Urinary system: Renal function

Outline
Functions
Anatomy
Urine formation:
- Filtration
- Reabsorption
- Proximal Convoluted Tubule (PCT)
- Loop of Henle
- Distal Convoluted Tubule (DCT)
- Secretion
Regulation of GFR
Micturition

Outline
Functions
Anatomy
Urine formation:
- Filtration
- Reabsorption
- Proximal Convoluted Tubule (PCT)
- Loop of Henle
- Distal Convoluted Tubule (DCT)
- Secretion
Regulation of GFR
Micturition

Renal functions
1- Regulation of plasma ionic composition
2- Regulation of plasma volume
3- Regulation of plasma osmolarity
4- Regulation of plasma hydrogen ion
concentration (pH)
5- Removal of metabolic wastes and
foreign substances
6- Secondary endocrine organ

Outline
Functions
Anatomy
Urine formation:
- Filtration
- Reabsorption
- Proximal Convoluted Tubule (PCT)
- Loop of Henle
- Distal Convoluted Tubule (DCT)
- Secretion
Regulation of GFR
Micturition

Figure 18.1
Kidney anatomy
Nephron

Figure 18.5
The juxta-glomerular apparatus

Figure 18.6
Blood supply to the kidney

Outline
Functions
Anatomy
Urine formation:
- Filtration
- Reabsorption
- Proximal Convoluted Tubule (PCT)
- Loop of Henle
- Distal Convoluted Tubule (DCT)
- Secretion
Regulation of GFR
Micturition

Renal exchange processes
1- Glomerular filtration in renal capsule
2- Reabsorption in renal tubules
3- Secretion in renal tubules

Glomerular filtration
Plasma is filtered through
fenestrated epithelium

About 180 liters of plasma
are filtered per day filtrate

Filtrate = plasma - proteins

About 2 liters of urine
produced per day
Overall fluid movement in the kidneys

Forces acting on filtration
Glomerular capillary hydrostatic
pressure due to blood hydrostatic
pressure against capillary wall (BHP)

Glomerular osmotic pressure due to
the presence of solutes (proteins) in
the blood (BOP)

Bowmans capsule hydrostatic
pressure pressure of filtrate against
Bowmans capsule wall (CHP)

Bowmans capsule osmotic pressure
due to the pressure of solutes in the
filtrate (COP)

Net filtration rate fluid moves from
the glomerulus into the capsule


Glomerular filtration
The glomerular filtration
rate (GFR) = volume of
plasma filtered per unit of
time = 125 ml/min 180
liters per day

Filtration fraction =
GFR/renal plasma flow =
20%
Outline
Functions
Anatomy
Urine formation:
- Filtration
- Reabsorption
- Proximal Convoluted Tubule (PCT)
- Loop of Henle
- Distal Convoluted Tubule (DCT)
- Secretion
Regulation of GFR
Micturition

Reabsorption:
Proximal convoluted
tubule (PCT)


Glucose, amino-acid, sodium
will be pumped out of the
tubules, by active transport
(ATP needed)
Chloride will follow sodium into
the peritubular space
(accumulation of positive
charges draws chloride out)
Water will move into the
peritubular space because of
osmosis
Some compounds present in
high concentration in the
filtrate but low in the blood can
move through diffusion


Glucose reabsorption
The transporter for glucose on the basolateral membrane has a limited
capacity to carry glucose back into the blood. If blood glucose rises
above 180 mg/dl, some of the glucose fails to be reabsorbed and
remains in the urine glucosuria

Reabsorption:
Proximal convoluted
tubule (PCT)


70% of sodium and water
are reabsorbed in PCT

Reabsorption is not
regulated

Amino-acids, glucose
should be 100%
reabsorbed at the end of
the PCT

The filtrate, at the end of
the PCT should be iso-
osmolar to the filtrate at
the beginning
Outline
Functions
Anatomy
Urine formation:
- Filtration
- Reabsorption
- Proximal Convoluted Tubule (PCT)
- Loop of Henle
- Distal Convoluted Tubule (DCT)
- Secretion
Regulation of GFR
Micturition

Reabsorption: Loop of Henle
Characteristics of Loop of Henle:
-- Descending tubule: permeable to
water has no sodium pumps

-- Ascending loop: thick epithelium is
impermeable to water but has
many sodium pumps

-- Na+, Cl- and K+ are pumped out
into the interstitial fluid Cl-
follows (electrochemical gradient)
water follows by osmosis =
counter-current multiplier

-- formation of an osmotic gradient in
the renal medulla which is
important for water reabsorption in
the CT

Figure 19.7 (1 of 6)
Figure 18.4
Reabsorption: Loop of Henle
Additional filtrate is reabsorbed

The filtrate is concentrated as it travels
through the loop but returns to a
concentration similar to the other end.

