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Common learning issues Test 5 MOSBY’S Urine Osmolality Urine Osmolality • 12-14 hr fluid restriction: >850 mOsm/ kg H2O • Random specimen: 50-1200 mOsm/ kg H2O (depending on fluid intake) • This test is an accurate determination of the kidney's concentration capabilities • Also used to evaluate ADH abnormalities and fluid and electrolyte balance • Measures the number of dissolved particles in the urine • Most commonly measured by determining the freezing point • More exact measurement of urine concentration than specific gravity • because specific gravity depends on the weight and density of particles, temperature, and requires correction for presence of glucose or protein • Urine osmolality is more easily interpreted when the serum osmolality is simultaneously measured • Normal ratio of urine to serum osmolality of 1:3 Urine Osmolality • Increased levels: • SIADH • ADH is inappropriately secreted despite factors normally would inhibit its secretion. As a result, large quantities of water are reabsorbed by the kidney. (Low serum, high urine) • Shock • The normal response minimizes the loss of free body water. The kidney therefore absorb all the free water possible. • Hepatic cirrhosis and CHF • These illnesses are associated with water retention because of reduced perfusion of the kidneys. • Paraneoplastic syndromes associated with carcinoma • Ectopic secretion of ADH. • Decreased levels: • Diabetes insipidus • Insufficient secretion of ADH in context of high serum osmolality, kidneys have diminished concentrating ability (high serum, low urine) • Excess fluid intake • Renal tubular necrosis • Severe pyelonephritis • When kidneys are damaged the concentrating ability can be diminished Blood Culture and Sensitivity • Bacteremia can be intermittent and transient, except in endocarditis or suppurative thrombophlebitis. • Episodes of bacteremia are usually accompanied by chills and fever. Blood drawn at times with these signs increases the likelihood of yielding bacteria on culture. • Draw at least 2 samples from 2 different sites. This helps eliminate growth that may occur as a result of contamination. When both cultures grow the infecting agent, bacteremia exists and is a result of that organism. • If the patient is currently receiving antibiotics, resin can be added to the culture medium to negate the antibiotic effect in the culture. • Cultures ideally are drawn before initiating antibiotics. • Blood drawn from IV catheters are frequently contaminated. Only draw blood from these in cases of suspected catheter sepsis to help identify the causative organism. • Most organisms require 24hrs to grow. 48-72 hours are required for growth and identification of the organism. Anaerobic organisms may take longer to grow. Stool culture • • • Usually performed on patients with unrelenting diarrhea, fever and abdominal bloating. Especially if patient has traveled outside the USA, has been drinking well water, or has been receiving prolonged course of antibiotics. The normal stool flora can become pathogenic is bacterial overgrowth occurs as a result of antibiotics or immunosuppression. Most common bacteria in stool: (in no particular order) • • • • • • • • • Pathogenic Bacteria: • • • • • • Enterococcus Escherichia coli Proteus Pseudomonas Staphylococcus aureus Candida albicans (fungus) Bacteroides Clostridium Salmonella Shigella Camplylobacter Yersinia Pathogenic E. coli, Clostridium, and Staphylococcus Common parasites in stool: • • • • Ascaris (hookworm) Strongyloides (tape worm) Giardia (protozoans) Cryptosporidium (esp in AIDs patients) Note C. difficile normal in stool, problem when overgrown. H. Pylori can be found in stool, usually better cultured from stomach or determined by serologic blood test. Stool Culture • Tape test: • Tests for Pinworms (Enterobius) • Clear tape in patient’s perianal region at night before bedtime. Remove it in the AM before patient leaves bed. Female worm lays eggs at night around this region. • Press sticky side directly onto a glass slide. • Can take up to 6 weeks to isolate. • Parasitic enterocolitis: • These organisms