Download Glomerular Filtration

Urinary system physiology
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Mechanisms of Urine Formation



The kidneys filter the body’s entire plasma volume
60 times each day
The filtrate:

Contains all plasma components except protein

Loses water, nutrients, and essential ions to
become urine
The urine contains metabolic wastes and unneeded
substances
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Basic processes of urine formation

Glumerular Filtration




The fluid that is forced out of capillaries into the Bowman’s
space is called glumerular filtrate
Similar to blood plasma without the proteins
Tubular reabsorption and secretion

The fluid in the DCT and PCT is called tubular fluid

Differs from the filtrate because substances are moving in
and out the tubules
Water conservation

Occur in the collecting duct

The fluid is called urine
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Reminder - Capillary Beds of the Nephron


Every nephron has two capillary beds

Glomerulus

Peritubular capillaries
Each glomerulus is:

Fed by an afferent arteriole

Drained by an efferent arteriole
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Anatomy of the Glomerular Capsule

The external parietal layer is a structural layer
(Bauman’s capsule)

The visceral layer consists of modified, branching
epithelial podocytes

Extensions of the octopus-like podocytes terminate
in foot processes
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Glomerular filtration membrane

Fluid from capillaries need to pass through 3
barriers to get to the capsular space:

Fenestrated endothelium of capillaries with pores
that allow the passage of relatively large molecules
but not blood cells (pores size – 70-90nm)


In addition, endothelial cells have negatively
charged glycoproteins on their surface that
“deny” entrance of negatively charged molecules
Basement membrane – negatively charged proteins
that do not allow the passage of large and
negatively charged molecules (stop molecules
>8nm)
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Glomerular filtration membrane

Filtration slits – form by the pedicles of the
podocyes that create filtration slits (slit size 30nm).
Filtrate on basis of size and negative charge

Water and some solutes pass from blood plasma in
the glomerulus capillaries to the capsular space of
the nephrone

Molecules smaller than 3 nm in diameter (water,
sodium, glucose, amino acids, nitrogen wastes)
pass freely from blood into capsule
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

http://members.aol.com/Bio50/LecNotes/lecnot37.html
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Most molecules smaller
than 3 nm can pass freely.
That includes water,
electrolytes, glucose, fatty
acids,
amino
acids,
nitrogenous wastes and
vitamins
Glomerular Filtration

Filtration is a passive process in which hydrostatic pressure
forces fluid and solutes through a membrane

The glomerulus is more efficient than other capillary beds
because:

Large surface area of the filtration membrane

filtration membrane is more permeable

Glomerular blood pressure is higher because


Arterioles are high-resistance vessels

Afferent arterioles have larger diameters than efferent
arterioles
Higher BP results in higher net filtration pressure
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Specials characteristics of glumerular filtration

Filtration depends on the balance between hydrostatic pressure
and colloid osmotic pressure on both sides of the capillary wall

Blood hydrostatic pressure (BHP) is much higher in the
glomerulus (60 mmHg as compared to 10-15)

Hydrostatic pressure in the capsular space is about 18 mm Hg
(compared to about 0 in the interstitial fluid).

This is a result of continuous filtration and the presence of
fluid in the space.

The colloid osmotic pressure (COP) of the blood is about the
same as elsewhere – 32 mm Hg

The glomerular filtrate is almost protein-free and has no
significant COP
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Glomerular filtration

Total forces in the renal corpuscle:

Forces that work to move fluid from capillaries into capsular
space:


Glomerular capillaries hydrostatic pressure (GHP) – 55-60
mm Hg
Forces that work to move fluid out of capsular space to
capillaries:

Blood colloid osmotic pressure (BCOP) – 32 mm Hg

Capsular space hydrostatic pressure (CsHP) – 18 mm Hg

60 out – 18 in – 32 in = 10 mmHg net filtration pressure
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Net Filtration Pressure
Filtration pressure across the filtration membrane is equal to the
blood hydrostatic pressure (BHP) minus the colloid osmotic
pressure (COP) in the glomerular capillary and minus the capsular
pressure (CP).
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Glomerular filtration rate (GFR)

Amount of filtrate produced by the two kidneys
each minute (~125 ml)

Factors that control GFR:


Total surface area available for filtration

Filtration membrane permeability

Net filtration pressure (NFP)
GFR is usually measured over 24 hr and it is about
180 L/day for males and 150 L/day in females
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Regulation of Glomerular Filtration

2 types of mechanisms control the GFR


Renal autoregulation (intrinsic system)

Myogenic mechanism

Tubuloglomerular feedback mechanism
Extrinsic mechanisms

Neural controls (extrinsic system)

Hormonal mechanism (the renin-angiotensin
system)
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Intrinsic Controls - autoregulation

Renal autoregulation is the ability of the nephron to
adjust the blood flow and GFR without external
control

Under normal conditions, renal autoregulation
maintains a nearly constant glomerular filtration rate

Autoregulation involves two types of control


Flow-dependent tubuloglomerular feedback –
senses changes in the juxtaglomerular apparatus
Myogenic – responds to changes in pressure in the
renal blood vessels
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Tubuluglomerular feedback mechanism

The juxtaglomerular apparatus (JGA) monitors the fluid entering
the DCT and adjusts the GFR

Components of the JGA:


The granular/juxtaglumerular (JG) cells – enlarged smooth
muscle cells in the afferent arteriole.

They respond to the cells of the macula densa to dilate or
constrict the arterioles

Act as mechanoreceptors that sense blood pressure

Can release renin when BP decrease
The macula densa is a patch of ET at the start of the DCT (in
some books it said to be in loop of Henle) directly across from
the JG cell

Sense NaCl concentration in the tubular fluid
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Autoregulation control of GFR

If GFR rises, flow of tubular fluid increases and rate of
NaCl reabsorption decreases.

The macula densa sense the change and stimulate the
contraction of JG cells

This results in constriction of the afferent arteriole thus
reducing GFR
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Intrinsic Controls: Myogenic Mechanism



The myogenic mechanism – base on the tendency of
smooth muscle to contract when stretches
 BP  constriction of afferent arterioles

Helps maintain normal GFR

Protects glomeruli from damaging high BP
 BP  dilation of afferent arterioles

Helps maintain normal GFR
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Extrinsic Controls – neural control



When the sympathetic nervous system is at rest:

Renal blood vessels are maximally dilated

Autoregulation mechanisms is controlling
Under stress:

Norepinephrine is released by the sympathetic nervous
system

Epinephrine is released by the adrenal medulla

Afferent arterioles constrict and filtration is inhibited
The sympathetic nervous system also stimulates the reninangiotensin mechanism
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Renin-Angiotensin Mechanism – hormonal control

A reduction in afferent arteriole pressure triggers the
JG cells release renin

Renin acts on angiotensinogen to release angiotensin I

Angiotensin I is converted to angiotensin II

Angiotensin II:


Causes mean arterial pressure to rise

Stimulates the adrenal cortex to release aldosterone
As a result, both systemic and glomerular hydrostatic
pressure rise
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Extrinsic Controls: Renin-Angiotensin Mechanism

Triggered when the granular cells of the JGA
release renin
angiotensinogen (a plasma globulin)
resin 
angiotensin I
angiotensin converting
enzyme (ACE) 
angiotensin II
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
http://www.cvphysiology.com/Blood%20Pressure/BP015.htm
Reabsorption and secretion

Conversion of the glomerular filtrate to urine
involves the removal and addition of chemicals by
tubular reabsorption and secretion

Accomplished via diffusion, osmosis, and carriermediated transport

Cells of the PCT reabsorb 60-70% of the filtrate
volume

Reabsorbed materials enter the peritubular fluid and
diffuse into the preitubular capillaries
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Nonreabsorbed Substances

Substances are not reabsorbed if they:

Lack carriers

Are not lipid soluble

Are too large to pass through membrane pores
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
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
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Regulation of Urine Concentration and Volume

Osmolality


The number of solute particles dissolved in 1L of
water
Reflects the solution’s ability to cause osmosis

Body fluids are measured in milliosmols (mOsm)

The kidneys keep the solute load of body fluids
constant at about 300 mOsm

This is accomplished by the countercurrent mechanism
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
The loop of Henle and countercurrent multiplication

Countercurrent multiplication –exchange occurs between
fluids moving in different directions; the effect of the
exchange increased as the fluid movement continues

Between the close ascending and descending limbs of loop

Difference in permeability in two arms:

Thin descending is permeable to water and almost not to
solutes

Thick ascending relatively impermeable to both but
contains active transport mechanism that pump sodium
and chloride ions from tubular fluid to peritubular fluid of
the medulla
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Countercurrent multiplication

Sodium and chloride are pumped out of the thick
ascending limb into the peritubular fluid by co-transport
carriers (Na+-K+/2Cl- transporter)

That elevates the osmotic concentration in the
peritubular fluid around the thin descending limb

The result is flow of water out of the thin descending
limb into the peritubular fluid and increased
concentration of solutes in the thin limb

The arrival of highly concentrated solution in the thick
limb accelerate the reabsorption of sodium and chloride
ions
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
The countercurrent multiplication:

Creates osmotic gradient in medulla

Facilitates reabsorption of water and solutes before
the DCT

Permits passive reabsorption of water from tubular
fluid in the collecting system
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Osmotic gradient

The kidney has an osmotic gradient from cortex to medulla

The outer layer of the kidney is isotonic with the blood:
~300 milliosmoles/liter

The innermost layer (medulla) is very hypertonic: ~1200
milliosmoles/liter
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Function of the vasa recta

Solutes and water reabsorbed in the medulla need to be
returned into circulation.

Blood enters the vasa recta with osmotic concentration
of ~300 mOsm/l

Blood descending in the medulla gradually increases in
osmotic concentration because of solute reabsorption
(plasma proteins limit osmotic flow out of the blood)

Blood flowing toward the cortex gradually decreases in
osmotic concentration mainly because of water flowing
into capillaries
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Reabsorption and secretion at the DCT

DCT performs final adjustment of urine by active
secretion or reabsorption

Tubular cells actively reabsorb Na+ and Cl- .

In the distal part of the DCT reabsorption of sodium
ions in exchange to another cation (usually K+)

The ion pumps and Na+ channels are regulated by
aldosterone

The DCT is a primary site of calcium ions
reabsorption (regulated by PTH and calcitriol)
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
The concentration of the urine is adjusted in the collecting ducts

The kidney uses osmosis in the collecting duct to control the
concentration and volume of urine

The collecting ducts pass through tissue with a very high osmotic
pressure in the medulla.

As the urine passes into the collecting duct it first passes through a
region of isotonic osmotic pressure (300 milliosmoles/liter) and then
through a region of hypertonic osmotic pressure (up to 1200
milliosmoles/liter)

If the collecting duct has low water permeability the dilute urine
in the kidney tubule passes through with little uptake of water

If the collecting duct has high water permeability much of the
water will be reabsorbed from the collecting duct into the
interstitial fluid
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
ADH and urine volume

The permeability of the wall of the collecting duct varies under the
influence of antidiuretic hormone (ADH).

ADH is released by the posterior pituitary in response to increased
osmotic pressure (decreased water or increased solutes in blood).

When ADH reaches the kidney, it increases the permeability of the
epithelial linings of the distal convoluted tubule and collecting duct
to water, and water moves rapidly out of these segments, eventually
into the blood, by osmosis (water is reabsorbed).

Consequently, urine volume falls, and urine concentrates soluble
wastes and other substances in minimal water. Concentrated urine
minimizes loss of body fluids when dehydration is likely.

If the osmotic pressure of the blood decreases, ADH is not released
and water stays in the collecting duct, leaves as part of the urine.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Aldosterone and urine concentration

Aldosterone is a steroid secreted by the adrenal cortex

It is secreted when blood sodium falls or if blood potassium
rises

It is also secreted if BP drops (indirectly through the release
of renin-angiotensin II that promotes aldosterone secretion)

Aldosterone secreted – increased tubular reabsorption of
Na+ in exchange for secretion of K+ ions – water follow

Net effect is that the body retains NaCl and water and urine
volume reduced

The retention of salt and water help to maintain blood
pressure and volume
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Atrial natriuretic peptide (ANP) and urine volume

Secreted from the atrial myocardium in response to high
BP

Has 4 actions that result in the excretion of more salt and
water in the urine:

Dilate afferent arteriole and constricts efferent –
increase GFR (more blood flow and higher GHP)

Antagonized angiotensin-aldosterone mechanism by
inhibiting both renin and aldosterone secretion

Inhibits ADH

Inhibits NaCl reabsorption by the collecting ducts
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
A Summary of Renal Function
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 26.16b