RENAL PHYSIOLOGY

Ogbe S. E.
Department of Human Physiology
Federal University, Karu
Figure 26-1 An Introduction to the Urinary System.

Organs of the
Urinary System
Kidney
Produces urine

Ureter
Transports urine
toward the
urinary bladder
Urinary bladder
Temporarily stores
urine prior
to urination
Urethra
Conducts urine to
exterior; in males,
it also transports
semen
Anterior view
 The urinary system
• The urinary system consist of the kidneys, ureters, urinary
bladder and urethra.
• It is the main excretory route in the body since it is
concerned with the formation and excretion of urine.
• The kidneys excretes most of the end products of metabolism
as well as many foreign substances and toxins.
• They also control the concentration of most constituents of
the body fluids particularly the ECF, so they are essential for
homeostasis
• The kidneys have a very high functional reserve, so one can
survive with only one half of a healthy kidney i.e with only
¼ of the functioning kidney mass which normally contains
about ½ million nephrons
Structure of the urinary system
 Functional anatomy of the kidney
• The kidney is surrounded by a thin tough fibrous
capsule which limits its distension and it consists of 2
distinct zones
• The outer cortex which appears red because it is richly
supplied with blood, it is granular because it contains
the renal glomeruli
• An inner medulla: this is paler than the cortex because it
is poorly supplied with blood and it is striated because it
contains the loop of Henle and collecting ducts. It
contains 10-15 pyramids, the apexes of which form the
renal papillae which drains into the calyces
• The functional unit of the kidney is called nephron
Figure 26-4a The Structure of the Kidney.

Renal cortex

Renal medulla
Inner layer of
fibrous capsule Renal pyramid

Renal sinus Connection to

minor calyx
Adipose tissue
in renal sinus Minor calyx

Renal pelvis Major calyx

Hilum Kidney lobe

Renal papilla
Renal columns

Ureter
Fibrous capsule

a A diagrammatic view of a frontal

section through the left kidney
 The nephron
• The nephron is the functional unit of the kidney,
each kidney is composed of about 1,300,000
nephrons or slightly more and each nephron is
capable of forming urine by itself.
• Nephrons functions independently to produce
urine and they constitute the functioning
kidney mass
• Renal function carried out by only ¼ of the
mass i.e. about 500000 nephrons
 Structure of the nephron
• Each nephron consists of 2 main parts: the glomerulus
and the tubule
The glomerulus
• It is about 200um in diameter, it is formed by the
invagination of a tuft of about 50 capillaries into the
dilated, blind end of the nephron (Bowman’s capsule).
• Both the glomerulus and Bowman’s capsule are called
the malpighian corpuscle
• Blood enters the glomerulus via the afferent arterioles
and leaves via the narrower efferent arterioles
• The glomerular capillary bed is a high pressure bed,
which facilitates filteration of plasma
• The total surface area of the glomerular capillaries in
both kidneys averages 0.8sq.m.
• It is noted that the glomerulus lies between 2
arterioles, and that the glomerular capillaries
are the only capillaries in the body that drain
into arterioles.
• The efferent arterioles are the only arterioles in
the body that collect blood from the capillaries
 The renal tubule
• This is concerned with urine formation and it’s
total length including the collecting duct is
about 45-65mm.
• It receives the glomerular filtrate
• Its main functions are reabsorption of the
wanted substances from the tubular fluid and
secretion of the unwanted substances into that
fluid.
 Parts of the renal tubule
i. Proximal convoluted tubule (PCT): this is the
first part of the tubule it’s length averages 15mm.
• It’s wall is made up of single layer of epithelial cells
united by tight junctions
• the luminal borders of these cells have a luminal brush
boarder due to presence of large number of microvilli
ii. Loop of Henle (LH): is the U-shaped segment of the
renal tubule that extends into the medulla for variable
lengths.
• It is about 20mm long and consists of the descending
and ascending limbs.
 Parts of the renal tubule
• The walls of the descending limb and lower part of
the ascending limb are thin because they are made
up of a single layer of flat epithelial cells.
• On the other hand, the wall of the upper part of the
ascending limb is thick and it is made of cuboidal
epithelial cells rich in mitochondria
iii. Distal convoluted tubule (DCT): it is about
5mm long, it receives tubular fluids from the
ascending limb of the LH.
• Its epithelium is lower than that of the PCT, and it
contains few microvilli.
 Parts of the renal tubule
• About 8DC Ts coalesce fo rmin g a co rtical
collecting duct (tubule), which passes downwards
into the medulla where it becomes a medullary
collecting duct.
• The medullary collecting ducts coalesce forming
larger ducts which drains into the minor calyces at
the tip of the renal papillae,
• the minor calyces unit together forming the major
calyces that empties into the renal pelvis (from
which the ureter arises)
 Parts of the renal tubule
• All PCTs and DCTs as well as glomeruli and
cortical collecting ducts are present in the renal
cortex
• The loops of Henle penetrates into the medulla
for variable lengths depending on the type of
nephron
• The LHs together with medullary CD and the
vasa recta are arranged parallel to each other in
the medulla producing the striated appearance
of the renal pyramids
 Parts of the renal tubule
The epithelium of CD is made up of 2 types of
cells
i. T h e P r i n c i p a l ( P ) c e l l s : T h e P c e l l s
predominate and are involved in Na
reabsorption and vasopressin-stimulated water
reabsorption
ii. The Intercalated (I) cells: Which are also
present in the DCT are concerned with H
secretion and bicarbonate reabsorption
 Types of Nephrons
• There are 2 types of nephrons depending on the
situation of the renal glomeruli
i. Cortical nephron: their glomeruli is in the outer
portion of the renal cortex and they constitute 85%
o f t h e to ta l n u m b e r o f n e p h ro n s . T h e i r L H
penetrates only a short distance into the outer part of
the medulla
ii. J u x ta m e d u l l a r y n e p h ro n s : t h e s e h ave t h e i r
glomeruli situated in the inner portion of the renal
cortex (near to the medulla), and they constitute
about 15% of the total number of nephrons. Their
LH penetrates deeply into the inner part of the renal
medulla, and they are essential for the process of
urine concentration
 The juxtaglomerular apparatus (JGA)
JGA is a secretory structure located at the region where the
initial part of the DCT comes in contact with the
glomerulus and passes close to afferent and efferent
arterioles. It is form of the following components
i. Macula densa which is close to the efferent and
particularly the afferent arteriole
ii. The Lacis cells
iii. The juxtaglomerular cells these are renin secreting cells
in the afferent arteriole
Functions of JGA
• Formation and release of renin which is essential for
auto-regulation of the GFR and renal blood flow
Figure 26-8a The Renal Corpuscle.