Reabsorption in this segment is also (like
PCT) not regulated
So, why is the loop of Henle
useful?
The longer the loop, the
more concentrated the
filtrate and the medullary
IF become

Importance: the collecting
tubule runs through the
hyperosmotic medulla
more ability to reabsorb
H
2
O
Desert animals have long nephron
Loop More H
2
O is reabsorbed
Outline
Functions
Anatomy
Urine formation:
- Filtration
- Reabsorption
- Proximal Convoluted Tubule (PCT)
- Loop of Henle
- Distal Convoluted Tubule (DCT)
- Secretion
Regulation of GFR
Micturition

Reabsorption: DCT and CT
DCT and CT tubular walls are
different from the PCT and
Loop of Henle wall:

-- DCT and CT walls have tight
junctions and the membrane is
impermeable to water

-- the cell membrane has
receptors able to bind and
respond to various hormones:
ADH, ANP and aldosterone

-- The binding of hormones will
modify the membrane
permeability to water and ions

Reabsorption: DCT and CT
ADH is low no binding to receptors
H
2
O is not reabsorbed back into
the blood
H
2
O remains in the renal tubule
high urine volume
ADH is released by post. Pituitary
Binds to receptors in CT
channels open H
2
O moves
into the IF and blood low urine
volume
Regulation of ADH secretion
The neurosecretory neurons
for ADH (in the hypothalamus)
are located near the center
monitoring blood osmotic
pressure
if BOP ADH secretion and
release water reabsorption
blood is diluted BOP
(typical homeostatic regulation)

If BOP ADH secretion and
release H
2
O reabsorption
BOP urine volume

Lack of ADH? Symptoms?
Sodium regulation
Hypernatremia causes water
retention and high blood
pressure
Hyponatremia hypotension

Because sodium is tightly
linked to BP, BP is regulating
sodium movement in the
tubules

Recall that BP directly affects
GFR GFR is sensed by the
macula densa of the Juxta-
glomerular Apparatus (JGA)

If too low, the juxta-glomerular
cells of the JGA secrete renin
into the blood


Sodium regulation
As a result, aldosterone
will be secreted by the
adrenal cortex
promotes sodium
reabsorption in the DCT
and CT.

Another hormone, Atrial
Natriuretic Peptide or ANP
promotes sodium dumping
by the DCT and CT.


Outline
Functions
Anatomy
Urine formation:
- Filtration
- Reabsorption
- Proximal Convoluted Tubule (PCT)
- Loop of Henle
- Distal Convoluted Tubule (DCT)
- Secretion
Regulation of GFR
Micturition

Secretion and excretion
Secretion: Selective transport of molecules
from the peritubular fluid to the lumen of
the renal tubules

Excretion: Molecules are dumped outside
the tubules

Example of excreted waste products: urea,
excess K
+
, H
+
, Ca
++
Clinical applications
Carbonic anhydrase
inhibitors:

Osmotic diuretics:

Thiazide diuretics

Loop diuretics:

K+ sparring diuretics:

Diuretics





Diuretic
Site of Action Mechanisms of Action Predictable Side Effects
Osmotic
diuretic
(e.g., mannitol)
Proximal tubule
Thin descending
limb
Distal tubule
Collecting ducts
- impedes water reabsorption
and indirectly impedes Na
+

reabsorption by blocking the
convective movement of Na
+

- volume contraction often
with increased serum
osmolality
Carbonic
anhydrase
inhibitors
Proximal tubule - impedes HCO
3
-
, H
+
, Na
+

reabsorption
- HCO
3
-
loss, .: acidosis
Loop diuretics
(eg.
furosemide)
TAL - blocks Cl
-
, Na
+
and K
+