can be grown on a special culture plates. Can also be detected in smears of stool. Urinalysis • Normal: • • • • • Appearance: clear Color: amber yellow Odor: aromatic pH: 4.6-8.0 (avg 6.0) Protein: 0-8 mg/dL • • • 50-80 mg/24 hr (at rest) <250 mg/24 hr (during exercise). Specific gravity: Adult 1.0051.030 (usually, 1.010-1.025) • • Elderly: values decrease with age Newborn: 1.001-1.020 • • • • • • • • Leukocyte esterase: negative Nitrites: none Ketones: none Bilirubin: none Urobilinogen: 0.01-1 Crystals: none Casts: none Glucose: Fresh sample – none • • • • 24 hr spec – 50-300mg/24hr WBCs: 0-4 low power field RBCs: <2 RBC casts: none Urinalysis • • • Indications: used as part of routine diagnostic and screening evaluations can give info on kidneys, performed on essentially everyone If UTI is suspected a clean-catch specimen is obtained and divided. Half is sent to UA the other half is cultured. Laboratory: • • Appearance: should be clear, cloudy indicates WBC, RBC or bacteria. Can also be cloudy due to some food. Color: color indicates concentration (urochrome) of urine and varies with specific gravity. Dilute is straw colored and concentrated is deep amber. • abnormal color may indicate bleeding from kidney (dark red) bleeding from lower UT (bright red) Dark yellow indicates urobilinogen or bilirubin Pseudomonas could cause green urine Beets cause red urine, rhumbarb causes brown urine Porphyria can cause wine-colored or even dark brown urine Chart on p 1002 goes over common drugs that change urine color. • • • • • • Ex (most commonly mentioned from all sources): Rifampin= red/orange urine UA • Odor: normal odor caused by presence of volatile acids. • • • • • • Diabetic ketoacidosis have strong, sweet smell of acetone UTI causes foul odor Fecal odor could be a fistulas Long standing if breaks down and begins to smell like ammonia Some food have characteristic urine odors Genetic disease: Maple syrup urine disease and Phenylketouria • pH • • Kidneys help maintain normal pH homeostasis. They assist in in acid-base balance by resorbing sodium and excreting hydrogen. Alkaline urine: indicates alkalemia, bacteria, UTI or citrus fruits or vegetables, common after eating • • Alkaline causes calcium carbonate, phosphate and magnesium phosphate stones Acidic urine: dehydration, high meats and cranberries, UA • Protein • • • • • • Indicates if glomerular membrane is intact like in glomerular nephritis, protein then seeps into urine and can lead to hypoproteinemia which decreases capillary oncotic pressure causing edema called nephrotic syndrome Proteinuria indicates renal disease or preeclampsia Indicates complications of DM, glomerular nephritis, amyloidosis, multiple myeloma Most commonly lost protein is albumin Over 24 hour period if protein lost is >3000mg/24hrs patient has nephrotic syndrome. Compared to creatinine to control for other factors such as hydration status • • Specific gravity • • • • • • Normal protein/creatinine ration is less than 0.15 High indicates concentrated urine Low is dilute urine Weight of urine compared to that of pure water Chronic diseases associated with low specific gravity measure of hydration status Dehydration causes it to be really high Leukocyte esterase • Positive indicates UTI. Tests form WBCs in urine. UA • Nitrites • Screening for UTI, bacteria produce reductase converting nitrates to nitrites • Ketones • Poorly controlled diabetes and hyperglycemia, massive fatty acid catabolism • Bilirubin and urobilinogen • Conjugated bilirubin is water soluble, indicates disease affecting bilirubin affecting bilirubin metabolism after conjugation or defects in excretion indicate previously suspected liver disease, gallstones, or drug toxicity • Crystals • • • Indicate renal stone formation is imminent Can be with high serum uric acid levels Parathyroid causes high phosphate and calcium crystals Urinanalysis: Casts • Casts Rectangular clumps that form renal distal and collecting tubules, pH must be acidic and urine concentrated. Always indicate renal origin. • Hyaline • • Cellular • Granular • • • • • Conglomerations of degenerated cells • After exercise and renal