Renal Physiology
AnS 536
Spring 2015
Regulation of Fetal Renal
Development

Nephrogenesis

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Begins at 7-8 weeks and continues through 32-34 weeks in
humans
20% nephrons morphologically mature at 11-13 weeks gestation
(humans)
30% nephrons morphologically mature at 16-20 weeks gestation
Number of nephrons increases from 350,000 at 20 weeks to
820,000 at 40 weeks gestation
Single adrenocorticoid injection at birth to rabbits results in
profound abnormalities in the development of later generations
of nephrons


Rabbits at birth functionally similar to 35 week human fetuses
Differences between fetal and adult renal function best explained
by decreased numbers of "mature" nephrons with a decreased
surface area for reabsorption
Fetal Excretion of Urine


Renal functions not necessary until after birth
Urine has been detected from fetuses as early as 6 weeks

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Increasingly large volumes of urine are formed from about the 10th
week of gestation
At birth, the bladder may contain up to 44 ml of urine
From about day 90 of gestation, the urethra is patent and urine
passes into the amniotic sac
Fetus produces and excretes urine into allantoic (amniotic
fluid sac) and is reabsorbed
Fetal urine excretion ↑ as gestation ↑


Osmolarity of amniotic fluid ↓
Urine osmolarity ↑ prior to parturition
Fetal Excretion of Urine


Hypotonic nature of fetal urine may help maintain the
osmotic pressure of fetal plasma such that fluid is not lost
to the maternal circulation
Allantoic fluid remains hypotonic and reflects tonicity of
fetal urine


Neonate is hypophosphatemic


May contribute to PTH insufficiency, decreasing glomerular filtration
rate and renal unresponsiveness to PTH for first few weeks of life
Newborns and premature newborns respond similarly to an
adult to water loading, but prior to 3 days postpartum there
is no diuretic response to water loading


Suggesting either a low rate of water transfer or that water transfer
is balanced by electrolyte removal
Many species differences in terms of this response
Increase in urine osmolarity as gestation advances
coincides with an increase in water reabsorption
Renal Function

Renin
 Proteolytic enzyme
 Catalyzes angiotensinogen
conversion to
angiotensin I


Angiotensin I (inactive) converted to
angiotensin II (active) by angiotensin
converting enzyme
Angiotensin II
 Angiotensin
II directly enhances sodium
reabsorption and water conservation
 Indirectly causes adrenal cortex to secrete
aldosterone, which also enhances water
reabsorption
Renal Function


Kidney also functions to regulate ECF ion
concentrations
Aldosterone affects sodium reabsorption


However, it is not considered to be a regulator of ECF Na
concentration
Regulation of ECF K+ concentration is accomplished
by increasing reabsorption or excretion in the distal
nephron


Aldosterone released in response to an increase in K
concentration
Aldosterone increases transport of K from tubular cells,
enhances Na reabsorption, and increases luminal
permeability to K
Renal Function

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Acid-base balance is regulated through excretion or
reabsorption of strong ions
Kidneys regulate plasma strong ion difference by
balancing sodium and chloride excretion rates
Changes in strong ion concentration cause changes in
the concentrations of bicarbonate and H+ across the
renal tubule



Acidosis increased chloride excretion raises SID H+ (+
charged water) follows chloride so pH increases in blood and
decreases in urine, reabsorption of bicarbonate
Alkalosis decreased chloride excretion decreases SID
secretion bicarbonate, reabsorption of H+ (follows Cl)
Renal regulation of strong ion difference is slow in
comparison to the respiratory control of pCO2
Renal Function

Regulation of ECF osmolality and volume is
major function of the renal system
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Volume and composition of body fluids remains almost
constant despite highly varied fluid intakes
Ability to conserve water is related to the
effective osmotic pressure of the ECF
Sodium has important role in the level and
regulation of ECF effective osmotic pressure and
volume
 Osmoregulation
is accomplished through the
regulation of the ratio of sodium to water
 Volume regulation occurs through control of
sodium and water quantities
Amniotic Fluid

