Download Renal physiology

Renal Physiology
&
Fluid and Electrolyte Balance
Keri Muma
Bio 6
Functions of the Urinary System

Kidneys – eliminate unwanted plasma constituents
through the urine while conserving materials of value to
the body






Excrete nitrogenous waste – urea, uric acid, creatinine
Regulate blood volumes – by regulating H2O balance and
release of erythropoietin
Regulates blood pressure – releases renin which triggers
vasoconstriction and aldosterone secretion
Regulates chemical composition of the blood – regulating
ions and osmolarity
Stabilizes pH – balances acids and bases
Converting Vitamin D into its active form
Anatomy of the Kidney

Cortex – outer region
Medulla – deep to the cortex

Renal pelvis – flat funnel shaped cavity

Microscopic Anatomy

The functional unit of the kidney is the nephron


Composed of vascular and tubular components
Responsible for the filtration of blood and urine
formation
Tubular Component



Bowman’s capsule – cup surrounding the glomerulus, collects
filtrate
Proximal convoluted tubule – extends from the Bowman’s
capsule
Loop of Henle – hairpin loop
Tubular Component


Distal convoluted tubule – leads away from the
ascending loop of Henle to the collecting duct
Collecting duct – receives filtrate from DCT of
numerous nephrons
Vascular Component





Afferent arterioles – supply glomerulus
Glomerulus – capillary knot
Efferent arterioles – drains the glomerulus
Peritubular capillaries – surround tubular portions of the
nephron in the cortex
Vasa recta – surround tubular portions of the nephron in the
medulla
Types of Nephron


Cortical nephron – majority of the nephron is within
the cortex with a short loop of Henle
Juxtamedullary nephron – glomeruli is deep in the
cortex and have a long loop of Henle that extends
deep into the medulla
Juxtaglomerular Apparatus (JGA)


Region between the beginning of the DCT and the
afferent arteriole
Contains cells that regulate the rate of filtration and
blood pressure
Juxtaglomerular Apparatus (JGA)


Macula densa – in the DCT, contain osmoreceptors
that monitor solute concentration and flow rate of
filtrate
Granular cells – smooth muscle cells in the afferent
arteriole, act as mechanoreceptors to monitor BP,
synthesize and secrete renin
Renal Processes

The four basic processes of the nephrons are:
 glomerular filtration
 tubular reabsorption
 tubular secretion
 excretion
Renal Processes

Glomerular filtration is the
first process.



Plasma is filtered from the
glomerulus into the
Bowman’s capsule.
Solutes and fluid are forced
through the filtration
membrane by hydrostatic
pressure
Blood cells and plasma
proteins normally do not
enter the filtrate
Glomerular Filtration

The glomerulus is more efficient at filtration than
other capillary beds because:



Its filtration membrane is significantly more permeable
to solutes and water due to capillary pores
Glomerular blood pressure is higher due to a larger
afferent arteriole than efferent arteriole
It has a higher net filtration pressure
Glomerular Filtration Rate (GFR)

Glomerular filtration rate - the total amount of
filtrate formed per minute by the kidneys


125mL/min or 180L/day!
Factors governing filtration rate at the
capillary bed are:



Net filtration pressure
Total surface area available for filtration
Filtration membrane permeability
Forces Involved in Glomerular Filtration



The glomerular capillary pressure (55 mm Hg) is the
result of the blood pressure pushing on the inside of
the capillary wall
The plasma-colloid osmotic pressure (30 mm Hg) is
due to the retention of plasma proteins in the blood of
the glomerulus.
 The concentration of water is higher in the capsule,
because proteins are absent there. Water tends to
return to the glomerulus by osmosis
There is also a hydrostatic pressure (15 mm Hg)
tending to move fluid from the Bowman’s capsule into
the glomerulus
Forces Involved in Glomerular Filtration

From the previous examples:



The net pressure = glomerular blood pressure (plasma-colloid osmotic pressure + Bowman’s capsule
hydrostatic pressure)
55 - (30 +15) = 10
The net filtration pressure
is 10 mm Hg by this
example.
Regulation of Glomerular Filtration

