With diseases and needs to be done oft

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.

33. Kidney Function
Tests
(KFTs)

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/dl
15 to 20 mg/dl
BUN (Blood Urea Nitrogen)
BUN (Blood Urea Nitrogen)

61. Pancreatic Function Test

62.  EXOCRINE- Enzymes- Amylase and Lipase
Meal tests
Fecal/Urine tests
 ENDOCRINE

64. Thyroid Function Test

66. THANK YOU