reabsorption (via Na
+
/K
+
/2Cl
-

pump)
- increased K
+
losses,
because of increased Na
+

delivery with increased
aldosterone
Thiazides Early distal tubule - blocks Cl
-
reabsorption,
creating intraluminal negative
charge which impedes Na
+

reabsorption
- increased K
+
losses,
because of increased Na
+

delivery with increased
aldosterone
Aldosterone
bockers
Late distal tubule
Early collecting
ducts
- blocks Na
+
/K
+
antiports,
impeding Na
+
reabsorption and
K
+
secretion (K
+
sparing effect)
- increased plasma [K
+
]
Clinical application: the Glomerular Filtration Rate
GFR: important value for estimating
the kidney function.

Calculated by using molecules which
are filtered but not secreted nor
reabsorbed.


P X GFR = U X V
P = plasma concentration of A, in
mg/mL
GFR = glomerular filtration rate of
plasma, in mL/min
U = urine concentration of A, in mg/mL
V = rate of urine production in, in
mL/min
Solving the equation for GFR will give:
GFR = (U X V)/P


GFR = (U X V)/P

Clinical application: the Glomerular Filtration Rate
Best molecule to use: inulin but not occurring naturally in
the body

Second best: creatinine


Urea: cannot be used since it is both secreted and
reabsorbed (why is it so?)

Outline
Functions
Anatomy
Urine formation:
- Filtration
- Reabsorption
- Proximal Convoluted Tubule (PCT)
- Loop of Henle
- Distal Convoluted Tubule (DCT)
- Secretion
Regulation of GFR
Micturition

Regulation of glomerular filtration rate
GFR needs to be constant (p. 519, Fig.
18.10)

Changes in BHP will affect GFR
strongly BHP is a function of SBP






GFR regulation:
- to increase GFR:
**vasoconstrict efferent vessel
** vasodilate afferent vessel





Regulation of glomerular filtration rate
Vasoconstriction of the efferent
vessel is under the control of:
--Epinephrine/Norepinephrine
from the ANS
-- Angiotensin II from the renin-
angiotensin system


Vasodilation of the afferent vessel
is under the control of:
- paracrines secreted by the
macula densa stimulate
vasodilation of neighboring vessel
- myogenic reflex (automatic
constriction of smooth muscles
lining the wall when the artery is
stretched by increased pressure

Outline
Functions
Anatomy
Renal exchange processes
Regional specialization of renal tubules
Excretion
Regulation of GFR
Micturition

Micturition
Controlled by the sacral
parasympathetic NS

Stretch sensors in the bladder wall
send impulses to the sacral spine

reflex opening of the urethral
smooth muscle

Impulses also sent to the cortex to
notify the brain of the need to urinate

if the moment is OK, the person will
go to the bathroom (hopefully!), and
will open the skeletal (voluntary)
muscle of the urethral sphincter the
person will be able to urinate


Figure 18.21
Micturition: Clinical cases
What will happen to a
person who has suffered
a spinal cord injury to
T10? Which kind of
problem(s) will (s)he
have?

Why cant baby control
urination? What type of
problem do they have?

What about older people
who dribble urine? What
causes that?


Applications: Sea-water raft
Billy is stuck on a raft in
the middle of the ocean,
without food or water.

In order to get a few extra
hours of life and a chance
to be found ( a boat),
should Billy drink some
sea-water or his own
urine?

Justify your answer.

Clinical applications:
Water intake:
- drink
- food
- catabolism



Overall, intake should equal
output

Urine output should be less
than water intake (drinks)

Urine is constantly formed at a
minimum rate of about 20-30
ml/h
Water output
- urine
- feces
- anabolism
- respiration


Clinical cases
1- Martha is a patient in a
nursing home. She is 84 year-
old, senile and weak. She is
bed bound and does not feed
herself anymore. She has a
urinary catheter and you
noticed, at the beginning of
your shift that the bag had a
small amount of dark yellow
urine.
I&O (intake and output): intake
650 cc and output 250 cc.

What do you think?
- are the numbers balanced?
- if not, what could be wrong?



2- Henrietta is Martha's
roommate, also in not very
good shape. She has been on
IV fluid receiving 100ml/h.
I&O 900ml. Her urine output is
250 ml (she has a catheter).

What do you think?
- are the numbers balanced?
- if not, what could be wrong?