1. Interpretation Of Laboratory & Diagnostic Tests ENDOCRINE & RENAL SYSTEM Nora Kalagi, MSc. 326 PHCL April 2016

2. Objectives 1.Identify the clinical application of laboratory & diagnostic tests specific to the endocrine and renal system 2.Solve patient cases that involve assessing common laboratory & diagnostic test results pertaining to the renal system and endocrine system

3. Endocrine system

4. Laboratory Tests for Endocrine System  Pituitary test  Thyroid tests  Parathyroid tests  Adrenal tests  Pancreatic tests

6. Laboratory Tests 1) Pancreatic Tests ◦ Glucose Serum glucose concentrations are used to assess pancreatic function & the response to insulin replacement therapy ◦ Fasting Plasma Glucose Obtained before breakfast after an overnight fast (at least 8 hrs) ◦ Random Plasma Glucose Obtained at any time without fasting or regards to meal

7. Laboratory Tests (Pancreatic Tests) ◦ Glucose Tolerance Test (GTT) ◦ Used to diagnose DM & gestational diabetes ◦ Patients fast for 10 to 16 hrs before test & then given 75 g of glucose ◦ Serial blood samples are obtained for glucose ◦ Normally, serum glucose is <200 mg/dL at 30, 60, & 90 min & <140 mg/dL at 2 hrs

8. Laboratory Tests (Pancreatic Tests) ◦ Glycosylated Hemoglobin (HB A1C) ◦ Formed when hemoglobin is irreversibly glycosylated after exposure to high amount of glucose ◦ Assesses long term control of hyperglycemia (2-3 months control) ◦ Normal values ≤ 7%

9. Laboratory Tests (Pancreatic Tests) ◦ C-Peptide ◦ Released from beta cells with insulin ◦ Sometimes used to assess pancreatic function ◦ Used to differentiate between type I & type II DM  Abnormally low levels of C-peptide suggest that insulin production is too low (or absent)  type I DM  Normal to high levels suggest good insulin production but inappropriate response (insulin resistance)  type II DM

10. Laboratory Tests 2) Thyroid Tests Thyroid function tests are used to:  Establish the level of thyroid function (T3, T4)  Diagnose hypo or hyperthyroidism  Assess response to suppressant or replacement therapy

11. Laboratory Tests (Thyroid Tests) ◦ Free Thyroxine ( Free T 4 ) ◦ Most sensitive test ◦ Elevated in hyperthyroidism, decreased in hypothyroidism ◦ Thyroid-Stimulating Hormone (Thyrotropin, TSH) ◦ Serum TSH is used to differentiate between thyroid hypothyroidism (primary) & pituitary hypothyroidism(secondary)

12. Laboratory Tests (Thyroid Tests) Free T4TSHInterpretation ↑↓Hyperthyroidism ↓↓Pituitary hypothyroidism ↓↑Thyroidal hypothyroidism

13. Laboratory Tests (Thyroid Tests) ◦ Thyroid Uptake of Radioiodine RAIU (Diagnostic Procedure) ◦ Radioactive iodine is administered orally, & radioactivity over the thyroid gland is measured at various intervals ◦ The normal RAIU is 10% - 35% ◦ A very high RAIU is seen in hyperthyroidism, while a low RAIU is seen in hypothyroidism.

14. Laboratory Tests 3) Parathyroid Glands ◦ The gland secretes parathyroid hormone (PTH) PTH  controls calcium and phosphorus levels in the blood ◦ Normally, High serum calcium levels suppress PTH secretion ◦ Gland function is tested by measuring the serum concentrations of PTH, calcium, & phosphorus ◦ PTH concentration is useful in differentiating between hypercalcemia resulting from hyperparathyroidism & hypercalcemia resulting from other causes

15. Laboratory Tests 4) Miscellaneous Tests ◦ Cholesterol Profiles ◦ Used in patients with diabetes or hypothyroidism ◦ Goal low-density lipoprotein cholesterol for patients with diabetes is < 100 mg/dL ◦ In patients with hypothyroidism, an elevated cholesterol is consistent with the diagnosis of hypothyroidism

