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109 Cards in this Set
- Front
- Back
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What exactly is a protein?
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Organic macromolecule made up of linear amino acid chains.
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What is the normal total plasma protein? Normal serum protein?
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Plasma: 6.3 - 8.7 mg/dL
Serum: 6.0 - 8.4 mg/dL (Serum is the plasma values minus 3) |
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What is the difference between serum and plasma?
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Serum = no fibrinogen/clotting factors
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What are the 5 main characteristics of proteins that determine whether they can pass through the glomerular membrane?
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Size
Charge pH Mass Isoelectric point |
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What type of kidney damage causes the appearance of small proteins in the urine? Why?
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Tubular disease - damaged tubules are no longer reabsorbing the small proteins.
Small proteins pass through the glomerulus in healthy people, it is the tubules' job to reabsorb them. |
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What type of kidney damage causes the appearance of large proteins in urine? Why?
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Sever glomerular damage - the membrane is damaged and larger proteins than should be able to fit through the pores are getting through.
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What protein is normally found (to a certain threshold) in urine?
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Albumin
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List at least 5 biological functions of enzymes.
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Hormones
Immunoglobulins Transport proteins (of oxygen, hemoglobin, etc) Coagulation factors Cellular signalling Structural strength Maintain acid-base balance Acute phase reactants |
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What are the 6 positive acute phase reactants?
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alpha-1-antitrypsin
alpha-1-acid glycoprotein haptoglobin ceruloplasmin C3/C4 C-reactive protein |
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What are the 3 negative acute phase reactants?
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Pre-albumin
Albumin Transferrin |
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What are the two primary functions of albumin?
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Maintain colloidal osmotic pressure.
Major binding and transport protein (maintain balance of theraputic drugs and bound vs free calcium) |
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Decreased albumin is indicative of what 4 conditions? Why is it indicative?
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Analbuminemia (genetic, abnormal lipid transport)
Hepatic Disease (not being made, classic marker) Glomerular damage (urinary loss) Inflammation (neg APR) |
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A patient demonstrates an elevated albumin level. Is this cause for concern, and why.
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No, isn't clinically significant unless exceeds certain threshold.
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A standard gel electrophoresis is performed. Is pre-albumin visible? Where does it appear?
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No, only visible in high-resolution protein electrophoresis.
Would appear before albumin band. |
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What is the main function of pre-albumin?
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Transport protein for T3 and T4 thyroid hormones.
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A patient with decreased pre-albumin levels might have what wrong with them? 3 main things - what is the biggest?
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Biggest is liver dysfunction/damage (isn't being made).
Malnutrition Inflammation |
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A patient has decreased pre-albumin, decreased albumin, elevated CRP, and elevated haptoglobin. What condition do they most likely have?
Explain. |
Generalized inflammation.
Pre-albumin and albumin decrease in cases of liver damage and inflammation, but if it was liver damage the positive APRs (CRP, haptoglobin) would not be elevated. |
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What is the main function of alpha-1-antitrypsin?
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Acts as an anti-protease and stops tissue breakdown.
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What positive APR has a particular association with emphysema? Why?
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alpha-1-antitrypsin.
It is an anti-protease that acts against neutrophil-released elastase that breaks down elastin in the pulmonary tract. Without it, nothing stops the elastase. |
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Which is more important in the clinical laboratory, alpha-1-acid glycoprotein or alpha-1-antitrypsin?
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alpha-1-antitrypsin
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A patient with a deficiency in alpha-1-antitrypsin might have what 3 generalized conditions?
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Genetic deficiency/congenital decrease.
Protein loss disorders. Liver disease. |
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What is the main function of alpha-1-glycoprotein?
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Binds and inactivates some hormones and drugs.
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Pregnancy screenings are performed on a woman and alpha-1-fetoprotein appears to be increased. What does this mean?
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Neural tube defect, developmental abnormalities, multiple fetuses.
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An enzyme panel is performed on a 15 year old, and alpha-1-fetoprotein comes back elevated. What could cause this?
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Hepatocellular tumor.
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What is the main purpose of haptoglobulin?
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Irreversibly binds free hemoglobin.
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What type of conditions cause elevated haptoglobin? (4)
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Hemolytic issues; intravascular hemolysis.
Nephrotic Syndrome. Biliary obstruction. Inflammation. |
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What occurs during biliary obstruction?
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A blockage in the bile duct causes a buildup of toxic material. The toxic material backs up and damages the liver, as well as causing inflammation - though liver damage occurs, it is still from POST biliary disease.
Haptoglobulin is increased because it is trying to bind the toxic hemoglobin that has built up. |
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When is haptoglobulin decreased? Why? (2)
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Intravascular hemolysis (busy binding up the free Hg).
Liver disese (production) |
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What protein, when increased in urine, is a particularly good marker of glomerular problems such as nephrotic syndrome?
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Any large protein, but especially alpha-2-macroglobulin.
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What does alpha-2-macroglobulin do?
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Protease inhibitor and binds generic foreign substances.
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What is the main function of ceruloplasmin? What is it's secondary function?