Glomerular capsule

Glomerular Capsular Visceral

capillary epithelium epithelium
Capsular (podocyte)
space

Efferent arteriole Proximal

convoluted
tubule
Distal convoluted
tubule

Juxtaglomerular
complex

Macula densa
Juxtaglomerular
cells

Afferent arteriole

a Important structural features of a renal corpuscle.

 Renal nerves
• The renal nerves travel along the renal blood vessels as
they enter the kidney.
i. Efferent ner ves: The kidneys receives mostly
symp athetic effe re nt n e r ve s f ro m t h e g re ate r
splanchnic nerve. Cholinergic innervations via the
vagus nerve also appear to be present but its function
is uncertain. The sympathetic fibres are distributed to:
g l o m e r u l a r a r t e r i o l e s , P C T a n d D C T, t h e
juxtaglomerular cells, thick ascending limb of the LH
ii. Afferent nerves: these accompany the sympathetic
efferent nerves, and they mediate pain from the kidney.
Other afferent nerves mediate reno-renal reflexes
(which produces adjustments in the function of one
kidney when the other is manipulated)
 Functions of the kidney
A. Excretory functions: through urine excretion,
the kidneys clear the plasma from unwanted
substances which include the following:
i. Non-essential substances: end products of
metabolism e.g. urea, uric acid, creatinine and
bilirubin. Foreign substances e.g. drugs and
toxins
ii. Excess amounts of essential substances (water
and electrolytes e.g. Na+ and K+
 B. Endocrinal function of the kidney
• The kidneys are endocrine organs, they secretes:
i. Renin: this is a glycoprotein that is secreted by the JG
cells and may be made by the messangial cells. Renin
converts angiotensinogen to angiotensin I which is
further converted to angiotensin II
ii. Erythropoietin: this is a glycoprotein hormone that is
secreted by the endothelial cells of the peritubular
capillaries in the renal cortex
iii. Prostaglandins: the kidney secretes 2 main types:
PGE2 and PGI2 (prostacyclin) the PG in the kidney
are concerned mainly with autoregulation of GFR and
RBF
iv. 1,25 Dihydroxycholecalciferol: this is the active form
of vitamin D it is form in the kidney from the inactive
25-HCC (calcidiol) mostly in the cells of the PCT by
the activity of 1 alpha-hydroxylase enzyme
 Mechanism of urine formation
• Urine is formed as a result of filtration of plasma in the
g l o m e r u l i ( i . e . g l o m e r u l a r f i l t rat i o n ) , t h e n by
reabsorption and secretion processes in the renal tubules
• Normally the glomerular capillary bed (GCB) receives
650ml plasma/minute of which only about 1/5 (125ml)
is filtered into the Bowman’s capsules the remaining 4/5
pass to the PTC
• The glomerular filtrate is essentially protein free and
devoid of all cellular elements including RBCs
• Other constituents of the GF are similar to that of the
plasma except some low molecular weight substances
like calcium and fatty acids that are not freely filtered
because they are partially bound to plasma proteins.
• In the renal tubules, about 124ml are reabsorbed
back into the PTC (together with the essential
substances e.g. glucose and electrolytes) and more
of the unwanted substances is secreted from the
PTC into the tubules
• By these processes of reabsorption and secretion,
the tubular fluid is changed into actual urine
(which is normally about 1ml/min i.e. about 0.1%
of the RPF)
 Tubular secretion
This is mostly an active process by which
substances are transported into the lumens of
the renal tubules from the following sources
• Blood of the PTC e.g. creatinine
• Tubular epithelial cells e.g. H+ and NH3
Tubular secretion and glomerular filtration are
processes that clear the plasma from unwanted
substances
 Tubular reabsorption
• This is the transport of substances (mainly the
essential substances) from the lumens of the
tubules to the blood in the PTC
Normal values
Glomerular filtration rate (GFR): 125ml/minute
Tubular reabsorption: 124ml/minute
Urine volume: 1ml/minute
• Tubular reabsorption is not a clearing process
 Renal circulation
• The kidney receives arterial blood via the renal
artery which arises directly from the aorta.
 Blood Supply to the Kidneys

– Kidneys receive 20–25 percent of total cardiac

output
– 1200 mL of blood flows through kidneys each
minute
– Kidney receives blood through renal artery
Figure 26-5a The Blood Supply to the Kidneys.
Cortical
radiate
veins
Cortical
radiate
arteries

Interlobar
arteries Cortex

Segmental
artery

Adrenal
artery

Renal
artery

Renal
vein

Interlobar Arcuate
veins veins

Medulla

Arcuate
arteries

a A sectional view, showing major

arteries and veins
 Segmental Arteries

– Receive blood from renal artery

– Divide into interlobar arteries
• Which radiate outward through renal columns
between renal pyramids
– Supply blood to arcuate arteries
• Which arch along boundary between cortex and
medulla of kidney
• Afferent Arterioles
– Branch from each cortical radiate artery
(also called interlobular artery)
– Deliver blood to capillaries supplying
individual nephrons
• Cortical Radiate Veins
– Also called interlobular veins
– Deliver blood to arcuate veins
– Empty into interlobar veins
• Which drain directly into renal vein
Figure 26-5b The Blood Supply to the Kidneys.

