What is the average adult daily volume of urine?
Term indicating a greatly reduced volume of urine.
What can cause states of dehydration which lead to oliguria?
- Excessive vomiting
- Severe burns
Term used to indicate a complete cessation of urine flow.
What can cause anuria besides dehydration?
- Serious kidney damage
- Decrease in blood flow to kidney
Termed used to indicate an increase in daily output of urine. What amount is considered an increase?
Polyuria (>3 L/day)
What type of urine specimen can be used for routine screening?
- First morning void
- Midstream clean-catch
What type of urine specimen is typically used for pregnancy tests and orthostatic protein?
First morning void
What type of urine specimen is typically used for diabetic screening/monitoring?
Fasting (second morning void)
What type of urine specimen is typically used for diabetic monitoring only?
What type of urine specimen is used in accompaniment to blood samples in the glucose tolerance test?
Glucose tolerance test
What type of urine specimen is typically used to perform quantitative chemical tests?
24-hr urine collection
What type of urine specimen can be used for bacterial culture?
- Midstream clean-catch
- Suprapubic aspiration
What type of urine specimen is typically used for cytology?
What type of urine specimen is typically used to detect prostatic infection?
What is a cause for proteinuria that is associated with non-renal diseases?
Prerenal proteinuria (multiple myeloma)
What are non-renal diseases that can cause prerenal proteinuria?
- Multiple myeloma
- Congestive heart failure
- Renal hypoxia due to renal artery stenosis
What is proteinuria caused by kidney diseases?
What are causes of renal proteinuria?
- Kidney disease
- Primary/induced glomerular proteinuria
- Tubular proteinuria
What diseases can cause primary glomerular proteinuria (protein leaks through glomerulus)?
- Nephrotic Syndrome
What diseases can cause induced glomerular proteinuria (protein leaks through glomerulus)?
- Systemic disease (diabetes mellitus)
What is tubular proteinuria and what can cause it?
- Defective tubular reabsorption (increased levels of low-molecular weight proteins)
- Caused by acute/chronic pyelonephritis, or drugs/toxins.
What is proteinuria caused by protein from the urinary tract below the level of the kidney parenchyma?
What are causes of postrenal proteinuria?
- Inflammation within the urinary tract, bladder, urethra, prostate gland.
- Contamination with vaginal secretions.
Why may glucose, that is normally reabsorbed in the proximal convoluted tubule, appear in the urine?
Renal threshold for glucose is exceeded.
What level (approximately) of serum glucose needs to be reached for the renal threshold of glucose to be exceeded?
What is the significance of a positive urine ketone result?
Indicates excess amounts of circulating intermediary products of fat metabolism in the blood (ketosis), therefore exceeding renal threshold for ketones.
Describe hematuria with regard to the appearance of urine and serum, and clinical significance.
- Cloudy red (urine)
- Normal color (serum)
- Significance: intact RBCs
Describe hemoglobinuria with regard to the appearance of urine and serum, and clinical significance.
- Clear red (urine)
- Pink to red (serum)
- Significance: abnormal intravascular hemolysis (hemolytic transfusion reaction, burns, strenuous exercise)
Describe myglobinuria with regard to the appearance of urine and serum, and clinical significance.
- Clear red-brown
- Normal color (serum)
- Significance: muscle damage (crushing musculoskeletal injuries, rhabdomylosis, MI)
What is the relationship of urinary bilirubin and urobilinogen to the diagnosis of pre-hepatic disorders?
Increased breakdown of Hgb causes increased levels of conjugated bilirubin which cause an increase in urinary urobilinogen and no urinary bilirubin.
What is the relationship of urinary bilirubin and urobilinogen to the diagnosis of hepatic (hepatocellular) disorders?
Liver is unable to remove reabsorbed urobilinogen from the portal circulation causing increased urinary urobilinogen (or may be absent) and increased urinary bilirubin (varies).
What is the relationship of urinary bilirubin and urobilinogen to the diagnosis of post hepatic disorders?
Intra/extra-hepatic obstruction decreases the normal amount of bilirubin being excreted into the intestinal tract, which causes an increase in urinary bilirubin (spills over) and no urinary urobilinogen (decreased).
