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Definitions!Definitions!Protons Protons ++ are positively charged are positively charged particles particles ((atomic number is the number of atomic number is the number of protons) example H+protons) example H+
Electrons Electrons -- are the negatively are the negatively charged particles that spincharged particles that spinNeutronsNeutrons uncharged particles uncharged particles that spin and are made up of quarks that spin and are made up of quarks ““A neutron walked into a bar A neutron walked into a bar and asked how much for a drink. and asked how much for a drink. The bartender replied, The bartender replied, "for you, no charge." "for you, no charge." -Jaime - Internet Chemistry Jokes-Jaime - Internet Chemistry Jokes
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ACIDACID//BASEBASE BALANCE AND THE BLOOD BALANCE AND THE BLOOD
AcidicAcidic Alkaline (Basic)Alkaline (Basic)
[OH [OH --]][H[H++]]
NeutralNeutral
pHpH
00 141477
AcidosisAcidosis AlkalosisAlkalosis
Normal7.35-7.45Normal7.35-7.45
Venous BloodVenous Blood Arterial BloodArterial Blood
6.86.8 8.08.0
7.47.4
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Small changes in pH can Small changes in pH can produce major disturbancesproduce major disturbances
Most enzymes function only with Most enzymes function only with narrow pH rangesnarrow pH rangesAcid-base balance can also affect Acid-base balance can also affect electrolytes (Naelectrolytes (Na++, K, K++, Cl, Cl--))Can also affect hormonesCan also affect hormones
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The body produces The body produces more acids than basesmore acids than bases
Acids take in with foodsAcids take in with foodsAcids produced by metabolism of lipids Acids produced by metabolism of lipids and proteinsand proteinsCellular metabolism produces COCellular metabolism produces CO22..
COCO2 2 + H + H220 ↔ H0 ↔ H22COCO33 ↔ H ↔ H++ + HCO + HCO33--
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Control of Control of AcidsAcids1.1. Buffer systemsBuffer systems
Take up H+ or release H+ as Take up H+ or release H+ as conditions changeconditions change
Buffer pairs – weak acid and a baseBuffer pairs – weak acid and a base
Exchange a strong acid or base for Exchange a strong acid or base for a weak onea weak one
Results in a much smaller pH Results in a much smaller pH changechange
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Acidosis (392)Acidosis (392)Principal effect of acidosis is Principal effect of acidosis is
depression of the CNS through depression of the CNS through ↓↓ in in synaptic transmission.synaptic transmission.Generalized weaknessGeneralized weaknessDeranged CNS function is Deranged CNS function is
the greatest threatthe greatest threatSevere acidosis causes Severe acidosis causes DisorientationDisorientationcoma coma deathdeath
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AlkalosisAlkalosis Alkalosis causes over excitability of the Alkalosis causes over excitability of the
central and peripheral nervous systems.central and peripheral nervous systems. NumbnessNumbness LightheadednessLightheadedness It can cause :It can cause :
NervousnessNervousnessmuscle spasms or tetany muscle spasms or tetany Convulsions Convulsions Loss of consciousnessLoss of consciousnessDeathDeath
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Anion GapAnion GapThe difference between [NaThe difference between [Na++] and the sum of ] and the sum of [HC0[HC033
--] and [Cl] and [Cl--].].
[Na[Na++] – ([HC0] – ([HC033--] + [Cl] + [Cl--]) = ]) =
140 - (24 + 105) = 11140 - (24 + 105) = 11Normal = 12 Normal = 12 ++ 2 2
Clinicians use the anion gap to identify the Clinicians use the anion gap to identify the cause of metabolic acidosis. cause of metabolic acidosis.