Glomerulus

Cortical radiate vein Afferent

arterioles
Cortical radiate artery

Arcuate artery

Arcuate vein Cortical

nephron

Juxtamedullary
Renal nephron
pyramid

Interlobar vein

Interlobar artery

Minor calyx

b Circulation in a single kidney lobe

• Renal Nerves
– Innervate kidneys and ureters
– Enter each kidney at hilum
– Follow tributaries of renal arteries to individual
nephrons
• Sympathetic Innervation
– Adjusts rate of urine formation
• By changing blood flow and blood pressure at
nephron
– Stimulates release of renin
• Which restricts losses of water and salt in urine
• By stimulating reabsorption at nephron
Figure 26-5c The Blood Supply to the Kidneys.

Renal vein Renal artery

Segmental arteries

Interlobar veins Interlobar arteries

Arcuate veins Arcuate arteries

Cortical radiate veins Cortical radiate arteries

Venules Afferent arterioles

NEPHRONS
Peritubular Glomerulus
capillaries

Efferent
arteriole

c A flowchart of renal circulation

 Average pressures in the renal circulation
Vessel P in vessel P in vessel % of total
(beginning) (end) in RVR
in mmHg mmHg
Renal artery 100 100 =0
Interlobar, arcuate, and 100 85 16
interlobular arteries
Afferent arterioles 85 60 26
Glomeruar capillaries 60 59 1
Efferent arterioles 59 18 43
Peritubular capillaries 18 8 10
Interlobar, interlobular and 8 4 4
arcuate veins
Renal vein 4 4 0
 Differences between glomerular and
peritubular capillary beds
Glomerular capillary Peritubular
bed capillary bed
1 Formed from Formed from the
afferent arterioles efferent arterioles
2 drains into the drains into the
efferent arterioles interlobar veins
3 A high pressure bed A low pressure
that favours filtration bed that favours
reabsorption
 Renal blood flow RBF
• Normally the renal blood flow is about 1200ml/minute
(300-400ml/gm/minute). The flow is much greater in
the renal cortex; only about 2% pass in the vasa recta
resulting in a sluggish flow in the renal medulla which
is important for the process of urine concentration
• kidneys receive an extremely high blood flow
compared with other organs
• The reason for the high flow to the kidney is to help in
GFR and for the regulation of body fluid volume and
solute concentrations
• The renal fraction: this is the portion of the cardiac
output that passes through the kidneys. Normally, it
averages 21% (1200/5600x 100) ranging from 12 to
30%
 Regulation (control) of the RBF
• The RBF is directly proportional to the MABP, and
inversely proportional to the renal vascular resistance
(RVR).
• Catecholamines and strong sympathetic stimulation
cause renal v.c leading to increase RVR and a
decrease in RBF
• Acetylecholine and other V.D drugs decrease the
RVR and increase in RBF
• Prostaglandins increase blood flow in the renal cortex
and decrease it in the renal meduallar
• Angiotensin II causes V.C particularly in the efferent
arterioles leading to a increase of RVR and a decrease
of RBF
 Auto-regulation of RBF
• This is an intrinsic mechanism in the kidney that
keeps the RBF nearly constant despite changes in
the ABP between 90 and 180mmHg
• The GFR is also auto-regulated within this range
but however, beyond that range both are markedly
changed
 Mechanism of auto-regulation of the RBF
1. When the ABP rises from 100 to 180mmHg, constriction
of afferent arterioles occur so the RBF is kept relatively
constant in spite of the increased BP. This is produced by 2
mechanisms
i. Myogenic mechanism: Rise of BP stretches the afferent
arterioles which subsequently constrict by a direct
contractile response of the smooth muscles in the walls to
stretch
ii. Tubuloglomerular feedback mechanism: Rise of BP
increase GF, so the rate of flow through the ascending limb
of LH and the first part of DCT also increases. This
initiates the signal from the macula densa (probably as a
result of the increase of Na+ and K+ conc.) that produces
V.C o f t h e affe re nt a r te r i o l e s ( w h i c h m ay b e by
thromboxane A2)
2. When the ABP falls from 100 to 90mmHg: In
this condition, dilatation of the afferent
arterioles occurs so the RBF is kept relatively
constant in spite of the decreased BP. This is
produced by tubuloglomerular feedback
mechanism. (this is due to the release of
prostaglandin PGI2)
 Measurement of RBF
The RBF can be measured by either
a. Electromagnetic or other types of flow meters
b. Determination of RPF and haematocrit (H) value
Determination of RPF
The RPF is determined by estimating the clearance of either
para-aminohippuric (PAH) acid or diodrast. The clearance
of a substance means the plasma volume that is cleared
from this substance per minute. These substances have the
following xtics.
i. They are nontoxic and can be easily measured
ii. They do not affect the RBF and are not metabolized,
stored or produced by the kidney
iii. They have a peculiar mode of handling in the kidney
 Use of PAH clearance for determining RBF
PAH is i.v injected at a low dose, then the following are measured
i. The volume of urine /minute (V), suppose it is 1ml/minute
ii. The concentration of PAH/ml urine (U), suppose it is 5.85mg/ml
iii. The concentration of PAH/ml plasma, suppose it is 0.01mg/ml
• The amount of PAH that is excreted in urine /minute = (v)x(u)= 1 x
5.85= 5.85mg/minute. Since (P) is 0.01mg/ml, and at this low
concentration, almost all PAH is excreted in urine, then the
excreted amount must be supplied by 5.85 x (v x u)
0.01(P) = 585ml
plasma (which is the RPF/minute)
N.B. (V x U)
(P) is the equation used for the determination of clearance,
and PAH is itself the RPF because almost all plasma is cleared
In fact only about 90% only of PAH in the arterial
plasma is excreted and this percentage is called the
extraction ratio of PAH therefore, RPF represents only
90% of the actual RPF.
585ml/minute represents 90% of the actual RPF and is
called the effective RPF(ERPF). This can be corrected
as follows:
Actual RPF = ERPF x 100 = 585 x 100 = 650ml/minute
90 90
The normal value of RPF is 650-700ml/minute
The use of H in calculating the RBF
• If the measured H is 45%, then the plasma
represents 55% (i.e. 1-H) of the total blood volume.
Consequently, when the actual RPF is 650ml/minute,
the RBF will be:
RBF = 650 x 1 = 650 x 1 = 1182ml/minute
1-H 0.55 (the normal value of
RBF is 1200-1300ml/minute)
N.B. the extraction ratio of diodrast is about 85%,
since the same rate for PAH is higher (about 90%),
PAH clearance is more commonly use for
determination of the RBF
 Renal oxygen consumption
• The renal cortical blood flow is relatively great and little
oxygen is extracted from the blood. Cortical blood flow is
abou t 5 m l /g o f k i d n ey t i s s u e / m i n ( co m p a re d w i t h
0.5ml/g/min in the brain)
• The arteriovenous oxygen difference for the whole kidney is
only 14ml/L of blood compared with 62ml/L for the brain
and 114ml/L for the heart
• Maintenance of the osmotic gradient in the medulla requires
a relatively low blood flow
• Blood flow is about 2.5ml/g/min in the outer medulla and
0.6ml/g/min in the inner medulla
• Metabolic work is being done particularly to
reabsorb Na+ in the thick ascending limb of
LH so relatively large amounts of oxygen are
extracted from the blood in the medulla
• The medulla is vulnerable to hypoxia due to
low PO2 (15mmHg)
• NO, protaglandins and many cardiovascular
peptides in this region function in a paracrine
fashion to maintain the balance between low
blood flow and metabolic needs
 Urine Formation I: Glomerular
Filtration
• Objectives
When you have completed this section, you should be
able to:

