RENALS LECTURE.pptx

RENAL PHYSIOLOGY
BY
Mahan Josiah Mallo
Department of Physiology
Bingham University, Karu
1

Figure 26-1 An Introduction to the Urinary System.
Kidney
Ureter
Urinary bladder
Urethra
Organs of the
Urinary System
Produces urine
Transports urine
toward the
urinary bladder
Temporarily stores
urine prior
to urination
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
3

Structure of the urinary system
4

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
5

Figure 26-4a The Structure of the Kidney.
Ureter
Inner layer of
fibrous capsule
Hilum
Renal pelvis
Renal sinus
Adipose tissue
in renal sinus
Renal papilla
Minor calyx
Renal pyramid
Fibrous capsule
Major calyx
Connection to
minor calyx
Renal medulla
Renal columns
Renal cortex
Kidney lobe
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
9

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.
10

• 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
11

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.
12

Parts of the renal tubule
i. Proximal convoluted tubule (PCT): this is the first part of the
tubule and it’s length averages 15mm it’s wall is made up of
single layer of epithelial cells united by tight junctions also, 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. 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.
14

• About 8DCTs coalesce forming a cortical
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)
15

• 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
The epithelium of CD is made up of 2 types of cells
i. The Principal (P) cells: The P cells 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
16

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%
of the total number of nephrons. Their LH
penetrates only a short distance into the outer part
of the medulla
ii. Juxtamedullary nephrons: these have their
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 17

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
18

Stimulants for renin secretion
i. Fall in arterial BP
ii. Reduction in ECF volume
iii. Increased sympathetic activity
iv. Decreased load of Na and Cl in macula densa
19

The renin angiotensin system
• Renin when released, converts
angiotensinogen into angiotensin I which then
converts into angiotensin II which is an
octapeptide. The conversion is by the activity
of ACE secreted from the lungs.
• Angiotensin II is usually rapidly converted to
Angiotensin III then IV by angiotensinases
20

Actions of angiotensin II
i. On blood vessels it causes vasoconstriction and
also stimulates the release of noradrenaline
ii. On the adrenal cortex it stimulates the release
of aldosterone which causes retention of Na
iii. On the kidney it constricts the efferent
arterioles and also increases Na reabsorption
iv. On the brain it inhibits the baroreceptor reflex,
increases water intake by stimulating the thirst
center and it increases the secretion of CRH
from the hypothalamus
21

Figure 26-8a The Renal Corpuscle.
Efferent arteriole
Macula densa
Afferent arteriole
Distal convoluted
tubule
Juxtaglomerular
cells
Juxtaglomerular
complex
Capsular
space
Glomerular
capillary
Capsular
epithelium
Visceral
epithelium
(podocyte)
Glomerular capsule
Proximal
convoluted
tubule
Important structural features of a renal corpuscle.
a

Renal nerves
• The renal nerves travel along the renal blood vessels as
they enter the kidney.
i. Efferent nerves: The kidneys receives mostly
sympathetic efferent nerves from the greater
splanchnic nerve. Cholinergic innervations via the
vagus nerve also appear to be present but its
function is uncertain. The sympathetic fibres are
distributed to: glomerular arterioles, PCT and DCT,
the 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)
23

Functions of the kidney
A. EXCRETORY/HOMEOSTATIC FUNCTIONS
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+
24

iii. Maintenance of water balance
iv. Maintenance of electrolyte balance
v. Maintenance of acid-base balance
B. HAEMOPOIETIC FUNCTION
i. The kidneys stimulate the production of
RBCs by secreting erythropoietin
ii. The kidneys also secretes thrombopoietin,
which stimulates the production of
thrombocytes
25

C. 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 PGs 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 26

D. REGULATION OF BLOOD PRESSURE
The kidneys regulates arterial blood pressure in 2
ways:
i. The regulating the ECF volume
ii. Through renin-angiotensin mechanism
E. REGULATION OF BLOOD CALCIUM LEVEL
The kidneys play a role in the regulation of
blood calcium level by activating 1, 25-
dihydroxycholecalciferol into vitamin D which is
essential for the absorption of calcium from the
intestine.
27

Mechanism of urine formation
• Urine is formed as a result of filtration of plasma in the
glomeruli (i.e. glomerular filtration), then 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.
28

• 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)
29

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
30

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
31

Renal circulation
• The kidney receives arterial blood via the
renal artery which arises directly from the
aorta.
33

