3Anion gap (pages 66-67)A venous blood evaluation of patients with acid-base disordersAttempts to identify cause of the disorder and also to monitor ongoing therapies for acid-base abnormalityTest explanation:Difference between cations and anions in extracellular space(sodium + potassium) – (chloride + bicarbonate) Normal: 12 (+/- 4)Test should be adjusted downwards if potassium is eliminated from test Normal: 16 (+/- 4)Bicarb is actually venous CO2 not arterial bicarb, because test is venous sampleDetermines cause of metabolic acidosis, most acidotic states result in increased AGThe build up of ketoacids and lactic acid will cause increased AGAlbumin is one of the leading factors in increasing AGNephrotic syndrome ( decrease in anions) or increased calcium or magnesium will cause decreased AGIncreased bicarb causes low AGHypoproteinemia and increased immunoglobulins can lower AGGives a complex metabolic picture along with ABGInterfering factors:Decreasing factors: hyperlipidemia, acetazolamide, lithium, polymyxin B, spironolactone, and sulindacIncreasing factors: carbenicillin, carbonic anhydrase inhibitors (acetaloamide), diuretics, ethanol, methanol, penicillin, and salicylateFA Mnemonic: Acidosis w/ increased anion gap: MUDPILESMethanol, Uremia, DKA, Propylene glycol, Iron tablets/INH, lactic acidosis, Ethylene glycol, Salicylates (late)Normal anion gap acidosis: HARDASSHyperalimentation, Addison’s dz, Renal Tubular Acidosis, Diarrhea, Acetazolamide, Spironolactone, Saline infusion
4Anion Gap – Increased and Decreased Values Increased Levels:Lactic acidosis , DKA , alcoholic ketoacidosis , alcohol intoxication, starvation (b/c of increased ketoacids) , renal failure (b/c non-excretion of organic anions decreases bicarb) , diarrhea (loss of bicarb from GI triact) , hypoaldosteronism ( b/c of decreased H+/Na+ pump activity in distal renal tubule)Decreased levels:Excess alkali ingestion , multiple myeloma , chronic vomiting or gastric suction (b/c of loss of gastric acid) , hyperaldosteronism , hypoproteinemia ( b/c loss of anionic proteins increases bicarb), lithium toxicity
5Arterial blood gasesMonitor patients on ventilators, monitor critically ill nonventilator patients, establish preoperative baseline parameters, and regulate electrolyte therapypH –log[H+]Acids normally found in blood: carbonic, dietary, lactic and ketoacidsElevated indicates alkalosisDecreased indicates acidosisNormal pH: (slightly larger range in infants and children)pH (Venous): It is more acidic b/c it contains more CO2
6Blood gasesPCO2Measure of partial pressure of carbon dioxide in the bloodMeasure of ventilation (faster and deeper breathing removes more CO2) PCO2 is a major medullary drive for respiration.10% free floating in plasma, 90% carried by RBCsRespiratory component of acid-base determinationCo2 and pH are inversely proportionalNormal PCO2 = mmHg (again infants and v. young children wider range)PCO2 (venous) = mmHgThis is a measure of partial pressure, don’t confuse with HCO3- concentration.
7Blood gases HCO3- (or CO2 content) Concentration PO2 Measure of the metabolic component of the acid-base equilibriumRegulated by the kidneyDirectly proportional to pH (CO2 would be an indirect measure of bicarbonate)In alkalosis kidneys excrete more into the urine to lower pH (compensating)Adult Normal HCO3-: mEq/mL (infants lower)PO2Pressure of oxygen dissolved in plasmaIndirect measure of O2 contentDetermines effectiveness of oxygen therapyDetermines the force of oxygen to diffuse across the pulmonary alveoli membraneLow if O2 diffusion difficulties (eg Pneumonia, shock lung, congestive failure)Low if ventilation/profusion rations are off (under ventilated or over perfused alveoli)Normal PO2 = mmHg (newborns less)PO2 (venous) = mmHg
8Blood gases Oxygen saturation Oxygen content Base excess/deficit Percentage of hemoglobin saturated with oxygenAs PO2 decreases so does saturation of hemoglobin (think about the sigmoidal shape of the disassociation curve >75% stat, things are going very badly for the patient)Normal Adult/Child O2 saturation = 95%-100%Oxygen contentThe amount of oxygen in the bloodNearly all of it is bound to hemoglobinArterial: vol%Venous: vol %Base excess/deficitAmount of anions in the blood, bicarbonate being the largest. Also hemoglobin, proteins, phosphates.Normal Base Excess = 0 +/- 2 mEq/LNegative base excess indicates metabolic acidosis (eg lactic acidosis)positive alkalosis (either metabolic or compensation to prolonged respiratory acidosis)Alveolar to Arterial O2 differenceNormally should be <10 mmHg