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
Placenta, fetal skin, membranes, lung,
intestine, and fetal and maternal kidneys all
play a role in fluid balance
Amniotic fluid is considered an extension of
the ECF space during the first half of
pregnancy
Fetal skin is freely permeable to water and
sodium early in gestation
 Injection
of hypertonic saline into the amniotic fluid
through mid-gestation induces abortion
 Amniotic fluid removal at mid pregnancy results in
death of fetus; removal near term permits survival
Amniotic Fluid

Amniotic fluid is composite of secretions from
lungs and kidneys late in gestation
 Urea,
creatinine, and uric acid concentrations
increase steadily
 Concentrations at term are much higher than in fetal
plasma


Fetal kidney is the primary source for formation
of amniotic fluid
Primary source of disposal is the fetal digestive
tract
 Hydroamnios
caused by failure of fetal swallowing,
compromises fetal viability
Fluid Changes During Growth

Primary changes in fluid balance during
maturation:
 Decreases
in total body water, extracellular
water, and chloride
 Increases in potassium, protein, and fat
content

Disturbances in volume and composition
of body fluids more common in perinatal
period than at any other age
Fluid Changes During Growth

Decrease in extracellular water during
development results from
 1)
Decreasing proportion of body weight
accounted for by tissues that are high in
extracellular water
 2) Decrease in the percentage of extracellular
water in skeletal muscle

Water and chloride content of the body both
decrease with increasing growth and
development
 Due
to decreasing ECF and increasing fat and
protein
 Chloride content of newborn is proportionately
higher than that of the adult
Fluid Changes During Growth
Newborn brain contains 11% of total body
water; adult brain contains 2%
 Muscle contains more extracellular water
and less intracellular water earlier in
development
 Heart muscle matures earlier and does not
show changes as in striated muscle
 Bone water content decreases while
sodium content increases during growth

Regulating Fluid Balance in the
Neonate

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Fluid balance is regulated in the kidneys
Conservation or excretion dependent upon:
 Water
present
 Electrolytes present

Absorption/excretion occurs in proximal tubule
 Reduced

rate
Neonates
 Balance
maintained at a reduced rate
 Glomerular filtration rate reduced
Regulating Fluid Balance in the
Neonate


Neonatal mammals more susceptible to fluid
and electrolyte disorders than adults
Newborns have limited capacity to excrete water
or electrolyte load, produce concentrated urine,
or react to ADH or aldosterone, and limited
glomerular filtration rate
 Capacity
of infants to excrete a water load is only
10% of that of adults (mature function by 1 month)
 Ability to produce concentrated urine—3 month
 GFR is limited until nearly 18 months of age
 Different species, different rates of maturation
Regulating Fluid Balance in the
Neonate

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Neonatal limitations quickly lead to dehydration
and are important in association with diarrhea
Estimates of newborn fluid and electrolyte
replacement are complicated by species
differences
Human infants need approx 2.5L of water to
produce 1000 mOsm urinary solute; neonatal
calf or adult human requires less than 1L
Renal Function

Excess sodium administration
 Expands ECF
 Renal excretion
of sodium stimulated to normalize
volume


Sodium is conserved by the kidney in response
to decreases in ECF volume
Changes in ECF volume detected by pressure
receptors
 Heart atria, carotid sinuses, aortic arch
 Also in the kidney, in juxtaglomerular cells
of the
afferent arterioles and macula densa cells of the distal
tubules
Renal Function
Plasma regulation controlled by adjusting
water intake and excretion
 Hypothalamus regulates the secretion of
antidiuretic hormone (ADH) and the thirst
mechanism

