MEDICAL TERMS AND VALUES

• ALBUMIN-TO-CREATININE RATIO (ACR)

• Background
• The albumin-to-creatinine ratio is a urine test that is used to assess the amount of protein that is passing from the kidneys into the urine
• Albumin is the main protein found in the blood, and it is the main protein that passes into the urine when kidney damage is present
• Normal kidneys typically allow a small amount of protein to pass into the urine, but larger amounts are a sign of kidney damage
• Diabetic kidney disease is one of the main causes of albumin in the urine (albuminuria)


• Albumin-to-creatinine ratio (ACR)
• The ACR is measured from a sample of urine
• The ratio is calculated by dividing the amount of albumin in the sample by the amount of creatinine in the sample
• Comparing the amount of albumin to the amount of creatinine corrects for the variations in urine concentration that can occur from factors such as dehydration, diuretics, etc. [6]


• Technique
• The test is best performed on a morning urine sample
• Ideally, the patient should not have eaten within 2 hours of the test
• If a test is positive, it should be repeated in 3 - 6 months
• The diagnosis of proteinuria can be made if 2 out of 3 tests are found to be positive
• In practice, all of these guidelines are rarely followed [6, 7]


• Factors that can affect the test


• The following factors can affect the test results:
• Dietary protein intake
• Exercise within 24 hours
• Urinary tract infection
• Fever
• Heart Failure
• Very high blood sugar
• Very high blood pressure [7,8]


• Ranges
• The following ranges are used in the diagnosis of diabetic kidney disease

Reference [7]

Category	Urine ACR (mcg of albumin/mg of creatinine)
Normal	< 30
Microalbuminuria	30 - 299
Macroalbuminuria	≥ 300

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• ALANINE AMINOTRANSFERASE (ALT)

• Other names
• ALT is also referred to as "SGPT" or "Serum Glutamic Pyruvic Transaminase"
• ALT is a part of the Liver Function Tests (LFTs)


• Physiology
• ALT is an enzyme that is found primarily in the liver and kidneys (it is also found to a smaller degree in heart and skeletal muscle)
• ALT breaks down amino acids so that they may be used as energy
• ALT activity in the liver is 3000-fold higher than in other organs
• Liver disease is the most important factor that causes an increase in ALT activity
• When liver disease is present, the amount of ALT in the blood is elevated [11,12]


• Values

ALT value (U/L)	Range
7 - 56	Normal
> 56	Elevated

• Factors that can affect the test
• Day-to-day variation can be 10-30% in some people
• Body weight - ALT tends to rise by as much as 40-50% as a person's body weight increases
• Normal exercise - ALT is 20% lower in people who exercise normally compared to people who do not exercise
• Strenuous exercise - very strenuous exercise can elevate ALT levels
• Hemolysis (cell breakdown) - cell breakdown in a blood sample will cause a modest increase in ALT
• Muscle injury - muscle injury will cause a moderate increase in ALT levels [11]


• Other
• NIH liver toxicity website - search medications, herbs, and supplements for information on liver toxicity

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• ANTINUCLEAR ANTIBODIES (ANAs)

• See antinuclear antibodies on the lupus page for a review

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• ASPARTATE AMINOTRANSFERASE (AST)

• Other names
• AST is also referred to as "SGOT" or "Serum Glutamic Oxaloacetic Transaminase"
• AST is part of the Liver Function Tests (LFTs)


• Physiology
• AST is an enzyme that is found primarily in the liver, heart, muscle and kidney
• AST breaks down amino acids so that they may be used as energy
• AST activity in the liver is 7000-fold higher than in other organs
• Liver disease is the most important factor that causes an increase in AST activity
• When liver disease is present, the amount of AST in the blood is elevated [11,12]


• Values

AST value (U/L)	Range
5 - 35	Normal
> 35	Elevated

• Factors that can affect the test
• Day-to-day variation can be 5 - 10% in some people
• Race - values can be 15% higher in African-American men
• Body weight - AST tends to rise by as much as 40-50% as a person's body weight increases
• Strenuous exercise - strenuous exercise can cause a three-fold increase
• Hemolysis (cell breakdown) - cell breakdown in a blood sample will cause a significant increase in AST
• Muscle injury - muscle injury will cause a significant increase in AST levels [11]