9How to interpret ABG levels 1. Evaluation the pHIf the pH is < acidosis is presentIf the pH is > alkalosis is present2. Next look at the PCO2 (careful: text same, order different from book)A. If the PCO2 is high with acidosis = Respiratory acidosis (primary problem is with decreased breathing eg drugs or lung disease)B. If the PCO2 is low with acidosis = Metabolic acidosis (with increased ventilation to blow off of CO2)C. If PCO2 is high with alkalosis = Metabolic alkalosis (with compensatory retention of CO2, down ventilation)D. If PCO2 is low with alkalosis = Respiratory alkalosis (Primary problem is hyperventilation)3. Next look at the bicarbonate ion (HCO3-)Respiratory acidosis you would expect to see high HCO3- [kidneys compensating with increased reabsorption]Metabolic acidosis you would expect to see a low HCO3- [lack of bicarb is part of primary problem Ex: diabetes, renal failure]Metabolic alkalosis you would expect to see a high HCO3- [excess bicarb is part of primary problem Ex: prolonged vomiting]Respiratory alkalosis you would expect to see a low HCO3- [kidneys decrease reabsorption to compensate]
10CholesterolNormal Findings:Adult: <200 mg/dLChild: mg/dLNewborn: mg/dL-Needed for production of steroids, sex hormones, bile acids, and cellular membranes-The main lipid associated with arteriosclerotic disease-Metabolized by the liver-75% bound inside LDL and 25% is in HDL- Main component of LDL (minimal in HDL and VLDL)- Testing is typically part of a lipid profile (by itself is not an accurate predictor of heart disease)- Individual cholesterol levels can vary daily by 15%-Positional changes affect levels (15% decrease seen in lateral recumbent position, often seen in hospitalized patients)-Repeat tests should be done for abnormal values and an average will be established-Used to predict risk of CHD within the Framingham Coronary Prediction algorithm (determines overall risk of ischemic event)
11CholesterolIncreased levels: liver disease, pregnancy, oorophorectomy, postmenopausal status, familial hyperlipidemias or hypercholesterolemias, hypothyroidism, uncontrolled diabetes mellitus, nephrotic syndrome, xanthomatosis, hypertension, atherosclerosis, biliary cirrhosis, stressDrugs that increase levels: adrenocorticotropic hormone, anabolic steroids, beta-adrenergic blocking agents, corticosteroids, cyclosporine, epinephrine, oral contraceptives, phenytoin, sulfonamides, thiazide diuretics, and vit D
13Creatinine kinase Isoenzymes: CK-MM: 100%, CK-MB: 0%, CK-BB: 0% Adult/elderly (values higher after exercise): units/L (males); units/L (females)Newborn: units/LIsoenzymes: CK-MM: 100%, CK-MB: 0%, CK-BB: 0%This test is used to support the diagnosis of myocardial muscle injury…it can also be used to indicate neurologic or skeletal muscle diseases.CK is predominantly found in heart muscle, skeletal muscle, and brain…CK levels elevate when muscles or nerve cells are damaged:Rise within 6 hrs. after damageLevels peak at 18 hours (if damage is not persistent)Return to normal in 2-3 daysInterfering Factors:IM injections, strenuous exercise, early pregnancy, muscle massDrugs that cause increased CK levels: alcohol, amphotericin B, ampicillin, anesthetics, anticoagulants, aspirin, colchicine, dexamethasone, lithium, lidocaine, morphine, statins.
14Creatinine kinaseElectrophoresis is used to detect the 3 CK isoenzymes:CK-BB (CK1): Found predominantly in the brain and lungCK-MB (CK2): specific for myocardial cells.Rise 3-6 hrs. post-infarction, levels peak at 12-24hrs., return to normal in hrs.Do not usually rise with transient chest pain cause by angina, PE, or CHF.Will see a rise in patients with shock, malignant hyperthermia, myopathies, or myocarditis.CK-MB levels used to determine the appropriateness of thrombolytic therapy (MI)CK-MM (CK3): makes up almost all of the circulatory total CK enzymes in healthy people. Increases in CK-MM suggest skeletal muscle damage.*See Chart p. 201—levels of Troponin, CK-MB, and Myoglobin post-MI*
15Creatine kinase, pp.CK is the main cardiac enzyme used to detect MI…others used include: Lactic dehydrogenase (LDH), and aspartate amino transferase (AST)*See Chart p. 201—levels of Troponin, CK-MB, and Myoglobin post-MI*AVOID IM injections in patients with cardiac disease (they cause elevated CK levels)Interfering Factors:IM injections, strenuous exercise, early pregnancy, muscle massDrugs that cause increased CK levels: alcohol, amphotericin B, ampicillin, anesthetics, anticoagulants, aspirin, colchicine, dexamethasone, lithium, lidocaine, morphine, statins.
