Cardiac Markers

Approximately every 42 seconds an American will suffer from a myocardial infarction. A MI occurs in a hypoxic state and sections of the heart are unable to get the oxygen it needs. According to the CDC about 610,000 die of heart disease in the United States every year, an occurrence of about 1 in every 4 deaths. Heart disease is the leading cause of death in both men and women.

Also about 47% of sudden cardiac deaths occur outside a hospital environment suggesting that many people with acute heart disease either don’t recognize the early signs or they don’t act on them.

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There are cardiac markers that can give a physician a better picture of what is going on. These are routinely measured in a clinical laboratory and are almost all of the time STAT tests. The quick turn-around-time of these tests is imperative, because the sooner a patient with a heart condition gets treated, the better their prognosis.

The Troponin test is the most sensitive and specific test for myocardial damage. Troponin is released during and MI from the cytosolic pool of the myocytes. Its release is prolonged by the degradation of the actin and myosin filaments. Isoforms of protein, T, and I are specific markers for myocardium. After myocardial injury, troponin is released in 2-4 hours and peaks after 12 hours. It persists for up to 7 days after MI.

The Creatine Kinase-MB test is relatively specific when skeletal muscle damage is not present. Creatine kinase is an enzyme that is present in various tissues and cell types. It catalyzes the conversion of creatine to phosphocreatine utilizing adenosine triphosphate (ATP). The phosphocreatine serves as an energy reservoir in tissues that consumes ATP, especially the skeletal muscle and the brain. When mitochondrial creatine kinase is involved in the formation of phosphocreatine from mitochondrial ATP, cytosolic CK regenerates ATP from ADP and phosphocreatine kinase. In this instance, CK acts as an ATP regenerator. Clinically creatine kinase levels are assayed as a marker for damage of the CK-rich tissues in pathological states of myocardial infarction, rhabdomyolysis, muscle dystrophy, autoimmune diseases, and acute kidney injuries. There are two subunits of the cytosolic CK enzymes; Brain type (B) or Muscle type (M). The two subunits create three different isoenzymes CK-MM, CK-BB, and CK-MB. The different isoenzymes are present in different levels in various tissues. In skeletal tissue CK-MM is predominantly expressed, and in myocardial tissue, CK-MM and CK-MB is measured. Therefore measuring CK-MB levels is a good diagnostic test for heart damage from myocardial infarctions. CK-MB peaks about 10-24 hours after the attack and normalizes within 2-3 days.

Lactate dehydrogenase (LDH) was talked about in one of my previous posts and it can aid in the diagnosis of MI. Although it has been most recently replaced by the more specific and sensitive troponin test. LDH catalyzes the conversion of pyruvate to lactate. LDH-1 is found in the myocardium and LDH-2 is found in the serum. Normally LDH-2 is the predominate isoenzyme, but in cases of MI, LDH-1 is the predominate isoenzyme assayed and found. LDH takes about 72 hours to peak and normalizes within 10-14 days.

Myoglobin is an iron and oxygen binding molecule found in the muscle tissue. Myoglobin is a cytoplasmic protein that only harbors one heme group, although in contrast it has a much higher affinity for oxygen than does hemoglobin because its primary role is to store oxygen, where hemoglobins function is to transport oxygen. It contains a porphyrin ring with a proximal histidine group attached to the iron in its center. Myoglobin is only found in the bloodstream after muscle injury such as rhabdomyolysis. Myoglobin is a sensitive marker for muscle injury, making it a potential marker for MIs. However it lacks specificity and should be taken into account with other clinical findings to make a diagnosis. Myoglobin peaks the earliest of all other cardiac markers, that is within two hours, but it also falls quickly, usually before troponin or CK-MB.

Pro-brain natriuretic peptide is used as marker for acute congestive heart failure. The BNP is a hormone secreted by the cardiomyocytes in the ventricles of the heart in response to stretching caused by increased ventricular blood volume. The actions of BNP cause a decrease in systemic vascular resistance and venous pressure which causes a drop in blood pressure and causes after load. This causes a decrease in cardiac output.