• Other
• NIH liver toxicity website - search medications, herbs, and supplements for information on liver toxicity

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• B-TYPE NATRIURETIC PEPTIDE (BNP)

• Overview
• Natriuretic peptides include Atrial Natriuretic Peptide (ANP), B-type Natriuretic Peptide (BNP), and C-type Natriuretic Peptide (CNP)
• ANP is released by the atria of the heart in response to distension
• BNP is released by the ventricles of the heart in response to distension from volume overload
• CNP is released by vascular endothelial cells in response to inflammatory mediators
• BNP is sometimes referred to as "brain natriuretic peptide" because it was originally identified in pig brain extracts
• Illustration of natriuretic peptide physiology


• Physiological actions of natriuretic peptides include the following:
• Promote renal excretion of fluid and sodium
• Promote myocardial relaxation and inhibit hypertrophy and fibrosis
• Suppress sympathetic outflow in the brain
• Stimulate vasodilation

• BNP and congestive heart failure
• Because BNP is released in response to ventricular wall distension, blood levels of BNP can be used to help diagnose patients with congestive heart failure
• BNP measurements have better predictive value when they are drawn in patients who have symptoms of congestive heart failure (e.g. shortness of breath, fluid overload)
• BNP values have a high sensitivity and moderate specificity for congestive heart failure. This means a normal value makes congestive heart failure unlikely, but an elevated value does not conclusively "rule in" congestive heart failure.
• A meta-analysis of BNP trials found that at a cutoff value of 100 pg/ml, BNP had a sensitivity of 95% and a specificity of 63% for a diagnosis of heart failure giving it a positive predictive value of 67% and negative predictive value of 94% [19]
• BNP values increase naturally with age and can also be affected by other conditions (see table below)

• Reference [20]

BNP value	Heart failure
≤ 100 pg/ml	Heart failure unlikely
> 100 pg/ml	Heart failure more likely

• NT-proBNP
• NT-proBNP stands for "N-terminal of the prohormone brain natriuretic peptide." It is the inactive amino acid fragment that is released when proBNP is cleaved to BNP.
• Levels of NT-proBNP are directly proportional to BNP levels and therefore, also serve as a marker of congestive heart failure
• The clearance of NT-proBNP differs from BNP (see table below). In general, they perform about equally in predicting heart failure.
• One difference between NT-proBNP and BNP is that NT-proBNP levels are not affected by the neprilysin inhibitor sacubitril (Entresto®). BNP levels will rise when patients are taking sacubitril, but NT-proBNP levels are unaffected by the drug. [31]
• NT-proBNP values have a high sensitivity and moderate specificity for congestive heart failure. This means a normal value makes congestive heart failure unlikely, but an elevated value does not conclusively "rule in" congestive heart failure.
• A meta-analysis of NT-proBNP trials found that at a cutoff value of 300 pg/ml, NT-proBNP had a sensitivity of 99% and a specificity of 43% for a diagnosis of heart failure giving it a positive predictive value of 64% and negative predictive value of 98% [19]
• NT-proBNP values increase naturally with age and can also be affected by other conditions (see table below)

• Reference [20]

NT-proBNP value	Heart failure
≤ 300 pg/ml	Heart failure unlikely
> 300 pg/ml	Heart failure more likely

• Reference [20]

Differences between NT-proBNP and BNP
	Half-life	Clearance
BNP	22 minutes	Endopeptidase
NT-proBNP	60 - 120 minutes	Renal

• Reference [20]