16D-dimerNormal Findings: <0.4 mcg/mLELISA and ELFA test, (Enzyme-linked fluorescent immunoassay is faster and more reliable)D-dimer is used to identify intravascular clotting by assessing both thrombin and plasmin activity. (Disseminated intravascular coagulation).D-dimer is a fibrin degradation fragment that is made through lysis of cross-linked (d-dimerized) fibrin. The D-dimer assay provides a highly specific measurement of the amount of fibrin degradation that occurs…normal plasma does not have detectable amounts of d-dimer fragments.
17D-dimerD-dimer may be used in combination with the Fibrin Degradation Products assay for high sensitivity and specificity of disseminated intravascular coagulation (DIC).Levels of D-dimer will increase during thrombolytic therapy of fibrin clots and can be used to determine the duration of anticoagulant therapy in patients with DVT.High D-dimer levels are associated with PE, DVT, sickle cell anemia, and thrombosis of malignancy.
18Factor V-Leiden Normal: Negative FVL The test is used to diagnose factor V-Leiden thrombophiliaFactor V is an important factor in reaction 4 (common pathway) of normal hemostasis. The term “factor V-Leiden” refers to an abnormal form of factor V in which there is a specific glutamine to arginine substitution at nucleotide 1619 in the gene of factor V.FVL is inactivated 10 times slower than regular factor V due to a mutation in the site where protein C normally binds to deactivate and breakdown factor V. Result: increased thombin generation and a mild hypercoagulable state.FVL is the most common hereditary blood coagulation disorder in the US.(5% of Causcasian, 1.2% of Black Americans). Only about 10% of patients with FVL experience a thrombotic event.Testing for FVL is sometimes preceded by a screening coagulation test called the activated protein C (APC) resistance test, used to identify the resistance of factor V to activated protein C.
19Factor V-LeidenIndividuals who are candidates for FVL testing include those who have:Experienced a thrombotic event without any predisposing factorsA strong family history of thrombotic eventsExperienced a thrombotic event before 30 years of ageExperienced DVT during pregnancy or while on birth control pillsHad venous thrombosis at usual sitesExperienced an arterial clot
20Lipoproteins Lipoproteins Should be collected after a 12-14 hour fast. Measured and classified by their density.Interfering Factors: smoking and alcohol ingestion decrease HDL, binge eating alter lipoproteins, HDL values are age and sex-dependent, HDL values (similar to cholesterol) decrease for 3 months post-MI, elevated HDL in hypothyroid, high triglyceride levels make LDL calculations inaccurate.General Categories:Chylomicrons-carry TAGs from the intestine à liver, skeletal muscle, adipose tissueVLDLs- carry newly synthesized TAGs from liver adipose tissue. VLDLs are the predominant carriers of triglycerides. To a lesser degree, VLDLs are also associated with increased risk of CAD because they can be converted to LDL by lipoprotein lipase in skeletal muscle.IDLs- intermediates between VLDLs and LDLs, not detectable in bloodLDLs- carry cholesterol from liver cells of the body. “bad cholesterol”HDLs- collects cholesterol from the body’s tissues and brings it back to the liver, protective effect against heart disease. Out of the 5 subclasses of HDL, only 2b is cardioprotective
21LipoproteinsRisk for Coronary Heart Disease Based on Ratio of Cholesterol to HDLHigh levels of LDLs are atherogenic…target levels vary according to risk profile of patient (see p. 359). LDL= total cholesterol- ((TGs/5)-HDL). SGGE divides LDL into 7 classes based on particle size. IIIa and IIIb are the most commonly elevated forms, IVa and IVb are associated with aggressive arterial plaques (nearly all patients with IVa and IVb levels greater than 10% of total LDL have a cardiovascular events within months!)LDL patterns have been identified to assess risk of CAD:(LDLs can be lowered with diet, exercise, and statins)LDL Pattern A: mostly large LDL particles, no increased risk for coronary artery disease (CAD)LDL Pattern B: mostly small LDL particles associated with increased risk for CADIntermediate pattern: small and large LDL molecules, carries an intermediate risk.
22Lipoproteins Lipoproteins- accurate predictor of heart disease -Proteins in the blood whose main purpose is to transport cholesterol, triglycerides, and other insoluble fats-Used as markers to indicate the levels of lipidsRisk of CHDMaleFemale½ the average3.43.3Average (3:1)5.04.42x average (moderate)10.07.03x average (high)24.011.0Risk for Heart DiseaseMaleFemaleHigh60 mg/dL70 mg/dLModerate45 mg/dL55 mg/dLLow25 mg/dL35 mg/dL
23Prothrombin time Adequacy of extrinsic system and common pathway Activation of factor X in the presence of factor V and phospholipid and calciumStimulates platelet aggregation and converts fibrinogen to fibrin in clot stabilizationTests:Factors I (fibrinogen), II (prothrombin), V, VII, and X
24PTHepatocellular liver disease (cirrhosis, hepatitis, neoplastic invasive processes) Factors I, II, V, VII, IX, XObstructive biliary disease bile necessary for fat absorption decreases A,D,E and K are all fat soluble. II, VII, IX, X all dependent on vitamin K, differentiate from liver disease because it responds to vitamin KCoumarin ingestion (warfarin) interfere with vitamin K associated factors; effects long lasting, can be fixed by vitamin K. Monitors warfarin tx.
