Pathophysiology of Renal Disorders and Tests

DR NILESH KATE
MBBS,MD
ASSOCIATE PROF
ESIC MEDICAL COLLEGE, GULBARGA.
DEPT. OF PHYSIOLOGY
APPLIED RENAL
PHYSIOLOGY &
RENAL FUNCTION
TESTS

OBJECTIVES.
 Pathophysiology of common renal disorders
 Diuretics
 Renal function tests
 Dialysis and renal Transplantataion.

PATHOPHYSIOLOGY OF
COMMON RENAL DISORDERS
 Common urinary symptoms
 Renal failure
 Nephrotic syndrome
Tuesday, May 1, 2018

COMMON URINARY
SYMPTOMS
 Normal urine output
-800-2500ml/day
 Polyuria > 3L/day
 Common causes
 Physiological –
Psychogenic, drug induced
 Pathological – DI,
Mannitol infusion.
 Nocturia- Excess urine
excretion at night.

COMMON URINARY
SYMPTOMS
 Dysuria -pain or burning during micturition.
 Urgency of Micturirtion - Exagerrated sense or
urge to micturate
 Enuresis – Involuntary passage of urine at night.
 Oliguria- urine output< 500 ml/day.

INCONTINENCE
 Inability to retain
urine in bladder.
 Causes
 Neurogenic
 Stress
 Mechanical
 Overflow
 Psychogenic
 Functional

RENAL FAILURE
 Deterioration of Renal function resulting in
decline in Glomerular filtration rate & rise in
urea & Non-nitrogenous substances in blood.
 2 types
 Acute
 chronic

RENAL FAILURE
ACUTE RENAL FAILURE
 Sudden onset
 Invariably reversible
 Cause – Pre-renal or Post
renal
 Uremia – recent onset.
 Renal failure casts –
Absent
 Sp Gravity – High
 Dialysis – for short period.
CHRONIC RENAL FAILURE
 Gradual
 Usually irreversible.
 Mostly renal
 Uremia – more than 3
months
 Renal failure casts –
Present
 Sp Gravity – Low, fixed.
 Dialysis – repeated,chronic

NEPHROTIC SYNDROME
 Massive proteinuria ( 3.5g/day) mainly
albuminuria with
 Hypoalbuminemia
 Odema
 Hyperlipidemia
 Lipiduria
 Hypercoagulability.

DIURETICS
Sr
no
Class of Diuretics Site of action Mechanism of
action
Major effects
1 Loop Diuretics
Furosemide
Thick ascending
Limb
Inhibition of
Na+
-K+
-2Cl-
Nacl excretio
K+
Ca+
2 Thiazide Diuretics Early distal
tubule
Inhibition of
Na-Cl symport.
Nacl excretio
K+
3 Carbonic anhidrase
inhibitors –
Acetazolamide
Proximal tubule Inhibition of
Carbonic
Anhydrase.
HCo3 -
4 Osmotic diuretics Proximal tubule Retain water
isoosmotically
Nacl excretio
K+

RENAL FUNCTION TESTS
 Analysis of urine
 Analysis of blood
 Renal clearance tests
 Radiology & renal imaging.
 Renal biopsy.

ANALYSIS OF URINE
 Volume – normal 500-2500
ml/day
 Colour –
 Light yellow – due to urochrome
pigment
 Brownish yellow – d/t
conjugated bilirubin in
hepatic/post hepatic jaundice
 Frothy – Proteinuria
 Red dark brown – Porphyria.
 Cloudy – Ppt of Capo4

ANALYSIS OF URINE
 Osmolality – 50-1200
mosm/Kg
 Specific gravity –
1.003-1.030
 Urine pH – 4.5 -8

ANALYSIS OF URINE
 Chemical analysis for abnormal urinary
constituents
 Proteinuria
 Glycosuria
 Ketonuria
 Bilirubinuria
 Haemoglobinuria
 Haematuria.