16. RENAL SYSTEM

17. Laboratory Tests Creatinine ◦ Creatinine is a normal metabolic product of both creatine & phosphocreatine which are constituents of skeletal muscle ◦ Normal serum level SCr is 0.7 to < 1.5 mg/dl (adults) ◦ Daily production is determined by the individual’s muscle mass ◦ In normal patients at steady state, the rate of creatinine production equals its excretion. Very little variation from day to day in patients with normal renal function

18. Causes of changes in serum creatinine ◦ Not influenced much by changes in renal blood flow (urine flow), or diet ◦ An increase in creatinine almost always indicates worsening renal function i.e., decreased GFR ◦ Severely decreased muscle mass or activity may decrease SCr ◦ Vigorous exercise may temporarily increase SCr by ~0.5 mg/dl Laboratory Tests

19. Glomerular filtration rate estimation (GFR) ◦ Test used to check how well the kidneys are working. Specifically, it estimates how much blood passes through the glomeruli each minute. ◦ Glomeruli are the tiny filters in the kidneys that filter waste from the blood. ◦ GFR - is the best test to measure your level of kidney function and determine your stage of kidney disease. Your doctor can calculate it from the results of your blood creatinine test, your age, body size and gender.

20. Creatinine clearance ClCr in normal adult (90 - 140 ml/min/1.73m2) ◦ ClCr is an estimate of GFR ◦ Creatinine is primarily excreted via glomerular filtration, with about 10 to 15% eliminated by active tubular secretion Laboratory Tests

21. Clinical use of creatinine clearance: ◦ Assessing kidney function in patients with acute or chronic renal failure ◦ Monitoring patients on nephrotoxic drugs ◦ Determining dosage adjustments for renally eliminated drugs Laboratory Tests

22. Calculating creatinine clearance 1. Direct measurement by 24 hr urine collection: ◦ Clcr = (Uv) (Ucr) X 1.73m 2 (ScCr) (1440) BSA ◦ Uv is the 24 hour urine volume in ml ◦ Ucr is the urinary creatinine concentration in mg/dl ◦ SrCr is the serum creatinine concentration in mg/dl at the midpoint of the urine collection ◦ The units of ClCr are in ml/min Laboratory Tests

23. ◦ BSA equation:

24. Calculating creatinine clearance 2.Estimate of creatinine clearance (Cockcroft and Gault equation) ◦ Clcr = (140 – age) x (IBW) (ScCr) x 72 ◦ Multiply by 0.85 for females ◦ IBW for males = 50kg + 2.3 kg per inch > 60 inches ◦ IBW for females = 45.5 kg + 2.3 kg per inch > 60 inches Laboratory Tests

25. ◦ Example! ◦ Calculate ClCr (by using Cockcroft and Gault equation) for 60 year-old male patient if you know that he is 172 cm and his weigh is 80 kg, SrCr is 1.9 mg/dL Laboratory Tests

28. Blood Urea Nitrogen (BUN) ◦ Measures the amount of urea nitrogen in blood ◦ Urea is the end product of protein metabolism ◦ Excreted by glomerular filtration ◦ Used as indicator of renal function but less reliable than SrCr because some of the urea diffuses back into renal tubular cells after filtration + liver function & protein intake influence production of BUN ◦ As renal function declines  BUN ↑ Laboratory Tests

29. Electrolytes & Minerals ◦ Serum electrolytes and minerals that are useful when assessing the renal system include: ◦ calcium, chloride, magnesium, phosphorus, potassium, and sodium. ◦ In patient with chronic kidney disease the following electrolyte abnormalities may be present: ◦ Hyperkalemia ◦ Hypermagnesemia ◦ Hyperphosphatemia ◦ Hypocalcemia Laboratory Tests