What is the clinical significance of a positive urine test for nitrite?
Indicates presence of bacteria in significant numbers due to infection of the urinary system.
How is a positive nitrite result confirmed?
Microscopic examination (urine sediment)
What is the clinical significance of a positive urine test for leukocyte esterase?
Indicates increased number of WBCs in urine (may be due to infection/inflammation of genitourinary system).
What is the relationship between specific gravity and osmolality with regard to urine concentration?
- SG indicates the proportion (ratio) of dissolved solids to the total volume of the specimen (relative degree of concentration).
- Osmolality is a count of the number of particles in a fluid sample (urine/serum).
- (Greater concentration=higher osmolality).
What is the significance of the presence of RBCs in urinary sediment? What can cause this finding?
- Indicates bleeding in the urinary tract (without significant proteinuria).
- Caused by urinary tract stones, benign/malignant UT neoplasms, trauma, prostatitis.
What is the significance of the presence of WBCs in urinary sediment (pyuria)?
Indicates presence of infection/inflammation of the genitourinary system.
What does moderate/heavy proteinuria, WBC casts and hematuria most likely indicate?
What is the significance of the presence of squamous epithelial cells in urine?
- <5 cells/hpf means "clean" sample
- Most frequently seen and least clinically significant.
What is indicated by a urine sample with large numbers of squamous epithelial cells (>10 cells/hpf)? What can this sample not be used for?
- Indicates a poorly collected sample.
- Cannot be sent to micro lab for culture (contaminated).
What is indicated when a urine sample shows large numbers of transitional epithelial cells? What could be expected if the normal indication is not the case?
- Recent instrument procedure (ei, catheterization).
- Suspect a pathologic process if instrument procedure has NOT been performed.
What is indicated by an increased number of renal tubular epithelial cells?
- Severe kidney disease exists.
How are renal tubular epithelial cells that contain lipids described? When are they commonly seen?
- Oval fat bodies.
- Nephrotic syndrome
Where are casts primarily formed?
Lumen of the distal convoluted tubule and collecting duct.
What are factors that enhance the formation of casts? How are they described?
- Acidic pH: casts dissolve at alkaline pH
- High urine concentration: casts dissolve in dilute urine
- Proteinuria: increased protein level necessary for cast formation
- Stasis: diminished urine flow allows proteins to precipitate in tubules
What is the major constituent of casts? How is it excreted?
- Tamm-Horsfall Protein
- Renal tubular epithelial cells
What are the laboratory tests used for diabetic management?
- AMA panel for DM management:
- Basic metabolic panel
- Glycosylated hemoglobin (HbA1C)
- Anion gap
- Lipid profile
- Others to know:
- Ketone bodies
- Microalbumin (early indicator)
Why is HbA1c (glycosylated Hb) useful in monitoring glucose in diabetic patients?
HbA1c concentration represents the blood glucose levels over preceding 6-8 weeks.
What is the significance of elevated ketone bodies in diabetic patients? What causes increased ketone bodies and what can it lead to?
- Increased in uncontrolled diabetes.
- Results from increased lipolysis and decreased reesterification of FA in to TG, increasing circulating free FAs (ketone bodies).
- Leads to accumulation of acetoacetate and b-hydroxybutyrate in blood (ketoacidosis).
What levels of proteinuria define microalbuminuria?
>30, <300 mg/24 hrs of urine albumin excretion (UAE)
What does microalbuminuria (persistent UAE) indicate? What does it not indicate?
- Increase in transcapillary passage of albumin.
- Marker of micro-vascular disease.
- Does NOT indicate smaller than normal sized albumin (greater than normal amount of excretion but less than previously detected levels).
What are the clinically significant electrolytes tested in the laboratory?
What is the importance of electrolyte balance?
All metabolic processes are dependent on or affected by electrolytes.
What are the key roles of electroyltes in the body?
- Water homeostasis
- Acid-base balance (pH regulation)
- Proper heart and muscle function
- Oxidation-reduction reactions
- Enzyme cofactors
Describe sodium with regard to its location, whether it is a cation or anion and its main functions.