disease, result from disintegration of cellular material into granular particles within a WBC • Some diseases epithelial cells desquamate into renal tubule fatty droplets become free oval fat bodies or incorporated into proteins associate with nephrotic syndrome or nephrosis, fatty emboli or bone fractures Fatty Waxy • • Conglomerations of protein, proteinuria Cell, hyaline, renal failure or further degeneration of granular casts, associated with chronic renal disease and renal failure or diabetic nephropathy, malignant hypertension, and glomerularnephritis Epithelial • • Shed from bladder from tumor, infection, or polyps Tubule epithelial casts indicate glomerulonephritis • • • Five or more indicate UTI involving bladder, kidneys, or both Inflammatory nephritis, glomerulonephritis pyelonephritis • Bladder, urethral, and ureteral disease, tumor, trauma stones infection, glomerloneprhitis, renal infarct, goodpasture, vasculitis, sickle cell, interstitial nephritis, tubular necrosis, pyelonephritis WBC RBC Urinalysis: quick associations • • • • Bilirubin: Jaundice, hepatitis, fecal contamination of sample Blood: Stones, BPH, infection, Foley cath Glucose: DM, pancreatitis, steroids Ketones: Starvation, high fat diet, diabetic ketoacidosis, vomiting, diarrhea, aspirin overdose • Leukoesterase: UTI • Leukoesterase plus nitrates: 75% of UTI • Neither LE or nitrates: 92% not UTI • Protein: Renal failure, CHF • Glucose, Ketones, Leukoesterase and bilirubin in urine is never normal Arteriography • Injection of radiopaque contrast material (usually iodinated CO2 can be used and an alternative) into arteries, blood vessels can be visualized to determine arterial anatomy, vascular disease or neoplasms. • Catheter femoral or brachial artery and injected while x-ray films are being obtained. • Can see: • • • • • Blood flow dynamics abnormal blood vessels vascular anomalies Normal and abnormal vascular anatomy Tumors Arteriography • Digital subtraction angiography (DSA) • Allows bony structures to be removed from images, this enables better visualization of arteries especially the carotid and cerebral arteries • Renal Angiography • Differentiate cysts from hypervascular cancers (Highly vascular tumors can produce a “blush” of contrast material) • Evaluate blood flow dynamics • Adrenal Angiography • Hyperplasia, benign or malignant neoplasms can be detected • Risk of hemorrhage leading to adrenal insufficiency • With pheochromocytomas risk or hypertensive crisis • Cerebral Angiography • Injected into carotid or vertebral arteries • To ID: Aneurysms, occlusions, stenosis, AVMs, vascular and non-vascular tumors, abscesses, hematoma • Lower-Extremity Angiography • Allows identification and location of occlusions within the abdominal aorta and lowerextremity arteries. Also Aneurysmal dilations, arterial trauma such as intimal tearing, emboli. • Some vasculitis show up as characteristic “beading” Note that iodinated contrast is nephrotoxic DRUGS TO KNOW Drug Uses Side effects Contraindications Therapeutic considerations Captopril Pg 349 Class: ACE inhibitor Mech: decreases conversion of AT I to AT II decreasing arteriolar vasoconstriction, aldosterone synth, renal proximal tubule NaCl reabsorp. and ADH release. Also inhibit degradation of the vasodilator, Bradykinin Indications: • Hypertension • Heart failure • Diabetic Nephropathy • Myocardial Infarction • Angioedema (more frequent in black patients) • Agranulocytosis • Neutropenia • Cough • Edema • Hypotension • Rash • Gynecomastia • hyperkalemia • History of angioedema • Bilateral renal artery stenosis • Renal failure • pregnancy • Given as active drug and processed to active metabolite • Cough and angioedema caused by bradykinin action • Hyperkalemia risk increased when used with potassiumsparing diuretics • First-dose hypotension more common in patients with bilateral renal stenosis Drug Uses Side effects Contraindications Therapeutic considerations Cefazolin Class: Cephalosporins have a six-membered accessory ring attached to the Beta-lactam ring. Mech: Beta-lactams inhibit transpeptidase by forming a covalent (“dead-end”) acyl enzyme intermediate Indication: • Proteus mirabilis • E. Coli • Kiebsiella pneumoniae • Pseduomembranous enterocolitis • Leukopenia • Thromobocytopenia • Hepatotoxicty • Nausea • Vomiting • Diarrhea • Rash • Hypersensitivity to cephalosporins (rarely cross-react with penicillins) • First-generation cephalosporins • Relatively good Grampositive coverage • Sensitive to many betalactamases • • • • • Co-admin with tizanidine • Hypersensitivity • Resistance: thru chromosonal mutations in genes that encode type II tops, or thru alterations in expression of membrane porins and efflux pumps that determine drug lvls in bacteria • Bacteriostatic at low conc. • Bactericidal at high conc. First Aid: 1st Gen Cephalosporins Gram (+) and “PEcK” • Skin and soft-tissue infections • Surgical prophylaxis Ciprofloxacin pg596 Class: Quinolones: inhibitor of topoisomerase Mech: inhibit bacterial type II topoisomerases; causing dissociate of Top II (DNA gyrase) from cleaved DNA, leading to double stranded breaksand cell death Indication: • Gram (-) infections • Common Upper Resp Infections • UTI • GI infections • • • • Cartilage damage Tendon rupture Periph. Neuropathy Increased Intracranial pressure Seizure Severe hypersensitivity reaction Rash GI disturbance (Nausea/ Vomiting, diarrhea) Drug Uses Side effects Contraindications Therapeutic considerations Metronidazole Class : Nitroimidazole Mech: activated by enzymes in parasites and anaerobic bacteria to form reduced cytotoxic compounds (ROS) that damage microbial proteins, membranes, and DNA. Indication: • Anaerobic bacteria • Amebiasis • Giardiasis • Trichomoniasis • • • • Leukopenia Thrombocytopenia Ototoxicity Disulfiram-like effect with alcohol gastrointestinal disturbance H/A, Neuropathy Metallic taste Vaginitis • Hypersensitivity to metroniazole or other nitromidazole agents • Hypersensitivity to parabens (gel formulation) • First trimester of pregnancy • Concomitant alcohol administration leads to disulfiram-like reaction • Active against E. histolytica trophozoites in tissues, but much less active against intraluminal ameba • Individuals with invasive amebiasis are typically treated first with mitronidazole and then with a second agent such as iodoquinol or paromomycin Class: alpha2 adrenergic agonist Mech: selectively activate central alpha2-adrenergic auto-receptors to inhibit sympathetic outflow from CNS Indication: • Hypertension • Opioid withdrawal • Cancer pain • • • • • Bradycardia Hypotension Heart failure Hepatotoxicity (side effects related to depressed sympathetics and increased vagal response) • Not listed • Used for HTN and symptoms of opioid withdrawal From first aid (used for anaerobes below the diaphragm) Pharm 1-liners (DOC for pseudomembranous enterocolitis – C. diff) Clonidine Pg 144 • • • • • Drug Uses Side effects Contraindications Therapeutic considerations Linezolid Class: Oxazolidinones Mech Exact mechanism remains uncertain Indications: • Gram-postive bacterial infections Especially • vancomycin-resistant enterococcus • Methicillin-resistant S. aureus (MRSA) • S. agalactiae • S. pneumoniae (including multidrug resistant strains) • S. pyogenes • Nosocomial pneumonia • Complicated diabetic foot infections • Myelosuppression • Peripheral neuropathy • Optic neuropathy • Gastrointestinal disturbances • Headache • • Linezolid is available in both oral and IV formulations Cisplatin Pg 696 Class: Directly modify DNA structure Mech: Platinum compound that crosslinks intrastrand guanine bases Indications: • Genitourinary • Lung cancer • Nephrotoxicity • Myelosuppression • Peripheral neuropathy • Ototoxicity • Electrolyte imbalance • Severe bone marrow depression • Renal or hearing impairment • Can be injected intraperitoneally for treatment of ovarian cancer • Co-administration of amifostine can limit nephrotoxicity Etoposide aka VP-16 Pg 691 & 697 Class: Antineoplastic agent: Topoisomerase inhibitor Mech: bind topoisomerase II and DNA, trapping the complex in its cleavable state Indications: • Lung cancer • Testicular cancer • Leukemia • Heart failure • Myelosuppression • Alopecia (hair loss) • Rash • GI disturbance • hypersensitivity • Class breakdown: • Antineoplastic-> topoisomerase