Factors that may affect BNP and NT-proBNP values
Factor	Comment
Age	BNP and NT-proBNP levels increase naturally with age
Female sex	BNP and NT-proBNP levels are higher in females
Kidney disease	BNP and NT-proBNP may be elevated in patients with kidney disease Levels begin to rise with CrCl < 60 ml/min NT-proBNP levels may be more sensitive to kidney disease
Diastolic heart failure	BNP and NT-proBNP levels may be elevated in patients with diastolic heart failure
Acute coronary syndrome	BNP and NT-proBNP levels may be elevated in patients with acute coronary syndrome even in the absence of heart failure
Pulmonary disease	BNP and NT-proBNP levels may be elevated in pulmonary diseases including ARDS, severe COPD, pulmonary embolism, and primary pulmonary hypertension
Atrial fibrillation	BNP and NT-proBNP levels may be elevated in atrial fibrillation without heart failure
Obesity	BNP and NT-proBNP levels may be lower in obese patients In one study, a BNP of > 54 pg/ml was 90% sensitive for heart failure in patients with a BMI ≥ 35
Previous heart failure	BNP and NT-proBNP levels may be elevated in patients with a history of heart failure who do not have acute symptoms of volume overload
High output states	BNP and NT-proBNP levels may be elevated in high output states (e.g. sepsis, cirrhosis, hyperthyroidism)

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• C-REACTIVE PROTEIN (CRP)

• Overview
• C-Reactive Protein (CRP) is an "acute phase reactant"
• CRP is made in the liver and released into the bloodstream within a few hours of the start of an inflammatory process (ex. infection, tissue injury, trauma, etc.). CRP has a half-life of 19 hours.
• CRP levels can be measured to determine if inflammation is present. Much like the ESR test, CRP is nonspecific and can be elevated in patients who do not have an inflammatory process.
• CRP increases faster and decreases more rapidly than the ESR therefore it is a more acute measure of inflammation. [21,30]


• CRP values

• Reference [23]

CRP normal value (mg/L))
0 - 4.9

• Reference [21,22]

Causes of elevated CRP
Infection
Inflammatory conditions (e.g. Rheumatoid arthritis, inflammatory bowel disease, giant cell arteritis)
Pregnancy
Cancer
Medications (oral contraceptives, estrogens)
Obesity

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• CHILD-PUGH LIVER FAILURE CLASSIFICATION

• Overview
• The Child-Pugh classification for liver failure was originally described by Dr. Child and Dr. Turcotte
• Another doctor, Dr. Pugh, later modified it. Today, it is widely known as the Child-Pugh classification
• The system combines three laboratory values and two physical exam findings to assign a score
• The score is then used to categorize patients into three groups - A, B, and C
• Studies have shown that the Child-Pugh groups can be used to predict survival in liver disease [13]


• Child-Pugh scoring system


• To classify a patient with liver disease, the following five variables are measured and scored:

	Child-Pugh Score
Finding	1	2	3
Encephalopathy (see encephalopathy staging below)	None	1 and 2	3 and 4
Ascites	Absent	Slight	Moderate
Bilirubin(mg/dl)*	< 2	2 - 3	> 3
Albumin (g/dl)	> 3.5	2.8 - 3.5	< 2.8
Prothrombin time (PT) (seconds prolonged) OR	< 4	4 - 6	> 6
INR	< 1.7	1.7 - 2.3	> 2.3

• *In patients with primary biliary cirrhosis, bilirubin is scored as follows:

Bilirubin (mg/dl)	Child-Pugh score
< 4	1
4 - 10	2
> 10	3

• The 5 scores are added up and the patient is classified as follows:

• Reference [13]
• Surgical mortality based on 12-year study published in 1997 involving abdominal surgery [17]

TOTAL SCORE	CHILD-PUGH CLASS	EXPECTED MORTALITY
5 - 6	A	5-year survival 90% Surgical mortality 10%
7 - 9	B	5-year survival 80% Surgical mortality 32%
≥ 10	C	More than 33% die within one year Surgical mortality 82%

• Encephalopathy stage
• A number of authors have devised encephalopathy scales over the years
• Most scales are adaptations of a scale developed in the 1950s by Adam and Foley
• The scale below is a brief adaptation of the Adam and Foley and Gitlin scale

Reference [14,15]