• describe the glomerular filtration membrane and how it

excludes blood cells and proteins from the filtrate

• explain the forces that promote and oppose glomerular

filtration, and calculate net filtration pressure if given the
magnitude of these forces

• describe how the nervous system, hormones, and the

kidney itself regulate glomerular filtration
 Urine Formation I
• The kidney converts blood plasma to urine in three
stages:
I. glomerular filtration
II. tubular reabsorption and secretion,
III. water conservation
• As we trace fluid through the nephron, we will refer to it
by different names that reflect its changing composition:
1. The fluid in the capsular space, called glomerular
filtrate, is similar to blood plasma except that it has
almost no protein.
2. The fluid from the proximal convoluted tubule through
the
distal convoluted tubule will be called tubular fluid.
• It differs from the glomerular filtrate because of
substances removed and added by the tubule cells.
 GLOMERULAR FILTRATION
• Glomerular filtration is the process by which the
blood that passes through the glomerular
capillaries is filtered through the filtration
membrane.
• It is the first process of urine formation
Filtration membrane (glomerular membrane)
• The glomerular capillary membrane
• Basement membrane
• Visceral layer of bowman’s capsule
• When blood passes through the glomerular
capillaries, the plasma is filtered into the
Bowman’s capsule
• All the substances of plasma are filtered except
the plasma proteins.
• The filtered fluid is called glomerular filtrate
Structure of the Glomerulus
GLOMERULAR FILTRATION RATE
(GFR).
• GFR is defined as the total quantity of filtrate
formed in all the nephrones of both the kidneys
in the given unit of time
• The normal GFR is 125ml/min or about
180L/day
Filtration fraction: it is the ratio between renal
plasma flow and glomerular filtration rate. It is
express in % ( F.F = GFR x100)
RPF
 Factors that favors GFR
• High pressure in the glomerular capillaries
(about 55mmHg)
• Large surface area of the glomerular capillaries,
which is normally about 0.8square meters
• The high permeability of the glomerular
membrane
 Mechanism and dynamics of GF
Glomerular filtration is a passive process
Filtration forces:
• Hydrostatic glomerular capillary pressure (GCP)
55mmHG
• Colloid osmotic (oncotic) pressure (COP) in
Bowman’s capsule it is practically zero
Opposing forces: These antagonize the filtering
forces, and include
• Colloid osmotic pressure in the glomerular
capillaries (GOP), it is normally 30mmHg
• Intracapsular hydrostatic pressure (CP): This is the
pressure of the fluid in Bowman’s capsules, and is
normally about 15mmHg
 Net filtration pressure (NFP)
• This is the driving force for glomerular
filtration and it equals the algebraic sum of
hydrostatic and colloid osmotic pressures
across the glomerular membrane.
NFP = (GCP + COP) – (GOP + CP) = (55+0)-
(30+15)= 10mmHg
Starling forces
 Characteristics and composition of the GF
The GF has the same properties as the plasma:
• pH is 7.4
• Specific gravity: 1010
• Osmolality: 300mOsm/L
• Water and freely filtered substances at equal
concentration to plasma (e.g. glucose, urea,
creatinine, electrolyte and amino acids)
However, it differs from the plasma in the following:
• Trace of proteins (0.03%) particularly albumin
• The non protein anions are 5% greater than in the
plasma
 Characteristics of substances used for
measuring the GFR
• They should be of a small size and not bound to
plasma proteins
• They should be standard substances
• They should be non toxic, not metabolized in
the body, not stored in the kidney, easy to
measure in the plasma and urine and have no
effect on GFR
• e.g. of such substances are: inulin, mannitol
and radioactive iothalamite
 Significance of inulin clearance
determination
• It measures the GFR
• It is used as a reference value: substances
having lower clearances than that of inulin (e.g
urea) means that they are reabsorbed in the
renal tubules while those having higher
clearances (e.g creatinine) means that they are
secreted by the renal tubules
 Factors that affect the GFR
i. Renal blood flow (RBF): The GFR is generally
directly proportional to the RBF
ii. GFR is generally directly proportional to the
GCP, which is affected by the following:
afferent arteriolar diameter, efferent arteriolar
diameter, sympathetic stimulation, ABP
iii. GFR is reduced when the glomerular surface
area available for filtration is decreased: this
occurs due to decrease functioning of the
kidney mass (as in chronic renal failure)
iv. GFR is directly proportional to the glomerular
capillary permeability. The renal glomerular
capillary permeability is increased in nephritis,
fevers and hypoxia
v. GFR is inversely proportional to the plasma
oncotic pressure (GOP). Thus an increase in the
GOP (due to dehydration) reduces the GFR, while
a decrease in the GOP (due to hypoproteinaemia)
increases GFR
vi. GFR is directly proportional to Bowman’s
intracapsular pressure (CP). Thus an increase in
the CP (e.g. due to stone in the ureter) reduces the
GFR (which stops completely if the CP increases
to 28mmHg
 Autoregulation of the GFR
• This is an intrinsic mechanism in the kidney
that keeps the GFR nearly constant despite
changes in the ABP between 90 and 180mmHg
• Excessive decrease in GFR leads to inefficient
elimination of waste products
• If GFR is much increased essential substances
will be lost in the urine
 Clinical Application
• Edema
• Some kidney diseases result in a damage of
the glomerular Capillaries leading to an
increase in their permeability to large
proteins .
• Hence, Bowman’s capsule colloid pressure
will increase significantly leading to drawing
more water from plasma to the capsule (i.e
more filtered fluid).
• Proteins will be lost in the urine causing
deficiency in the blood colloid pressure
which worsens the situation, blood volume
decreases and interstitial fluids increases
causing edema.
Regulation of Glomerular Filtration