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ELECTROLYTESELECTROLYTES
Calcium (428-429)Calcium (428-429)Sodium(430)Sodium(430)
Potassium(175)Potassium(175)Magnesium(148)Magnesium(148)Phosphorus(170)Phosphorus(170)
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Uncorrected electrolyte abnormalities may Uncorrected electrolyte abnormalities may have life-threatening consequences. have life-threatening consequences. Important electrolytes include-Important electrolytes include-calcium (Ca), calcium (Ca), potassium (K), potassium (K), sodium (Na) and sodium (Na) and magnesium (Mg) magnesium (Mg)
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CALCIUMCALCIUMHypocalcemia Hypocalcemia Symptoms Symptoms Tetany, seizures Tetany, seizures Circumoral numbness Circumoral numbness Paresthesias Paresthesias Carpopedal spasm Carpopedal spasm Latent tetany may result in Trousseau and Latent tetany may result in Trousseau and Chvostek signs Chvostek signs Electrocardiogram (EKG) – prolonged QT, Electrocardiogram (EKG) – prolonged QT, Torsades de Pointes Torsades de Pointes
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HypercalcemiaHypercalcemia
Causes Causes Hyperparathyroidism Hyperparathyroidism Cancer with bone metastasis (in particular Cancer with bone metastasis (in particular prostate and breast) prostate and breast)
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Potassium (K) Potassium (K)
Cellular distribution affected by insulin and Cellular distribution affected by insulin and beta-adrenergic receptors, renal excretion beta-adrenergic receptors, renal excretion 3 mechanisms control potassium 3 mechanisms control potassium Intake Intake Distribution between intracellular and Distribution between intracellular and extracellular fluid extracellular fluid Renal excretion Renal excretion Rapid changes have life-threatening Rapid changes have life-threatening consequences consequences May affect serum pH (inverse relationship) May affect serum pH (inverse relationship)
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HypokalemiaHypokalemia
Defined as: Defined as: Mild: 3-3.2 mmol/L Mild: 3-3.2 mmol/L Moderate: 2.5-2.9 mmol/L Moderate: 2.5-2.9 mmol/L Severe: <2.5 mmol/LSevere: <2.5 mmol/LSymptoms Symptoms May vary from asymptomatic to fulminant May vary from asymptomatic to fulminant respiratory failure respiratory failure Most commonly manifests as weakness, Most commonly manifests as weakness, fatigue fatigue EKG – prolonged QT, Torsade de Pointes EKG – prolonged QT, Torsade de Pointes
Causes Causes Drugs (diuretics, beta Drugs (diuretics, beta agonists) agonists) Diarrhea (laxative abuse) Diarrhea (laxative abuse) Diabetes (uncontrolled) Diabetes (uncontrolled) Inadequate intakeInadequate intake
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HYPERKALEMIAHYPERKALEMIADefined as: Defined as: Mild: >5.1-6.0 mmol/L Mild: >5.1-6.0 mmol/L Moderate: 6.1-7 mmol/L Moderate: 6.1-7 mmol/L Severe: >7 mmol/L Severe: >7 mmol/L Symptoms Symptoms Usually only occur above 7 mmol/L Usually only occur above 7 mmol/L Muscle weakness, cardiac arrhythmias Muscle weakness, cardiac arrhythmias EKG – peaked waves, widening of QRSEKG – peaked waves, widening of QRS
Causes:Causes:Metabolic acidosis Metabolic acidosis Hypoglycemia Hypoglycemia Rhabdomyolysis Rhabdomyolysis Tumor lysis syndrome Tumor lysis syndrome Drugs Drugs Renal failureRenal failure
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Sodium (Na) Sodium (Na) Normal range: 136-144 mmol/L Normal range: 136-144 mmol/L Sodium-related disorders Sodium-related disorders
Hyponatremia Hyponatremia Defined as <136 mmol/L Defined as <136 mmol/L Symptoms Symptoms Headache, nausea, emesis, lethargy Headache, nausea, emesis, lethargy Severe hyponatremia can cause seizures, Severe hyponatremia can cause seizures, coma, death coma, death
Causes:Causes:thiazide diuretics, osmotic thiazide diuretics, osmotic diuresis, adrenal insufficiency, diuresis, adrenal insufficiency, ketonuria ketonuria syndrome of inappropriate syndrome of inappropriate antidiuretic hormone (SIADH), antidiuretic hormone (SIADH), hypothyroidism, HIV, certain hypothyroidism, HIV, certain forms of cancer forms of cancer psychogenic polydipsia, psychogenic polydipsia, multiple tap water enemas, multiple tap water enemas, congestive heart failurecongestive heart failure