Stage	Mental status	Neuro exam	EEG findings
0	normal	normal	none
1	mild confusion sleep disturbance	slight tremor	normal to slightly normal
2	disoriented abnormal behavior	significant tremor coordination problems	abnormal
3	confused, incoherent excessive sleep	muscle rigidity positive Babinski	abnormal
4	coma	none	abnormal

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• GLOMERULAR FILTRATION RATE (GFR) AND CREATININE CLEARANCE (CrCl)

• Overview
• The "glomerulus" is the microscopic, fundamental working unit of the kidney
• The glomerulus serves as a filter/barrier between blood in the circulation and fluid destined for elimination from the body as urine [4]
• The Glomerular Filtration Rate (GFR) is the rate at which blood is filtered by the glomerulus expressed as milliliters per minute (ml/min)


• GFR and CrCL
• Direct measurement of the GFR is tedious and involved
• The serum creatinine level (see creatinine above) provides an indirect way to estimate GFR that is easy and widely available
• The serum creatinine value is plugged into a formula along with other patient variables (age, sex, race, weight), and an estimation of "Creatinine Clearance" is made
• Creatinine Clearance is considered an estimation of the GFR
• In practice, the two terms are used interchangeable [5]

• Formulas
• In adults, there are primarily three formulas that are used to estimate the GFR

• Formula accuracy
• A number of studies have looked at the accuracy of these three formulas
• In general, the MDRD equation performs better than the Cockcroft-Gault equation
• In one study, the MDRD-calculated-GFR was within 30% of the true GFR in 91% of the patients
• In the same study, the Cockcroft-Gault-calculated-GFR was within 30% of the true GFR in 65% of the patients [5]
• Most laboratories estimate GFR with the MDRD formula
• CKD-EPI formula
• Recent studies have shown that the CKD-EPI formula is superior to the MDRD formula in predicting GFR and outcomes associated with GFR [16]
• Most laboratories estimate GFR with the MDRD formula

• ^✝Category 1 if kidney damage is present
• NKF - National Kidney Foundation

Stages of kidney disease
GFR (ml/min)	Degree of kidney disease	NKF stages
≥ 90	Normal	1✝
60 - 89	Mild	2
44 - 59	Moderate	3a
30 - 44	Moderate	3b
15 - 29	Severe	4
< 15	Kidney failure	5

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• CYCLIC CITRULLINATED PEPTIDE (CCP) ANTIBODIES

• Overview
• Citrullination is a chemical process in proteins where the amino acid arginine is replaced with the amino acid citrulline
• Cyclic citrullinated proteins serve as significant antigens for the formation of the autoantibodies seen in rheumatoid arthritis (RA)
• Anti-cyclic citrullinated peptide (CCP) antibodies are a very specific marker for RA [27]


• Diagnostic value
• Most modern Anti-CCP antibody tests have a very high specificity meaning there are a low number of false-positives, so a positive test result means RA is very likely. A negative test result is not as helpful since the test sensitivity is low (high false-negative).
• Specificity: ∼ 95%
• Sensitivity: ∼ 50 - 70% [24,27]
• Anti-CCP antibody levels are not recommended for monitoring disease activity [27]

• Reference [26]
• Normal range may vary by lab and may only be reported as positive or negative

Anti-CCP value	Range
< 20 units	negative
20 - 39 units	weak positive
40 - 59 units	moderate positive
> 59 units	strong positive

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• ERYTHROCYTE SEDIMENTATION RATE (ESR)

• Overview
• The ESR test measures how fast red blood cells separate from plasma and fall to the bottom of a test tube
• Results are reported in millimeters of clear plasma that are present at the top portion of the tube after one hour
• Cells tend to fall faster when inflammatory markers such as fibrinogen, immunoglobulins, and acute phase reactants are present; therefore, a higher ESR indicates more inflammation


• Diagnostic value
• An elevated ESR is an indicator that inflammation is present somewhere in the body
• The main drawback to the ESR is that it is nonspecific, and a number of noninflammatory processes can cause an elevated ESR (see below)


• ESR values

• Any value above these ranges is considered elevated
• Reference [23]

Patient population	ESR normal values (mm/hr)
Male 0 - 50 years	0 - 15
Male ≥ 50 years	0 - 30
Female 0 - 50 years	0 - 32
Female ≥ 50 years	0 - 40