• Homeostasis of body fluids requires constant

GFR by kidneys.
• 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

• GFR is directly related to the pressures that

determine NFP.
• Filtration ceases (become zero) if glomerular
hydrostatic pressure drops to 45 mmHg
However, NFP is increased very little when MAP
rises. GFR is nearly constant if MAP is 80-180
mmHg
Regulation of Glomerular Filtration

• Control of GFR normally result from adjusting

glomerular capillary blood pressure
• 3 mechanisms control the GFR
1. Renal autoregulation (intrinsic system)
2. Neural controls
3. Hormonal mechanism
 Effect of afferent and efferent arteriolar
constriction on glomerular pressure

Ra Re
PG PG
Blood Blood
Flow GFR Flow GFR

Ra GFR + Renal Re GFR + Renal

Blood Blood
Flow Flow
 Regulation of Glomerular Filtration
• Renal Autoregulation of GFR
– Under normal conditions (MAP =80-180mmHg)
renal autoregulation maintains a nearly constant
glomerular filtration rate
– 2 mechanisms are in operation for autoregulation to
adjust Renal blood flow and Glomerular surface area:
1. Myogenic mechanism:
– Arterial pressure rises, afferent arteriole stretches
– Vascular smooth muscles contract
– Increased arteriole resistance offsets pressure increase; RBF (&
hence GFR) remain constant.
– Opposite is true, when Arterial pressure drops, afferent arterioles
stretch less and smooth muscles relax.
 Renal Autoregulation of
GFR
2. Tubuloglomerular
feed back mechanism:
• Feedback loop consists of a flow
rate (increased NaCl in filtrate)
sensing mechanism in macula
densa of juxtaglomerular
apparatus (JGA)
• Increased GFR (& RBF) inhibits
release of the vasodilator ; Nitric
Oxide (NO) and stimulates renin
that leads to Ang II
production(vasoconstrictor)
• Afferent arterioles constrict
leading to a decreased GFR (&
RBF).
 Neural Regulation
• When the sympathetic nervous system is at rest; very low:
– Renal blood vessels are maximally dilated
– Autoregulation mechanisms prevail
• Under stress:
– Norepinephrine is released by the sympathetic nervous system
– Epinephrine is released by the adrenal medulla
– Afferent arterioles(Mainly) constrict (more than efferent)
and filtration is inhibited (GFR drops)
• The sympathetic nervous system also stimulates the renin-
angiotensin mechanism.
• Sympathetic stimulation causes reduction in urine out
put and permits greater blood flow to other vital organs.
• Under moderate sympathetic stimulation both afferent and
efferent arterioles constricts to same degree so GFR would
not be affected.
 Hormonal Regulation
Renin-Angiotensin Mechanism
• A drop in filtration pressure stimulates the
Juxtaglomerular apparatus (JGA) to release renin.
• Renin-Angiotensin Mechanism
• Renin acts on angiotensinogen to release
angiotensin I which 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
 Renin secretion regulation
Juxtaglomerular
apparatus
1- Perfusion Pressure
Glomeruli
low perfusion in afferent arterioles
stimulates renin secretion while high JG cells:
perfusion inhibits renin secretion. Secretes renin