Cardiac markers should be used to add to a clinical diagnosis, they should not be solely used to diagnose a patient with MI or CHF.

-Caleb

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Renal Function Markers

Proper renal function is important in normal homeostasis as they excrete waste products and remove excess fluid through steps of excretion and reabsorption. The kidneys regulate the bodies electrolytes as well as produce hormones such as EPO that stimulates the bone marrow to produce erythrocytes. The kidneys produce a second hormone called renin from the juxtaglomerular cells located in the renal arteries. When renin is secreted it acts on angiotensinogen and converts it to angiotensin I. Angiotensin I is then converted to angiotensin II by angiotensin converting enzyme. Angiotensin II acts on blood vessels and causes vasoconstriction that raises blood pressure.

The kidneys play such an important role in normal physiology that its imperative that they are kept functioning properly. It is common to have screening tests done annually to evaluate renal function. It is not uncommon for a physician to order a renal function test to role out chronic kidney disease (CKD). There are few tests that are important and can paint a picture as to how well the kidneys are functioning. Blood urea nitrogen (BUN) provides a rough measurement of the GFR. Urea is formed in the liver as an end product to protein metabolism. It is a breakdown product from use of amino acids. In impaired renal function, the kidneys will inadequately excrete urea, which elevates blood BUN levels. Serum creatinine is another important indicator of renal health because it is solely excreted by the kidneys. Creatinine is a waste product created by muscle metabolism. Creatinine is synthesized via creatine, phosphocreatine, and adenosine triphosphate (ATP). Creatine is synthesized in the liver and is transported through blood to the other major organs where through phosphorylation is converted to phosphocreatine. Creatine becomes phosphocreatine through a catalytic reaction by creatine kinase. The by-product produced by that reaction is creatinine. Little to no tubular reabsorption of creatinine occurs so if there are elevated levels detected in the blood, it is an indicator of renal impairment. The creatinine levels in the blood and urine can be used to calculate the creatinine clearance which correlates to the GFR.

It is important to note that a creatinine concentration in urine may also be tested during a drug of abuse screen. Normal creatinine levels indicate a test sample is undiluted, therefore if there are decreased levels of creatinine it indicates a manipulated test and the test must be repeated.

The GFR describes the flow rate of filtered fluid through the glomerular capillaries into the Bowman’s capsule per unit time. Its important to note that a normal GFR level decreases with age so that must be taken into account when screening patients with suspected CKD, for example the reference range for GFR in adults age 20-29 is 116, in adults 60-69, the GFR should be around 85. A physician can also properly stage CKD based on ones GFR. A progressively decreasing GFR indicates disease progression and more aggressive treatment needs to be considered. GFR is measured typically using a patients creatinine level in accordance with there age, sex, and body size. There are multiple equations that can be used that have all been validated, but are slightly different. Certain physicians or hospitals may have standardized ways of calculating the GFR. There is the Bedside Schwartz equation which should be used for patients 18 years of age and younger. The Modification of Diet and Renal Disease (MDRD study equation and the Chronic Kidney Disease Epidemiology Collabortion (CKD-EPI) equation are the most commonly used for adults 18 and older.

23ff1_Figure_1_Stage_of_chronic_kidney_disease_by_GFR_and_albuminuria_categories

Physicians may order microalbumin testing to screen individuals who are at high risk for developing CKD, especially diabetics. A urine microalbumin test detects minute levels of albumin in the urine. Albumin is one of the first proteins that be detected in the urine when renal function becomes impaired. Albumin is part of the globular protein family whose main function is to regulate the colloid osmotic pressure. Albumin also serves as a protein carrier for hydrophobic molecules such as lipid-soluble hormones, unconjugated bilirubin, free fatty acids, as well as some types of particular drugs like warfarin and phenytoin.

The kidneys are arguably one of the most important organs in homeostasis and its important that they are functioning properly. There are number of tests that can be performed to test renal function with each one giving a little piece of the puzzle. Physicians can use these tests to rule out CKD, or stage a patients disease progression.

-Caleb