- Major cation found in highest concentration in ECF.
- Maintains osmotic pressure and acid-base balance.
What conditions cause hyponatremia (decreased Na)?
- Severe polyuria
- Metabolic acidosis
- Addison's disease (rare endocrine disorder)
What conditions cause hypernatremia (increased Na)?
- Congestive heart failure
- Liver disease (ascites due to osmotic pressure imbalance)
- Renal disease
- Cushing's syndrome
Describe potassium with regard to location, whether it is a cation or anion, and its major functions.
- Major intracellular cation.
- Influences muscle activity of the heart.
What conditions cause hypokalemia (decreased Ka)?
- Prolonged diarrhea/vomiting.
- Inadequate intake of dietary potassium.
What conditions cause hyperkalemia (increased Ka)?
- Kidney dysfunction
- Urinary obstruction
Describe chloride with regard to location, whether it is a cation or anion, and its main functions.
- Major extracellular anion (along with bicarb).
- Found in serum, plasma, CSF, tissue fluid and urine.
- Key role in maintaining osmotic pressure and electrical neutrality (opposes sodium).
What conditions increase chloride levels?
- Congestive heart failure
- Excessive intake
What conditions decrease chloride levels?
- Salt loss (NaCl) as seen in chronic pyelonephritis
- Metabolic acidosis (DKA)
- Prolonged vomiting
Describe bicarbonate with regard to location, whether it is a cation or anion, and its main functions.
- Important extracellular anion (along with chloride).
- Is the main form of CO2 in the body, therefore it serves as a measurement of the metabolic component of the acid-base balance.
Increases or decreases in bicarbonate are not clinically significant without what? How is it evaluated?
- Consideration of the other major anions and cations.
- Evaluated using the Anion Gap
What is the anion gap?
A calculation of the mathematical difference between the anions and cations in the body.
What does an increased serum anion gap reflect?
Presence of unmeasured anions as seen in metabolic acidosis.
What are conditions that can elevate the anion gap?
- Uremia (phosphate, sulfate)
- Diabetic ketoacidosis (acetoacetate, beta-hydroxybutyrate)
- Exercise-induced physiologic anaerobic glycolysis
- Fructose & phenformin administration (lactate)
- Poisoning by methanol (formate), ethylene glycol (oxalate), salicylates
- Therapy with diuretics, penicillin, carbenicillin
What is a decreased anion gap typically associated with?
Increase in unmeasured cations which causes an increase in the corresponding measured anion.
What is a major function of calcium? What happens with hypocalcemia? What causes hypercalcemia?
- Essential for myocardial contraction.
- Decrease impairs cardiac function, produces irregular muscle spasms.
- Increase results from primary hyperparathyroidism or malignancies.
What is the major function of magnesium?
It is an essential cofactor for >300 enzymes.
How does hypomagnesemia manifest itself? In what patients is hypomagnesemia rare?
- Manifests in cardiovascular and neuromuscular systems.
- Rare in non-hospitalized patients.
What is the usual cause of hypermagnesemia?
- Decreased renal function.
- Intake of magnesium containing medication (antacids).
What are the classifications of metabolic disorders?
- Metabolic acidosis/alkalosis
- Respiratory acidosis/alkalosis
What are the characteristics of metabolic acidosis?
Detected by decreased plasma bicarbonate (lost in buffering of excess acid).
What are the characteristics of metabolic alkalosis/how does it occur?
- Excess base is added to the system.
- Base elimination is decreased.
- Acid-rich fluids are lost (ei. gastric contents from vomiting).
What are the characteristics of respiratory acidosis/how does it occur?
Decreased elimination of gaseous CO2 which causes increased retention of dissolved CO2.
What are the characterstics of respiratory alkalosis/how does it occur?
Increased rate/depth of respiration produces excess elimination of acid via respiratory system.
What levels of HCO3 and pCO2 can be expected in metabolic acidosis? How is it compensated for?
- HCO3 is low
- pCO2 is low
- Hyperventilation (excretes CO2)
What levels of HCO3 and pCO2 can be expected in metabolic alkalosis? How is it compensated for?
