Organ Function Tests
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This document discusses organ function tests, specifically focusing on liver function tests (LFTs) and kidney function tests (KFTs). It provides an overview of the major metabolic functions of the liver and kidney, including synthesis of proteins, detoxification, and regulation of water and electrolyte balance. It then describes various biomarkers that are used in LFTs and KFTs to evaluate organ function and detect injury, such as liver enzymes, bilirubin, albumin, and creatinine. The limitations of these tests are also noted.
Organ Function Tests
- 1. Organ Function tests Dr Kahkasha
- 2. Overview/Objectives Importance of Laboratory Tests in Clinical Medicine Normal ranges of Analytes Measured in the Laboratory Causes of Abnormal values of Analytes Measured in the Laboratory Variables that Affect Values of Analysis Validity of Laboratory Results Assessment of Validity of a Lab Test
- 3. LFT: Liver Function Test
- 4. Objectives the students should be able to understand: Major metabolic functions of the liver and causes of liver dysfunction. Discuss markers of liver function tests such as liver enzymes, bilirubin, albumin and prothrombin time that can diagnose hepatic injury and assess hepatic function.
- 5. Major Metabolic Functions of the Liver Synthetic Function Plasma proteins (albumin, globulins), cholesterol, triglycerides and lipoproteins Clotting factors Acute Phase proteins Detoxification and excretion Ammonia to urea (urea cycle), bilirubin, cholesterol, drug metabolites Storage Function Glycogen, Iron, Vitamins A, D, E, K and B12, Production of bile salts Helps in digestion
- 6. Some example of liver dysfunction Hepatocellular disease Cholestasis (obstruction of bile flow) Cirrhosis Hepatitis Liver cancer Steatosis (fatty liver) Genetic Disorders Hemochromatosis (iron storage)
- 7. Clinical Manifestations of Liver Dysfunction Jaundice Portal hypertension Ascites
- 8. Liver Function Tests (LFTs) Noninvasive methods for screening of liver dysfunction Help in identifying general types of disorder Assess severity and allow prediction of outcome Disease and treatment follow up
- 9. Liver Function Tests (LFTs) Broadly classified as: 1. Tests to assess hepatic function 2. Tests to detect hepatic injury: • Mild or severe; acute or chronic • Nature of liver injury (hepatocellular or cholestasis)
- 10. Classification of LFTs Group I: Markers of liver dysfunction ▫ Serum bilirubin: total and conjugated ▫ Urine: bile salts and urobilinogen ▫ Total protein, serum albumin and albumin/globulin ratio ▫ Prothrombin Time
- 11. Classification of LFTs Group II: Markers of hepatocellular injury ▫ Alanine aminotransferase (ALT) ▫ Aspartate aminotransferase (AST)
- 12. Classification of LFTs Group III: Markers of cholestasis ▫ Alkaline phosphatase (ALP) ▫ γ-glutamyltransferase (GGT)
- 13. Limitations of LFTs Normal LFT values do not always indicate absence of liver disease Liver a has very large reserve capacity Asymptomatic people may have abnormal LFT results Diagnosis should be based on clinical examination
- 14. Common serum liver chemistry tests
- 15. Bilirubin A byproduct of red blood cell breakdown It is the yellowish pigment observed in jaundice High bilirubin levels are observed in: Aute and chronic hepatitis, Gallstones
- 18. Serum bilirubin levels Normal 0.2 – 1.0 mg/dL Unconjugated (indirect): 0.2 – 0.6 mg/dL Conjugated (direct): 0.1 – 0.4 mg/dL Latent jaundice/Hyperbilirubinemia Above 1 mg/dL Jaundice: Above 2 mg/dL
- 19. Bilirubin levels and jaundice Class of Jaundice Causes Pre-hepatic or hemolytic Abnormal red cells; antibodies; drugs and toxins; thalessemia Hemoglobinopathies, Gilbert’s, Crigler-Najjar syndrome Hepatic or Hepatocellular Viral hepatitis, toxic hepatitis, intrahepatic cholestasis Post-hepatic Extrahepatic cholestasis; gallstones; tumors of the bile duct, carcinoma of pancreas
