This ppt only for study purpose

1. PATHOPHYSIOLOGY OF
COMMON
RENAL DISORDERS
Dr. Pandian M
Assistant Professor
Dept. of Physiology

2. SLO’s
The applied aspects of common renal
disorders which need some elaboration are:
• Common urinary symptoms
• Renal failure
• Nephrotic syndrome
DIURETICS
• Classification
• Site of action, mechanism of action and
major effects

3. COMMON URINARY SYMPTOMS
• Polyuria, nocturia and urinary frequency.
• Normal urine output per day is 800–2500
mL.
• Therefore, a reasonable criterion to
satisfy the definition of polyuria is
excretion of 3.0 L of urine daily, provided
the patient is not on high fluid diet.

4. Common causes of polyuria are:
I. Physiological (primary polydipsia or excessive
water drinking), which can be
• Psychogenic, or
• Drug induced (chlorpromazine, anticholinergics).
II. Pathological (defective water conservation by the
kidney):
• Diabetes insipidus.
• Solute diuresis, as in chronic renal failure, diabetes
mellitus and mannitol infusion.

7. Dysuria and urgency of micturition.
• Dysuria refers to pain or burning during
micturition.
• Urgency of micturition is the exaggerated
sense or urge to micturate.
• It is due to either irritative or inflammatory
disorders of the urinary bladder.
• This is often associated with an increased
frequency of urination.

8. Incontinence
• This refers to inability to retain
urine in the bladder.
• It results from the neurological or
mechanical disorders of the
complicated system that controls
normal micturition.

9. Common causes of incontinence are:
• Neurogenic incontinence due to disturbances of neural
control of micturition, Stress incontinence, e.g. in
post-menopausal parous women,
• Mechanical incontinence, e.g. damage to the urethral
sphincters.
• Overflow incontinence, e.g. in obstruction due to
benign prostatic enlargement,
• Psychogenic incontinence, as in anxious children and
• Functional incontinence is seen in very old persons
who have mental derangement.

10. Enuresis
• It refers to involuntary passage of urine at
night or during sleep.
• It is also called night bed-wetting or
nocturnal enuresis.
• It is normal in children up to 2–3 years of
age.
• In some children it continues for long.

11. Oliguria
• It refers to the urine output less
than 500 mL/day in an average
adult.
• It invariably occurs in acute on
chronic renal failure or acute
renal failure.

12. Anuria
• It is said to occur when patient does
not pass any urine or passes less than
50 mL of urine/day.
• In physiological sense, the term
anuria means less formation or
absence of formation of urine by the
kidney.

13. RENAL FAILURE
• It refers to the deterioration of renal
functions resulting in a decline in the
glomerular filtration rate (GFR) and rise
in urea and non-nitrogenous substances in
the blood.

14. Types of RF
It is of two types:
• Acute renal failure and
• Chronic renal failure.

15. Acute renal failure
• Acute renal failure refers to a
sudden decline in GFR over a
period of days or weeks
associated with the rapid rise in
blood urea.

16. Chronic renal failure
• It refers to a slow, insidious,
irreversible deterioration of renal
functions resulting in the
development of clinical syndrome of
uraemia, manifested by excretory,
metabolic, neurological,
haematological and endocrinal
abnormalities.

17. Acute versus chronic renal failure.
(nephrotic syndrome)

18. NEPHROTIC SYNDROME
• Nephrotic syndrome refers to a massive
proteinuria (more than 3.5 g/day), mainly
albuminuria and its associated
consequences
which include:
• Hypoalbuminaemia,
• Oedema,
• Hyperlipidaemia,
• Lipiduria and
• Hypercoagulability.

19. Pathophysiology nephrotic
syndrome
• A wide variety of disease processes
including immunological disorders,
toxic injuries, metabolic
abnormalities, biochemical defects
and vascular disorders involving
glomeruli contribute to the
development of nephrotic syndrome.

20. DIURETICS
• The diuretics are the drugs which
primarily cause a net loss of Na+
(natriuresis) associated with water
loss (secondary to natriuresis) and
thus increase the rate of urine flow.