2-Sympathetic nerve activity

Activation of the sympathetic nerve fibers
in the afferent arterioles increases renin
secretion.
Macula Densa:
3- NaCl delivery to macula densa: sensor cells
When NaCl is decreased, Renin Tubuloglomerular
secretion is stimulated and vice versa. Feedback
(Tubuloglomerular Feedback)
 Hormonal Regulation
Atrial Natriuritic Peptide ANP

• (ANP) release is stimulated from the atrium

under increased pressure/volume.
ANP causes:
• Vasodilation of the afferent arterioles
• Inhibition of Renin secretion
• Inhibition of aldosterone and ADH secretion
 Mechanism of autoregulation
1. When the ABP rises from 100 to 180mmHg: In
this condition, constriction of afferent arterioles
occurs, so both the RBF and GFR are kept
relatively constant in spite of the increased ABP
2. When the ABP falls from 100 to 90mmHg: in
this condition, V.D of the afferent arterioles and
V.C of the efferent arterioles occur. The former
increases the RBF while the later increases the
renal vascular resistance (RVR), and both effects
tend to increase the GCP, so the GFR is kept
relatively constant in spite of the decreased ABP
Response to a Reduction in the GFR
Response to a Reduction in the GFR
 Fate of glomerular filterate
• In the renal tubules, the glomerular filtrate is
changed to urine through the process of
reabsorption and secretion as follows:
1. Reabsorption: this process is either passive or
active process
2. Secretion: this process is almost only active,
and the secreted substances may be derived
from blood stream e.g. creatinine and K + or
synthesized in the tubular cells then secreted
e.g. H+ and NH3
 Reabsorption
• 99% of the glomerular filtrate are reabsorbed
• matter reabsorbed:
all glucose, amino acid
mineral salts
other useful substances
SELECTIVE REABSORPTION
• Method of reabsorption
diffusion  active transport
 The proximal convoluted tubules (PCT)
• Most of the renal tubular activities reabsorption
and secretion of various substances takes place in
the PCTs
• The PCTs are lined by highly metabolic epithelial
cells which contains enzymes and carrier proteins
that catalyzes the various processes and it is rich in
mitochondria which supplies the energy necessary
for the active transport processes
 Functions of the PCTs
A. Absorption: The following substances are absorbed in the
PCTs glucose, amino acids, vitamins and proteins are only
absorbed in the PCTs almost completely by active,
processes
B. About 65% of Na+ and a larger amount of K+ are actively
absorbed in the PCTs
C. About 65% of water in the glomerular filtrate is passively
absorbed in the PCTs
D. About 65% of Cl- is passively absorbed in the PCTs
E. HCO 3 - is completely reabsorbed in the PCTs in normal
conditions of metabolism and in cases of acidosis
F. About 50% of filtered urine is passively absorbed in the
PCTs
G. Uric acid is absorbed passively only in the
PCTs, and it is also slightly secreted
H. Phosphate is absorbed mostly by an active
process and this process is inhibited by
parathyroid hormone
I. About 60% of filtered calcium ion is absorbed
in the PCTs either by active transport or passive
diffusion
 The net absorption pressure (NAP)
This is the driving force for reabsorption in the PCTs, and it
is determined by the forces that act across the peritubular
capillaries: these are
Forces that favours absorption:
i. Colloid osmotic pressure in the PTCs (32mmHg)
ii. Hydrostatic pressurre of the interstitial fluid (6mmHg)
Forces that oppose absorption
i. Hydrostatic pressure in the PTCs (13mmHg)
ii. Colloid osmotic pressure in the interstitial fluid
(15mmHg)
iii. NAP = (32+6) – (13+15) = 10mmHg
2. secretion: this is an active process that
transports substances into the lumens of the
PTCs. The most important secreted substances
are: creatinine, uric acid H+ foreign substances
e.g. PAH and penicillin
3. Synthesis: the cells of the PCTs synthesize and
secrets NH3 that plays important role in acid
base balance
Transport Activities at the PCT (Part 2 of 2).

Tubular fluid

Cells of
proximal
convoluted
tubule

Glucose
and other
organic
solutes Osmotic
water
flow

Peritubular
fluid

KEY
Peritubular
Leak channel capillary
Diffusion
Countertransport
Reabsorption
Exchange pump