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Main binding and transport protein for copper
Assists with the incorporation of iron into transferrin (oxidation-reduction reactions). |
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What is a characteristic finding in Wilson's Disease?
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Decreased ceruloplasmin and subsequent appearance of copper deposits in tissues, especially the liver.
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What type of APR is ceruloplasmin?
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Late-positive
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What four conditions cause decreased ceruloplasmin?
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Genetic
Liver disease Wilson's Disease Neurologic/Renal protein loss |
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What does transferrin do in the body?
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Provides most of iron binding capacity; transports iron
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What happens to transferrin in iron deficiency anemia?
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Increases, remains unsaturated. Excess production trying to "find" any iron that may be present in the body.
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If transferrin is slightly low but highly saturated, what is wrong with the patient?
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Iron cannot be incorporated into red blood cells - the transferrin has picked all of it up but can't do anything with it.
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How are complement factors C3 and C4 related to hepatic disease?
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Are synthesized in the liver and will appear decreased in severe liver disease or damage.
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Why is complement, especially C3 and C4, a positive APR?
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Inflammation triggers cells to release cytokines that tell the liver to produce more complement.
C3 and C4 are the complement factors that appear in the highest levels in the body. |
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beta-2-microglobulin is independently prognostic for what hematologic cancer?
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Acute Myeloid Leukemia
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What cell-surface protein is useful in monitoring renal tubular disease and transplant rejection?
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beta-2-microglobulin.
Very small, so if it appears in urine it means tubules aren't reabsorbing correctly. |
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What are the four main protein measurement methods/assays?
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Colorimetric Assays.
Immunochemical Assays (nephelometry, turbidometry. enzyme immunoassay). Electrophoresis. Immonofixation electrophoresis. |
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What pH is used in serum protein electrophoresis? Why?
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8.6
all proteins have net negative charge at this pH. |
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What are the 5 major electrophoretic regions?
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Albumin
alpha-1 alpha-2 beta gamma |
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What is electroendosmosis?
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When negatively charged gamma-globulins move towards the anode instead of the cathode.
hydroxyl ion cloud is attracted to the anode and pushes back the gammaglobulins. |
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What is the healthy reference range and optimal range for the albumin/globulin ratio?
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Healthy: 1.0 - 2.0
Optimal: 1.7 - 1.9 |
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How do you determine the albumin/globuin ratio?
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total protein analysis is both together.
perform albumin test, and subtract that value from the total to get the globulin level. |
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What five broad conditions cause a DECREASED albumin/globulin ratio? (albumin down and/or globulins up)
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Neoplasm
Infection Intestinal disease Liver disease Renal disease |
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What two conditions cause an INCREASED albumin/globulin ratio? What is notable about these?
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Severe hypergammaglobulinemia
Hypothyroidism Notable: the albumin isn't increasing, it's a decrease in globulins. |
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What is the difference between a monoclonal and polyclonal immunoglobulin increase on an electrophoretic scan?
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Monoclonal shows up as a peak in one area of the scan.
Polyclonal shows up as a large "hill" across more than one area of the scan. |
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What conditions cause a monoclonal IgG increase?
hint: both are cancers |
Multiple Myeloma and B-cell tumor
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What condition causes a monoclonal IgA increase?
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Liver cirrhosis (but better cirrhosis tests exist)
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What condition classically causes a monoclonal IgM increase?
hint: learned this in another class too |
Waldenstrom's Macroglobulinemia
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What three generic conditions cause a polyclonal immunoglobulin increase?
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Infection
Autoimmune responses Liver disease |
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What method of urine testing primarily detects albumin?
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Dipstick
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What are two benign form of glomerular proteinuria?
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Exercise-induced
Orthostatic |
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What clearance test measures glomerular function?
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creatinine clearance
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What are the two types of tubular problems?
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Absorption and Secretion problems.
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What is kidney overload?
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When a non-kidney related condition bombards a healthy kidney with protein/toxins so that it cannot keep up with processing.
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What are the three most predominant CNS proteins? What two characteristics do they share in common?
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Albumin, Pre-albumin, Transferrin.
All low molecular weight and negative APR. |
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What are the two main causes of increased CNS protein?
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increased blood-brain-barrier permeability
increased immunoglobulin synthesis due to infection or a demyelination disease (such as MS) |
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What is the normal glucose level in the CSF?
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80 mg/dL
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What are the 4 types of meningitis?
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Bacterial
Fungal Tubercular Viral |
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What type of meningitis is culture negative?
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Viral
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What type of meningitis can produce a normal glucose level?
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Viral, sometime bacterial
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What types of specimen does amino acid screening use?
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blood, urine
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What is the most common cause of an amino acid disorder?
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Genetic abnormality of metabolic pathway that causes the pathway to stop at a certain point.
Either the amino acid isn't produced, or it builds up and can't be broken down, or their byproducts build up and are not removed. |
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What happens if an amino acid disorder isn't treated or detected?
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neurologic issues, often leading to death
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What are the three primary conditions causing secondary aminoaciduria?