21. Classification
• Depending upon their efficacy,
the diuretic drugs can be
classified as:
• High ceiling
• Medium efficacy
• Weak/ adjunctive

22. Site, Mechanism of action & Major effects

23. Renal function test
Dr. Pandian M
Assistant Professor
Dept. of Physiology

24. SLO’s
• RENAL FUNCTION TESTS
• Analysis of urine
• Analysis of blood
• Renal clearance tests
• Radiology and renal imaging
• Renal biopsy

25. Renal function tests
• To assess the functional capacity of the kidney
• To detect the renal impairment as early as possible
• To detect kidney disease well before the symptoms
develop and determine the etiology of renal
disease
Renal function tests are divided into
1. Analysis of urine
2. Analysis of blood
3. Renal clearance tests
4. Radiology and renal imaging
5. Renal biopsy

26. Analysis of urine
1. Volume – normal urine output 800 to 2500ml.
Abnormalities –polyuria >3L,
oligouria<500ml,
anuria<50ml
2.Colour- light yellow due to urochrome pigment
brownish yellow- post hepatic jaundice
cloudy- due to calcium po4,
frothy- proteinuria,
red dark brown- porphyria

27. 3.Osmolality and specific gravity-
• normal osmolality - 50 to 1200 mOsm/kg
• specific gravity - 1.003 to 1.030
• Abnormality-
fixed osmolality of 300mOsm/kg with sp.
Gravity 1.010 is an evidence of advanced
urinary failure
Persistent low urine osmolarity
<100mOsm/kg H2O even after 8 hrs of water
deprivation is diagnostic of Diabetes Insipidus.

28. 4. pH – normal urine pH 4.5 to 8 slightly acidic
abnormal pH-infection with urea splitting organisms,
- impairment of tubular acidification
5.Microscopic examination-
• Casts- proteinaceous plugs due to coagulation of
Tamm-Horsfall protein within renal tubules,
• Red cell cast, leukocytic casts, epithelial casts,
fatty acid casts
• Crystals- calcium oxalate, calcium phosphate, triple
phosphate, uric acid
• Cells – RBCs, leucocytes, tubular epithelial cells,
Often, WBC casts are the result of infections
that have reached the kidneys. Bacterial casts:
Bacterial casts can also signal infection.
Sometimes, a bacterial casts are found mixed
in with WBC casts.
Red blood cell casts are seen in many kidney
diseases. Renal tubular epithelial cell casts
reflect damage to tubule cells in the kidney
RTE cell casts appear as clear cylinders
containing RTE cells. These casts indicate
tubular damage. In some RTE cell casts, the
RTE cells may appear in rows, indicating that
the epithelium of an entire tubule has
sloughed off.

29. Chemical analysis for abnormal
constituents of urine
1. Proteinuria: >150mg/day
2. Glycosuria: DM, Renal impairments, Inborn
errors of metabolism
3. Ketonuria: Severe DM, Prolong starvation
4. Bilirubinuria:
5. Haemoglobinuria: intravascular hemolysis,
Black water fever
6. Haematuria: renal stone, glomerulonephritis,
Renal Cell Carcinoma

30. Analysis of blood
1. Blood urea- normal 20-40mg%
it is an index of glomerular function. BUL begins to
rise after about 50% glomerular damage occurs
If >50% indicates glomerular damage
2. Plasma creatinine concentration(normal 0.6 to
1.5).more reliable than urea.
GFR must fall to about 50% of its normal value
before a significant increase in serum creatinine occurs
3. Se.proteins – normal total protein 6.7-8gm%, albumin
3-5gm%, globulin 2-3gm% and A/G ratio 1.7:1.
In nephrotic syndrome albumin levels decrease and
globulin levels increase, leading to reversal of A/G ratio

31. 4. Se. cholesterol increase in nephritic syndrome
5. Se. electrolyte- normal
Na+ 152 mEq/L
K+ 5mEq/L
Ca++ 9-11mg%
po4 3-4.5mg%
SO4- 0.5 -1.5mEq/L
Mg++ 1.5 -2.5mEq/L
Chronic renal failure -high K+ and PO4-,
low Na+, low Ca ++ levels

32. Measurement of GFR
• Direct method : micro puncture technique
• Indirect method : clearance measurements
• Use of clearance Methods: The rates at which
different substances are cleared from the plasma
provide a useful way of determining the
effectiveness with which the kidneys excrete
various substances.
• Renal clearance: of a substance is the volume of
the plasma that is completely cleared of a
substance by the kidney per unit time. i.e in one
minute.

33. Plasma Clearance (ml /min) = Urinary concentration x Urinary flow
(Cs) -----------------------------------------------
Plasma Concentration
Cs –Clearance of a substance S
Us – Urine concentration of substance
V—Volume of urine
Ps—Plasma concentration of a substance.