- HCO3 is high
- pCO2 is high
- Hypoventilation (retention of CO2)
What levels of HCO3 and pCO2 can be expected in respiratory acidosis? How is it compensated for?
- HCO3 is high
- pCO2 is high
- Retention of HCO3 and increased H+ secretion
What levels of HCO3 and pCO2 can be expected in respiratory alkalosis? How is it compensated for?
- HCO3 is low
- pCO2 is low
- Excretion of HCO3 and decreased H+ secretion
Describe urea/urea nitrogen with regards to what it is a component of, what kind of product it is, and its concentration in ICF and ECF.
- Chief component of NPN (renal function) material in blood.
- Principle waste product of protein degradation.
- Equal in concentration in ICF and ECF.
What is increased plasma levels of urea specifically referred to as?
What term loosely describes an increase in all NPN (renal function) compounds?
What by itself is only a rough estimation of renal function, and typically requires <50% glomerular filtration to show clinically significant levels in the blood?
Urea (urea nitrogen/BUN)
What can cause a benign increase in urea?
Increased protein consumption.
Describe creatinine with regard to what it is a product of, the rate in which it is produced and what it is proportional to.
- Degradation product of creatine phosphate in muscle (waste product).
- Produced at a fairly constant rate (readily passed through glomerulus, not reabsorbed).
- Proportional to muscle mass.
What is a rough measure of glomerular filtration and is indicative of the number of functioning nephrons? What amount of substance does it measure?
- Creatinine clearance
- Measure milliliters of plasma cleared of creatinine by the kidneys in one minute.
What are the drawbacks of creatinine clearance as a measure of glomerular filtration?
- Creatinine production has substantial individual variation.
- Can also be derived from dietary meat (may influence values not associated with muscle mass).
- Many interfering substances may alter results.
As a consequence of varying creatinine results, as well as other factors, what has been recommended by the National Kidney Foundation to estimate GFR and what patients it is most useful for?
- Prediction equations.
- Patients with chronic kidney disease.
- Patients at risk for developing chronic kidney disease.
What are the uses for the calculation of glomerular filtration rate (GFR)?
- Detect onset of renal insufficiency
- Adjust drug dosages for drugs excreted by kidneys
- Evaluate therapies for patient with chronic renal disease
- Document eligibility for Medicare reimbursement (end-stage renal disease)
- Accrue points for patients awaiting kidney transplants
Describe phosphorus with regard to its main functions, what it is a component of, and the forms in which it exists in the body.
- Essential for structural integrity of cell membranes.
- Component of nucleic acid and high-energy nucleotides (ATP).
- Key role as a buffer to facilitate excretion of H+ (85% exists as HPO4/H2PO4).
What can cause an increase in phosphorus excretion?
- Renal tubular damage
- Non-renal acidosis
What is the traditional combination of assays for diagnosis of an acute mycardial infarction (heart attack)?
- CK isoenzyme (CK-MB)
Describe myglobin with regard to location, what it is a marker of, and when it is detectable.
- Heme protein found in muscle.
- Early marker of injured muscle tissue (NOT cardiac specific).
- Elevated levels detectable in 1-3 hours.
Describe troponins with regard to its location, what it is a marker of, and when it is detectable.
- Complex of 3 regulatory proteins present in skeletal and cardiac muscle.
- Is the "gold standard" of cardiac biomarkers (TnI & TnT released into circulation after myocardial tissue damage/more specific for heart injuries than other markers).
- Levels remain elevated for days after MI.
Describe creatine kinase (CK) with regard to its location, what it is a marker of, and when it is detectable.
- Found in skeletal muscle, heart muscles, and brain tissue.
- MB (CK-MB) is the most useful marker for evaluating MI.
- Levels increase in 4-6 hours but does not remain elevated as long as troponins.
What is the 32 amino acid polypeptide secreted by the ventricles of the heart in response to excessive stretching of its muscle cells called?
Natriuretic peptides (B-type (BNP), N-terminal pro B-type (NT-proBNP)).
What is the significance of an increase in circulating concentrations of natriuretic peptides? What type of condition and prognosis are levels of BNP or NT-proBNP related to/indicate?
- Circulating concentrations increase in chronic heart failure.