25PT and INR Evaluate extrinsic and common pathway Fibrinogen, prothrombin, V, VII, XDecreased levels: hepatocellular disease affect factors I, II, V, VII, IX, and XObstructive biliary disease causes fat malabsorption A, D, E, and K affectedCoumarin (warfarin) ingestionINR is a stardardized ratio to correct for laboratory, environmental variations in clotting time, unrelated to sample quality.Warfarin interferes with vitamin K may be enhanced by aspirin, quinidine, sulfa, and indomethacinBarbituates, chloral hydrate and oral contraceptives cause increased coumarin drug binding decreasing the effectsAlcohol can prolongDiet high in fat or leafy vegetables may shorten OTDiarrhea or malabsorption can prolong
26Troponins Normal Findings: Cardiac Troponin T: <0.2 ng/mL Cardiac Troponin I: <0.03 ng/mLThis test is performed on patients experiencing chest pain to determine if the pain is caused by cardiac ischemia. It is a specific indicator of cardiac muscle injury.Cardiac troponins are biochemical markers for cardiac disease and can actually be used in patients with unstable angina to determine the likelihood of a cardiac event. Their sensitivity and specificity are similar to that of CK-MB (but troponins are even more sensitive)—Cardiac troponin levels become elevated as early as 3 hrs. post-myocardial injury and stay elevated for 7-14 days (7-10 days for troponin I, days for troponin T)ELISA method w/monoclonal Abs—fast, can be done bedside.
27TroponinsIf reinfarction is suspected, troponins may not be as helpful because levels could still be elevated from the first ischemic event. [Stay elevated longer than CK-MB]Cardiac troponins are useful for the following situations:Evaluation of patient with unstable anginaDetection of reperfusion associated with coronary recanalizationEstimation of MI sizeDetection of perioperative MIEvaluation of severity of PECongestive heart failureInterfering factors: Troponin T levels are falsely elevated in dialysis patient.
28Oximetry >95% is normal Monitors arterial oxygen saturation in patients at risk for hypoxemia. Surgery, cardiac stress testing, mechanical ventilation, heavy sedation, lung function testing or traumaNon-invasive measures how many hemoglobin have oxygen attached to themFetal oxygen saturation monitoring: if heart is in distress but saturation is fine you can avoid c-section, placed on cheek between 30 and 70%Interfering factors:Falsely elevated in carboxyhemoglobin poisoningSevere anemiaNail polish (can put monitor on pt’s ear)
29Radiology, Ch 1Be familiar with the different kind of views and when you might use Lateral, versus AP, versus PAEg, PA and AP have similar appearances, but difference in magnification of the heartAP is the standard portable technique w/ the pt sitting or supineThe density of the object determines how much of the x-ray beam will be absorbed or attenuated. As the density of an object increases, fewer x-rays pass through it.Table 1.1-Basic radiograph film densities or appearancesRadiographic films, photographic films and the currently used phosphor plates for digital radiography all respond in a similar manner to light and x-raysAir, Fat-> black on radiograph (fat slightly less so)Bone, Metal, calcium-> whiteOrgans, muscles, soft tissues, shades of gray (50, in fact, referred to as water density)
30Radiology, Ch 1Computed radiography (CR) or digital radiography (DR) is the process of producing a digital radiographic image; instead of film, a special phosphor plate is exposed to the x-ray beam.The intensity of the emitted light depends on local radiation exposureContrast media: The use of intravascular pharmaceuticals to differentiate between normal and abnormal tissues, to define vascular anatomy, and to improve visualization of some organs (use chemically bound iodine)Generally, there is a difference in uptake between normal and abnormal tissues; the whiter the contrast media appears is referred to as enhancementThere are complications using high-osmolar contrast agents in infants and individuals w/ compromised renal functionVomiting, pain at injection site, respiratory sx, urticarial, generalized burning sensationLow osmolar contrast agents reduces these, but not for pts w/ nephropathies; alternatives should be sought for pts w/ DM, vascular dz or renal dysfx