RENAL BLOOD FLOW (RBF) AND
GLOMERULAR FILTRATION RATE (GFR)
BY
Mahan Josiah Mallo
Department of Human Physiology
Faculty of Basic Medical Sciences
Bingham University, Karu

OBJECTIVES
At the end of the lecture the students should be
able to:
i. To describe the blood supply to the kidney, the
various blood vessels involved in renal
circulation and their pressures
ii. Differentiate between glomerular and
peritubular capillaries
iii. Describe the various mechanisms involved in
the regulation of renal blood flow
iv. Describe the measurement of RBF

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

Interlobar
arteries
Interlobar
veins
Cortical
radiate
arteries
Cortical
radiate
veins
Arcuate
veins
Cortex
Medulla
Arcuate
arteries
Renal
artery
Renal
vein
Adrenal
artery
Segmental
artery
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.
Interlobar artery
Interlobar vein
Cortical radiate artery
Cortical radiate vein
Cortical
nephron
Juxtamedullary
nephron
Afferent
arterioles
Arcuate vein
Arcuate artery
Renal
pyramid
Glomerulus
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

Renal artery
Renal vein
Segmental arteries
Interlobar arteries
Arcuate arteries
Cortical radiate arteries
Afferent arterioles
Venules
Cortical radiate veins
Arcuate veins
Interlobar veins
Efferent
arteriole
Glomerulus
Peritubular
capillaries
NEPHRONS
A flowchart of renal circulation
c

Average pressures in the renal circulation
Vessel P in vessel
(beginning)
in mmHg
P in vessel
(end) in
mmHg
% of total
RVR
Renal artery 100 100 =0
Interlobar, arcuate, and
interlobular arteries
100 85 16
Afferent arterioles 85 60 26
Glomeruar capillaries 60 59 1
Efferent arterioles 59 18 43
Peritubular capillaries 18 8 10
Interlobar, interlobular and
arcuate veins
8 4 4
Renal vein 4 4 0

Differences between glomerular and
peritubular capillary beds
Glomerular capillary
bed
Peritubular capillary
bed
1 Formed from
afferent arterioles
Formed from the
efferent arterioles
2 drains into the
efferent arterioles
drains into the
interlobar veins
3 A high pressure bed
that favours
filtration
A low pressure
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
• Acetylcholine 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 an increase in RVR and a
decrease in 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 of the afferent arterioles (which may be 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 x1 (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 about 5ml/g of kidney tissue/min
(compared with 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

Glormerular Filtration Rate (GFR)

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

• 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 favours 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

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

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

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, seesential 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.

• 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

• 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

• 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
1- Perfusion Pressure
low perfusion in afferent arterioles
stimulates renin secretion while high
perfusion inhibits renin secretion.
2-Sympathetic nerve activity
Activation of the sympathetic nerve fibers
in the afferent arterioles increases
renin secretion.
3- NaCl delivery to macula densa:
When NaCl is decreased, Renin
secretion is stimulated and vice versa.
(Tubuloglomerular Feedback)
Glomeruli
Macula Densa:
sensor cells
Tubuloglomerular Feedback
Juxtaglomerular
apparatus
JG cells:
Secretes renin

• (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
Hormonal Regulation
Atrial Natriuritic Peptide ANP

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
by 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+
3. 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. HCO3
- 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).
Cells of
proximal
convoluted
tubule
Glucose
and other
organic
solutes
Tubular fluid
Osmotic
water
flow
Peritubular
fluid
Peritubular
capillary
KEY
Leak channel
Countertransport
Exchange pump
Cotransport
Diffusion
Reabsorption
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 secretion 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, and 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

 Vasa recta
~ narrow capillaries situated close to loop of
Henle
~ freely permeable to ions, urea & water
~ Counter current exchanger system

 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) by 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
hyperosmolality in the MI by the under listed
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

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)
Renal medulla
Thick
ascending limb
(impermeable
to water;
active solute
transport)
KEY
Impermeable to water
Impermeable to solutes
Impermeable to urea;
variable permeability to water
Permeable to urea
Transport of NaCl along the ascending thick limb results
in the movement of water from the descending limb.
b

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

Counter current exchange system

RENALS LECTURE.pptx

More Related Content

Similar to RENALS LECTURE.pptx

Recently uploaded

RENALS LECTURE.pptx