Kidney, how it functions

1. Development of kidney, its functions and
KFT
Dr. Ashik Majumder
PEDIATRICS

2. Development of Kidney
The urogenital system is derived from the intermediate
mesoderm and the primitive urogenital sinus (UGS) which is
a part of the cloaca.
The kidneys starts developing in three stages:
1) Pronephros
2) Mesonephros
3) Metanephros

3. Intermediate Mesoderm:
Intra-embryonic mesoderm is subdivided
into:
– Paraaxial mesoderm which becomes
segmented to form the somites,
– Lateral plate mesoderm in which
intra-embryonic coelom appears, and
– Intermediate mesoderm lying between
the two.
Intermediate mesoderm gives rise to
“Paired Glands” (Kidneys, Adrenals and
Gonads)

4. Pronephros
• It is rudimentary &
nonfunctional
• At the beginning of fourth
week
7-10 solid cell groups appears
in cervical region
forms vestigeal excretory
units (called Nephrotomes)
At the end of 4th week,
pronephric system disappears.

5. Mesonephros
• The mesonephros and mesonephric ducts are
derived from intermediate mesoderm from
upper thoracic to upper lumbar (L3)
segments
• Early in the fourth week of development,
during regression of the pronephric system,
the first excretory tubules of the
mesonephros appear
• They lengthen rapidly, form an S-shaped
loop, and acquire a tuft of capillaries that
will form a glomerulus at their medial
extremity

6. • Around the glomerulus, the tubules form Bowman capsule,
and together these structures constitute a renal corpuscle
• Laterally, the tubule enters the longitudinal collecting duct
known as the Mesonephric or Wolflian duct
• In the middle of the second month, the mesonephros forms a
large ovoid organ on each side of the midline
• Because the developing gonad is on its medial side, the ridge
formed by both organs is known as the urogenital ridge
• By the end of the second month, the majority have disappeared
• In the male, a few of the caudal tubules and the mesonephric
duct persist and participate in formation of the genital system,
but they disappear in the female.

7. Metanephros- definitive kidney
• The metanephros or definitive kidney,
begins when the metanephric ducts
(ureteric buds) sprout from the distal end
of the mesonephric duct at about 5th
weeks.
• The ureteric buds induce intermediate
mesoderm in the sacral region to form a
metanephric blastema which forms the
glomeruli and tubules of the nephrons.

8. Evaluation of Collecting System
• Most active period of nephrogenisis is from 20-36 weeks. Full no. of
nephrons is developed around 36 weeks
• Post natal growth of kidney is similar to somatic growth & is due to
increase in size of kidney
• The ureteric buds bifurcate again and again to
form the intrarenal calyces, pelvis, ureter &
collecting duct system of the definitive kidney
• The kidneys begin producing urine by week 12,
and it adds to the volume of the amniotic fluid.
The fetus drinks this fluid in utero
• The fetal kidneys are not responsible for excretion
as the placenta serves this function

9. Ascent of the Kidneys
• In the 6th week the kidneys begin to
ascend from the sacral region to their
position in the upper abdomen
• The metanephric ducts elongate and
become the ureters
• As the kidney ascends it receives new segmental arteries from the aorta
and loses those vessels below. Thus sometimes there is more than one
renal artery
• Sometimes one kidney fails to ascend resulting in pelvic kidney
• Sometimes the left and right kidneys become attached in the pelvis then
the horseshoe kidney can’t ascend above the inferior mesenteric artery

10. Position of kidneys
• Kidneys lie on the psoas muscle beside the vertebral bodies
• The diaphragm and 11th and 12th ribs lie behind the upper half of
each kidney, therefore they move with breathing
• Left kidney is higher than right (due to liver)
• Upper poles corresponds to T12 & Lower poles at L3
• Hilum is at L1/2
• Upper poles are more medial (due to psoas ms).
• In the hilum:
– Renal vein is the most anterior.
– Followed by renal artery & pelvis/ureter
• The left renal vein is longer.

11. Functional units of kidney
• 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.

13. • Each nephron is a complex apparatus comprised of five basic
parts:
1. Glomerulus: functions to filter incoming blood.
The plasma of the blood is filtered in the glomerulus of
capillaries
The plasma pass into the capsular space (lumen) and into
the proximal tubules at a rate of about 125 ml/min/kidney
All from blood except the cells and the largest elements
(proteins) pass into original filtrate = primary urine
The primary urine has essentially the same composition as
plasma

14. 2. Proximal convoluted tubule: responsible for absorption
from the filtrate:
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
3. Loop of Henle:
Facilitates the reabsorption of water, sodium, and chloride

15. 4. Distal convoluted tubule:
The filtrate entering this section of the nephron is close to its
final composition
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.
The DCT and collecting ducts absorb most of the water remaining
so that 99 % of original filtrate has been returned to the tissues and
1 % passes into the minor calyces.