31Radiology, Ch 1Uses for iodinated compounds: angiography, myelography, arthrography, CTAngiography: injection of iodinated contrast media directly into a vein or artery via a needle/catheterArthrography: injection of contrast media or air into a joint; less important since the invention of CT and MRIAir can improve contrastMyelography: placement of contrast media in the spinal subarachnoid space, especially by LP; useful for dx of dz near the spinal canal/cordAlso generally less useful since the invention of CT/MRIBarium is used for contrast in the GI tract (introduced by swallowing, an intestinal tube, or an enema); called a double-contrast studySafer, better tolerated, sensitive, specific; lower concentration, not volume can be used for bowel visualization in CTBarium studies are contraindicated if there is any potential for extravasation of the barium into the mediastinum or peritoneumUse water-soluble contrast agents in this caseStandard iodinized compounds are NOT used in MRIUse gadolinium; other medals like iron oxideGadolinium does NOT produce an MR signal but causes changes in local magnetic fields by inducing TI shortening in tissues where it has localizedUseful for imaging tumors, infx, cerebral vascular accidentsLesions will be whiter than the surrounding tissuesGadolinium is low-risk for rxns, but can cause a severe connective tissue disorder called nephrogenic sclerosing fibrosis; usually only happens in pts on dialysis or creatinine clearance e< 30 mg/DLBottom line on gadolinium-consult a radiologist before doing a gadolinium study on pts w/ renal dx
32Radiology, Ch1CT-sectional anatomy imaging in the sagittal, coronal, axial planes (Fig 1.7)Looks at “slices of bread” as opposed to the “whole loaf”)CT images are produced by a combination of x-rays, computers and detectorsPts generally don’t have problems w/ breath holding since images only take a few secondsAverage scan takes minutesSee figsAs in a radiography, the amount of X-ray beam that passes through each slice is inversely proportional to the density of the tissuesX-rays strike detectors, and the detectors convert incident x-rays to an electron stream; this stream is digitized into CT units or “Hounsfield” unitsDensity principles are the same as radiography; one major difference is that a radiograph displays the entire anatomic structure, whereas a CT image visualizes “slices”Can be accomplished w/ or w/o contrast-contrast will highlight pathologic tissuesContrast not needed for intracerebral hemorrhage, suspected fracture, or fracture fragment within a jointContrast used for evaluating liver, kidney, and brain for suspected neoplasmsTable 1.2-indications for CT imagingHelical-/Spiral CT; patient continuously moves through the gantry (see Fig 1.11)
33Radiology, Ch 1Multislice/Dynamic CT-multiple contiguous rows of detectors w/ only one rotation around the X-ray tube around the pt; large volumes can be scanned at one timeEspecially beneficial in CT angiography, dynamic CTTable 1.3-advantages and disadvantages of multislice CTDual Source: 2 different x-ray energies that originate from a single tube; use multiple detectors and helical scanningGray value in CT images dependent on density, thickness, and energy of x-rays (same object could have different gray values depending on if you used hih versus low energy)Dual energy applications: direct removal of bone for angiographic imagine, plaque characterization, lung perfusion, identifying tendons, ligaments, assessment of tissue compositionRadiation dose is a concern using dual-source scanners
34Radiology, CH 1MRI-essentially the imaging of photons; displays anatomy in the axial, sagittal and coronal plane; slice thickness varies between 1 and 10 mmAlthough the magnetic fields are generally believed to be harmless, caution should be used in the first trimester (teratogenic, possible acoustic damage)Can be a problem for pts w/ claustrophobiaTable 1.4 and 1.5Hydrogen protons absorb the broadcast radio wave energy and resonate; as the protons decay back to normal state and relax, they continue to resonate and broadcast radio waves that can be detected by a radio wave receiver set to the same frequency as the broadcast radio waves and the H+ spin frequencyBottom line: there are many H+ atoms/protons in fat-> the image will be very bright; bone will be blackRadio wave signal intensity is determined by the number of H+ atoms and the T1/T2 relaxation timesT1-if listening early during decay after radio signal discontinuedT2- listening late; water will be a lighter gray and fat appears grayTable 1.6T1 used for anatomic information; T2 used for pathology because pathology has + water/hydrogen and will light up wellT1 has better resolution; T2 has better contrastTo differentiate between CT and MR; look at the fat; subcutaneous fat will be black on CT and white on MRI; bones will have a gray medullary canal and white cortex on radiographs and CT images; on TI MR all of the bone medullary cavities will be white and bone cortex will be black