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Liver disease (protein synth issue)
Renal tubular dysfunction Malnutrition (body isn't breaking down proteins) |
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What are the four basic components of chromatography?
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Mobile phase
Stationary phase Column/support Separated components |
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Are amino acid screening tests qualitative or quantitative?
What are two types of aa screening tests? |
Qualitative.
Thin Layer chromatography and Photometric Color Screening Tests. |
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Name the four amino acid disorders covered in class:
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Phenyleketonuria
Aklaptonuria Homocystinuria Maple Syrup Urine Disease |
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What enzyme is deficient in phenyleketonuria, and what is the normal function of this enzyme?
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phenylalanine hydroxylase. normally changes phenylalanine to tyrosine, which itself is then changed into other amino acids.
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saproprotein dihydrochloride can be used to treat what?
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people with low levels of phenylalanine hydroxylase, but not those who are entirely deficient.
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What deficiency occurs with alkaptonuria?
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homgenistic acid oxidase deficiency
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What does homogenistic acid oxidase do in the body?
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Breaks down phenylalanine and tyrosine - when they aren't broken down, the body breaks down tyrosine by alternate pathway and creates toxic homogenistic acid.
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What happens to homogenistic acid in the body if it isn't broken down?
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Deposited in connective tissues, causing arthritis, heart problems, kidney stones, and prostate stones.
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What are isoenzymes?
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Groups of related enzymes that can catalyze the same reaction, but have different molecular structures and physical/biochemical/immunological properties.
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What enzyme is deficient in homocystinuria? What does this enzyme normally do?
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Cystathione beta synthase. Normally helps break down homocysteine, sothe homocysteine accumulates and is oxidized to become toxic.
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Why is testing for homocystinuria especially important?
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Symptoms are not immediately apparent.
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What enzyme is deficient in maple syrup urine disease?
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branched chain alpha keto acid dehyrogenase
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What societal factor leads to an increased incidence of MSUD?
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intermarriage within a population
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What is a cofactor?
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A nonprotein entity that must bind to particular enzymes before a reaction can occur.
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What is K(m)
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An expression of the velocity of a relationship between a specific enzyme and substrate under defined conditions.
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What is the fixed-time method of enzyme analysis?
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Reactants are combined, the reaction proceeds for a specific time, then stopped, and the amount of reaction that has occurred is measured.
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What is the continuous-monitoring method of enzyme analysis?
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Reactants are combined, reaction proceeds and is measured at intervals or continuously generally using absorbance. Track linearity.
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What are first order kinetics vs. second order kinetics?
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In first-order, the reaction rate is directly proportional to substrate concentration. In second-order, the reaction rate is proportional to the product concentration.
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List two main characteristics of enzymes:
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High specificity for substrates.
Lower the energy of activation. |
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What pH range and temperature do enzymes function best in?
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pH 7-8
temp 35-37 |
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What are three main cellular enzymes?
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Lactate dehydrogenase
Aminotransferases Alkaline phosphatases |
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What are 3 serine protease procoagulants?
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thrombin
factor XII factor X |
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List 6 secreted enzymes:
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lipase
alpha-amylase trypsinogen cholinesterase prostatic acid phosphatase prostate-specific antigen |
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What are the 4 main enzymes of clinical signifcance?
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ALT Alanine Aminotransferase
AST Asparatate Aminotransferase CK Creatinine Kinase LD Lactate Dehydrogenase |
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In inflammatory liver conditions, is ALT or AST higher?
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ALT
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Where are ALT and AST found?
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ALT = hepatocyte cytoplasm
AST = hepatocye cytoplasm, mitochondria |
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What is cholestasis?
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Bile duct blockage
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If the AST is increased but the ALT is normal, what is most likely wrong?
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heart muscle damage
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What is the main function of kinase/phosphotranferase?
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transfer phosphate groups from ATP to a substrate
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What CK (1, 2, or 3) is elevated in heart disease?
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CK-2 (MB)
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What are the isoenzymes of lactate dehydrogenase?
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LD1 and LD2 = cardiac, kidney, RBC
LD4 and LD5 = skeletal muscle, liver |
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ALP is increased in what conditions (2) and normal in what conditions (general)?
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Increased in biliary obstruction and bone disease, normal in most hepatic diseases
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NTP is short for what?
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5-nucleotidase
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NTP is increased in what condition? What makes it best for monitoring this condition?
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Hepatobiliary disease (bile blockage), is best because it doesn't increase in bone conditions where ALP does.
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Rank ALP, GGT, and NTP in order of usefulness for testing for liver disease
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GGT
NTP ALP |
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What makes GGT ideal for liver disease testing?
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Rises earlier, stays higher longer, doesn't increase in bone conditions
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What are the 3 main pancreatic enzymes?
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amylase
lipase cholinesterase |
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A patient has pancreatitis, but their amylase levels are normal. How is this possible?
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Amylase concentration not associated with severity; also tends to rise quickly then return to normal.
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A person has elevated lipase. Can you definitively diagnose them?
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Good marker for acute pancreatitis but can have elevated lipase without it so no
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What unique problem is cholinesterase testing used to detect?
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insecticide poisoning
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