16. Function of Kidney & Urinary System
• 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

17. Kidney in adults
• Urine excreted daily in adults: 0.5-1.5L
• Kidney is only 1% of total body weight.
• The renal blood flow = 20% of cardiac output
• Plasma renal flow (PRF) = 600 mL/Min./1.73 M2
• Reflects two processes
–Ultrafiltration (GFR): 180 L/day
–Reabsorption: >99% of the amount filtered

18. Glomerulus in children
• The differentiation of glomerulus is not completed in children.
• The glomerular epithelium in Bowman’s capsule is cylindrical
versus flat epithelium in adults.
• The glomerular capillary endothelium is composed of higher
cells than in adults.
• All peculiarities result in smaller filtrate surface of kidney and
lower permeability of glomerulus barrier.

19. Tubules in children
• Relatively shorter and more narrow than in adult, especially in
the peripheral parts of the kidney
• Henle’s loop is shorter and immature in structure

20. Kidney function in early infancy
• Glomerular filtration rate is low and does not reach adult values until the
child is between 1 and 2 years of age
• The concentrating ability of the newborn kidney does not reach adult levels
until about the third month of life.
• The newborn retains large quantities of nitrogen and essential electrolytes
in order to meet needs for growth in the first weeks of life.
• Newborn infants are unable to excrete a water load at rates of older
persons.
• Hydrogen ion excretion is reduced.
• Acid secretion is lower for the first year of life.
• Infants have a diminished capacity to reabsorb glucose that results in
physiological glucosuria of neonates.
• Infants have a diminished capacity to produce ammonium ions during the
first few days.

21. • As a result of these inadequacies of the kidney:
 The newborn is more liable to develop severe acidosis.
 Kidneys are less able to adopt to deficiencies and excesses
of sodium. An isotonic saline infusion may produce edema
because the ability to eliminate excess sodium is impaired.
Conversely inadequate reabsorption of sodium from tubules
may compound sodium losses in disorders such as vomiting
or diarrhea.
 The newborn develops physiological anuria during the first
few days.

22. Laboratory evaluation
• Urinalysis:
– Specific Gravity- Full term infants have a limited concentrating
ability with a maximum sp. gravity of 1.021 to 1.025
– Protein excetion- It is varies with gestational age. Urinary protein
excretion is higher in premature infants and decreases progressively
with postnatal age. In normal full term infants, protein excretion is
minimal after the second week of life.
– Glycosuria- It is commonly present in premature infants of <34
weeks’ gestation. The tubular resorption of glucose is <93% in infants
born before 34 weeks’ gestation compared with 99% in infants born
after 34 weeks’ gestation.

23. – Hematuria- It is abnormal and may indicate intrinsic renal damage or
result from a bleeding or clotting abnormality
– The sediment examination will usually demonstrate multiple
epithelial cells for the first 24 to 48 hrs. In infants with asphyxia, there
is an increase in epithelial cells and transient microscopic hematuria
with leukocytes is common. Hyaline and fine Granular casts are
common in dehydration or hypotension. Uric acid crystals are
common in dehydration states and concentrated urine samples.

24. Methods of Collection
• Suprapubic aspiration- It is the most reliable method of
detecting urinary tract infection
• Bladder catheterisation- It is used if infant has failed to pass
urine by 36 to 48 hrs and is not apparently hypovolemic, or if
urine volume, flow, or sedimentary examination is important.
• Bag collection- It is for determination of sp. gravity, pH,
electrolytes, protein, glucose, and sediment but not urine
culture. It is the preferred methods for detecting red blood cells
in the urine.
• Diaper urine sample- It is reliable for estimation of pH and
qualitative determination of the presence of glucose, protein
and blood.

25. Kidney Function Test
• Routine KFTs include the measurement of :
Serum creatinine (Cr)
Creatinine clearance
Serum urea
• 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.

26. Creatinine
• Creatinine is the end product of creatine catabolism.
• 98% of the body creatine is present in the muscles where it
functions as 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

27. • 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

28. Creatinine clearance
• The most frequently used clearance test is based on the
measurement of creatinine.
• Small quantity of creatinine is reabsorbed by the tubules and other
quantities are actively secreted by the renal tubules. So creatinine
clearance is approximately 7% greater than inulin clearance.
• The difference is not significant when GFR is normal but when the
GFR is low (less 10 ml/min), tubular secretion makes the major
contribution to creatinine excretion and the creatinine clearance
significantly overestimates the GFR.

29. 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.