• Causes of elevated ESR values

• Reference [21]

Causes of elevated ESR
Infection
Inflammatory conditions (e.g. Rheumatoid arthritis, inflammatory bowel disease, giant cell arteritis)
Anemia
Pregnancy
Advanced age
Immune disorders (e.g. multiple myeloma, Waldenstrom's macroglobulinemia)
Menstruation
Medications (oral contraceptives, methyldopa, theophylline)
Vitamin A
Fatty liver
Obesity

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• EJECTION FRACTION

• Definition
• Ejection fraction (EF) is a measure of heart function that is typically obtained with an echocardiogram
• Another common way to measure EF is during a heart catheterization or during a radionuclide stress test
• The EF is calculated with the following formula:




• EF can be thought of in the following manner:
• A full ventricle of blood would be at its "end-diastolic volume"
• The full ventricle then contracts and forces a portion of that blood into the circulation (stroke volume)
• The volume of blood forced into the bloodstream divided by the volume of a full ventricle is the EF
• In short, it's the percent of blood in a full ventricle that the ventricle can pump (eject) into the circulation


• EF in Heart Failure
• EF is commonly used to help quantify the severity of heart failure
• There are two main types of heart failure: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF)
• In HFrEF, the left ventricle does not contract normally and the EF is reduced. HFpEF (formerly called diastolic heart failure) is thought to occur when the left ventricle does not relax properly and ventricular filling is reduced.
• In HFrEF, a decreased EF means that the heart is less efficient in circulating blood than a normal heart. This can cause fluid to back up in the lungs and extremities
• Even though a decrease in EF is associated with a decline in cardiac function, studies have shown that the EF does not always correlate well with symptoms of heart failure. Because of this, the diagnosis of heart failure should not be based solely on the EF. [9]

Reference [1,2]

EF value	Interpretation
> 50%	Normal
40 - 50%	Decreased, but does not typically cause symptoms
< 35%	Significant decrease in EF

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• IRON STUDIES

• Iron studies are reviewed here - Iron review

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• MODIFIED RANKIN SCALE

• Overview
• The modified Rankin scale is used to measure disability in stroke patients
• It is widely used as an outcome measure in stroke treatment trials. It has also been incorporated into guidelines for certain stroke treatments (e.g. endovascular treatment)
• The definition for each Rankin score is given in the table below

• Reference [18]

Grade (Rankin score)	Symptoms
0	No symptoms at all
1	No significant disability: despite symptoms, able to carry out all usual duties and activities
2	Slight disability: unable to perform all previous activities but able to look after own affairs without assistance
3	Moderate disability: requiring some help but able to walk without assistance
4	Moderately severe disability: unable to walk without assistance and unable to attend to own bodily needs without assistance
5	Severe disability: bedridden, incontinent and requiring constant nursing care and attention
6	Death

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• NEW YORK HEART ASSOCIATION HEART FAILURE CLASSIFICATION (NYHA)

• Overview
• The NYHA heart failure classification system is widely used to classify patients by the severity of their heart failure symptoms
• NYHA class III and IV are associated with poor prognosis in heart failure patients [10]

Reference [10]

NYHA class	Symptoms
I	No limitation of physical activity. Ordinary physical activity does not result in symptoms.
II	Slight limitation of physical activity. Comfortable at rest, but ordinary activity results in fatigue, palpitations, or shortness of breath.
III	Marked limitation of activity. Comfortable at rest, but less than ordinary activity results in fatigue, palpitations, or shortness of breath.
IV	Symptoms at rest. Unable to carry on any physical activity without discomfort. Any physical activity results in discomfort.