30. Electrolytes & Minerals ◦ Sodium Increased sodium (hypernatremia)Decreased sodium (hyponatremia) - increased Na intake - increased fluid loss (e.g. dehydration, gastroenteritis, administration of hypertonic solutions) - decrease in total body sodium (e.g. diuretics) - accumulation of water (dilutional hyponatremia) e.g. CHF, cirrhosis, chronic renal failure

31. Laboratory Tests Electrolytes & Minerals ◦ Potassium increased potassium (hyperkalemia)decreased potassium (hypokalemia) metabolic or respiratory acidosis, renal failure, dehydration, medications such as (ACEI, ARBs), potassium supplements, spironolactone severe diarrhea and/or vomiting, respiratory alkalosis, use of thiazide or loop diuretics

32. Laboratory Tests Electrolytes & Minerals ◦ Chloride ◦ Extracellular electrolyte ◦ Increased chloride (hyperchloremia) may be seen in metabolic acidosis, respiratory alkalosis, dehydration, renal disorders ◦ Decreased chloride (hypochloremia) may be associated with prolonged vomiting, metabolic alkalosis, CHF, thiazide & loop diuretics

33. Laboratory Tests Electrolytes & Minerals ◦ Calcium ◦ The majority of calcium in body is found in bones and teeth. The remainder is found in the blood, muscle, and other tissues ◦ In the blood, half of the calcium is in the ionized "free" state, and the other half is bound to proteins or complexed with anions ◦ Only calcium in the free state may be utilized in physiologic functions ◦ Total calcium is the sum of free and bound calcium

34. Laboratory Tests Electrolytes & Minerals ◦ Calcium ◦ Causes of increased calcium (hypercalcemia) are malignancies and primary hyperparathyroidism, thiazide diuretics ◦ Causes of decreased calcium (hypocalcemia): hypoparathyroidism, vitamin D deficiency, hyperphosphatemia, renal disease, loop diuretics ◦ A decreased albumin concentration may lead to a decreased total serum calcium concentration (pseudohypocalcemia) ◦ Corrected calcium=Reported serum calcium+ 0.8 (4- patient’s albumin)

35. Laboratory Tests Electrolytes & Minerals ◦ Phosphate ◦ Increased phosphate (hyperphosphatemia) can result from renal dysfunction, increased vitamin D intake, increased phosphate intake, hypoparathyroidism ◦ Decreased phosphate (hypophosphatemia) can be associated with overuse of aluminum- and calcium-containing antacids (these bind phosphorus in the GI tract), malnutrition, hyperparathyroidism

36. Laboratory Tests Electrolytes & Minerals ◦ Uric Acid ◦ Increased uric acid (hyperuricemia) may be caused by renal dysfunction, use of Furosemide, Thiazide diuretics, and Niacin ◦ Hyperuricemia may be associated with the development of gout ◦ Decreased uric acid levels (hypouricemia) are usually of little clinical significance but may occur with a low-protein diet, or use of allopurinol, probenecid

37. Osmolality ◦ The urine and serum osmolalities are measured & compared to assess the kidneys' ability to concentrate the urine Laboratory Tests

38. Urinalysis The urinalysis consists of: ◦ macroscopic assessment ◦ chemical screening by dipstick ◦ microscopic assessment of the urine sediment ◦ Urinalysis is used to screen for renal & nonrenal disease & to monitor the patient's response to therapy Laboratory Tests

39. Macroscopic Assessment  Color ◦ Freshly voided urine is normally pale yellow ◦ Normal urine may range in color from nearly colorless if very dilute to orange if very concentrated  Turbidity ◦ Freshly voided urine is normally clear ◦ The urine is turbid if bacteria, WBCs, RBCs, yeast, or crystals are present Laboratory Tests Urinalysis

40. Dipstick Screening  Bilirubin ◦ Not normally present in the urine ◦ It is excreted in the urine in the presence of severe liver disease or obstructive biliary disease ◦ The urine appears dark yellow to brown if bilirubin is present Laboratory Tests Urinalysis