Uncontrolled shifts in the GFR can lead to fluid
and electrolyte imbalances


If the GFR is too high:
 Needed substances cannot be reabsorbed quickly
enough and are lost in the urine
If the GFR is too low:
 Everything is reabsorbed, including wastes that are
normally disposed of
Regulation of Glomerular Filtration

Changes in GFR primarily result from changes
in glomerular capillary blood pressure

Three mechanisms control the GFR:
1.
2.
3.
Renal autoregulation (intrinsic control)
Sympathetic NS (extrinsic control)
Hormonal mechanisms (the RAA system)
Intrinsic Controls


Autoregulation - regulates the GFR by factors
within the kidneys.
Under normal conditions, it prevents inappropriate
changes in the GFR
Intrinsic Controls

Autoregulation entails two types of control:


Myogenic – responds to changes in pressure in
the renal blood vessels
Tubuloglomerular feedback mechanism - senses
changes in flow rate in the nephron’s tubular
component
Autoregulation of the GFR

Myogenic mechanism –
controlled by arteriole
smooth muscle cells


If the arterial pressure
increases, the afferent
arterioles constrict to lower
GFR.
If the arterial pressure
decreases the afferent
arterioles dilate to increase
GFR.
Autoregulation of GFR

Tubuloglomerular feedback – involves the
cells of the JGA

Macula densa cells – detect change in flow-rate
and osmolarity


Increase in flow rate – releases vasoactive chemicals
that cause vasoconstriction of afferent arteriole
Decrease in flow rate – inhibits release of vasoactive
chemicals causing vasodilation of afferent arteriole
Tubuloglomerular Feedback
Extrinsic Controls


When the sympathetic nervous system is at rest
or low levels then autoregulation mechanisms
prevail and afferent arteriole is dilated
However, the sympathetic nervous system can
override the autoregulatory mechanisms to carry
out long term adjustments for blood pressure if
blood volume drops
Extrinsic control of the GFR




If arterial blood pressure severely drops, the
baroreceptor reflex triggers vasoconstriction
of systemic arterioles
The afferent arterioles constrict by
sympathetic innervation. Less blood flows
through the glomeruli, lowering the blood
pressure in these capillaries.
The decrease in the GFR reduces urine
volume.
This helps to conserve plasma volume,
increasing blood pressure.
Extrinsic Controls


The sympathetic nervous system also stimulates the
renin-angiotensin-aldosterone mechanism
Renin release is triggered by the following:
 Reduced stretch of the granular cells
 Stimulation of the granular cells by activated
macula densa cells
 Direct stimulation of the granular cells via 1adrenergic receptors by renal nerves
Renin-Angiotensin Mechanism




Is triggered when the granular cells release renin
Renin acts on angiotensinogen to produce
angiotensin I
Angiotensin I is converted to angiotensin II
Angiotensin II:



Causes systemic arteriole vasoconstriction
Stimulates the adrenal cortex to release aldosterone
As a result, both systemic blood pressure and
blood volume increase
Summary: Control of GFR
Figure 25.10
Tubular Reabsorption

Tubular Reabsorption - is the selective transfer
of substances needed by the body from the
filtrate back into the peritubular capillaries

Reabsorption rates are high: 124 of 125 ml of
filtered fluid per minute, 99% for water, 100% for
glucose, and 99.5% for Na+
Tubular Reabsorption


By transepithelial transport a reabsorbed substance must
cross the tubule wall, enter the interstitial fluid, and pass
through the wall of the peritubular capillaries, entering the
blood.
Epithelial cells of the nephron tubule have a luminal
membrane and a basolateral membrane
Sodium Reabsorption

Sodium reabsorption is mostly driven by active
transport


Na+ enters the tubule cells at the luminal membrane by
diffusion
Then it is actively transported out of the tubules by a
Na+-K+ pump at the basolateral membrane
Sodium reabsorption



67% of sodium reabsorption occurs in the
proximal tubule at a constant rate
The reabsorption of sodium in the loop of Henle
plays a role in the production of varying
concentrations and volumes of the urine
In the distal tubule, reabsorption of sodium is
variable and depends on aldosterone