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HypernatremiaHypernatremiaDefined as serum sodium >144 mmol/L Defined as serum sodium >144 mmol/L Symptoms:Symptoms:Mimics symptoms of hyponatremiaMimics symptoms of hyponatremiaCauses Causes Insensible losses (e.g., fever) Insensible losses (e.g., fever) Diabetes insipidus (central, nephrogenic) Diabetes insipidus (central, nephrogenic) Cushing disease Cushing disease Hyperaldosteronism Hyperaldosteronism
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Magnesium (Mg) Magnesium (Mg)
Physiologically – magnesium aids in Physiologically – magnesium aids in cellular cellular transport of Ca, Na, K transport of Ca, Na, K Balance maintained by kidneys Balance maintained by kidneys Normal range in serum: 1.6-2.6 mg/dL Normal range in serum: 1.6-2.6 mg/dL
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HypomagnesemiaHypomagnesemia
Is a common disorderIs a common disorder Symptoms Symptoms Neurologic manifestations similar to Neurologic manifestations similar to
hypocalcemia hypocalcemia Tetany, muscle weakness, Chvostek and Tetany, muscle weakness, Chvostek and
Trousseau signs Trousseau signs EKG – widening QRS or QT and peaked T EKG – widening QRS or QT and peaked T
waves, premature ventricular contractions waves, premature ventricular contractions (PVCs) (PVCs)
Causes Causes Gastrointestinal losses – diarrhea, small Gastrointestinal losses – diarrhea, small bowel surgery, malabsorption, pancreatitis bowel surgery, malabsorption, pancreatitis Renal losses – diuretics, nephrotoxic Renal losses – diuretics, nephrotoxic drugs, tubular necrosis drugs, tubular necrosis Uncontrolled diabetes mellitusUncontrolled diabetes mellitus
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Hypermagnesemia Hypermagnesemia
Defined as serum Mg >2.6 mg/dL Defined as serum Mg >2.6 mg/dL Symptoms Symptoms Usually mild elevation and therefore no symptoms Usually mild elevation and therefore no symptoms Symptoms when Mg ≥4 mg/dL Symptoms when Mg ≥4 mg/dL 4-6 mg/dL: nausea, lethargy, flushing 4-6 mg/dL: nausea, lethargy, flushing 6-10 mg/dL: somnolence, hypocalcemia, 6-10 mg/dL: somnolence, hypocalcemia, hypotension, bradycardia hypotension, bradycardia >10 mg/dL: respiratory paralysis, complete heart >10 mg/dL: respiratory paralysis, complete heart block, cardiac arrestblock, cardiac arrest
Causes Causes Impaired renal function Impaired renal function Patient receiving large load of Patient receiving large load of magnesium or magnesium-containing magnesium or magnesium-containing drugs drugs Parenteral magnesium therapy Parenteral magnesium therapy for preeclampsia for preeclampsia Elderly patients with gastrointestinal Elderly patients with gastrointestinal disease on catharticsdisease on cathartics
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PhosphorusPhosphorusPhosphates are vital for energy production, muscle and nerve function, and Phosphates are vital for energy production, muscle and nerve function, and bone growth bone growth An important role as a buffer, helping to An important role as a buffer, helping to maintain the body’s acid-base maintain the body’s acid-base balance balance 70% to 80% as calcium phosphate –70% to 80% as calcium phosphate – bones/teethbones/teeth10% in muscle10% in muscle1% in nerve1% in nerveBeans, peas and nuts, cereals, dairy products, eggs, Beans, peas and nuts, cereals, dairy products, eggs, beef, chicken, and fish beef, chicken, and fish
contain significant amounts of phosphoruscontain significant amounts of phosphorusIntestinal absorption and renal excretion maintains blood levels Intestinal absorption and renal excretion maintains blood levels
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PhosphorusPhosphorusPhosphorus testing often is performed as a Phosphorus testing often is performed as a follow-up to an abnormal calcium level and/or follow-up to an abnormal calcium level and/or related symptoms, such as fatigue, muscle related symptoms, such as fatigue, muscle weakness, cramping, or bone problemsweakness, cramping, or bone problemsTo ensure patient is not excreting or retaining To ensure patient is not excreting or retaining excessive amounts in the presence of kidney excessive amounts in the presence of kidney disorder, kidney stones, or uncontrolled disorder, kidney stones, or uncontrolled diabetesdiabetes
