiratory rate is high and tidal volume is low. Rapid shallow breaths: Pulmonary fibrosis, pulmonary edema, ARDS.
Diseases that cause high airflow resistance: Asthma, COPD, fixed upper airway obstruction (large goiter) cause patients to breath at lower rate to minimize work of breathing. Slow deep breaths.
Alpha1 anti-trypsin deficiency=panacinar emphysema a type of COPD.
Celiac disease
Small intestinal mucosa become inflamed and atrophic in response to gluten which results in defective mucosal absorption of vitamins and nutrients. Malabsorption of vitamin D occurs due to excess excretion in bulky fatty stools. Resulting decrease in vitamin D levels causes rickets in kids and osteomalacia in adults.
Vitamin D deficiency: Ca and P absorption are decreased. Hypocalcemia causes increased PTH. High levels of PTH induce increase in urinary phosphate excretion.
Oral thrush in adult
White patches on oral mucosa that can easily be scraped off revealing arythematous mucosal surface underneath. KOH treated scrapings will show pseudohyphae and Candida yeast.
Oral thrush=in denture wearers, diabetics, immunosuppressed, steroids, antibiotics, chemotherapy. Common presentation of HIV infection.
Tobacco use can cause leukoplakia (precancerous lesion that manifests as white patches or plaques on oral mucosa but these cannot be easily scraped off).
Campylobacter species
Can be transmitted from domestic animals to humans. Campylobacter is curved Gram negative rod with filament that allows it to move in corkscrew fashion. Inflammatory diarrhea (watery then bloody), cramping, leukocytes in stool, abdominal pain that mimics appendicitis. ASSOCIATED WITH GUILLAIN BARRE.
Acute gastoenteritis in kids and adults. Fecal oral route. Acquired from domestic animals; contaminated food (unpasteurized milk and undercooked poultry).
S. aureus gastroenteritis: Preformed exotoxin associated with consumption of precooked foods, diary products, custard, mayonnaise. Vomiting and abdominal cramps>diarrhea.
Shigella: Fecal oral route; daycare; food contamination.
Bacillus cereus: Steamed/fried rice. Heat stable enterotoxin.
Vibrio parahemolyticus: Contaminated shellfish.
Giardia lamblia: Drinking contaminated water. Camping/hiking.