More or less is reabsorbed, depending on the needs of
the body.
Sodium reabsorption

Aldosterone increases Na+ absorption in
the DCT and collecting ducts by promoting
the insertion of:


Additional Na+ channels in the luminal
membrane
Additional Na-K+ pumps into the basolateral
membranes

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About 8% of the filtered Na+ is dependent on
aldosterone for reabsorption
If aldosterone is absent it is lost in the urine
Action of Aldosterone
Atrial Natriuretic Peptide Activity

ANP inhibits Na+ reabsorption which:


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Decreases blood volume
Lowers blood pressure
ANP lowers blood volume and pressure by:



Acting directly on collecting ducts to inhibit Na+
reabsorption
Inhibits RAA pathway
Dilates afferent arteriole triggering an increase in
GFR which reducing water and sodium
reabsorption
ANP
Reabsorption by PCT Cells

The reabsorption of water, glucose, amino acids, and
anions is linked to the active reabsorption of Na+

Active pumping of Na+ drives reabsorption of:


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Water by osmosis, aided by water-filled pores called aquaporins
Anions follow by diffusion, down electrochemical gradient
Glucose and amino acids by secondary active transport
Tubular Reabsorption of Water

The accumulation of sodium in the lateral spaces produces
an osmotic gradient and hydrostatic pressure that drives the
water into the peritubular capillaries.
Tubular Reabsorption of Water

80% of water reabsorption is obligatory in the
proximal tubule and loop of Henle


Occurs by osmosis, no control
20% of water reabsorption is facultative in the
distal tubule and collecting duct

Based on the secretion of ADH, depends on body’s
needs
Role of ADH on Water Reabsorption



ADH works on tubule cells through a cyclic AMP mechanism
Promotes the insertion of aquaporins on the luminal membrane
thus increasing water reabsorption
Produces concentrated urine
Tubular Reabsorption

Glucose and amino acids are reabsorbed by
secondary active transport and cotransported
with sodium on the luminal membrane
Nonreabsorbed Substances

A transport maximum (Tm):



Reflects the number of carriers in the renal tubules available
Exists for nearly every substance that is actively reabsorbed
When the carriers are saturated, excess of that
substance is excreted
Nonreabsorbed Substances

Substances are not reabsorbed if they:


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Lack carriers
Are not lipid soluble
Are too large to pass through membrane pores
Urea, creatinine, uric acid and other nitrogen
containing wastes are usually excreted
Renal Processes

Tubular secretion is a
selective process by
which substances from
the peritubular capillaries
enter the lumen of the
nephron tubule.

Provides a mechanism to
speed up the elimination
of substances from the
blood
Tubular Secretion

Tubular secretion is important for:

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Disposing of substances not already in the filtrate
Eliminating undesirable substances such as urea
and uric acid
Ridding the body of excess potassium ions
Controlling blood pH
Tubular Secretion of K+

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K+ is almost completely reabsorbed in the proximal tubule
Aldosterone stimulates the tubular cells to secrete potassium if
plasma levels are elevated
K+ secretion occurs in the distal tubule
As the basolateral pump transports sodium into the lateral spaces,
it pumps potassium into the tubular cells where it diffuses into the
lumen for elimination.
Role of
Aldosterone
Acid-Base Balance

Concentration of hydrogen ions is regulated
sequentially by:



Chemical buffer systems – act within seconds
The respiratory center in the brain stem – acts
within 1-3 minutes
Renal mechanisms – require hours to days to
effect pH changes
Renal Mechanisms of Acid-Base Balance

The most important renal mechanisms for
regulating acid-base balance are:

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
Conserving (reabsorbing) or generating new
bicarbonate ions
Excreting bicarbonate ions
Losing a bicarbonate ion is the same as gaining a
hydrogen ion; reabsorbing a bicarbonate ion is the
same as losing a hydrogen ion
Summary of Renal Response to
Acidosis & Alkalosis
Reabsorption of Bicarbonate