- 20. Urobilinogen (UBG) and bile salts Most UBG is metabolized in the large intestine but a fraction is excreted in urine (less than 4 mg/day) Normally bile salts are NOT present in urine Obstruction in the biliary passages causes: Leakage of bile salts into circulation Excretion in urine
- 21. Sample Indices Normal Hemolytic Jaundice Hepatic Jaundice Obstructive Jaundice Serum Total Bil ＜ 1mg/dl ＞ 1mg/dl ＞ 1mg/dl ＞ 1mg/dl Direct Bil 0 ～ 0.8mg/dl ↑ ↑↑ Indirect Bil ＜ 1mg/dl ↑↑ Urine Color normal deeper deep deep Bilirubin — — ＋＋ ＋＋ Urobilinogen A little ↑ uncertain ↓ Urobilin A little ↑ uncertain ↓ Stool Color normal deeper lighter or normal Argilous (complete obstruction)
- 22. Serum Albumin The most abundant protein synthesized by the liver Normal serum levels: 3.5 – 5 g/dL Synthesis depends on the extent of functioning liver cell mass Longer half-life: 20 days Its levels decrease in all chronic liver diseases
- 23. Serum Globulin Normal serum levels: 2.5 – 3.5g/dL α and β-globulins mainly synthesized by the liver High serum γ-globulins are observed in chronic hepatitis and cirrhosis: IgG in autoimmune hepatitis IgA in alcoholic liver disease
- 24. Albumin to globulin (A/G) ratio Normal A/G ratio: 1.2/1 – 1.5/1 Globulin levels increase in hypoalbuminemia as a compensation
- 25. Prothrombin Time (PT) Prothrombin: synthesized by the liver, a marker of liver function Half-life: 6 hrs. (indicates the present function of the liver). 10-15 sec, expressed in INR PT is prolonged only when liver loses more than 80% of its reserve capacity Vitamin K deficiency also causes prolonged PT Intake of vitamin K does not affect PT in liver disease
- 26. Aspartate aminotransferase (AST) Normal range: 5 – 40 U/L A marker of hepatocellular damage High serum levels are observed in: Chronic hepatitis, cirrhosis and liver cancer
- 27. Alanine aminotransferase (ALT) • More liver-specific than AST • Normal range (U/L): ▫ Male: 13-35 ▫ Female: 10-30 • High serum levels in acute hepatitis (300-1000 U/L) • Moderate elevation in alcoholic hepatitis (100- 300U/L) • Minor elevation in cirrhosis, hepatitis C and non- alcoholic steatohepatitis (NASH) (50-100 U/L)
- 28. Alanine aminotransferase (ALT) Appears in plasma many days before clinical signs appear A normal value does not always indicate absence of liver damage Obese but otherwise normal individuals may have elevated ALT levels
- 29. Alkaline phosphatase (ALP) A non-specific marker of liver disease Produced by bone osteoblasts (for bone calcification) Present on hepatocyte membrane Normal range: 40 – 125 U/L Modearte elevation observed in: Infective hepatitis, alcoholic hepatitis and hepatocellular carcinoma
- 30. Alkaline phosphatase (ALP) High levels are observed in: Extrahepatic obstruction (obstructive jaundice) and intrahepatic cholestasis Very high levels are observed in: Bone diseases
- 31. γ-glutamyltransferase (GGT) Used for glutathione synthesis Normal range: 10 – 30U/L Moderate elevation observed in: Infective hepatitis and prostate cancers GGT is increased in alcoholics despite normal liver function tests Highly sensitive to detecting alcohol abuse
- 32. Take Home Messages LFTs help detect liver injury and function. LFTs do have some limitations.
- 34. Objectives Upon completion of lectures, students should be able to: 1. know the physiological functions of the kidney. 2. describe the structure and function of the nephron. 3. identify the biochemical kidney function tests with special emphasis on when to ask for the test (indications) 4. Limitataions of KFT test 5. interpret the kidney function tests properly.