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• POTASSIUM (K⁺)

• Physiology
• Potassium is one of the main electrolytes found in the body (others include sodium (Na⁺), chloride (Cl⁻), calcium (Ca²⁺), bicarbonate (HCO₃⁻), magnesium (Mg²⁺))
• Electrolytes are ions that have a positive or negative charge (potassium has a positive charge)
• Because electrolytes have a charge, they participate in a number of physiological processes including forming gradients and controlling blood pH
• Muscles use electrical gradients to contract, and nerves use electrical gradients to conduct nerve impulses
• Blood pH is tightly controlled by moving electrolytes in and out of cells
• Electrolytes are continually being lost through bodily functions (sweat, urine, feces) and therefore must be replaced through food and liquids


• Cardiac conduction and kidney disease
• Potassium is a very important electrolyte because it is involved in the conduction of electrical impulses in the heart
• Elevated or decreased potassium levels can lead to heart arrhythmias
• The kidneys play an important role in maintaining appropriate potassium levels
• A number of commonly prescribed medications (ex. diuretics, ACE inhibitors, ARBs, etc.) affect the way the kidneys manage potassium
• When using these medications, it is important that potassium levels be checked periodically
• Significant kidney disease will also affect the kidney's ability to eliminate excess potassium from the body

• Values
• Reference ranges vary by laboratory
• The ranges presented here are typical ranges

Potassium (K+) (meq/L)	Range
< 3.0	Decreased
3.0 - 3.4	Mild - moderate decrease
3.5 - 5.0	Normal
5.1- 6.0	Mild - moderate elevation
> 6.0	Elevated

• Errors in measurement
• Potassium is primarily located inside cells
• If blood is drawn and not stored properly, the cells in the blood sample can "lyse" or fall apart
• If blood cells fall apart (hemolysis), the measurement of potassium in the serum will be falsely elevated
• Depending on the situation, high potassium levels should often be repeated to account for this possible effect

• Potassium homeostasis
• Potassium is absorbed from food sources in the intestine. Potassium is removed from the body by the kidneys (90%) and in the stool (10%).
• Under normal conditions, daily potassium intake matches daily potassium excretion
• For healthy adults, the World Health Organization recommends potassium intake of at least 90 mEq/day (3510 mg) while the 2015 Dietary Guidelines for Americans recommends 120 mEq/day (4700 mg)
• Potassium is found in foods and supplements. Potassium content is often expressed in three different ways: milligrams (mg), milliequivalents (mEq), and millimoles (mmol). One milliequivalent of potassium is equal to one millimole. For food, milligrams (mg) of potassium should be divided by 39 to convert to milliequivalents (mEq). The table below gives conversion ratios for the potassium content of various potassium supplements.

• One milliquivalent (mEq) of potassium is equal to one millimole (mmol)
• References [29, Manufacturer's PI]

Elemental potassium content in potassium supplements (mEq of K+ per mg)
Potassium source	Conversion ratio (mEq of K+ per mg)
Elemental potassium (K+)	1 mEq = 39 mg
Potassium chloride (KCL)	1 mEq = 75 mg
Potassium bicarbonate (KHCO3)	1 mEq = 100 mg
Potassium citrate (K2C6H5O7*H2O)	1 mEq ∼ 36 mg
Potassium gluconate (KC6H11O7)	1 mEq ∼ 230 - 250 mg

• Potassium content of foods
• Potassium is found in a variety of foods. Fruits, vegetables, nuts, and seeds tend to have the highest content.
• The table below lists common foods from each food group that contain higher amounts of potassium
• The potassium content of a large number of foods can be found by searching the USDA food database