35Radiology, Ch 1MRA-non-interventional study to image vessels w/o needles, catheters, contrast media (though gadolinium could be used)Flowing blood will be black, but special imagine techniques can light it up3D images of vasculatureImaging arteries/veins in head and neck, abdomen, chest, and extremitiesF-MRIAssesses brain/cardiac function as oxygenated/deoxygenated blood cause variationsIdentifies areas that are active/inactive as working areas of the brain consume more oxygen; changes in hemoglobin oxygenation= BOLD method; Images are T2-weightedGood for cognitive tests
36Radiology Ch 1Functional Cardiac MRI- measures left ventricular volume and ejection fractionDelayed contrast enhancement can distinguish infarct from normal myocardium (bright signal=regions of infarct/scar)Diffusion-Weighted MRISensitive to cell injuries of multiple etiologiesUsed in the diagnosis of ischemic stroke, can reliably detect hypoxic ischemia within minutes of symptom onsetSusceptibility-weighted MRI-sensitive to venous blood hemorrhage and iron storage; useful for assessing TBI, stroke, hemorrhage, MS, tumorsMagnetic Resonance Spectroscopy-metabolite concentrations in the body; protons from water are suppressed so that NAA, choline, creatinine etc can be detected. Used to evaluate lesions to determine cancer, since cancer has shown and elevation of choline and a reduction in NAA. Also used for stroke imaging and inflammatory dz
37Radiology Ch 1 Ultrasonography-Table 1.7 and 1.8 Safe, painless, inexpensive, well-toleratedProduces sectional images in multiple planes (like CT and MRI)Solid organs usually have a homogenous echo pattern; fluid filled organs have fewer “internal echoes”Digitizes sound waves, converting images to black, white and gray
38Radiology 101:Pages 25-32 Reading frontal chest x-ray Designed to look at lungs, not trauma to the ribs etc.R marker should be on your left sideGlance over the image for any obvious abnormality always look at your four cornersAnterior posterior and posteroanteriorStart at top and make sure trachea is midlineMove to heart, transverse diameter of cardiac silhouette should not be more than 50% transverse diameter of thoracic cageGreater the distance between and object and film, the greater the magnification
39Radiology 101: Frontal chest X-ray (continued) Right heart convex, left cardiac border at the top should be concaveLeft ventricle makes up left heartSVC makes straight right borderIn enlargement left superior border becomes convexLeft enlargement cardiac apex moves down and outRight enlarges right border is more protuberantLeft and right pulmonary arteries form hilar shadows, left should be more cephaladAorta forms knobAortopulmonary window between knob and pulmonary artery shadow; should be concave or suspect mass or adenopathy
40Radiology 101:Pages 25-32 Frontal chest X-ray (continued) Mediastinum shadow is caused by great vessels and vascular pediclePedicle extends from thoracic inlet to base of heart; right border is SVC left is aortic knobDivide lungs into horizontal thirdsDomed diaphragm with right side higher than leftLateral costophrenic angles should be sharp and acuteLook at lower cervical spine and ribsRibs we see are posterior arcs anterior ribs are angled downward
41Radiology 101: Lateral radiograph Right ventricle is anterior borderLeft ventricle is inferior-posterior cardiac borderLeft atrium forms superior-posterior cardiac borderIVC can be seen as it enters from abdomenIf left ventricle is 2 cm or more posterior to IVC then it is enlargedEvaluating hila left is posterior to line drawn down from tracheal air column and one third the size of the rightSilhouette sign when two objects of similar density are in direct juxtaposition interface or borders are lost
43Therapeutic considerations DrugUsesSide effectsContraindicationsTherapeutic considerationsAspirin(ASA)MOA-Inhibits synthesis of prostaglandin by cyclooxygenase; inhibits platelets aggregation; has antipyretic (anti-fever) and analgesic activity. Metabolized by the liver.Prophylaxis against transient ischemic attack, MI, acute coronary syndrome, prevent reocclusion, arthritis, mild pain or feverGI bleeding, acute renal insufficiency, thrombocytopenia, Reye dz, asthma, tinnitus, dyspepsia, occult bleeding, prolonged bleeding, rashNSAID induced sensitivity, chickenpox of flu like symptoms, G6PD deficiencyBleeding like hemophilia, von Willebrand thrombocytopeniaInhibit both Cox 1 and 2Use cautiously with GI bleeds impaired renal function, vit K deficiency, purpura, hepatic impairment