- Levels of BNP or NT-proBNP in blood relate to the severity of heart failure.
- Higher levels of BNP or NT-proBNP also may be associated with a poor prognosis for the patient.
Describe what C-reactive protein (CRP) is, where it is made, and when/why it is secreted.
- It is an acute phase reactant.
- Made by the liver.
- Secreted into the bloodstream within a few hours after the start of an infection or inflammation.
When are increased levels of C-reactive protein (CRP) observed? What can it be valuable for?
- Increased levels are observed after heart attack, in sepsis, after surgery.
- Can be valuable in monitoring disease activity (level can jump thousand-fold due to inflammation).
Is C-reactive protein (CRP) a specific biomarker for diseases or injuries?
No, it is non-specific.
What conditions have studies linked excess homocysteine levels with?
Increased risk for coronary heart disease, stroke, vascular disease.
What causes homocysteine levels to rise?
Folate (B9), B6, or B12 deficiencies.
What is homocysteine as a biomarker useful for?
Potential marker of cardiac disease when there is familial history or lifestyle risk factors.
What are aspartate aminotransferase (AST) and alanine aminotransferase (ALT) responsible for?
Metabolizing aspartate and alanine.
Where are aspartate aminotransferase (AST) and alanine aminotransferase (ALT) found?
- ALT: found primarily in liver and kidney
- AST: found in liver, heart, kidney, pancreas, skeletal muscle
What conditions can cause increases in aspartate aminotransferase (AST)?
Increases are seen in any condition involving necrosis of hepatocytes, myocardial cells, RBCs or skeletal muscle cells.
What general condition of the liver results in increases in both alanine aminotransferase (ALT) and aspartate aminotransferase (AST)? Which enzyme level exceeds the other?
- Inflammation of the liver.
- AST usually exceeds ALT
What can cause liver inflammation, thereby raising levels of ALT and AST?
- Hepatic hypoxia (ei. CHF=chronic heart failure)
- Chemical poisoning (ei. Reye's Syndrome)
- Infectious mononucleosis
- Active cirrhosis (ei. from chronic alcohol abuse)
Which enzyme (AST or ALT) is more specific for hepatocyte damage when present?
Alanine aminotransferase (ALT)
What is the clinical significance of testing liver enzymes (ALT/AST) in comparison to testing other substances that reflect liver function such as albumin, bilirubin or coagulation proteins?
Serum enzyme levels of ALT/AST are more sensitive to hepatic disease.
How can the nature and degree of liver disease be discerned?
- By combining elevations of various liver-associated enzymes into a pattern.
- Typically: increased AST & ALT=liver disease, increased ALP & GGT=biliary disease
What does the liver enzyme gamma-glutamyltransferase (GGT) do? Where is it found?
- Transfers gamma-glutamyl groups from peptides.
- Present in proximal renal tubule, liver, pancreas and intestine.
When is gamma-glutamyltransferase (GGT) markedly increased before ALT/AST? Why are mild unexpected/unexplained elevations in GGT common?
- In conditions that cause obstruction of bile ducts.
- It is a very sensitive test for liver damage (alcohol consumption is a common culprit of unexplained/unexpected elevations).
Describe alkaline phosphatase (ALP) with regard to location, function, and what tissues it is epecially associated with.
- Present on cell surfaces in most tissues.
- Catalyzes alkaline hydrolyses of many substrates.
- Especially associated with small intestine, bone, liver and placenta.
What disorders/diseases are elevated levels of alkaline phosphatase (ALP) typically associated with?
Bone disorders and liver disease.
What are some examples of liver and bone diseases/disorders that elevate alkaline phosphatase (ALP) levels?
- Biliary obstructive disorders; Cholestasis
- Paget's disease of the bone
- Osteogenic sarcoma
- Hyperparathyroidism (disorders involving osteoblasts)
How are increases of alkaline phosphatase (ALP) due to cholestatic disease or bone disease distinguished from each other?
With patterns of clinical findings and other lab tests.
Describe amylase (AML, AMY, AMS) with regard to location (sources), function, and the significance of an elevated level of activity.
- Main sources are centroacinar cells of the pancreas and salivary glands.