- 35. Contents: • Functional units • Kidney functions • Routine kidney function tests (KFTs): • Serum creatinine • Creatinine clearance • Cockcroft-Gault formula for GFR estimation • Serum Urea
- 36. Functional units : The nephron is the functional unit of the kidney Each kidney contains about 1,000,000 to 1,300,000 nephrons. The nephron is composed of glomerulus and renal tubules. The nephron performs its homeostatic function by ultra filtration at glomerulus and secretion and reabsorption at renal tubules.
- 37. Representation of a nephron and its blood supply
- 38. Each nephron is a complex apparatus comprised of five basic parts: 1.Glomerulus: functions to filter incoming blood. • Factors facilitate filtration: • high pressure in the glomerular capillaries, which is a result of their position between two arterioles. • the semipermeable glomerular basement membrane, which has a molecular size cutoff value of approximately 66,000 Da. The volume of blood filtered per minute is the glomerular filtration rate (GFR), and its determination is essential in evaluating renal function.
- 39. Each nephron is a complex apparatus comprised of five basic parts: 2.Proximal convoluted tubule- Returns the bulk of each valuable substance back to the blood circulation. • 75% of the water, sodium, and chloride. • 100% of the glucose (up to the renal threshold) • almost all of the amino acids, vitamins, and proteins • varying amounts of urea, uric acid, and ions, such as magnesium, calcium and potassium. • With the exception of water and chloride ions, the process is active; that is, the tubular epithelial cells use energy to bind and transport the substances across the plasma membrane to the blood. •Secretes products of kidney tubular cell metabolism, such as hydrogen ions, and drugs, such as penicillin.
- 40. Each nephron is a complex apparatus comprised of five basic parts: 3.Loop of Henle: •Facilitates the reabsorption of water, sodium, and chloride. The osmolality in the medulla in this portion of the nephron increases steadily from the corticomedullary junction inward
- 41. Each nephron is a complex apparatus comprised of five basic parts: 4.Distal convoluted tubule: • The filtrate entering this section of the nephron is close to its final composition. • Effects small adjustments to achieve electrolyte and acid-base homeostasis (under the hormonal control of both antidiuretic hormone (ADH) and aldosterone). The distal convoluted tubule is much shorter than the proximal tubule, with two or three coils that connect to a collecting duct.
- 42. Each nephron is a complex apparatus comprised of five basic parts: 5.Collecting duct: • The collecting ducts are the final site for either concentrating or diluting urine. • The hormones ADH and aldosterone act on this segment of the nephron to control reabsorption of water and sodium. • Chloride and urea are also reabsorbed here.
- 43. Regulation of : - water and electrolyte balance. - acid base balance. - arterial blood pressure. Excretion of metabolic waste products and foreign chemicals. Hormonal Function: Secretion of erythropoietin & activation of vitamin D and activation of angiotensinogen by renin Metabolic Function: site for gluconeogenesis Kidney functions :
- 44. • Many diseases affect renal function. • In some, several functions are affected. • In others, there is selective impairment of glomerular function or one or more of tubular functions. • Why to test the renal functions?
- 45. Routine KFTs include the measurement of : • Serum creatinine (Cr). • Serum urea. • S. uric acid Both serum Cr and creatinine clearance are used as kidney function tests to : • Confirm the diagnosis of renal disease. • Give an idea about the severity of the disease. • Follow up the treatment.
- 47. Serum creatinine • Creatinine is the end product of creatine catabolism. • 98% of the body creatine is present in the muscles, store of high energy in the form of creatine phosphate. • About 1-2 % of total muscle creatine or creatine phosphate pool is converted daily to creatinine through the spontaneous, non enzymatic loss of water or phosphate.
- 48. Serum creatinine • Creatinine in the plasma is filtered freely at the glomerulus and secreted by renal tubules (10 % of urinary creatinine). • Creatinine is not reabsorbed by the renal tubules. • Plasma creatinine is an endogenous substance not affected by diet. • Plasma creatinine remains fairly constant throughout adult life.