 Intake>excretionADH
secretion inhibited,
water excretion is enhanced
 Excretion>intakeADH secretion stimulated,
thirst mechanism stimulated
Renal Function
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Neonatal calves unique because of highly
developed renal system at birth
Renal function is similar to that of adult cattle by
2-3 days postpartum
Can produce highly concentrated urine during
dehydration as early as 2 days of age
 Calves
may lose 5% of their body weight during
starvation and up to 15% by 96 hrs
 During this period, urine output may decrease as
much as 90%, while osmolality may increase by
400%
Renal Function


Calves also able to dilute urine and excrete
large volume loads
Calves given large volumes of milk, water, or
hypotonic electrolyte solutions respond by
increasing urine output up to 10-fold
 Diuretic response occurs very quickly
 Peak urine output by 60-90 min
 70-100% of the volume excreted within

4 hrs
Calves can handle volume load of 50% of their
body weight during the first day of life
 Neonatal
rats show no increase in urine output with a
4.5% load
Renal Function
Rapid response to volume loading in
calves due to mature GFR
 Diuretic response in calves is closer to
adult humans or dogs than to adult cows

 Adult
cow response is slower in onset, slower
to peak urine, and longer in duration than the
calf
Renal Regulation of Blood
Pressure

Blood pressure regulation
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Premature infants
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Kidney excretes water and electrolytes (Na+, Cl-, K+)
Avoids huge fluxuations in blood pressure
↓ in ability to maintain blood pressure
Underdeveloped organs not able to regulate salt and water
balance
Newborns


Decreased ability to regulate blood pressure compared to adult
Sufficient for their needs
Newborn Renal System


Major filtration organ
eliminating waste from the
body
Renal system

Nephrons
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Capillary bed
Tubule


Where filtration occurs
Glomerulus
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Collection of urine
Ureters
Bladder
Urethra
Varies slightly as
compared to adults
Neonatal kidney is
lobulated

Kidneys
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Lobulation lost by 4-5 years
of age
Glomeruli and tubular
functions operate at a low
level at birth in humans
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Fully functional at 6 weeks
of age
Limits the capacity of the
infant to conserve
substances

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Certain amino acids
Phosphates
Bicarbonate
Renal Function in the Newborn

Renal function tests:
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Urine volume
Renal plasma flow
Glomerular filtration rate
Filtration fraction
Concentrating capacity
Urea clearance
Glucose urinary pH
Urinary hydrogen excretion
Bicarbonate
Renal bicarbonate threshold
Renal Function in the Newborn

Renal plasma flow
 Increases

with age
Glomerular filtration rate
 Measured
through inulin or mannitol clearance
 Increases with age

Filtration fraction
 Calculated
from:
[glomerular filtration rate]/[renal plasma flow]
 Decreases with age
Renal Function in the Newborn

Concentrating capacity
 Measures
urinary osmolarity
 Measured after 12-18 hrs of water deprivation
 Increases with age

Urea clearance
 Calculated
from urea concentration in urine
 Increases with age

Glucose
 [glucose
filtration rate]-[glucose excretion rate]
 Increases with age
Renal Function in the Newborn

Urinary pH and urinary hydrogen excretion
 Determined
after 3-5 days of ammonium chloride
administration
 Increases with age

Bicarbonate
 [bicarbonate
filtration rate]-[bicarbonate excretion in
urine]
 Increases with age

Renal bicarbonate threshold
 Determined
by continuous infusion of sodium
bicarbonate
 Increases with age
Renal Function in the Newborn

Blood Urea Nitrogen (BUN)
 Blood
test
 Decreases with age

Creatinine
 Waste
product from muscle metabolism
 Eliminated in urine
 Newborns have high levels
 As kidney function develop, levels decline
Function of the Urea Cycle in
Neonates
Urea formation is determined by level of
dietary proteins
 Milk is high in protein
 Neonatal kidneys

 Immature
 Elimination
of waste not as efficient
 BUN levels within first 48-72 hrs elevated due
to inability to excrete waste
 Kidneys become more functional

BUN decreases