• Reference: USDA food database

Approximate potassium content of select foods
Food	Potassium content (mEq of elemental K+ per 100 gram or 100 ml)
FRUITS
Apricots, dried	30 mEq (1162 mg)
Prunes, dehydrated, uncooked	27 mEq (1058 mg)
Raisins, seedless	19 mEq (749 mg)
Plums, dried, uncooked	19 mEq (732 mg)
Dates, medjool	18 mEq (696 mg)
Avocados, raw	13 mEq (507 mg)
Bananas, raw	9 mEq (358 mg)
Orange juice	5 mEq (208 mg)
Grapefruit juice	4 mEq (142 mg)
VEGETABLES
Yam, cooked, boiled, drained, or baked	17 mEq (670 mg)
Spinach, fresh	14 mEq (558 mg)
Parsley, fresh	14 mEq (554 mg)
Potatoes, white, flesh and skin, baked	14 mEq (544 mg)
Mushrooms, Chanterelle, raw	13 mEq (506 mg)
Beets, cooked, boiled	8 mEq (305 mg)
Carrots, raw	8 mEq (320 mg)
Mushrooms, Shiitake, raw	8 mEq (304 mg)
Tomatoes, raw, red, ripe	6 mEq (237 mg)
Radishes, raw	6 mEq (233 mg)
NUTS AND SEEDS
Pistachio nuts, dry roasted	26 mEq (1007 mg)
Pumpkin and squash seed kernels, roasted	20 mEq (788 mg)
Sunflower seed kernels, dry roasted	22 mEq (850 mg)
Almonds, dry roasted	18 mEq (713 mg)
Brazil nuts, dried	17 mEq (659 mg)
Cashews, dry roasted	14 mEq (565 mg)
Walnuts, English	11 mEq (441 mg)
Pecans	11 mEq (410 mg)
BEANS
Soybeans, mature, boiled	13 mEq (515 mg)
Lima beans, mature, boiled	13 mEq (508 mg)
Black beans, mature, boiled	9 mEq (355 mg)
Chickpeas (garbanzo beans), mature seeds, boiled	7 mEq (291 mg)
Peas, green, raw	6 mEq (244 mg)
Beans, snap, green, raw	5 mEq (211 mg)
DAIRY PRODUCTS
Yogurt, low fat, plain	6 mEq (234 mg)
Milk, 2%	5 mEq (182 mg)
Egg, whole, cooked, omelet	3 mEq (117 mg)
Cheese, cheddar	2 mEq (76 mg)
BEEF
Beef, round cut, pan fried	12 mEq (484 mg)
Beef, tenderloin steak, grilled	11 mEq (443 mg)
Beef, ground, 90% lean meat, pan-browned	11 mEq (433 mg)
Beef, top sirloin steak, broiled	10 mEq (380 mg)
Beef, rib, roasted	8 mEq (319 mg)
Beef, brisket, braised	7 mEq (275 mg)
POULTRY
Chicken, breast, grilled	11 mEq (420 mg)
Turkey, breast, roasted	6 mEq (249 mg)
FISH
Mahimahi, cooked, dry heat	14 mEq (533 mg)
Trout, cooked, dry heat	12 mEq (463 mg)
Salmon, coho, wild, cooked, moist heat	12 mEq (455 mg)
Tuna, white, canned in water	6 mEq (237 mg)

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• RHEUMATOID FACTOR (RF)

• Overview
• Rheumatoid factors are antibodies to the Fc fragment of IgG antibodies
• The rheumatoid factors are typically IgM antibodies, but may also be IgG or IgA
• Rheumatoid factors are present in the majority of patients with rheumatoid arthritis at some point over the course of their disease


• Diagnostic value
• About 80% of all patients with rheumatoid arthritis (RA) will eventually be positive for rheumatoid factors
• Only 40% of patients with RA are RF-positive at first symptoms of the disease [25]
• In studies, the sensitivity of RF for RA has been found to be 69%, the specificity has been found to be 85% [24]
• The higher the level of RF, the greater the risk of developing RA
• Patients with RF levels < 25 IU/ml have a very low risk of developing RA [25]

• Reference [23]
• Normal range varies by lab

RF value	Range
≤ 14 IU/ml	negative
> 14 IU/ml	positive

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• SERUM CREATININE (SCr)

• Physiology
• Creatinine is a byproduct of muscle metabolism
• Creatinine is released into the bloodstream at a steady rate throughout the day
• The kidneys filter creatinine from the blood and excrete it into the urine
• The constant dumping of creatinine into the blood by muscle and removal of creatinine from the blood by the kidneys creates a steady concentration of creatinine in the blood [3]


• Kidney disease
• If the kidneys become diseased or damaged, they do not filter creatinine as effectively, and the equilibrium between muscle dumping and kidney removal will shift
• The change in equilibrium will cause a rise in the serum concentration of creatinine
• Creatinine concentration in the serum provides a measure of kidney function