ANALYSIS OF URINE
 Proteinuria - >150
mg/day
 Congestive heart
failure
 Orthostatic proteinuria
 Glomerular proteinuria
– Acute glomerular
Nephritis,
Pylonephritis

ANALYSIS OF URINE
 Glycosuria – presence
of Glucose in urine
 DM
 Renal Glycosuria
 Alimentary Glycosuria.
 Ketonuria – ketone
bodies in urine
 Severe DM
 Prolonged starvation

ANALYSIS OF URINE
 Bilirubinuria – > 1.35 mg
 Bilirubin in urine with
increased conjugated
bilirubin in hepatic, post
hepatic jaundice.
 Haemoglobinuria –
haemoglobin in urine
 Intravascular haemolysis
in black water fever in
falciparum malaeria.

ANALYSIS OF URINE
 Microscopic
examinations
 Casts
 Crystals
 Cells
 Bacteriological
examination of urine
– for Pus cells &
Bacteria

MICROSCOPIC EXAMINATIONS
 Casts – Proteinaceous
plugs formed by
coagulation of Tamm-
Horsfall proteins
 Cellular – coagulated
with protein material
 Non-cellular – hyaline
& granular casts.

MICROSCOPIC EXAMINATIONS
 Crystals – Normally seen
are crystals of Ca oxalate,
CaPO4, Ca-NH4-Mg-PO4
 Uric acid crystals &
cystine crystals -
significant
 Cells – RBC, WBC,
tubular epithelial cells,
squamous epithelial cells.

ANALYSIS OF BLOOD
 Blood urea level – normal 20-40mg/dl
 50% glomerular damage.
 Plasma creatinine concentration.(0.6-1.5
mg/dl)

ANALYSIS OF BLOOD
 Serum protein levels
 6.7-8 gm/dl
 Albumin – 3-5 gm/dl
 Globulin – 2-3 gm/dl
 Serum cholesterol levels – 150-200 mg/dl.
 Nephrotic syndrome
 Serum electrolyte levels
 Na – 152 mEq/L, K - 5 mEq/L, Ca 9-11 mg/dl.

MEASUREMENT OF GFR
 If a substance (W) is neither reabsorbed nor secreted
by tubule:
 The amount excreted in urine/min. will be equal
to the amount filtered out of the glomeruli /min.
 Amount of substance excreted in urine/min
= UW V ……………….. 1
UW–Urine conc of w
V – Urine volume per unit time

MEASUREMENT OF GFR
 Rate at which a substance is filtered by the glomeruli
can be calculated:
Quantity filtered = GFR x PW …………… 2
 P = Concentration in plasma.
 Amount filtered = amount excreted
GFR x PW= UW V from eq 1 & 2
GFR = UW V
------------
PW

CRITERION FOR W
 Freely filterable at renal corpuscle
 Not reabsorbed
 Not secreted.
 Not synthesized by renal tubules.
 Not metabolized by renal tubules.
only one substance --- INULIN

CLEARANCE
 Definition :-
Amount of plasma completely cleared of the
substance by kidney in unit time by excretion of that
substance in urine.
Basic clearance formula
Cw = mass of w excreted / time
---------------------------
Pw
= Uw V
----------------------
Pw

INULIN CLEARANCE
 Inulin –
dye, fructopolysaccharide,
does not exist naturally,
measure of GFR – not reabsorbed, nor secreted, nor-
metabolized, non-toxic,
Method – single bolus dose
i/v infusion,
urine/ plasma conc,
urine flow rate,
Cin = Uin V / Pin

CLINICAL APPLICATION
 An indicator of plasma clearance mechanism.
 Cw = Cin clearance ratio 1
e.g. mannitol, sorbitol, vit B12, sucrose
 Cw < Cin clearance ratio < 1
e.g. Glucose, xylose, fructose
 Cw > Cin clearance ratio > 1
e.g. Para-amino hippuric acid (PAH),
phenol red

CREATININE CLEARANCE
 Adv.– More preferred
No intravenous dose needed.
Endogenous substance from metabolism of muscle
creatine
Filtered & marginally secreted
Method:-
24 hr urine collection, urine conc,
mid-point plasma conc sample,
Normal Value – 130 ml/min

UREA CLEARANCE
 Urea- End product of protein metabolism.
 Filtered & partly reabsorbed
 Clearance less than GFR
 Influenced by protein content of diet.
METHOD :-
Empty bladder,
urine collected at the end of 1 hour,
blood sample collected at mid point
estimate blood & urine urea.