- Catalyzes the breakdown of glycogen and starch.
- Elevated level of activity suggests acute pancreatitis, mumps, parotitis (salivary gland infection).
How does acute pancreatitis cause significant tissue damage?
By releasing digestive enzymes into the plasma and interstitial fluid.
Describe lipase (LPS) with regard to location, function, and concentration in the tissue it is predominantly found in as compared to any other tissue.
- Found predominantly in the pancreas.
- Hydrolyzes ester linkages of fats to produce alcohols and fatty acids.
- Concentration in the pancreas is 9000 fold greater than any other tissue.
What is the significance of an elevated level of lipase (LPS)?
Suggests diagnosis of acute pancreatitis.
What two enzyme tests are commonly ordered together during the evaluation of suspected pancreatitis? Which is more specific for pancreatic disease?
- Lipase (LPS) and amylase (AML).
- Lipase is more specific for pancreatic disease.
Levels of AML and LPS rise together and remain elevated for different amounts of time. How long does each enzyme remain elevated?
- LPS remains elevated for up to 7 days.
- AML remains elevated for up to 3 days.
- (After acute inflammatory event).
What are the classes of plasma proteins?
What proteins comprise the albumin class of plasma proteins?
What proteins comprise the globulin class of plasma proteins?
- Alpha-1 globulins
- Alpha-2 globulins
What proteins comprise the miscellaneous class of proteins?
What are the Alpha-1 globulins?
- Alpha-1 antitrypsin (AAT)
- Alpha-1 fetoprotein (alpha fetoprotein, AFP)
What are the Alpha-2 globulins?
- Alpha-2 macroglobulin
What are the beta-globulins?
- Complement proteins
- C-Reactive Protein (CRP)
What are the gamma-globulins?
Immunoglobulins A, D, E, G, and M
Which protein is present in the highest concentration in plasma (approx. 60% total protein level)? What are its functions?
- Contributes nearly 80% of the colloid osmotic pressure of intravascular fluid (maintains fluid balance in tissues).
- Acts as carrier protein for bilirubin, hormones, fatty acids, drugs, calcium and magnesium.
A decrease in albumin level is observed in what conditions?
- Liver disease
- Renal disease
- Gastrointestinal loss (inflammation)
- Muscle-wasting diseases
What causes an increased albumin level?
What are the functions of pre-albumin (transthyretin)?
- Carrier protein for thyroid hormones thyroxine (T4) and triiodothyronine (T3).
- Transports vitamin A (complexed w/retinol binding protein).
What is the clinical significance of pre-albumin?
- Is a sensitive marker of inadequate dietary protein intake.
- Is decreased in hepatic disease, acute inflammatory responses and tissue necrosis.
What is the function of alpha-1 antitrypsin (AAT)?
Neutralizes trypsin-like enzymes (elastase) that can damage structural proteins in surrounding tissue.
What is the clinical significance of alpha-1 antitrypsin (AAT)?
Deficiency is associated with severe degenerative emphysematous pulmonary disease.
What is the function of alpha-1 fetoprotein (AFP)?
Protects fetus from "attack" by mother's immune system.
When is pre-natal screening of the mother's blood for alpha-1 fetoprotein (AFP) routinely performed?
Between 15th and 20th wk of gestation (freely crosses placenta).
What is the clinical significance of elevated and low levels of alpha-1 fetoprotein (AFP)?
- Elevated AFP: suggests possible open neural tube defect, atresia of the GI tract, and/or fetal distress.
- Low AFP: associated with increased risk of Down's syndrome and trisomy 18.
What type of cancers are associated with high concentrations of AFP?
- Liver cancer
- Some adult gonadal cancers
Where is haptoglobin synthesized?
Hepatocytes and cells of the reticuloendothelial (RE) system.
What is the function of haptoglobin?
It binds free Hgb.
What is ceruloplasmin?
A copper-containing protein with enzymatic activity.
Where is more than 90% of total serum copper found?
What is the clinical significance of low levels of ceruloplasmin?
Indicates Wilson's disease (inherited disease where copper is deposited in the liver, brain and skin causing brain and neurologic damage).