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Secreted hydrogen ions form carbonic acid with filtered
bicarbonate
Carbonic acid dissociates to release carbon dioxide and
water
Carbon dioxide then diffuses into tubule cells, triggering
further hydrogen ion secretion and bicarbonate reabsorption
Thus, bicarbonate disappears from filtrate at the same rate it
is reabsorbed
Figure 26.12
Generating New Bicarbonate Ions


Dietary hydrogen ions must be counteracted
by generating new bicarbonate
Two mechanisms generate new bicarbonate
ions:


Both involve renal excretion of acid via secretion
and excretion of hydrogen ions or ammonium ions
(NH4+)
The excreted hydrogen ions must bind to
buffers in the urine (phosphate buffer system)
Hydrogen Ion Excretion

In response to acidosis:



Kidneys generate
bicarbonate ions and
add them to the blood
An equal amount of
hydrogen ions are
added to the urine
H+ binds with buffers in
the filtrate
(monohydrogen
phosphate)
Figure 26.13
Ammonium Ion Excretion

Another response to
acidosis:
 This method uses
ammonium ions produced
by the metabolism of
glutamine in PCT cells
 Each glutamine
metabolized produces two
ammonium ions and two
new bicarbonate ions
 Bicarbonate moves to the
blood and ammonium ions
are excreted in urine
Bicarbonate Ion Secretion

When the body is in
alkalosis, type B
cells:


Exhibit bicarbonate
ion secretion
Reclaim hydrogen
ions and acidify the
blood
Varying Urine Concentration


Kidneys excrete varying concentrations and
volumes of urine depending on the body’s
needs
Can produce urine ranging from 0.3ml/min at
1200 mosm/L to 25 ml/min at 100 mosm/L
Varying Urine Concentration

This variation in reabsorption
is made possible by a large,
vertical osmotic gradient in
the interstitial fluid of the
medulla



From 300 to 1200 mosm/liter
This increase follows the
juxtamedullary nephron’s loop
of Henle deeper and deeper
into the medulla.
The gradient is established by
means of the countercurrent
system
Varying Urine Concentration

Countercurrent – the movement in opposite
directions of filtrate through the ascending
and descending limbs of the loop of Henle

Also applies to the flow of blood through the vasa
recta
Countercurrent Mechanism


Countercurrent multiplier – refers to the ability to
increase the osmolarity of the interstitial fluid
Due to the properties in the two limbs of the loop:


The descending loop of Henle:
 Is relatively impermeable to solutes
 Is permeable to water
The ascending loop of Henle:
 Is permeable to solutes
 Is impermeable to water
Countercurrent Multiplier


The ascending limb actively
transports NaCl out of the
tubular lumen into the
surrounding interstitial fluid.
It is impermeable to water.
Therefore, water does not
follow the salt by osmosis.
The ascending limb produces
an interstitial fluid that
becomes hypertonic to the
descending limb. This
attracts the water by osmosis
for reabsorption.
Countercurrent Mechanism

Countercurrent exchanger - The hairpin structure of the
vasa recta allows the blood of the vasa recta to
equilibrate with the interstitial fluid


Prevents the dissipation of the medullary osmotic gradient
Blood is isotonic when it enters and when it leaves the
medulla
Formation of Concentrated Urine



ADH is the signal to produce concentrated urine
Allowing the distal and collecting ducts to become
permeable to water
In the presence of ADH, 99% of the water in filtrate is
reabsorbed
Diuretics

Osmotic diuretics include:




High glucose levels – carries water out with the
glucose
Alcohol – inhibits the release of ADH
Caffeine and most diuretic drugs – inhibit sodium
ion reabsorption
Lasix and Diuril – inhibit Na+-associated
symporters
Renal Processes

Urine Excretion –
elimination of what
remains in the tubular
lumen

The unwanted filtrate
material
Transport and Storage of Urine

Urine is transported from the kidney to the
bladder by the ureters


Due to gravity or peristaltic waves
The bladder temporarily stores urine
Micturition Reflex

Micturition – act of emptying the bladder



The filling of the bladder activates stretch receptors
which trigger reflex contractions of the bladder and
relaxation of the internal sphincter
Urine is forced past the internal sphincter
Must voluntary relax external sphincter to void the
bladder of urine
Micturition Reflex