41. Dipstick Screening  Blood ◦ Not normally present in the urine ◦ The urine may be visibly bloody, or blood may be found on microscopic or dipstick examination. ◦ Urinary tract infections, renal stones, sickle cell disease, and glomerulonephritis, are associated with blood in the urine Laboratory Tests Urinalysis

42. Dipstick Screening  Glucose ◦ Glucose is not normally present in the urine ◦ Urine glucose may be present in diabetes mellitus (when glucose >180 mg/dL) Laboratory Tests Urinalysis

43. Dipstick Screening  Ketones ◦ Ketones are not normally present in the urine. ◦ Urinary ketones may be seen before serum ketones are detectable in diabetic ketoacidosis ◦ May be found also in patients who are dieting or are malnourished Laboratory Tests Urinalysis

44. Dipstick Screening ◦ Leukocyte Esterase ◦ Leukocyte esterase is not normally present in the urine ◦ This enzyme is present in WBCs and may be found in the urine during urinary tract and vaginal infections Laboratory Tests Urinalysis

45. Dipstick Screening  Nitrites ◦ Nitrites are not normally present in the urine ◦ Escherichia coli converts dietary nitrates to nitrites ◦ Urinary nitrites are associated with E. coli urinary tract infections but may only be found if the urine is retained in the bladder for at least 4 hours Laboratory Tests Urinalysis

46. Dipstick Screening  PH ◦ Reflects the overall acid-base balance of the body & the kidneys' ability to handle acids & bases ◦ The formation of kidney stones is pH dependent ◦ An alkaline pH (pH >7.0) is commonly associated with the presence of urea- splitting organisms such as Proteus mirabilis Laboratory Tests Urinalysis

47. Dipstick Screening  Protein ◦ Small amounts of protein are normally present in the urine (as much as 0.5 g/day) ◦ Urinary protein is increased in a variety of renal diseases Laboratory Tests Urinalysis

48. Microscopic Assessment ◦ Obtained by centrifugation for a variety of casts, cells, & crystals  Casts ◦ Objects formed within renal tubules ◦ Composed mostly of proteins ◦ Example: red blood cell casts found in acute glomerulonephritis, WBC casts found in pyelonephritis Laboratory Tests Urinalysis

49. WBC casts RBC casts

50. Microscopic Assessment.. Cells ◦ RBCs: ◦ Normally, 2 RBCs/high power field may be present in urine ◦ Number increases with UTIs, stones, and tumors ◦ WBCs: ◦ Normally, 5 neutrophils/high power field maybe present in urine ◦ Number increases with UTIs Laboratory Tests Urinalysis

51. Microscopic Assessment  Crystals Found in acidic & alkaline urine Calcium phosphate & magnesium phosphate crystals form in alkaline urine Uric acid and calcium oxalate crystals form in acidic urine May reflect tendency to form stones Laboratory Tests Urinalysis

52. Gram's Stain & Culture ◦ Normal urine contains no bacteria or yeasts ◦ Bacteria are present in urinary tract infections & pyelonephritis ◦ The Gram's stain & culture identify the cause of the infection & aid in monitoring the patient's response to drug therapy ◦ Yeasts are found in the immunocompromised host and sometimes are associated with broad-spectrum antibiotic therapy Laboratory Tests

53. Calcium phosphate crystals

54. Urine Toxicology ◦ Urinalysis is used to detect the presence of drugs in patients with suspected drug overdoses, patients experiencing altered mental status, & patients in drug rehabilitation programs Laboratory Tests

55. Basic Metabolic Panel (BMP) ◦ Includes sodium, potassium, chloride, carbon dioxide (CO 2 ), glucose, blood urea nitrogen (BUN), and creatinine ◦ An abbreviated method for reporting the BMP in practice: Na K Cl CO 2 BUN SrCr Glucose

56. GOOD LUCK