inhibitors-> epipodophyllotoxin • Action is specific to late S and G phases of cell cycle Hypersensitivity to linezolid Drug Uses Side effects Contraindications Therapeutic considerations Vancomycin pg614 Class: Inhibitor of murein polymer synthesis Mech: Bind to D-Ala-D-Ala terminus of the murein monomer and inhibit PGT preventing addition of murein units to the growing chain Indication: • MRSA (IV admin) • Serious skin infections involving staph or strep (IV admin) • C. Difficile enterocolitis(oral) • • • • • Neutropenia Ototoxicity Nephrotoxicity Anaphylaxis “Red-man syndrome” (flushing and erythroderma) • Drug fever • Hypersensitivity rash • Co-admin with Gentamycin • Solutions containing dextrose in patients with known corn allergy • Increased nephrotox with aminoglycosides • “red-man syndrome” can be avoided by slowing infusion rate or preadministering antihistamines • Resistance: arises thru acquisition of DNA encoding enzymes that catalyze formation of D-Ala-D-lactate • Used for Gram (+) rods and cocci • Gram(-) rods are resistant Methicillin Pg 615 Class: Penicillins: inhibitors of polymer cross-linking Mech: Beta-Lactams inhibit transpeptidase by forming a covalent (“dead-end”) acyl enzyme intermediate Indication: • Skin and soft tissue infections or systemic infection with Blactamase- producing methicillin-senstive S. aureus • All side effects listed are for the other drugs in this class • Hypersensitivity to penicillins • Beta-lactamase resistant (staphlococcal) • Narrow-spectrum antibacterial activity • Gram (+) only • Is a hydrophobic substance • Penicillins have a 5membered ring attached to the betalactam ring For boards this drug is important because of the resistance of MRSA. Methicilin is actually quite toxic (acute interstital nephritis) and rarely used clinically. • MRSA has the gene mecA which changes the binding site. Drug Uses Side effects Contraindications Therapeutic considerations Trimethoprim Pg 579 Class: Antimicrobial dihydrofolate reductase inhibitor Mech: folate analogue; competitively binds microbial DHFR to prevent regeneration of tetrahydrofolate from dihydrofolate Indications: • Urinary Tract Infection • Stevens-Johnson syndrome • Leukopenia • Megaloblastic anemia • Rash • pruritus • Megaloblastic anemia due to folate deficiency • Used with medication below to limit resistance development • Excreted unchanged into urine Class: Antimircrobial dihydropteroate synthase inhibitor Mech: PABA analogue that competitively inhibit microbial dihydropteroate synthase and thereby prevent the synthesis of folic acid Indications: • Pneumocystis carinii pneumonia (CD4<200) • Shigellosis • Traveler’s diarrhea • UTI • Granuloma inguinale • Acute otitis media • • Infants less than 2 months old • Pregnant women at term • Breastfeeding • Megaloblastic anemia due to folate deficiency • Co-administration with PABA • Used with medication above to limit resistance development • Indications listed for TMP/SMX combinations • Compete with bilirubin for binding sites on serum albumin and can cause kernicterus in newborns; can also cause brain damage • “Bactrim” = Trimethoprim/ Sulfamethoxazole Sulfamethoxazole Pg 579 • “Bactrim” = Trimethoprim/ Sulfamethoxazole TMP/SMX is an acceptable appreivation • • • • • • • • Kernicterus in newborns Brain damage in newborns Crystalluria Stevens-Johnson syndrome Agranulocytosis Aplastic anemia Hepatic failure GI disturbance rash Guide to bacterial tests Directly from powerpoint Catalase Test Differentiates -Streptococci (-) from Staphylococci (+) -Clostridia (-) from Bacillus (+) 4/16/2013 • Detects the presence of catalase, and enzyme the converts hydrogen peroxide to water and oxygen. The liberated oxygen causing bubbles. Catalase Test Cocci 4/16/2013 Gram Positive Rod Catalase Test Positive Negative Staphylococcus Positive Negative Bacillus Streptococcus Clostridia COAGULASE Test 4/16/2013 • Detects the presence of coagulase. This enzyme acts with a plasma factor to convert fibrinogen to a fibrin clot • Used to differentiate Staphylococcus aureus (pos) from Staphylococcus epidermidis (neg) KNOW THIS FREAKING FIGURE KNOW THIS ONE TOO