44Therapeutic considerations DrugUsesSide effectsContraindicationsTherapeutic considerationsAtenololMOA: Blocks response to beta-adrenergic stimulation; cardio selective for beta 1 receptors at low doses with little to NO effect on beta two (safer in asthmatics) Limited metabolization in liver.Beta-blocker (B1 specific)HTN, angina, thyroid storm, HFAV block, bradyarrythmia, sedation, decreased libido, mask hypoglycemia, depression, dyspnea, wheezingBronchial asthma, COPD, cardiogenic shock, decompensated heart failure, 2nd and 3rd degree AV block, severe sinus bradycardiaBeta one selective adrenergic antagonists
45Therapeutic considerations DrugUsesSide effectsContraindicationsTherapeutic considerationsAtorvastatinPg 330MOA: HMG-COA reductase inhibitor, inhibits rate-limiting step in cholesterol biosynthesis by competitively inhibiting HMG-COA reductaseClass: Inhibitor of cholesterol synthesis (Statin)Mech: inhibits HMG-CoA reductaseIndications:HypercholesterolemiaFamilial hypercholesterolemiaCoronary atherosclerosisProphylaxis for coronary aterosclerosisMyopathy-increased riskRhabdomyolysisHepatotoxicityAbdominal pain (constipation, diarrhea, nausea)HeadacheActive liver diseasePregnancy and lactationUp to 60% dec. in LDL10% HDL increase40% Triglyceride dec.Drug of choice for lowering LDL, one of the most potentMetabolism by P450 3A4Combo with bile acid sequestrant yields lower LDLCo-admin with Niacin-> inc. risk of myopathyCo-admin with gemfibrozil can induce rhabdomyolysis
46Therapeutic considerations DrugClinical appAdverse affectsContraindicationsTherapeutic considerationsAtropineMOA: Antimuscarinic; inhibits action of acetylcholine at parasympathetic sites in smooth muscle, CNS, and secretory glands. Increases cardiac output and dries secretions. Metabolized: LiverAnticholinergic Agent, Anticholinesterase overdose, bradycardia, excessive salivation and mucus production during surgery“No See, No Pee, No Spit, No Sh*t” Blurry vision, xerostomia (dry mouth), constipation, urinary hesitancy, increased IOP, loss of taste, hypotension, confusion, coma, ataxia, insomnia, headache,Actions of PNS inhibitedNarrow Angle glaucomamarginal nicotinic effect; more effective at reversal of exogenous rather than endogenous cholinergic activity
47Therapeutic considerations DrugUsesSide effectsContraindicationsTherapeutic considerationsClopidogrel (Plavix)MOA: Inhibitor of adenosine (ADP)- induced pathway for platelet aggregation.Metabolized in liver by CYP450 enzymes.ACS, recent MI, stroke, peripheral artery disease, CAD, cardioembolic stroke1-10% URI, chest pain, headache, flu like syndrome, arthralgias, pain, dizziness, diarrhea, depression, rhinitis, rash, UTI <1% neutropenia, acute liver failure, TTP, hypotension, hepatitis, myalgia, eczemaActive bleeding disorderNeeds loading dose. Less side effects tha ticlopidneBrand name only FYI, will not be tested on PBL exams as such, not in book.Ticlodipine=same MOA, famous for myelosuppression
48Therapeutic considerations DrugClinical appAdverse affectsContraindicationsTherapeutic considerationsEptifibatide (integrelin)- antiplatelet agentMOA: blocks binding of fibrinogen & von willebrand factor of glycoprotein IIB/IIIA receptor on platelet surface.Acute coronary syndrome, percutaneous coronary interventionMajor bleeding, intracerebral hemorrhage, hypotension, bleedingHistory of bleeding, recent major surgery, recent stroke, intracranial hemorrhage, uncontrolled hypertensionDon’t give with second , second anti GIIb-IIIa agent, minimize arterial and venous puncture, synthetic peptide as parenteral
49Therapeutic considerations DrugClinical appAdverse affectsContraindicationsTherapeutic considerationsHeparin- AnticoagulantMOA:Low dose: inactivates factor Xa and inhibits conversion of prothrombin to thrombinHigh dose: inactivates factor IX, X, XI, & XII and thrombin and inhibits conversion of fibrinogen to fibrin Also inhibits activation of factor VIIIPrevent embolism, thrombosis, prevent systemic embolism with MI, unstable angina, open heart surgery, DIC, maintain patency IV cathHemorrhage, heparin induced thrombocytopenia, hypersensitivity, prolonged clotting time, mucosal ulceration, hematomaHeparin induced thrombocytopenia, active major bleeding, bleeding tendencies, open ulcerative wounds, conditions that increase capillary permeability, severe HTN, bacterial endocarditisUnfractionated causes thrombocytopenia more than LMW, antihistamines, cardiac glycosides, nicotine and tetracycline affect abilityCephalosporins, penicillins, oral anticoagulants, platelet inhibitors may increase affectsDon’t use ginger, garlic, ginkgoLow and high dose, may be a typo, Low molecular weight vs unfractionated?
