Dr Ihsan R Ebrahim/Physiology /college of pharmacy

Renal Physiology
Each kidney contains approximately 1 million similar subunits called
nephrons. Each nephron consists of (1) renal corpuscle, (2) Renal
tubule that extends out from the renal corpuscle..

1- Renal capsule: Each renal corpuscle contains a compact tuft of

interconnected capillary loops called the glomerulus Each
glomerulus is supplied with blood by an arteriole called an
afferent arteriole. The glomerulus protrudes into a fluid-filled
capsule called Bowman’s capsule.. As blood flows through the
glomerulus, a portion of the plasma filters into Bowman’s capsule.
The remaining blood then leaves the glomerulus by another
arteriole, the efferent arteriole.

. Fluid filters first across the endothelial cells, then through the basement
membrane, and finally between the foot processes of the podocytes.
In addition to the capillary endothelial cells and the podocytes, there is a
third cell type, mesangial cells, which are modified smooth-muscle cells
that surround the glomerular capillary loops but are not
part of the filtration pathway.
2-Renal tubule
the segment of the tubule that drains Bowman’s capsule is the proximal
tubule. The next portion of the tubule is the loop of Henle, which is
consisting of a descending limb coming from the proximal tubule and an
ascending limb leading to the next tubular segment, the distal
convoluted tubule. Fluid flows from the distal convoluted tubule into the
collecting duct system, the first portion of which is the connecting
tubule, followed by the cortical collecting duct and then the medullary
collecting duct .

There are important regional differences in the kidney .The outer portion
is the renal cortex, and the inner portion the renal medulla. The cortex
contains all the renal corpuscles. The loops of Henle extend from the
cortex for varying distances down into the medulla. The medullary
collecting ducts pass through the medulla on their way to the renal pelvis.
All along its length, each tubule is surrounded by capillaries, called the
peritubular capillaries.
there is a patch of cells in the wall of the ascending limb called the
macula densa, and the wall of the afferent arteriole contains secretory
cells known as juxtaglomerular (JG) cells. The combination of macula
densa and juxtaglomerular cells is known as the juxtaglomerular
apparatus (JGA) .The juxtaglomerular cells secrete the hormone renin
 Dr Ihsan R Ebrahim/Physiology /college of pharmacy

Structure of nephrone
Dr Ihsan R Ebrahim/Physiology /college of pharmacy
 Dr Ihsan R Ebrahim/Physiology /college of pharmacy

Glomerular Filtration Rate (GFR)

the filtration of plasma from the glomerular capillaries into Bowman’s
space. This process is termed glomerular filtration, and the fluid is
called the glomerular filtrate .

The volume of fluid filtered from the glomeruli into Bowman’s space per
unit time is known as the glomerular filtration rate (GFR). GFR is
determined not only by the net filtration pressure but also by the
permeability of the membranes and the surface area available for
filtration
. It is possible to measure the total amount of any nonprotein substance
(assuming also that the substance is not bound to protein) filtered into
Bowman’s space by multiplying the GFR by the plasma concentration of
the substance. This amount is called the filtered load of the substance.
For example, if the GFR is 180 L/day and plasma glucose concentration
is 1 g/L, then the filtered load of glucose is 180 L/day × 1 g/L = 180
g/day.
 Dr Ihsan R Ebrahim/Physiology /college of pharmacy

. Whenever the quantity of a substance excreted in the urine is less than

the filtered load, tubular reabsorption must have occurred. Conversely, if
the amount excreted in the urine is greater than the filtered load, tubular
secretion must have occurred.

The Concept of Renal Clearance

The renal clearance of any substance is the volume of plasma from which
that substance is completely removed (―cleared‖) by the kidneys per unit
time. Every substance has its own distinct clearance
value, but the units are always in volume of plasma per time. The basic
clearance formula for any substance S is

Clearance of S =

the mass of S excreted per unit time is equal to the urine concentration of
S multiplied by the urine volume during that time, the formula for the
clearance of S becomes

____
where CS _ clearance of S
US _ urine concentration of S
V _ urine volume per unit time
PS _ plasma concentration of S

Let us take the particularly important example of a polysaccharide named

inulin. This substance is an important research tool in renal physiology
because its clearance is equal to the glomerular filtration rate. It is not
found normally in the body, but it administered intravenously to a person
at a rate sufficient to maintain plasma concentration constant at 4 mg/L.
Urine collected over a 1-h period has a volume of 0.1 L and an inulin
concentration of 300 mg/L; thus, inulin excretion equals 0.1 L/h _ 300
mg/L, or 30 mg/h.

