This document discusses clinical chemistry (chemical pathology) and the use of biochemical tests in medicine. It provides examples of how biochemical tests can be used to diagnose metabolic diseases, monitor disease response to treatment, and screen for subclinical conditions. Key factors that influence biochemical test results like age, sex, nutrition, and exercise are reviewed. Tests of renal function include measuring the glomerular filtration rate using creatinine or isotopes, as well as assessing tubular function and integrity through tests of sodium, glucose, and amino acid handling. Imaging, biopsy and detection of antibodies can also provide diagnostic information for renal diseases.

1. CHEMICAL PATHOLOGY
(CLINICAL CHEMISTRY)
PROF.DR.ARSHAD P.MALIK
MBBS,M.Phil,DIP.NEPH.
V.Principal (Academics)
Pathology,KGMC

2.  To provide biochemical information for management
of patients
 These information would be of value
1. Accurate
2. Relevant

3. USE OF BIOCHEMICAL TESTS
IN MEDICINE TO
1 . Diagnose metabolic diseases
a) DM b) Hypothyridism etc
2. Diseases which give rise to
metabolic changes
a) Rf b) Malabsorbtion etc

4. Principle function of biochemical tests
1. Diagnosis
a) confirmation b) Rejection of disease
2. Prognosis---information regarding
outcome of diseases
example:
serial measurement of creatinin clearance
in Renal failure

5. 3) Monitoring of diseases----response to treatment
Example:
 Glucose in DM
 Hypokalaemia patients on diuretics
 Digoxin patients on CCF
4) Screening----detection of subclinical diseases
Example:
 mass screenig of (PKU) Phenylketonuria in newborns
 hepatitis screening etc

6. Sampling
Test request
 Pt.name
 Sex
 Ward/clinic
 address
 Dr.name
 clinical diagnosis
 test required
 type of specimen
Example of urine specimens
1.Morning specimen is concentrated, more reliable
2.Afternoon specimen 2 to 4pm for urobilinogen in jaundiced
patients
3. 2hrpp specimen
4. Random specimen

7. 5.24hr specimen (VMA, nephrotic synd, crystraluria,
17 ketosteril (inborn error of metab)
 -Date/ time –expalin
 relevant drugs

8. FACTORS INFLUENCING
BIOCHEMICAL TESTS
 Age----- alp
 Sex--- gonadal steroid
 Pregnancy---- thyroxine
 Posture------proteins
 Exercise--- creatin kinase
 Nutritional status--- glucose
 Time---- cortisol

9. BIOCHEMICAL TESTS OF RENAL
FUNCTION
FUNCTION OF KIDNEY INCLUDES
1. Excretory function
2. Regulatory function
3. Endocrine function

10. EXCRETORY FUNCTION
The undesirable end products of
metabolism like urea, creatinine,uric
acid and phosphates
In urine formation
a)Filtration
b)Reabsorbtion
c)Secretion
d)Excretion

12.  Kidney receives 1300 cc /mint (25%
of cardiac output)
 One million nephron in each kidney
(total – two million)
 In proximal tubules we get
ultrafiltrate of plasma, same
constituent as that of blood except
protein)

13.  Substances with molecular weight of
68kdalton or 68000 daltons are
filtrable, albumin molecular weight is
close to 68KD, so first of all appears
in urine in injury to memb.

14. REGULATORY FUNCTION
It has major role in homeostasis and
includes:
i) Acid base regulation
ii)Maintainance of fluid and
electrolytes balance

15. EDOCRINE FUNCTION
i) Renin, produced by juxta medullary
apparatus
ii)25 dihydroxycholicalceferol(D2) hepatic
hydroxylation
in kidney 1, hydrolase , finally we get
1,25, or calcitriol)
.

16. iii)Erythropoietin plays very importan
in renal failure
(Also called hematopoietin or hemopoietin, it is
produced by interstitial fibroblasts in the kidney in
close association with peritubular capillary and tubular
epithelial cells.
It is also produced in perisinusoidal cells in the liver.
While liver production predominates in the fetal and
perinatal period,
renal production is predominant during adulthood

17. RENAL FUNCTION TESTS
1. Measurement of GFR
UXV/P X TIME (t)--- 120ml/mint
 Subs. Which are neither reabsorbed nor
secreted by the tubules are selected like
i) Inulin (plant polysaccharide)
ii) Cr51- labelled EDTA
iii) I125 Iothalamate

18. Procedure:
Two ways
1) Serial of blood samples are taken after
injecting isotopes and GFR is calculated
from rate of fall of plasma radioactivity
of isotopes.
2) Blood and urine are collected and
standard clearance formula is used.
UxV/P ml/mint
Demerits:
 It is diificult to perform in out patient
deptt.
 Error lies on behalf pf patients
(incontinent,add water, adding some
others persons urine)