50Therapeutic considerations DrugClinical appAdverse affectsContraindicationsTherapeutic considerationsMetoprolol (Lopressor) – Beta Blockers, Beta 1 selectiveMOA: Blocks response to beta-adrenergic stimulation; cardio selective for beta 1 receptors at low doses with little to NO effect on beta two (safer in asthmatics) [B2 are in bronchiole smooth muscle, blocking causes bronchoconstriction]Metabolized in liver by CYP2D6.AMI, CHF, HTN, Angina, Hyperthyroidism, Acute Tachy,Side Effects: 1-10% Dizziness, headache, tiredness, depression, diarrhea, pruritus, dyspepsia, heart failure, wheezing, nauseaAsthma or COPD, cardiogenic shock, Decompensated cardiac failure, 2nd & 3rd degree AVBeta 1 selective adrenergic antagonists
51Therapeutic considerations DrugClinical appAdverse affectsContraindicationsTherapeutic considerationsRamipril (Altace) – ACE Inhibitor “End in pril”MOA: Competitively inhibits angiotensin-converting enzymes, resulting in decreased plasma angiotensin II concentrations; BP may be reduced in part through decreased vasoconstriction increased renin, activity, and decreased aldosterone secretion; increases renal blood flowHypertension, heart failure, diabetic nephropathy, myocardial infarction>10% Cough (if cough switch to an ARB), hypotension, 1-10% headache, angina, dizziness, N/V, postural hypotension, syncope, vertigo, <1% angioedemaHx of angioedema, bilateral renal artery stenosis [They depend on RAA axis for renal perfusion], renal failure, pregnacny3 patterns of metabolism: 1) active drug --> active metabolite 2)prodrug -->active drug 3) active drug and excreted unchanged. Cough and angioedema are caused by bradykinin action: potentially life-threatening. Delay progression of cardiac contractile dysfunction in heart failure and after MI, and delay progression of diabetic nephropathy
52(Zocor) – Lipid Lowering Agent, Statin DrugClinical appAdverse effectsContraindicationsTherapeutic considerationsSimvastatin(Zocor) – Lipid Lowering Agent, StatinMOA: HMG-COA reductase inhibitor, inhibits rate-limiting step in cholesterol biosynthesis by competitively inhibiting HMG-COA reductaseHypercholesteremia, familial, coronary atherosclerosis, prophylaxis for coronary atherosclerosisMyopathy, rhaddomyolysis, hepatotoxicity, dermatomyositis, abdominal pain, constipation, diarrhea, nausea, headacheActive liver disease pregnancy and lactationLowering LDL metabolized by P450, 3A4 inhibitors increase risk of myopathy, combo with bile acid sequestrant or cholesterol absorption inhibitor additive decrease in LDL, combo with niacin maybe used in high LDL and low HDL increases risk of myopathy, gemfibrozil decreases statin clearance induce rhabdo
53Therapeutic considerations DrugClinical appAdverse affectsContraindicationsTherapeutic considerationsTissue plasminogen activator (t-PA) (Alteplase, Activase) – ThrombolyticsMOA: Recombinant human tissue-type plasminogen activator (t-pa); produces local fibrinolysis. Promotes thrombolysis by converting plasminogen to plasmin which degrades fibrin and fibrinogen.AMI = acute MI, PE, Acute Ischemic Strokepulmonary edema, arterial embolism, bleeding, DVT, hypotension, intracranial hemorrhage, stroke, fever, chills, N/V, sepsis, shockInternal bleeding, intracranial/spinal trauma, surgery, masses, recent stroke, uncontrolled hypertensionBinds to newly formed thrombi with high affinity, causing fibrinolysis at the site of a thrombusCan generate a systemic lytic state and cause unwanted bleeding
54Hydrocholorothiazide (Maxide,Dyazide) – Thiazide Combos, HTN DrugClinical appAdverse effectsContraindicationsTherapeutic considerationstriamterene/Hydrocholorothiazide (Maxide,Dyazide) – Thiazide Combos, HTNTriamterene – Direct effect on renal distal tubule to inhibit Na reabsorption. Inhibits Na/K-ATPase, decreases Ca and MG and hydrogen excretion=Postassium sparing diureticHCTZ- inhibits Na reabsorption in distal renal tubules; results in increased excretion of Na and water also K and H ions.-is a sulfa drugHTN, adjunct in edema states associated with HF, cirrhosis, renal dysfunction, corticosteroid and estrogenArrhythmia, stevens-johnson, pancreatitis, hepatotoxicity, SLE, hypotension, alkalosis, vasculitis, photosensitivity, electrolyte abnormalities, impotence, restlessness, blurrred vision, headache, hyperglycemia, hyperuricemiaAnuria, hypersensitivity to sulfonamides, co administration with agents that prolong QTFirst line in treating HTN, diminish hypercalcuria in patients at risk for nephrolithiasis, decreases glucose tolerance may unmask diabetes, don’t use with antiarrhythmic
55Therapeutic considerations DrugClinical appAdverse affectsContraindicationsTherapeutic considerationsWarfarin (Coumadin) – AnticoagulantsMOA: Interferes with hepatic synthesis of vitamin K dependent clotting factors II, VII, IX, & X as well as proteins C and S.Venous Thrombosis, DVT, Afib, Cardiac Valve Replacement, Post MI1-10% Intraocular Hemorrhage, UNK Freq – abd pain, rash, pruritus, tissue necrosis, headache, lethargy, anemia, hemorrhage, fever, purple toe syndrome,Pregnancy, Hemorrhage, Bleeding tendency, uncontrolled HypertensionMonitor with PT/INR. Many drug-drug interactions, never give to pregnant woman, can cause skin necrosis, receive fresh frozen plasma if hemorrhaging occurs