- 49. • The glomerular filtration rate (GFR) provides a useful index of the number of functioning glomeruli. • It gives an estimation of the degree of renal impairment by disease. Creatinine clearance:
- 50. Accurate measurement of GRF by clearance tests requires determination of the concentration in plasma and urine of a substance that is: • Freely filtered at glomeruli. • Neither reabsorbed nor secreted by tubules. • Its concentration in plasma needs to remains constant throughout the period of urine collection. • Better if the substance is present endogenously. • Easily measured. Creatinine meets most of these criteria.
- 51. • Creatinine clearance is usually about 110 ml/min in the 20-40 year old adults. • It falls slowly but progressively to about 70 ml/min in individuals over 8o years of age. • In children, the GFR should be related to surface area, when this is done, results are similar to those found in young adults.
- 52. • Clearance is the volume of plasma cleared from the substance excreted in urine per minute. • It could be calculated from the following equation: Clearance (ml/min) = U × V P U = Concentration of creatinine in urine µmol/l V = Volume of urine per min P = Concentration of creatinine in serum µmol/l
- 53. Cockcroft-Gault Formula for Estimation of GFR As indicated above, the creatinine clearance is measured by using a 24-hour urine collection, but this does introduce the potential for errors in terms of completion of the collection. An alternative and convenient method is to employ various formulae devised to calculate creatinine clearance using parameters such as serum creatinine level, sex, age, and weight of the subject.
- 54. An example is the Cockcroft-Gault Formula: K × (140 – age) × Body weight GFR = ────────────────── Serum creatinine (µmol/L) where K is a constant that varies with sex: 1.23 for male & 1.04 for females. The constant K is used as females have a relatively lower muscle mass.
- 55. Cockcroft-Gault Formula for Estimation of GFR: Limitations It should not be used if Serum creatinine is changing rapidly the diet is unusual, e.g., strict vegetarian Low muscle mass, e.g., muscle wasting Obesity
- 56. Serum Cr is a better KFT than creatinine clearance because: •Serum creatinine is more accurate. •Serum creatinine level is constant throughout adult life Creatinine clearance is only recommended in the following conditions: • Patients with early ( minor ) renal disease. • Assessment of possible kidney donors. • Detection of renal toxicity of some nephrotoxic drugs.
- 57. Normal adult reference values: Urinary excretion of creatinine is 0.5 - 2.0 g per 24 hours in a normal adult, varying according to muscular weight. - Serum creatinine : 0.6-1.4 mg/dL - Creatinine clearance: 90 – 140 ml/min (Males) 80 – 125 ml/min (Females) A raised serum creatinine is a good indicator of impaired renal function But normal serum creatinine does not necessarily indicate normal renal function as serum creatinine may not be elevated until GFR has fallen by as much as 50%
- 58. Serum Urea ( 20-40 mg/dL) in adult: Urea is formed in the liver from ammonia released from deamination of amino acids. As a kidney function test, serum urea is inferior to serum creatinine because: • High protein diet increases urea formation. • Any condition of ↑ proteins catabolism (Cushing syndrome, diabetes mellitus, starvation, thyrotoxicosis) →↑ urea formation. • 50 % or more of urea filtered at the glomerulus is passively reabsorbed by the renal tubules.
- 60. SODIUM 135 to 145 mEq/L POTASSIUM 3.5 to 5.5 mEq/L CHLORIDE 100 to 110 mEq/L BICARBONATE 24 to 26 mEq/L CALCIUM 8.6 to 10 mg/dl MAGNESIUM 1.6 to 2.4 mg/dl PHOSPHORUS 3.0 to 5.0 mg/dl URIC ACID 2.5 to 6.0 mg/dl pH 7.4 CREATININE 0.8 to 1.4 mg/dl Normal values of Internal Chemical Environment controlled by the Kidneys: 15 to 20 mg/dl15 to 20 mg/dlBUN (Blood Urea Nitrogen)BUN (Blood Urea Nitrogen)
- 62. EXOCRINE- Enzymes- Amylase and Lipase Meal tests Fecal/Urine tests ENDOCRINE
- 66. THANK YOU
Editor's Notes
- #21: Obstruction can occur in obstructive jaundice and also in hepatic jaundice due to obstruction of microbiliary channels caused by inflammation