34. • Clearance of a substance is equal to GFR
if there is no net tubular secretion or
reabsorption. E.g. Inulin.
• Clearance of a substance is less than GFR
if there is net tubular reabsorption e.g. urea.
• Clearance of a substance will be greater
than GFR if there is net tubular secretion.
E.g. PAH,

35. Renal clearance provides a useful way of
quantifying.
• The excretory function of the kidney.
• Quantify the rate at which blood flows through
the kidneys i.e renal plasma flow, Renal blood
flow
• Quantify the basic functions of the kidneys like
Glomerular filtration
Tubular reabsorption
Tubular secretion

36. Criteria for a substance used for
measurement of GFR
• Substance should be freely filtered by the
glomerular membrane
• it should not be reabsorbed or secreted by renal
tubule.
• it should not be metabolized or stored or synthesized
in the body.
• it should not be protein bound
• it should not affect GFR.
• it should not be toxic.
• The concentration of the substance should be
measurable in the plasma or urine.

37. Renal clearance tests
A.Test for Glomerular functions
1. Inulin clearance
2. Creatinine clearance
3. others –
Renal plasma flow and
Renal blood flow

38. Inulin clearance:-
• It is used to estimate GFR and therefore used
for measuring GFR.
• Inulin is freely filtered, it is neither
reabsorbed nor secreted by the renal tubules
therefore its rate of filtration is equal to rate
of excretion.
• Glomerular filtrate has some Conc. of inulin
as does plasma and all glomerular filtrate
formed is cleared of inulin.
• Thus plasma clearance per minute of inulin is
equal to GFR.

39. • Inulin is soluble polysaccharide not produced
in the body,
• It is nontoxic and physiologically inert and
therefore safe for use.
• Inulin, which is not produced in the body, is
found in the roots of certain plants and must
be administered intravenously to a patient to
measure GFR
• The plasma concentration is 1 mg/ml,
• Urine concentration is 125 mg/ml, and
• Urine flow rate is 1 ml/min.

40. • Therefore, 125 mg/min of inulin passes
into the urine.
• Then, inulin clearance is calculated as
the urine excretion rate of inulin divided
by the plasma concentration,
• which yields a value of 125 ml/min.
• Thus, 125 milliliters of plasma flowing
through the kidneys must be filtered to
deliver the inulin that appears in the
urine.

41. • Inulin clearance is calculated by the formula
• Inulin Clearance = U V
--------
P
• U-------Urinary concentration of inulin.
• V------- Volume of urine.
• P-------- Plasma concentration of inulin.
• Inulin is not the only substance used for determining
GFR.
• Other substances that have been used clinically to
estimate GFR include creatinine and radioactive
iothalamate.

42. Inulin clearance test
• Polysaccharide, polymer of fructose MW5200,does
not occur naturally in body
• Large initial dose in injected i.v. f/b constant inulin
infusion
• Inulin conc. of venous blood(Pin),urinary
conc.(Uin)and volume of urine excreted per minute(V)
are determined and the clearance is calculated
• Uin.V
Cin=
Pin

43. Comparison of clearance of given
substance with that of Inulin clearance
• When Cx = Cin, excretion is by filtration alone, e.g..
Mannitol, Sorbitol, vit. B12 and sucrose
• When Cx < Cin , excretion is by filtration and
reabsorption. E.g. Glucose, Fructose, xylose
• When Cx > Cin , excretion is by filtration and
secretion. E.g. PAH, creatinine, phenol red

44. Creatinine Clearance:-
• Creatinine clearance is also used to measure GFR.
• It is a by product of skeletal muscle metabolism
• It is present in the plasma at a relatively constant
concentration does not require intravenous infusion
into the patient.
• For this reason creatinine clearance is the most
widely used method of estimating GFR clinically.
• Though its value is sometimes lesser and
sometimes greater than GFR because of
reabsorption and secretion of creatinine by renal
tubules respectively.