UREA CLEARANCE
 Urea clearance drastically changes – urine output <
2ml /min
 So 2 urea clearance values
1 Maximal :- urine output > 2 ml.
CU = UV/ P
Normal value = 75 ml / min
2 Standard :- urine output < 2 ml.
CU = U √ V/ P
Normal value = 54 ml / min

MEASUREENT OF RENAL PLASMA
FLOW
 FICK’S Principle to kidney
“ Amount of substance excreted by
the kidney per unit time (UV) is equal
to the product of renal plasma flow
(RPF) and arteriovenous difference in
its plasma concentration.”
UV = RPF (Pa- Pv)
RPF = UV / (Pa-Pv)……………(1)

PAH CLEARANCE – TO
MEASURE RPF
 PAH clearance is used to measure
RPF
b’coz–
1 Completely extracted.
2 Neither metabolized nor
reabsorbed.
3 Does not affect RBF.
4 Actively secreted.
5 Conc. easily measured.

METHOD
 RPF = UV/ (Pa – Pv)
 All PAH excreted in urine nothing returned
so Pv is 0
RPF = UV / Pa
 Also PAH not excreted by any other organ so plasma PAH
conc can be used.
RPF = UV / P PAH
 BUT UV / P PAH= PAH Clearance
So RPF = PAH Clearance.
ERPF = PAH Clearance.
TRUE ERPF = CPAH / 0.9

RENAL CLEARANCE TESTS TO ASSESS
OSMOTIC AND FREE WATER CLEARANCE
 Osmotic clearance –
Amount of plasma
completely cleared of
osmotically active
solutes that appear in
the urine each min.
 Free water clearance –
The quantitative
measure of kidneys
ability to excrete water.

TESTS FOR TUBULAR
FUNCTIONS
 Urine concentration tests
 Urine dilution tests
 Urine acidification tests
 Other methods of study of tubular functions.

URINE CONCENTRATION
TESTS
 Measuring specific gravity of urine after 12 hrs of
water deprivation or after giving vasopressin
 If above 1.020 normal

URINE DILUTION TESTS
 Pt asked to drink 1 l of water & measure urine
sample for 4 hours, - 750 ml should be collected &
one sample osmolality should be less than
100msom/Kg of water.

URINE ACIDIFICATION TESTS
 Pt given NH4Cl (0.1 gm/kg) & urine sample
collected after 6 hrs
 Urine pH should be below 5.3

OTHER METHODS OF STUDY
OF TUBULAR FUNCTIONS.
 Micro Puncture technique
 Micro Cryoscopic studies
 Micro Electrode studies.

RADIOLOGY & RENAL IMAGING.
 Plain radiograph of
abdomen
 Intravenous
pyelography.
 Ultrasonography.
 Computed
tomography.
 Radionuclide
studies.

RENAL BIOPSY
 Per cutaneously with
the help of Vim-
silvermann needle.

DIALYSIS AND RENAL
TRANSPLANTATAION.
 Dialysis – diffusion of
solute from an area of
higher conc to lower
conc through
semipermeable
membrane
 Uremia – when 75%
of nephrons are
damaged.

HAEMODIALYSIS OR
ARTIFICIAL KIDNEY
 In acute renal failure,
circulatory shock or
mecury poisoning.
 Radial artery is
connected to
haemodialysis machine &
blood is passed through
long & coiled cellophane
tube immersed in dialysis
fluid.

PERITONIAL DIALYSIS
 Peritonium is used as
semipermeable
membrane

RENAL TRANSPLANTATION
 For end stage renal
disease
 Reverses Metabolic &
Excretory
abnormalities.

Pathophysiology of Renal Disorders and Tests

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