Cotransport Secretion
 Mechanisms of renal tubular transport
• The transport processes in the tubules include
both reabsorption and secretion of various
substances
• The reabsorptive processes may be passive or
active, whereas the secretory processes are
mostly active
• There are 2 mechanisms of active transport, a
primary and a secondary active transport
mechanism
 Glomerulotubular balance (GTB)
• An increase in the GFR causes an increase in
the reabsorption of solutes (and consequently
water) primarily in the PCTs, so that generally
the % of the solute absorbed is held constant
• This process is called GTB, and is prominent
for Na+ (indicating that the renal tubules
reabsorbs a constant fraction of the filtered Na+
rather than a constant amount)
• Na+ is the only substance that is transported by
primary active transport in the PCT other
substances are transported by secondary active
transport or diffusion
 Secondary active transport
• The energy of secondary active transport is not
directly provided by breakdown of ATP.
• Instead, it is provided by the active transport of
Na+ out of the renal tubular cells into the
interstitial fluid
• Secondary active transport is Na+ dependent
since it is coupled with Na+ reabsorption, and
such coupled transport is 2 types
i. co-transport (e.g. glucose or amino acids)
ii. Counter-transport (e.g. H+ )
 Glucose and amino acid reabsorption
• This is usually complete in normal conditions
and occurs only in the PCTs by secondary
active transport.
• Both glucose and Na+ are co-transported into
the cells by binding to symport carrier called
SGLT
• Amino acids are absorbed only in the PCTs and
by same mechanism of glucose reabsorption.
• The symport carriers involved are different and
each amino acid seems to have its specific
carrier
 Calcium and phosphate reabsorption
• About 98-99% of filtered calcium is reabsorbed in
the renal tubules (60% in the PCTs and the
remainder in the ascending limbs of the LH and
the late DCTs)
• Ca++ reabsorption in the DCTs is by secondary
active transport while in the PCTs and LH it is by
either secondary active transport or passive
diffusion down the electrochemical gradient
• Phosphate is reabsorbed only in the PCTs mostly
by primary active transport, and it is inhibited by
parathyroid hormone
 Fanconi’s syndrome
• This syndrome occurs secondary to a decrease in
ATP in the cells of the PCTs (often as a result of
certain toxins or a congenital abnormality).
• This causes a decrease in Na+ reabsorption, and
consequently, impairment of secondary active
transport of other substances
Manifestations
i. Metabolic acidosis
ii. Glucosuria
iii. Amino aciduria
iv. Phosphaturia
 Tubular transport maximum ™
• Tm of a substance is the maximal amount of this
substance that can be transported by the tubular
cells per minute. Such transport can be
reabsorption e.g. glucose or sectretion e.g. PAH
and creatinine
• This is carried out by gradually increasing the
concentration of the substance in the blood, and
each time the amount transported is measured till
maximal transport is attained
• Tm glucose= 375mg/min in males and 300mg/min
in females
• Tm protein = 30mg/min, Tm PAH = 80mg/min,
Tm creatinine = 16mg/min
 Renal threshold of glucose
• Renal threshold of glucose is the plasma
glucose level at which glucose starts to appear
in the urine
• It is normally about 180mg%.
• At this level the filtered amount of glucose is
about 225mg/min, but although this amount is
far less than the normal TmG (375mg/min), yet
glucosuria occurs.
 Sites of reabsorption
 Loop of Henle
~ conserve water in terrestrial mammal
~ creates & maintain an increasing osmotic
gradient in the medulla
~ Na+ in medulla vigorous osmotic
extraction of water from collecting ducts
hypertonic urine
Formation of hypertonic urine
 Sites of reabsorption
 Vasa recta
~ narrow capillaries situated close to loop of
Henle
~ freely permeable to ions, urea & water
~ Counter current exchanger system
 Sites of reabsorption
 Distal convoluted tubule
~ fine control of salt, water & pH balance of the
blood
 Collecting duct
~ water is extracted by osmosis conc.
hypertonic urine
 The renal counter current mechanism
• The countercurrent system is a system of ‘U’ shaped
tubules in which, the flow of fluid is in opposite
direction in two limbs of the ‘U’ shaped tubules.
• Is the mechanism by which urine is concentrated in the
kidney.
• It depends on the production and maintenance of a state
of hyperosmolality (hypertonicity) in the renal
medullary interstitium (MI)
• This is through the action of structures that pass in the
renal medulla which include the following:
a. LH of the juxtamedullary nephrons: this constitute a
counter current multiplier system
b. The vasa recta (VR)these constitute a counter current
exchanger system
c. The medullary collecting duct (MCD)
 The counter current multiplier system
• This system consist of the LH of the juxtamedullary
nephrons which dips deeply in the renal medulla
• It is concern with the production of graded
hy p e ro s m o l a l i t y i n t h e M I by t h e u n d e r l i ste d
mechanisms
i. The descending limb of LH receives isotonic fluid
from the PCTs and their walls are highly permeable to
water and poorly soluble to Na+, Cl- and urea.
• Water diffuses outward down an osmotic gradient into
the MI
• As a result the tubular fluid becomes hypertonic and the
hypertonicity increases gradually as it follows
downwards reaching 1200 (up to 1400mOsm/L at the tip
of the renal pyramids
 The counter current multiplier system
ii. The ascending limbs of the LH are the segments responsible
for creating graded hyperosmolality in the MI.
• They receive hypertonic fluid from the descending limbs
• The initial thin part is impermeable to water and poorly-
permeable to urea but highly permeable to Na+ and Cl
• Na+ and Cl- diffuses passively into the MI and
hyperosmolality is developed in the MI
• The distal thick part is impermeable to water and poorly-
permeable to all solutes.
• Both Na+ and Cl- are actively transported from the tubular
lumen into the MI.
• This produces hyperosmolality in the MI and the tubular
fluid becomes hypotonic with an osmolality of about 150 to
100 mOsm/L
Figure 26-13b Countercurrent Multiplication and Urine Concentration.

Thin
descending
limb
(permeable
to water;
impermeable
to solutes)

KEY Thick
Impermeable to water
ascending limb
(impermeable
Impermeable to solutes
to water;
Impermeable to urea; active solute
variable permeability to water transport)
Permeable to urea

Renal medulla

b Transport of NaCl along the ascending thick limb results

in the movement of water from the descending limb.
 Causes of hyperosmolality of the MI
i. Na+ and Cl- transported from the ascending limbs
of LH and at the upper thick parts of the LH
ii. Small amounts of Na+ and Cl- transported from
the MCT
iii. Urea: the MCDs are partially permeable to urea at
the PCTs and they become highly permeable to
urea in the presence of ADH
• Importance of hyperosmolality of MI
• It is essential for urine concentration because it
leads to passive water reabsorption from the
medullary collecting ducts
 The vasa recta
• The main function of the vasa recta is to maintain the MI
hyperosmolality. This is achieved by operating as a
countercurrent exchanger system which:
• Provides a trapping mechanism for NaCl and urea in the MI
• Removes excess water from the MI. such effects occurs as
follows:
i. The solutes diffuses from the MI into the blood while water
diffuses from the blood into the MI in the descending limb
(so the blood osmalality rises)
ii. The solutes diffuse from the blood into the MI while water
diffuses from the MI to the blood in the ascending limb
(the blood osmolality falls)
• The solutes are trapped in the MI by continuous recirculation
while excess water is removed from it, and both effects help
in the maintenance of the MI hyperosmolality
14-31b
Counter current exchange system
Reabsorption of Bicarbonate and Secretion of H+

