Early Filtrate Processing

Gambaran seluler dari tubulus

renalis
Tubulus proximal: simple cuboidal cells
(brush border cells ok terdapat microvilli)
Thin loop of henle: simple squamous cell,
highly permeable to water not to solute
Thick ascending loop of henle & early
distal tubule: cuboidal cells, highly
permeable to solutes, particularly NaCl but
not to water
Late distal tubule and cortical collecting
duct: cuboidal cells has two distinct
function:
1. principal cells; permeability to water
and solutes are regulated by hormones
and,
2. intercalated cells; secretion of hydrogen
ion for acid/base balancing
Medullary collecting duct; principal cells;
hormonally regulated permeability to
water and urea
Tubular Reabsorption
By passive diffusion
By primary active transport: Sodium
By secondary active transport: Sugars and
Amino Acids
Endositosis ; small proteins and peptide
hormones

Reabsorption Pathways
There are two reabsorption pathways:

1. the transcellular pathway (>>)

2. the paracellular pathway
Reabsorpsi Filtrat
Trancellular pathway : Through luminal
and basolateral membranes of the tubular
cells into the interstitial space and then
into the peritubular capillaries.
Paracellular pathway : through the tight
junctions into the lateral intercellular
space.
Water and certain ions use both
pathways, especially in the proximal
convoluted tubule.
Diffusion of Water
Water diffuses from the lumen through the
tight junctions into the interstitial space:
1. Water will move from its higher
concentration in the tubule through the
tight junctions to its lower concentration in
the interstitium.
2. Water will also move through the
plasma membranes of the cells that are
permeable to water
Air dapat berdifusi di seluruh bagian tubulus
kecuali di ascending limb loop of Henle
Sodium Reabsorption
Keluar dari sel ke interstiital
Lumen
Plasma
Cells
PUMP: Na/K ATPase
Sodium
Potassium
Chloride
Water
Tubular Secretion
Protons (acid/base balance)
Potassium
Organic ions
Zat-zat lain yg tidak normal ada dalam
darah spt obat-obatan dan bahan-bahan
toksik
Transport Maximum (Tm)

For most actively reabsorbed solutes, the
amount reabsorbed in the PCT is limited only by
the number of available transport carriers for
that specific substance.
This limit is called the transport maximum, or Tm.
If the volume of a specific solute in the filtrate
exceeds the transport maximum, the excess
solute continues to pass unreabsorbed through
the tubules and is excreted in the urine.
Reabsorption: Receptors can Limit
Figure 19-15: Glucose handling by the nephron
The final processing of filtrate in the
late distal convoluted tubule and
collecting ducts comes under direct
physiological control in response to
changing physiological conditions and
hormone levels.
Membrane permeabilities and cellular
activities are altered in response to the
body's need to retain or excrete specific
substances.
Distal Tubule & Collecting Duct
The Late Distal Tubule & CCT are
composed of principal cells & intercalated
cells
Intercalated cells secrete hydrogen ions
into filtrate
Principals cells perform hormonally
regulated water & sodium reabsorption &
potassium secretion
Role of Aldosteron
Principal cells are more permeable to
sodium ions and water in the presence of
Aldosterone & ADH
Low level of Aldosterone result in little
basolateral sodium/potassium ATPase ion
pump activity & few luminal sodium &
potassium channel


Aldosteron increases the number of
basolateral Na/K pump and luminal Na
& K channels
Since there are no basolateral K
channel, K ion are secreted into the
instead of returning to the interstitium
Without an increase in water
permeability, the interstitial osmolarity
increases
Role of ADH
Principals cells are more permeable to
water on the presence of ADH
Reabsorption in Proximal Tubule
Glucose and Amino Acids
67% of Filtered Sodium
Other Electrolytes
65% of Filtered Water
50% of Filtered Urea
All Filtered Potassium
Juxtaglomerular apparatus
As the thick ascending loop of henle
transition into early distal tubule, the
tubule runs adjacent to the afferent and
efferent arteriole.
Where these structure are contact they
form the monitoring structure called the
juxtaglomerular apparatus (JGA), which is
composed macula densa and JG cells
Figure 19-9: The juxtaglomerular apparatus
TUBULOGLOMERULAR FEEDBACK &
GLOMERULOTUBULAR BALANCE
Signals from the renal tubule in each nephron
feedback to affect filtration in its glomerulus. As the
rate of flow through the ascending limb of the loop
of Henle and first part of the distal tubule increases,
glomerular filtration in the same nephron decreases,
and, conversely, a decrease in flow increases the
GFR
This process, which is calledtubuloglomerular
feedback, tends to maintain the constancy of
the load delivered to the distal tubule.
The sensor for this response is the macula densa.
The amount of fluid entering the distal
tubule at the end of the thick ascending
limb of the loop of Henle depends on the
amount of Na
+
and Cl

in it.
The Na
+
and Cl

enter the macula densa

cells via the NaK2Cl cotransporter in
their apical membranes.
The increased Na+ causes increased Na, K
ATPase activity and the resultant
increased ATP hydrolysis causes more
adenosine to be formed.
Presumably, adenosine is secreted from
the basal membrane of the cells. It acts
via adenosine A1 receptors on the macula
densa cells to increase their release of
Ca
2+
to the vascular smooth muscle in the
afferent arterioles.
This causes afferent vasoconstriction and
a resultant decrease in GFR.
Presumably, a similar mechanism
generates a signal that decreases renin
secretion by the adjacent juxtaglomerular
cells in the afferent arteriole but this
remains unsettled


Conversely, an increase in GFR causes an
increase in the reabsorption of solutes,
and consequently of water, primarily in
the proximal tubule, so that in general the
percentage of the solute reabsorbed is
held constant.
This process is called glomerulotubular
balance, and it is particularly
prominent for Na
+
.
The change in Na+ reabsorption occurs within
seconds after a change in filtration, so it seems
unlikely that an extrarenal humoral factor is
involved.
One factor is the oncotic pressure in the
peritubular capillaries.
When the GFR is high, there is a relatively large
increase in the oncotic pressure of the plasma
leaving the glomeruli via the efferent arterioles and
hence in their capillary branches.
This increases the reabsorption of Na
+
from the
tubule. However, other as yet unidentified
intrarenal mechanisms are also involved.
Sympathetic control

In extreme stress or blood loss,
sympathetic stimulation overrides the
autoregulation

Increased sympathetic discharge cause
intense constriction of renal blood vessel
Blood is shunted to other vital organs
GFR reduction causes minimal fluid loss
from blood
Reduction filtration can not go indefinitely,
a waste product build up & metabolic
imbalances increase in blood
IV fluid increases blood volume restores
blood pressure to resting levels reduced
sympathetic stimulation allows for normal
arteriole diameter GFR & filtrate flow is
normalized

Sympathetic Regulation of GFR
Insert fig. 17.11