Dilution and concentration of urine

1. DESCRIPTION OF KIDNEY
FUNCTION
 From elementary knowledge, the kidney rids the
body of waste product of metabolism
 A second and very critical function is the
regulation of the volume and composition of the
body fluids.
 The above is achieved by balancing the intake
and output of the constituents of the internal
environment (Homeostasis) i.e water and virtually
all electrolytes
 The kidneys perform their most important
functions by filtering the plasma and removing
substances from the filtrate at variable rates,
depending on the needs of the body.

2. Structure of the Kidney……1
Each kidney of the adult human
weighs about 150grams and is
about the size of a clenched fist.
 The medial side of each kidney
contains an indented region
called the hilum
 The kidney is surrounded by a
tough, fibrous capsule that
protects its delicate inner
structures.
 The kidney has two regions, an
outer cortex and the inner
medulla

3. Renal Blood Supply
Blood flow to the two kidneys is normally about
22 per cent of the cardiac output, or 1100
ml/min

4. The Nephron
 The functional unit of the
kidney is the nephron
 Each kidney in the human
contains about 1 million
nephrons, each capable of
forming urine.
 The kidney cannot regenerate
new nephrons.
 Each nephron contains a tuft of
glomerular capillaries called the
glomerulus, and a long renal
tubule
 The glomerulus contains a
network of branching and
anastomosing glomerular
capillaries that have high
hydrostatic pressure (about 60

5. Structure of the Glomerulus
 is about 200 μm in diameter
 two cellular layers (Filtration
Barrier) separate the blood from
the glomerular filtrate in Bowman’s
capsule: the capillary endothelium
and the specialized epithelium of
the capsule(podocyte)
 filters several hundred times more
water and solutes than the usual
capillary
 High filtration rate due to several
thousand fenestrae 70–90 nm in
diameter
 Endothelialcells and proteoglycans
of the BM have strong negative
charges that repel plasma proteins
 Podocytes have foot like processes
called pedicels that interdigitate to
form slit pores(25nm wide)

6. proximal convoluted tubule
 is about 15 mm long and 55 μm in diameter.
 wall is made up of cells united by apical tight junctions
Loop of Henle
 descending portion of the loop(DTL) and the proximal portion
of the ascending limb(ATL) are made up of thin, permeable
cells
 The thick portion of the ascending limb(TAL) reaches the
glomerulus of the nephron from which the tubule arose and
nestles between its afferent and efferent arterioles.
 Specialized cells at the end of the TAL form the macula densa
 The macula, the neighboring lacis cells, and the renin-
secreting granular cells in the afferent arteriole form the
juxtaglomerular apparatus

7. Distal convoluted tubule
 starts at the macula densa, and is 5 mm long.
 epithelium is lower than that of the proximal tubule
 possess a few microvill
Collecting ducts
 distal tubules coalesce to form the collecting ducts which is
20mm in diameter
 The initial parts of 8 to 10 cortical collecting ducts join to form
a larger collecting duct that runs downward into the medulla
and becomes the medullary collecting duct
 The collecting ducts merge to form progressively larger ducts
that empty into the renal pelvis
 The epithelium of the collecting ducts is made up of principal
cells (P cells) and intercalated cells (I cells).

8. Cortical and Juxtamedullary nephrons
A) Cortical Nephrons
 Glomeruli are located in the outer cortex
 have short loops of Henle that penetrate only a short
distance into the medulla
 entire tubular system is surrounded by an extensive
network of peritubular capillaries
B) Juxtamedullary Nephrons
 glomeruli lie deep in the renalcortex near the medulla
 have long loops of Henle that dip deeply into the medulla
 Loop of Henle is surrounded by specialized peritubular
capillaries called vasa recta
 Play an essential role in the formation of concentrated
urine

9. Structure of Cortical and Juxtamedullary
nephrons

10. Nerve supply to the kidney
 The renal nerves travel along the renal blood
vessels as they enter the kidney.
 contain many postganglionic sympathetic efferent
fibers and a few afferent fibers.
 sympathetic preganglionic innervation comes
primarily from the lower thoracic and upper
lumbar segments of the spinal cord
 fibers are distributed primarily to the afferent and
efferent arterioles, the proximal and distal tubules,
and the juxtaglomerular apparatus

11. Renal blood flow…….2
 The RBF can be determined by applying the Fick’s
principle
 Since plasma volume is 55% and RBF is 1100ml/min,
therefore , Renal plasma
flow(RPF)=0.55x1100=605ml/min
 Since the kidney filters plasma, renal plasma flow
(RPF) is appropriate and equals the amount of a
substance excreted per unit of time divided by the
renal arteriovenous difference
 Any excreted substance can be used if it fulfills the
following criteria: (i) concentration in arterial and renal
venous plasma can be measured (ii) if it is not
metabolized, stored, or produced by the kidney and
(iii) it does not affect blood flow.

12. Glomerular filtration
Glomerular filtration rate (GFR) is the amount
of plasma ultrafiltrate formed each minute
 Measured in ml/min or L/day;
value=125ml/min or 180L/day
 can be measured in intact experimental
animals and humans by measuring the plasma
level of a substance and the amount of that
substance that is excreted.(By Clearance)
 The glomerular capillaries have a much higher
rate of filtration than most other capillaries
because of a high glomerular hydrostatic
pressure and a large Kf

13.  The fraction of the renal plasma flow that
is filtered (the filtration fraction) averages
about 0.2 or 20% of RPF
of the 605 ml of plasma(RPF) that enters
the glomeruli via the afferent arterioles,
125 ml(GFR), or 20%, filters into Bowman’s
space.
This fraction, determined by GFR/Renal
plasma flow is termed the filtration
fraction(FF).