45. Creatinine clearance test
• It is more commonly used to measure GFR
• It determines 24-hour endogenous creatinine
clearance as estimate of GFR
• Does not require administration of exogenous
creatinine as it is product of muscle metabolism
• It is easy to measure and used clinically as an
estimate of GFR
• Normal range of creatinine clearance 80 –
110ml/min
• Some creatinine is reabsorbed by the tubules and
some may be secreted

46. Urea clearance (Curea)
• It measures the rate of excretion of waste
products
Uurea x V
• Curea=
Purea
When rate of urine flow is <2ml/min, clearance of
urea is called as U√V
Standard urea clearance=
(40 -65ml/min) P urea

47. • When rate of urine flow
>2ml/min it is called max. urea
clearance (60-90ml/min)

48. Renal plasma flow and renal blood
flow
• RBF based on Fick’s principle i.e. the amount of
substance taken up by any organ per unit time is
equal to the arterio-venous difference for the
substance across the organ times the blood flow
• Amount of substance taken= (A-V) diff. of
substance x blood flow / minute
amount of substance taken/min
Blood flow /min =
(A-V) diff. of the substance

49. Criteria for the substance used
1. It should be completely excreted from the blood during
its passage thr. Kidney
2. Neither metabolised, stored, nor produced by kidney
3. does not itself affect RBF
4. Its conc. In arterial and renal venous plasma can be easily
measured
5. actively secreted by tubules from blood into the lumen
e.g. Diodrast- organic iodine compound
Para amino hippuric acid (PAH) – most preferred
because of high extraction ratio
More than 90% of PAH in arterial blood is removed in single
circulation

50. • So, RPF can be measured by modifying Fick’s principle
( amount of PAH excreted in urine/min)
UPAH. V
RPF=
APAH – VPAH
At low conc. Of PAH in plasma renal clearance is nearly
complete therefore PAH conc. In renal venous plasma taken
as zero thus,
UPAH. V
RPF=
APAH
RPF = C PAH

51. • 10 - 15% of total renal plasma flow perfuses non-
excretary portion of kidney this plasma can’t be
completely cleared of PAH by filtration and secretion
thus, CPAH doesnot measure RPF to this region
• Thus 10% of PAH remains in renal venous plasma ,
RPF calculated from CPAH underestimates actual flow
by 10% thus CPAH actually measures Effective renal
plasma flow (ERPF)
UPAH.V UPAH.V
• ERPF= =CPAH =
APAH PPAH
• RBF= ERPF / 100- Haematocrit

52. B. Tests for tubular functions
1. Urine concentration test: ability of tubules to
conc. Urine assessed by measuring sp.gravity
of urine after 12 hrs. of water deprivation.
If sp. Gravity remains >1.020 its normal
2. Urea Dilution test: one urine sample with
osmolarity <100mosm/kg, with atleast 750 ml
urine collected
3. Phenol Sulphonepthalein (PSP) Excretion
test

53. Phenol sulphonephthalein (PSP)
Excretion test
• Administerd i.m or i.v, its conc. In urine is
measured easily
• The time of 1st appearance in urine and
quantity eliminated within definite period are
taken as measure of functional capacity of
kidney
• Decrease in PSP excretion indicates general loss
of nephron function
• Increase in PSP excretion indicates early stage of
renal inflammation or hyperthyroidism

54. Other methods of study of tubular
functions
• Micropuncturing: analyse tubular fluid at
various levels
• Microcryoscopic studies: renal tissue slices at
different depths
• Microelectrode studies: to measure membrane
potential of the tubular cells

55. Miscellaneous tests
1. Plain radiograph of abdomen (KUB):
2. Intravenous pyelography(I.V.P) – urographin
3. Ultrasonography
4. CT scan : to detect abnormalities in and
around kidney
5. Isotope perfusion studies/ radionuclide studies
6. Renal biopsy- FNAC, percut. Vim –Silverman
needle diagnosis of proteinurea, renal
failure,systemic diseases

56. Calculations
Q.1 Calculate GFR from the following data:
urinary conc. of Inulin=60mg/ml
Plasma conc. Of Inulin= 0.5 mg/dl
Volume of urine = 1 ml/min
U.V
GFR=
P
60 X 1
=
0.5
=…..
Q.2 Which clearance test is used to measure GFR
clinically?

57. Q.2 Calculate PAH clearance value from following data:
Urinary conc. Of PAH= 120 mg/ml
Plasma conc. Of PAH = 0.3 mg/ml
Volume of urine = 1.5 ml/min
UPAHV
CPAH=
PPAH
120 x 1.5
=
0.3
= ……ml/min
Q.2 what does PAH clearance indicates?

58. References
• Ganong's Review of Medical Physiology, 26 edition.
• Text book of Medical Physiology
– Guyton & Hall
• Human Physiology
– Vander
• Text book of Medical Physiology
– Indukurana
• Principles of Anatomy and Physiology
– Totora
• Net source

59. THANK YOU . . .