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PhosphorusPhosphorusAlso known as P, PO4, Phosphate Also known as P, PO4, Phosphate When to get tested?When to get tested?As a follow-up to:As a follow-up to: an abnormal calcium levelan abnormal calcium level kidney disorder kidney disorder uncontrolled diabetes, and uncontrolled diabetes, and On calcium or phosphate supplementsOn calcium or phosphate supplements
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Hypophosphatemia Hypophosphatemia Dietary deficiencies in phosphorus are rare but may be seen with alcoholism Dietary deficiencies in phosphorus are rare but may be seen with alcoholism and malnutritionand malnutritionMay be associated with:May be associated with:Hypercalcemia, especially due to hyperparathyroidism Hypercalcemia, especially due to hyperparathyroidism Overuse of diuretics Overuse of diuretics Severe burns Severe burns Diabetic ketoacidosis (after treatment) Diabetic ketoacidosis (after treatment) Hypothyroidism Hypothyroidism Hypokalemia Hypokalemia Chronic antacid use Chronic antacid use Rickets and osteomalacia (due to Vitamin D Rickets and osteomalacia (due to Vitamin D deficiencies) deficiencies)
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Hyperphosphatemia Hyperphosphatemia May be due to or associated with: May be due to or associated with: Kidney failure Kidney failure Hypoparathyroidism (underactive parathyroid gland) Hypoparathyroidism (underactive parathyroid gland) Diabetic ketoacidosis (when first seen) Diabetic ketoacidosis (when first seen) Phosphate supplementationPhosphate supplementation
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STEP 1: Determine lipoprotein levels - obtain complete STEP 1: Determine lipoprotein levels - obtain complete
lipoprotein profile after 9- to 12-hour fastlipoprotein profile after 9- to 12-hour fast (78) (78)ATP III Classification of LDL, Total, and HDL Cholesterol (mg/dL)ATP III Classification of LDL, Total, and HDL Cholesterol (mg/dL)•LDL Cholesterol - Primary Target of TherapyLDL Cholesterol - Primary Target of Therapy
<100<100 OptimalOptimal
100-129100-129 Near Optimal/Above Near Optimal/Above OptimalOptimal
130-159130-159 Borderline HighBorderline High
160-189160-189 HighHigh
190190 Very highVery high
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Total CholesterolTotal Cholesterol
•<200<200 DesirableDesirable
200-239200-239 Borderline HighBorderline High
240240 HighHigh
HDL CholesterolHDL Cholesterol <40<40 LowLow
6060 HighHigh
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Determine presence of major Determine presence of major risk factors risk factors
Major Risk Factors (Exclusive of LDL Cholesterol) Major Risk Factors (Exclusive of LDL Cholesterol) That Modify LDL GoalsThat Modify LDL Goals
Cigarette smoking Cigarette smoking Hypertension (BP 140/90 mmHg or on antihypertensive Hypertension (BP 140/90 mmHg or on antihypertensive medication) medication) Low HDL cholesterol (<40 mg/dl)* Low HDL cholesterol (<40 mg/dl)* Family history of premature CHD (CHD in male first degree Family history of premature CHD (CHD in male first degree relative <55 years; CHD in female first degree relative <65 years) relative <55 years; CHD in female first degree relative <65 years) Age (men 45 years; women 55 years) Age (men 45 years; women 55 years) * HDL cholesterol 60 mg/dL counts as a "negative" risk factor; * HDL cholesterol 60 mg/dL counts as a "negative" risk factor; its presence removes one risk factor from the total count. its presence removes one risk factor from the total count. Note: in ATP III, diabetes is regarded as a CHD risk equivalent.Note: in ATP III, diabetes is regarded as a CHD risk equivalent.
3333
Identify metabolic syndrome and treat, if present, after 3 Identify metabolic syndrome and treat, if present, after 3 months of TLCmonths of TLC..