What is alpha-2 macroglobulin?
Large protein synthesized by hepatocytes found mainly in intravascular spaces.
What is the function of alpha-2 macroglobulin?
Inhibits a variety of protease enzymes (trypsin, pepsin, plasmin).
What is the clinical significance of elevated levels of alpha-2 macroglobulin?
Seen in renal disease.
Describe transferrin with regard to where it is synthesized and what it is a major component of.
- Synthesized by liver.
- Major component of the beta-globulin fraction.
What is the function of transferrin?
- Transport of iron.
- Prevents loss of iron through the kidneys.
How many molecules of ferric iron (Fe+3) can bind to each molecule of transferrin? How many iron binding sites on transferrin are occupied at any given time?
What is the clinical significance of decreased levels of transferrin?
Seen in liver disease (decreased synthesis).
Where is hemopexin synthesized?
What is the function of hemopexin? What is the clinical significance of increased levels?
- Removes circulating heme and porphyrins.
- Increased in malignant melanoma (skin cancer).
What proteins are involved in immune and inflammatory responses, and circulate in blood as non-functional precursors, becoming activated when antigen-antibody complexes are present?
What is the function of complement proteins?
- Lysis of cell to which Ag-Ab complexes are attached.
- Opsonization (increases phagocytosis).
What is the clinical significance of elevated and decreased levels of complement proteins?
- Increased levels: found in inflammatory states.
- Decreased levels: found in systemic lupus erythematosis.
What is one of the largest proteins in blood plasma?
What is the function of fibrinogen?
Formation of fibrin clot when activated by thrombin (not seen in serum).
What is the clinical significance of decreased levels of fibrinogen?
- Disseminated Intravascular Coagulation (DIC)
- Afribinogenemia (rare inherited disorder)
What is one of the first proteins to increase in response to inflammatory disease?
C-reactive protein (CRP)
What is the function of c-reactive protein (CRP)?
Facilitates complement coating (opsonization) of bacteria, fungi, etc.
What is the clinical significance of elevated levels of c-reactive protein (CRP)?
- Acute rheumatic fever
- Myocardial infarction
- Viral/bacterial infections
- Rheumatoid arthritis
What plasma proteins comprise approx. 25% of all plasma proteins? Which of these is most abundant?
- IgG is most abundant
Where are immunoglobulins synthesized? What stimulates synthesis?
- Plasma cells (B lymphs)
- Stimulated by an immune response to foreign material.
Which immunoglobulin is increased in liver disease, autoimmune diseases, and infections?
Which immunoglobulin is increased in liver disease, infections, connective-tissue disorders, and multiple myeloma?
Which immunoglobulin is increased in asthma, allergic rhinitis, parasitic infections?
Which immunoglobulin is increased in liver disease, infections, and collagen disease?
Which immunoglobulin is the first antibody to appear in the immune response to a foreign antigen?
What is the clinical significance of increased levels of immunoglobulins?
- Monoclonal gammopathies
- Multiple myeloma (increased IgA, IgD, IgE, IgG)
- Waldenstrom's Macroglobulinemia (increased IgM)
What is the clinical significance of decreased levels of immunoglobulins?
Is caused by inherited immunodeficiency disorders (faulty plasma cell function).
Describe myoglobin and its function.
- Heme protein found in cardiac and striated skeletal muscle.
- Function is to reversibly bind oxygen.
What is the clinical significance of increased levels of myoglobin?
- Seen in skeletal or cardiac muscle damage.
- Early indicator of acute myocardial infarction.
Describe troponin and its function.
- Inhibitory protein found in cardiac muscle.
- Functions to bind calcium, permitting contraction of the heart muscle.
What is the clinical significance of elevated levels of troponin?
- Seen in acute myocardial infarction (AMI).
- Remain elevated for about 1 week after AMI.
What proteins are the acute phase reactants and what percentage do they increase in response to traumatic events?
- C-reactive protein (CRP): can increase up to 1000%
- Alpha-1 antitrypsin: increases by 200-400%
- Fibrinogen: increases by 200-400%
- Haptoglobin: increases by 200-400%
- Complement proteins: increase by 50%