How much plasma had to be completely cleared of its inulin to supply

this 30 mg/h? We simply divide 30 mg/h by the plasma concentration, 4
 Dr Ihsan R Ebrahim/Physiology /college of pharmacy

mg/L, to obtain the volume cleared—7.5 L/h. In other words, we are

calculating the inulin clearance (CIn) from the measured
urine volume per time (V), urine inulin concentration (UIn), and plasma
inulin concentration (PIn):

For clinical purposes, the creatinine clearance (CCr) is commonly used

to approximate the GFR as follows. The waste product creatinine
produced by muscle is filtered at the renal corpuscle and does not
undergo reabsorption. It does undergo a small amount of secretion,
however, so that some plasma is cleared of its creatinine by secretion.
Accordingly, the CCr overestimates the GFR but is close enough to be
highly useful

Regulation of Glomerular Filtration Rate

Vasoconstriction or dilation of afferent arterioles affects the rate of blood
flow to the glomerulus, and thus affects the glomerular filtration rate.
Changes in the diameter of the afferent arterioles result from both
extrinsic regulatory mechanisms (produced by sympathetic nerve
innervation), and intrinsic regulatory mechanisms (those within the
kidneys, also termed renal autoregulation). These mechanisms are
needed to ensure that the GFR will be high enough to allow the kidneys
 Dr Ihsan R Ebrahim/Physiology /college of pharmacy

to eliminate wastes and regulate blood pressure, but not so high as to

cause excessive water loss.

1-Sympathetic Nerve Effects (Extrinsi regulatory mechanism)

An increase in sympathetic nerve activity, as occurs during the fight-or-
flight reaction and exercise, stimulates constriction of afferent arterioles.
This helps to preserve blood volume and to divert blood to the muscles
and heart. A similar effect occurs during cardiovascular shock, when
sympathetic nerve activity stimulates vasoconstriction.

2-Renal Autoregulation (Intrinsic regulatory mechanism)

. The ability of the kidneys to maintain a relatively constant GFR in the
face of fluctuating blood pressures is called renal autoregulation.

Renal autoregulation is achieved through the effects of locally produced

chemicals on the afferent arterioles .When systemic arterial pressure falls
toward a mean of 70 mmHg, the afferent arterioles dilate, and when the
pressure rises, the afferent arterioles constrict.

. Autoregulation is also achieved through a negative feedback relationship

between the afferent arterioles and the volume of fluid in the filtrate. An
increased flow of filtrate is sensed by a special group of cells called the
macula densa in the thick portion of the ascending limb When the macula
densa senses an increased flow of filtrate, it signals the afferent arterioles
to constrict. This lowers the GFR, thereby decreasing the formation of
filtrate in a process called tubuloglomerular feedback.
 Dr Ihsan R Ebrahim/Physiology /college of pharmacy

Reabsorption of Salt and Water

. The return of filtered molecules from the tubules to the blood is

called reabsorption .
Most of the salt and water filtered from the blood is returned to the
blood through the wall of the proximal tubule. The reabsorption of water
occurs by osmosis, in which water follows the transport of NaCl from the
tubule into the surrounding capillaries.

Most of the water remaining in the filtrate is reabsorbed across the wall
of the collecting duct in the renal medulla. This occurs as a result of the
high osmotic pressure of the surrounding tissue fluid, which is produced
by transport processes in the loop of Henle.
 Dr Ihsan R Ebrahim/Physiology /college of pharmacy

Although about 180 L of glomerular ultrafiltrate are produced each day,

the kidneys normally excrete only 1 to 2 L of urine in a 24-hour period.
Approximately 99% of the filtrate must thus be returned to the vascular
system, while 1% is excreted in the urine. The urine volume, however,
varies according to the needs of the body

. Reabsorption by osmosis cannot occur unless the solute concentrations

of plasma in the peritubular capillaries and the filtrate are altered by
active transport processes. This is achieved by the active transport of Na+
from the filtrate to the peritubular blood.

Active Transport of Na

. The epithelial cells of the tubule, however, have a much lower Na+
concentration. This lower Na+ concentration is partially due to the low
permeability of the plasma membrane to Na+ and partially due to the
active transport of Na+ out of the cell by Na+/K+ pumps, .

In the cells of the proximal tubule, the Na+/K+ pumps are located in the
basal and lateral sides of the plasma membrane
.. The transport of Na+ from the tubular fluid to the interstitial (tissue)
fluid surrounding the proximal tubule creates a electrical gradient.

This electrical gradient favors the passive transport of Cl– toward the
higher Na+ concentration in the interstitial fluid.. As a result of the
accumulation of NaCl, the osmolality and osmotic pressure of the
interstitial fluid surrounding the epithelial cells are increased above those
of the tubular fluid.

., water moves by osmosis from the tubular fluid into the epithelial cells
and then into the interstitial fluid.
Dr Ihsan R Ebrahim/Physiology /college of pharmacy