Clinical Identification of the Metabolic Syndrome - Any 3 of the FollowingClinical Identification of the Metabolic Syndrome - Any 3 of the Following :
Risk FactorRisk Factor Defining LevelDefining Level
Abdominal obesity*Abdominal obesity* Men Men Women Women
Waist circumference**Waist circumference** >102 cm (>40 in) >102 cm (>40 in) >88 cm (>35 in) >88 cm (>35 in)
TriglyceridesTriglycerides 150 mg/dL150 mg/dL
HDL cholesterolHDL cholesterol Men Men Women Women
<40 mg/dl<40 mg/dl<50 mg/dl<50 mg/dl
blood pressureblood pressure 130/ 130/ 85 mmHg85 mmHg
Fasting glucoseFasting glucose 110 mg/dL110 mg/dL
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Treat elevated Treat elevated triglycerides. (207) triglycerides. (207)
ATP III Classification of Serum Triglycerides (mg/dL)
< 150< 150 NormalNormal
150-199150-199 Borderline Borderline highhigh
200-499200-499 HighHigh
500500 Very highVery high
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Coronary Risk ScreenCoronary Risk ScreenCHOLESTEROL:CHOLESTEROL: is normally synthesized by the liver and is important as a is normally synthesized by the liver and is important as a constituent of cell membranes and a precursor to steroid hormones. Its level in the constituent of cell membranes and a precursor to steroid hormones. Its level in the bloodstream can influence the pathogenesis of certain conditions, such as the bloodstream can influence the pathogenesis of certain conditions, such as the development of atherosclerotic plaque and coronary artery diseasedevelopment of atherosclerotic plaque and coronary artery diseaseTRIGLYCERIDES:TRIGLYCERIDES: Triglycerides are esters of glycerol and fatty acids. Since Triglycerides are esters of glycerol and fatty acids. Since they and cholesterol travel in the blood stream together, they should be assessed they and cholesterol travel in the blood stream together, they should be assessed together.together.HDL:HDL: A complex of lipids and proteins in approximately equal amounts that A complex of lipids and proteins in approximately equal amounts that functions as a transporter of cholesterol in the blood. High levels are associated functions as a transporter of cholesterol in the blood. High levels are associated with a decreased risk of atherosclerosis and coronary heart disease.with a decreased risk of atherosclerosis and coronary heart disease.LDL:LDL: A complex of lipids and proteins, with greater amounts of lipid than protein, A complex of lipids and proteins, with greater amounts of lipid than protein, which transports cholesterol in the blood.which transports cholesterol in the blood.CHOL/HDL RATIO:CHOL/HDL RATIO: A ratio of lipids for determining possible cardiac risk factors. A ratio of lipids for determining possible cardiac risk factors.
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High RiskHigh Risk GroupGroup Have either CAD or any one of five CAD "risk Have either CAD or any one of five CAD "risk
equivalents": equivalents": 1.1. Diabetes mellitus Diabetes mellitus 2.2. Peripheral vascular disease Peripheral vascular disease 3.3. Carotid artery disease Carotid artery disease 4.4. Abdominal aortic aneurysm Abdominal aortic aneurysm 5.5. A calculated 10-year risk for a coronary A calculated 10-year risk for a coronary
event that exceeds 20% event that exceeds 20%
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Characterized by five Characterized by five major major abnormalitiesabnormalities
1. Obesity (central body and visceral)1. Obesity (central body and visceral)
2. Hypertension2. Hypertension
3. Insulin resistance (hyperinsulinemia)3. Insulin resistance (hyperinsulinemia)
4. Glucose intolerance 4. Glucose intolerance
5. Dyslipidaemia5. Dyslipidaemia
3838
Emerging Risk FactorsEmerging Risk Factors
Lipoprotein (a)Lipoprotein (a)C-reactive protein (66)C-reactive protein (66)Homocysteine (133)Homocysteine (133)Prothrombotic factorsProthrombotic factorsProinflammatory factorsProinflammatory factorsImpaired fasting glucose Impaired fasting glucose Subclinical atherosclerosisSubclinical atherosclerosis
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TESTS FOR TESTS FOR ACUTE HEART ATTACKS ACUTE HEART ATTACKS (MYOCARDIAL INFARCTION)(MYOCARDIAL INFARCTION)
CK-II MB (CREATININE KINASE) (88)CK-II MB (CREATININE KINASE) (88)TROPONINS(209)TROPONINS(209)Creatine Kinase (CK)(87)Creatine Kinase (CK)(87)CK is an enzyme found in the heart and muscles. Increased CK-CK is an enzyme found in the heart and muscles. Increased CK-MB is seen with heart muscle damage. MB is seen with heart muscle damage. Increased CK-MM is noted with skeletal muscle injury. Strenuous Increased CK-MM is noted with skeletal muscle injury. Strenuous exercise, weight lifting, surgical procedures, high doses of aspirin exercise, weight lifting, surgical procedures, high doses of aspirin and other medications can elevate CK.and other medications can elevate CK.