• The cells of the proximal tubule use Na+/H+ pumps to

transport H+ into the filtrate in exchange for Na+ from the
filtrate
• This exchange is “antiport” cotransport because the Na+ and
H+ move in opposite directions across the apical portion of the
plasma membrane.
• Antiport cotransport is a form of secondary active transport,
• In this case Na+ diffuses down the concentration gradient
maintained by primary active transport Na+/K+ pumps in the
basolateral portion of the plasma membrane.
• Most of the H+ secreted into the filtrate this way from the
proximal tubule is used for the reabsorption of bicarbonate.
Reabsorption of Bicarbonate and Secretion of H+

• The apical membranes of the tubule cells (facing the

lumen) are impermeable to bicarbonate.
• The reabsorption of bicarbonate must therefore occur
indirectly.
• When the urine is acidic, HCO3– combines with H+ to
form carbonic acid.
• Carbonic acid in the filtrate is then converted to CO2
and H2O in a reaction catalyzed by carbonic anhydrase.
• This enzyme is located in the apical cell membrane of
the proximal tubule in contact with the filtrate.
 Reabsorption of Bicarbonate and Secretion of H+

• The tubule cell cytoplasm also contains carbonic

anhydrase.
• As CO2 concentrations increase in the filtrate, the CO2
diffuses into the tubule cells.
• Within the tubule cell cytoplasm, carbonic anhydrase
catalyzes the reaction in which CO2 and H2O form
carbonic acid.
• The carbonic acid then dissociates to HCO3– and H+
within the tubule cells.
• The bicarbonate within the tubule cell can then diffuse
through the basolateral membrane and enter the blood
Acidification of the urine
 Reabsorption of Bicarbonate and Secretion of H+

• Under normal condition, the proximal tubule reabsorbs

80% to 90% of the filtered bicarbonate.
• This process of HCO3– reabsorption in the proximal
tubule leaves very little H+ in the filtrate.
• Despite this, urine is usually more acidic than blood
plasma.
• This is because the distal tubule secretes H+ into the
filtrate using primary active transport H+ (ATPase) pumps
• This activity is primarily responsible for the acidification
of the urine.
• The H+ in the urine is mostly buffered by ammonium and
phosphate buffers.
 Reabsorption of Bicarbonate and Secretion of H+

• If a person has alkalosis, less H+ is present in the filtrate, so

that less HCO3– is reabsorbed; the resulting urinary excretion
of HCO3– then helps to compensate for the alkalosis.
• If a person has acidosis, the proximal tubule cells can make
extra bicarbonate—over that which is reabsorbed from the
filtrate—that can enter the blood.
• This extra HCO3– comes from the metabolism of a molecule
called glutamine.
• In this process, HCO3– is formed and released into the blood,
while ammonia (NH3) and ammonium ion ( NH+4 ) are
produced and enter the filtrate.
• The extra bicarbonate produced by the kidneys helps
compensate for the acidosis, while ammonia serves as a
urinary buffer
 Reabsorption of Bicarbonate and Secretion of H+

• By these mechanisms, disturbances in acid-

base balance caused by respiratory problems
can be partially compensated for by changes in
plasma bicarbonate concentrations.
• Metabolic acidosis or alkalosis—in which
changes in bicarbonate concentrations occur as
the primary disturbance
• Similarly can be partially compensated for by
changes in ventilation.
Acidification of the urine
Categories of Disturbances in Acid-Base Balance
RENAL CONTROL OF ELECTROLYTE AND ACID-BASE BALANCE

• The kidneys regulate the blood concentrations of Na+, K+,

HCO3– and H+ and thereby are responsible for maintaining the
homeostasis of plasma electrolytes and the acid-base balance.
• Renal reabsorption of Na+ and secretion of K+ and H+ are
stimulated by aldosterone.
• The kidneys help regulate the concentrations of plasma
electrolytes—sodium, potassium, chloride, bicarbonate, and
phosphate
• They do so by matching the urinary excretion of these
compounds to the amounts ingested.
• The control of plasma Na+ is important in the regulation of
blood volume and pressure;
• The control of plasma K+ is required to maintain proper
function of cardiac and skeletal muscles.
 Role of Aldosterone in Na+/K+
Balance
• Approximately 90% of the filtered Na+ and K+ is
reabsorbed in the early part of the nephron before the
filtrate reaches the distal tubule.
• This reabsorption occurs at a constant rate and is not
subject to hormonal regulation.
• The final concentration of Na+ and K+ in the urine is
varied according to the needs of the body by processes that
occur in the late distal tubule and in the cortical region of
the collecting duct
• Renal reabsorption of Na+ and secretion of K+ are
regulated by aldosterone, the principal mineralocorticoid
secreted by the adrenal cortex
 Role of Aldosterone in Na+/K+
Balance
• The kidneys help regulate the blood pH by excreting H+ in
the urine and by reabsorbing bicarbonate.
• Because the kidneys normally reabsorb almost all of the
filtered bicarbonate and excrete H+,
• Normal urine contains little bicarbonate and is slightly
acidic (with a pH range between 5 and 7).
• The mechanisms involved in the acidification of the urine
and reabsorption of bicarbonate