19. Indications of creatinine clearance:
 Kidney transplant donors
 For diagnosis of minor renal
impairments
 Calculation of initial doses of
potentially toxic drugs that are
eliminated by body by renal
excretion

20. Plasma creatinine concentration
Normal :0.5mg/dl------1.5mg/dl
 Most reliable simple biochemical test
 Ingestion of meat may interfere as much
as 30 % several hrs after meal
 Ideally blood sample should be taken after
an over night fast
 Strenous exercise increases creatinine
concentration
 As Muscle declines with age so does GFR
decreses---hence plasma craetinine
remains fairly constant
 Plasma creatinie is proportional 1/GFR
(inversly related)

21. Changes in plasma creatinie
concentration occurs independently
of renal function:
Decreases in;
 Startvation
 Wasting
 Patients on corticosteroids
(Refeeding increases the creatinine
concentration)

22. BLOOD UREA CONCENTRATION
normal:20------40 mg/dl
 Synthesized in liver as byproduct of
deamination of amino acids
 Urea enters gut where it is broken down
to ammonium & CO2
 Much of ammonium is recycled in liver to
reform urea or amino acids

23.  Eliminated in urine, represents major
route of excretion of nitrogeneous compd.
 Filtered ar glomerulous level and
significant tubular reabsorbtion occurs
through passive diffusion
 Tubular reasorbtion, increases at low rates
of urine flow(in fluid depletion) and this
can cause increase urea cons. even when
RF is normal
 Creatinine is more reliable index than urea

24. Urea productiion is increased:
 Increase protein intake
 GI bleeding(due to absortion of amino
acids & peptides)
 Hypercatabolic state
 Dehydration
 Urinary stasis
Urea production is decreased in:
 Low protein intake
 Dialysis (Urea diffuses across dialysis
memb.)
 Severe liver diseases

27. Plasma beta 2 microglobulin
 Small peptide molecular wt 11.8 KD
 Effected by diet
 Muscle mass
 Increases in malignancy
 Inflammatory diseases
 It is reabsorbed and catabolized by
tubules so its excretion provides
sensitive method of assesing tubular
integrity.

28. Cystatin C
 Low molecular weight 13 KD
 Produced by all nucleated cell
 Cleared by glomeruli
 Its plasma concentration reflects GFR

29. ASSESSMENT OF GLOMERULAR
INTEGRITY
GLOMERULAR DAMAGE:
• Proteinuria
• Haemeturia
• Red cell cast

30. TESTS OF RENAL TUBULAR
FUNCTION
 Tubular function tests involve
evaluation of functions of the
proximal tubule (i.e. tubular
handling of sodium, glucose,
phosphate, calcium, bicarbonate
and amino acids)
 Distal tubule (urinary acidification

31.  Proximal tubules---- renal
glycosuria (Shows proximal tubular
defect)
 Aminoaciduria ( tubular defect can
be investigated by amino acid
chromatography)

32. TESTS OF DISTAL TUBULES
WATER DEPRIVATION TEST
a) to assess urine acidification
b) distal renal tubular acidosis

33. Lab diagnosis in renal diseases:
 B.Urea
 S.Creatinine
 Creatinine clearance
 S.Sodium(Na+)

34.  Fractional excretion of sodium(FE
Na%)-
a)represents the fraction of filtered
sodium that is ultimatly excreted in
urine
b)Very useful index to differentiate
between prerenal failure and renal
failure

35. c)Early diagnosis is clinically very
important because treatment
modalities are entirely different in
these two disease
Calculation for FE Na%:
Urinary Na x Serum creatinine x100
Serum Na X Urinary creatinine
 In prerenal uraemia the ratio is< 1%
In renal >1.5%

36.  Serum Potassium(K+)
 Plasma and urine Osmolality
 Plasma osmolality=285+ 10mmol/kg
 Urine osmolality= 50--1200mmol/kg
 (Osmolality is measured with the
help of an instrument named
osmometer

37. Other techniques include:
 IMAGING AND RENAL BIOPSY
 ultrasound (including Doppler studies
to assess blood flow)
 plain and contrast radiography (e.g.
intravenous urography,
arteriography),
 computerized tomography (CT) and
magnetic resonance imaging (MRI),
to provide anatomical

38.  percutaneous renal biopsy, to
provide a histopathological diagnosis.
 The detection of specific antibodies in
serum (e.g. antiglomerular basement
membrane
 antibodies, positive in Goodpasture's
disease, and antineutrophil cyto-
plasmic antibodies,positive in
systemic vasculitis)

39.  other proteins (e.g. complement
components, often low in systemic
lupus erythematosus) can also
provide valuable diagnostic
information.

40. Thank you