KIDNEY


 Kidney Function

 Excretion of metabolic waste products and foreign
chemicals
 Regulation of water and electrolyte balances
 Regulation of body fluid osmolality and electrolyte
concentrations
 Regulation of arterial pressure
 Regulation of acid-base balance
 Secretion, metabolism, and excretion of hormones
 Gluconeogenesis
 Physiologic Anatomy of
the Kidneys

 The two kidneys lie on the posterior wall of the
abdomen, outside the peritoneal cavity
 Each kidney of the adult human weighs about 150
grams and is about the size of a clenched fist.
 The medial side of each kidney contains an indented
region called the hilum through which pass the renal
artery and vein, lymphatics, nerve supply, and
ureter, which carries the final urine from the kidney
to the bladder, where it is stored until emptied.
 The kidney is surrounded by a tough, fibrous
capsule that protects its delicate inner structures.
 Physiologic Anatomy of
the Kidneys
 Outer Cortex
 Inner Medulla
 Renal pyramids multiple cone-
shaped masses of tissue
 Each pyramid
 originates at the border
between the cortex and
medulla
 terminates in the papilla →
projects into the space of the
renal pelvis
 Major calyces
 Minor calyces
 The walls of the calyces, pelvis,
and ureter contain contractile
elements that propel the urine
toward the bladder, where urine
 Renal Blood Supply

 Blood flow - about 22 per
cent of the cardiac output, or
1100 ml/min.
 Renal artery → interlobar
arteries → arcuate arteries →
interlobular arteries (radial
arteries) → afferent arterioles
→ glomerular capillaries →
filtration → efferent arteriole
→ (peritubular capillaries)
second capillary network →
venous system
Nephron

 Functional unit of kidney
 Does not regenerate
 (1) a tuft of glomerular
capillaries called the
glomerulus, through which
large amounts of fluid are
filtered from the blood;
 and (2) a long tubule in
which the filtered fluid is
converted into urine on its
way to the pelvis of the
kidney
 Nephron
 network of branching and

anastomosing glomerular
capillaries → Bowman’s capsule
→ proximal tubule (cortex) →
loop of Henle (medulla)
(descending and ascending limb;
thin and thick segment) →
macula densa → distal tubule
(cortex) → connecting tubule →
cortical collecting tubule
→cortical collecting duct → 8 to
10 cortical collecting ducts join to
form a single larger collecting
duct → medullary collecting duct
→ larger ducts → renal papillae
→ renal pelvis → ureter
 Micturition

 Micturition is the process by which the urinary
bladder empties when it becomes filled.
 First, the bladder fills progressively until the tension
in its walls rises above a threshold level
 Second step, which is a nervous reflex called the
micturition reflex that empties the bladder or, if this
fails, at least causes a conscious desire to urinate.
 Autonomic spinal cord reflex
 Can also be inhibited or facilitated by centers in the
cerebral cortex or brain stem.
Urinary Bladder

 Micturition Reflex
 Abnormalities of UB
 Atonic Bladder
 Automatic Bladder
 Uninhibited
Neurogenic Bladder
 Urine Formation

 Urine formation begins when a
large amount of fluid that is
virtually free of protein is
filtered from the glomerular
capillaries into Bowman’s
capsule.
 As filtered fluid leaves
Bowman’s capsule and passes
through the tubules, it is
modified by reabsorption of
water and specific solutes back
into the blood or by secretion of
other substances from the
peritubular capillaries into the
tubules.
 Urine Formation

 Glomerular Filtration Rate (GFR) = 180L/day
 Reabsorption is quantitatively more important than Secretion
 But secretion plays an important role in determining the amounts of
potassium and hydrogen ions and a few other substances that are
excreted in the urine.
 Most substances that must be cleared from the blood
 end products of metabolism such as urea, creatinine, uric acid, and
urates, are poorly reabsorbed
 Certain foreign substances and drugs are also secreted from the blood
into the tubules
 Highly reabsorbed
 Water
 Electrolytes (sodium ions, chloride ions, and bicarbonate ions)
 Nutritional substances (amino acids and glucose) are completely
reabsorbed
 Each of the processes is regulated according to the needs of the body.
Glomerular Filtration