• Variables that affect creatinine
• Because creatinine comes from muscle, its concentration is proportional to muscle mass


• Factors that can affect muscle mass include:
• Age - people tend to lose muscle mass as they age
• Resistance training - athletes may have more muscle mass and higher creatinine levels
• Gender - men generally have more muscle mass than women
• Race - African-Americans tend to have more muscle mass than whites
• Diet - people who eat less protein may have lower creatinine concentrations [5]


• Values
• Serum Creatinine (SCr) levels vary by a person's age, sex, race, weight, and muscle mass, therefore it is not possible to ascribe "normal" values that apply to everyone
• A more accurate estimate of kidney function is derived by using the serum creatinine in formulas that take these variables into account (see glomerular filtration rate for more)
• The values presented here are general measures

Serum creatinine (mg/dl)	Range
≤ 1.2	Normal
1.3 - 1.5	Mild-to-moderate elevation
> 1.5	Significant elevation

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• VOLUME OF DISTRIBUTION (Vd)

• Definition
• The volume of distribution is a pharmacological measure that reflects how a drug is distributed in the human body
• In simple terms, it is the volume of fluid that a specific amount of drug would have to be dissolved in in order to achieve the observed concentration
• Volume of distribution is calculated with the following formula:


• Vd = A / C
• where:
• A = amount of drug in body (bioavailable dose)
• C = concentration of drug in plasma


• Volume of distribution is typically expressed as liters and standardized to a 70 kg person


• Interpretation
• Because the Vd is inversely related to the concentration of the drug in plasma, drugs that stay in the plasma (high plasma concentration) will have a lower Vd and drugs that pass from plasma into other body compartments (lower plasma concentrations) will have a higher Vd
• After a drug is absorbed from the intestines or infused intravenously, there are 5 primary ways it can distribute itself. The five main compartments and their volume based on body weight are as follows:
• Intravascular fluid - 0.08 L/kg body weight
• Extracellular fluid - 0.20 L/kg body weight
• Intracellular fluid - 0.40 L/kg body weight
• Whole body fluid (extracellular and intracellular fluid) - 0.60 L/kg body weight
• Body fat - 0.2 - 0.35 L/kg body weight
• If a drug stays primarily in the circulation (intravascular), its volume of distribution will usually be < 10 L
• If a drug distributes throughout fluid but cannot cross cell membranes, then its volume of distribution will around 10 - 20 L
• If a drug is able to cross cell membranes (intracellular) and accumulate in tissues, then its volume of distribution will be 25 - 30 L
• If a drug distributes in whole body fluid, then its volume of distribution will be around 40 liters
• If a drug is very lipophilic and accumulates in fat, then its volume of distribution may exceed body weight, and in some cases, quite substantially (e.g. chloroquine has a volume of distribution of 13,000 L)

• Reference: Pharmaceutical Calculations, 9th ed. Stoklosa, Ansel (1991)

Vd and drug distribution
Vd (Liters)	Distribution
< 10	Intravascular Drugs that are large molecules Drugs that are highly protein-bound (e.g. warfarin)
10 - 20	Extracellular fluid Drugs with low lipid solubility that cannot cross cell membranes
25 - 30	Intracellular fluid Drugs that can cross cell membranes Drugs that are actively transported across cell membranes
40	Whole body fluid Drugs that pass freely across cell membranes (e.g. alcohol, caffeine)
> 40	Fat tissue Lipophilic drugs that accumulate in fat (e.g. chloroquine, amiodarone)

• Clinical use
• The Vd is most often used to estimate the required dose of a drug in order to achieve a desired plasma concentration (Drug dose = Desired concentration X Vd)
• The Vd is also important to consider when plasma concentrations are closely associated with a drug's therapeutic effect. Highly lipophilic drugs (large Vd) may have altered pharmacokinetics in obese patients. Abnormal fluid accumulation (e.g. ascites, edema) can also change the pharmacokinetics of certain drugs.

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• BIBLIOGRAPHY

• What is PMID?
• PI = Manufacturer's Package Insert

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