30. 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 mol/l, V = Volume of
urine per min & P = Concentration of creatinine in serum mol/l.
Schwartz Formula: Clearance = Cs  1.73
Surface Area(m2)
Where Cs= Clearance of substance (mL/min) & Clearance is in
mL/min/1.73m2

31. Cockcroft & Gault Formula
• The accurate measurement of creatinine clearance is difficult,
especially in outpatients, since it is necessary to obtain a complete
and accurately timed sample of urine. So an alternative and
convenient method is employed to calculate creatinine clearance
using parameters such as serum creatinine level, sex, age, and
weight of the subject.
k  (140 – age)  Body wt.
GFR = ─────────────────
Serum creatinine (mol/L)
Where, k = 1.224 for males & 1.04 for females
• Modifications required for children & obese subjects
• Can be modified to use Surface area

32. Cockcroft-Gault Formula : 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

33. • 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.

34. Normal data of creatinine clearance
Age Creatinine
clearance
Daily
creatinine
Newborn 40-65 ml/min/1.73 m2 8-20 mg/kg/d
Child 80-120 ml/min/1.73 m2 8-22 mg/kg/d
Adult 80-120 ml/min/1.73 m2 14-26 mg/kg/d

35. Normal serum creatinine reference values:
• Urinary excretion of creatinine: 500-2000 mg/day
• Serum creatinine:
• Male serum range
- Age 1-4 years: 0.1 - 0.5 mg/dl
-Age 5-9 years :0.2 - 0.6 mg/dl
-Age 10-15 years: 0.5 - 0.8 mg/dl
-Age >16 years. : 0.8 - 1.3 mg/dl
•Female serum range
- Age 1-4 years: 0.1 - 0.4 mg/dl
-Age 5-9 years : 0.2 - 0.5 mg/dl
-Age 10-15 years: 0.4 - 0.7 mg/dl
-Age >16 years. : 0.6 - 1.1 mg/dl

36. • 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%

37. Serum Urea: ( normal blood level: 5-39 mg/dl )
• Urea is the major nitrogen-containing metabolic product of protein
catabolism in humans and elimination in the urine represents the
major route for nitrogen excretion
• More than 90% of urea is excreted through the kidneys, with losses
through the GIT and skin. Urea is filtered freely by the glomeruli
• Plasma urea concentration is often used as an index of renal
glomerular function
• Urea production is increased by a high protein intake and it is
decreased in patients with a low protein intake or in patients with
liver disease.

38. • As a kidney function test, serum urea is inferior to serum
creatinine because:
 High protein diet increases urea formation.
 Any condition of increased proteins catabolism (Cushing
syndrome,diabetes mellitus, starvation, thyrotoxicosis)
causes increase in urea formation.
 50 % or more of urea filtered at the glomerulus is
passively reabsorbed by the renal tubules.

39. Normal values of Internal Chemical Environment
controlled by the Kidneys:
SODIUM 135 to 145 mEq/L
POTASSIUM 3.5 to 5.5 mEq/L
CHLORIDES 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
BUN (Blood Urea Nitrogen) 15 to 20 mg/dl

40. Radiological Studies
• Ultrasonography- It is the initial imaging study to see the renal
parenchymal architecture. Color doppler flow techniques can
estimate RBF. The length of the kidneys in millimeters is
approximately the gestational age in weeks. The renal cortex
has echogenicity similar to that of the liver or spleen in neonate,
in contrast to the hypoechoic renal cortex seen in adults and
older children. In addition, the medullary pyramids in the
neonate are much more hypoechoic than the cortex and hence
are more prominent in appearance.
• Intravenous Pyelography (IVP)- It is rarely used in neoborn
period, because the neonates has a limited concentrating ability
and difficulty in excreting a highly osmolar load.

41. • Voiding Cystourethrography (VCUG)- It is indicated in
infants with UTIs or with renal anomalies on ultrasound to rule
out vesicourethral reflux (VUR), and in neonates with
obstructive uropathy to define associated reflux and define
lower tract anatomy more specially. Radionuclide cystography
is often used to evaluate VUR because of its lower radiation
dose. However, VCUG produces better static imaging for
anatomical defects and is preferred for the initial evaluation of
obstructive uropathy.

42. • Radionuclide scintography- It is useful in demostrating the
position and relative function of the kidneys. Isotopes such as
technetium-99m-diethylene triamine pentacetic acid (DTPA) or
mercaptoacetyltriglycine (MAG 3) are handled by glomerular
filtration and can be used to assess RBF and renal function. In
conjunction with intravenously administered furosemide, it can help
differentiate obstructive from nonobstructive hydronephrosis.
Isotopes that bind to the renal tubules, such as technetium-99m-
dimercaptosuccinic acid (DMSA), produce static images of the
renal cortex. This may be helpful for assessing acute pyelonephritis
and renal scarring from renal artery emboli, or renal vascular
disorders and to quantify the amount of renal cortex in patients with
renal dysplasia and hypoplasia.

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