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Troponin T (cTNT)Troponin T (cTNT)
Troponin T is a protein found in the blood and is Troponin T is a protein found in the blood and is related to contraction of the heart muscle. related to contraction of the heart muscle. Troponin T is valuable for detecting heart muscle Troponin T is valuable for detecting heart muscle damage and risk. damage and risk.
4242
Ultra Sensitive C-reactive Ultra Sensitive C-reactive Protein (US-CRP)(66)Protein (US-CRP)(66)
Goal values: Goal values: Less than 1.0 mg/L = Low Risk for CVD Less than 1.0 mg/L = Low Risk for CVD 1.0-2.9 mg/L = Average Risk for CVD 1.0-2.9 mg/L = Average Risk for CVD Greater than 3.0 mg/L High Risk for CVD Greater than 3.0 mg/L High Risk for CVD (levels above these ranges indicate (levels above these ranges indicate increased risk for heart and blood vessel increased risk for heart and blood vessel disease)disease)
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B-Type Natriuretic Peptide B-Type Natriuretic Peptide (BNP) blood test (BNP) blood test
BNP is a substance secreted from the BNP is a substance secreted from the ventricles or lower chambers of the heart in ventricles or lower chambers of the heart in response to changes in pressure that occur response to changes in pressure that occur when heart failure develops and worsens. when heart failure develops and worsens. Increases when heart failure symptoms Increases when heart failure symptoms worsen, and decreases when the heart failure worsen, and decreases when the heart failure condition is stable. condition is stable.
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B-Type Natriuretic Peptide B-Type Natriuretic Peptide (BNP) blood test(BNP) blood testBNP levels below 100 pg/mL indicate no heart failure BNP levels below 100 pg/mL indicate no heart failure BNP levels of 100-300 suggest heart failure is present BNP levels of 100-300 suggest heart failure is present BNP levels above 300 pg/mL indicate mild heart failure BNP levels above 300 pg/mL indicate mild heart failure BNP levels above 600 pg/mL indicate moderate heart failure. BNP levels above 600 pg/mL indicate moderate heart failure. BNP levels above 900 pg/mL indicate severe heart failure. BNP levels above 900 pg/mL indicate severe heart failure.
BNP accurately detected heart failure 83% of the time BNP accurately detected heart failure 83% of the time and reduced clinical indecision from 43% to 11%. and reduced clinical indecision from 43% to 11%. -January 2008 issue of the Journal of the American -January 2008 issue of the Journal of the American College of CardiologyCollege of Cardiology
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Homocysteine (Hcy) Homocysteine (Hcy) (133) (133)
An amino acid. High levels are related to early development of heart and blood An amino acid. High levels are related to early development of heart and blood vessel diseasevessel diseaseGoal value: Goal value: less than 10 umol/L less than 10 umol/L High levels of homocysteine are related to the early development of heart and blood High levels of homocysteine are related to the early development of heart and blood vessel disease. In fact, it is considered an independent risk factor for heart disease. vessel disease. In fact, it is considered an independent risk factor for heart disease. High homocysteine is associated with low levels of vitamin B6, B12 and folate and High homocysteine is associated with low levels of vitamin B6, B12 and folate and renal disease.renal disease. For the most accurate results, wait at least two months after For the most accurate results, wait at least two months after a heart attack, surgery, infection, injury or pregnancy to check a heart attack, surgery, infection, injury or pregnancy to check this blood level.this blood level.Evaluation of hyperlipidemia (431)Evaluation of hyperlipidemia (431)