14.  GFR is determined by (1) the sum of the hydrostatic
and colloid osmotic forces across the glomerular
membrane, which gives the net filtration pressure, and
(2) the glomerular capillary filtration coefficient, Kf.
Expressed mathematically, GFR = Kf X Net filtration
pressure
the above normal values for the determinants of GFR
have not been measured directly in humans, they
have been estimated in animals such as dogs and

15.  The GFR can therefore be expressed as:
GFR = Kf X (PG – PB – ∏G + ∏B )
 Some of these values can change markedly under
different physiologic conditions and others altered
mainly in disease states.
 Of all of the determinants of GFR, Changes in
glomerular hydrostatic pressure serve as the primary
means for physiologic regulation of GFR.
 Glomerular hydrostatic pressure is determined by
three variables, each of which is under physiologic
control: (1) arterial pressure, (2) afferent arteriolar
resistance, and (3) efferent arteriolar resistance.
 The afferent and efferent arterioles are influenced by
the sympathetic nervous system, hormones and
autacoids

17. Filtered Load
 Filtered load associated with GFR, is the
amount of substance that is filtered per unit
time.
For freely filtered substances, the filtered load
is just the product of GFR and plasma
concentration.
 For instance sodium with plasma concentration
of 140mEq/L or 0.14mEq/ml, its filtered load
will be, 0.14 x 125 = 17.5mEq/min
The filtered load is what is presented to the
rest of the nephron to handle.

18. Autoregulation……3
 Since a rise in blood pressure causes increased
excretion of salt and water (pressure natriureis), the
kidneys keep GFR and RBF at near constant levels
despite changes in arterial pressure
 Achieved by intrinsic feedback mechanisms, a process
called autoregulation
 Autoregulation in the kidneys is to maintain a
relatively constant GFR and to allow precise control of
renal excretion of water and solutes.
 GFR and RBF normally are autoregulated between the
arterial pressure range of 75 to 160mmHg

19. Mechanisms of Autoregulation
A) Tubuloglomerulo feedback
 Signals from the renal tubule in each nephron feed
back to affect filtration in its glomerulus (as the
flow through the loop of henle and beyond
increases, GFR decreases and vice versa
 This process tends to maintain the constancy of
the load (Nacl precisely) delivered to the distal
tubule.
 The feedback mechanisms depend on the
juxtaglomerular apparatus, and the sensor for this
response is the macula densa.
 As the flow rate through the loop of Henle
increases following rise in GFR, the Na+ and Cl-
entering the macula densa cells via the Na–K–2Cl
cotransporter in their apical membranes increases
 The Na,K ATPase activity increases with resultant
increased ATP hydrolysis and formation of more
adenosine
 Acts via adenosine A1 receptors on the macula
densa cells to increase their release of Ca2+ to the
vascular smooth muscle in the afferent arterioles.

20.  a similar mechanism generates a signal that decreases renin
secretion by the adjacent granular cells in the afferent arteriole
and decreases angiotensin II release
 When both of these mechanisms are functioning together, the
GFR changes only a few percentage points, even with large
fluctuations in arterial pressure
B) Myogenic response
 Intrinsic ability of individual blood vessels to resist stretching
when arterial pressure increases
 the vessels respond to increased wall tension or wall stretch by
contraction of the vascular smooth muscle.
 Stretch of the vascular wall allows increased movement of
calcium ions from the extracellular fluid into the cells
 This contraction prevents overdistention of the vessel and at
the same time, by raising vascular resistance, helps prevent
excessive increases in renal blood flow and GFR

21. Clearance
 Renal plasma clearance is the volume
of plasma from which a substance is
completely removed by the kidney in
a given amount of time (usually
minutes)
 The easiest way to think of this is to
ask what volume of plasma contains
the amount excreted in a given time.
Suppose 5 mg of a substance is
excreted per hour and 200ml of
plasma contains 5 mg. Then the
clearance of the substance is 200
ml/hr
 Amount cleared = Cx • Px while
Amount in urine=V • Ux
 The amount removed from the
plasma must equal the amount
appearing in the urine.

22.  The clearance of several substances that are
important for the quantification of renal
function
1. Inulin
• is a polysaccharide that is freely filtered and neither
reabsorbed nor secreted
• The volume of plasma cleared per unit time, is the
same as the GFR, therefore inulin clearance is the
hallmark method for measuring GFR
• The method is cumbersome because inulin must be
infused, and at a rate that is sufficient to keep the
plasma concentration constant during the period of
urine formation and collection

23. • For routine assessment of GFR in hospitalized
patients, creatinine clearance is used
• Creatinine is an end product of creatine metabolism
and is released into the blood continuously by skeletal
muscle.
• Creatinine is freely filtered and not reabsorbed, rather
a small amount, is secreted by the proximal tubule.
• Because of the secretion, creatinine clearance is
slightly higher than the GFR, a degree of error which
is acceptable
• Usually, a patient’s urine is collected for 24 h, and a
blood sample is taken sometime during the collection
period. Blood and urine are assayed for creatinine
concentration,and the clearance formula is applied

24. 2. Para-aminohippuric acid(PAH)
• PAH has a clearance greater than the GFR
• It is a water-soluble organic anion with a small
molecular weight of 194 Da
• It is freely filtered and also avidly secreted by the
proximal tubule epithelium via the transcellular
route).
• Its secretion is saturable
• At low plasma concentrations, about 90% of the
PAH entering the kidney is removed from the
plasma and excreted in the urine
• PAH clearance is used as a measure of renal
plasma flow, usually called the effective renal
plasma flow