 Glomerular Filtrate

 Urine formation begins with filtration of large amounts
of fluid through the glomerular capillaries into
Bowman’s capsule.
 Glomerular filtrate is essentially protein-free and
devoid of cellular elements, including red blood cells.
 The concentrations of most salts and organic molecules
are similar to the concentrations in the plasma.
 Exceptions: calcium and fatty acids, that are not freely
filtered because they are partially bound to the plasma
proteins.
 GFR
 GFR is determined by

 (1) the balance of hydrostatic and colloid osmotic forces
acting across the capillary membrane
 (2) the capillary filtration coefficient (Kf),the product of the
permeability and filtering surface area of the capillaries.
 In the average adult human, the GFR is about 125 ml/min,
or 180 L/day.
 The fraction of the renal plasma flow that is filtered (the
filtration fraction) averages about 0.2; this means that
about 20 per cent of the plasma flowing through the kidney
is filtered through the glomerular capillaries.
 The filtration fraction is calculated as follows:
 Filtration fraction = GFR/Renal plasma flow
 Glomerular Capillary
Membrane

 Has three (instead of the usual two)
major layers:
 (1) the endothelium of the capillary,
 (2) a basement membrane, and
 (3) a layer of epithelial cells
(podocytes) surrounding the outer
surface of the capillary basement
membrane.
 Together, these make up the filtration
barrier, which, despite the three layers,
filters several hundred times as much
water and solutes as the usual capillary
membrane.
 Even with this high rate of filtration, the
glomerular capillary membrane
normally prevents filtration of plasma
proteins.
GCM

 Fenestrae – small holes in
capillary endothelium;
endowed with fixed
negative charges
 Basement membrane -
consists of a meshwork of
collagen and proteoglycan
fibrillae that have large
spaces (water and small
solutes); strong negative
electrical charges associated
with the proteoglycans.
 Epithelial cells - cells are
not continuous but have
long footlike processes
(podocytes) that encircle
the outer surface of the
capillaries. The foot
processes are separated by
gaps called slit pores
through which the
glomerular filtrate moves.
 also have negative
charges
 Determinants of the
GFR

 Increased Glomerular Capillary Filtration Coefficient
Increases GFR
 Increased Bowman’s Capsule Hydrostatic Pressure
Decreases GFR
 Increased Glomerular Capillary Colloid Osmotic
Pressure Decreases GFR
 Increased Glomerular Capillary Hydrostatic Pressure
Increases GFR
 Renal Blood Flow

 22 % of cardiac output (1100ml/min) in a 70kg adult
 O2 consumption – twice as great as brain
 Blood flow – seven times as much as brain
 ↑blood flow, ↑O2 consumption, ↑Na filtration and
reabsorption
 pressures), divided by the total renal vascular resistance:
 Determinant of renal blood flow:
 Pressure gradient of renal vasculature
 (Renal artery pressure - Renal vein pressure) / Total renal
vascular resistanc
 Blood Flow in the Vasa Recta of the Renal Medulla Is Very
Low Compared with Flow in the Renal Cortex
 Physiologic Control of
Glomerular Filtration and
Renal Blood
 Flow
 Sympathetic nervous system,
 Decrease Blood flow → decrease GFR
 Hormones and autacoids (vasoactive substances that
are released in the kidneys and act locally),
 and other feedback controls that are intrinsic to the
kidneys
 Autoregulation of GFR
and RenalBlood Flow
 Autoregulation – relative constancy of RBF and GFR
 maintain a relatively constant GFR and to allow
precise control of renal excretion of water and solutes
 Normally, GFR = 180 L/day and tubular reabsorption
= 178.5 L/day, and 1.5 L/day = excreted in the urine.
 Autonomic nervous system
 Tubuloglomerular feedback – macula densa
 Myogenic Autoregulation
 Protein and Glucose intake
Juxtaglomerular complex

Tubular Processing
of the Glomerular
Filtrate

 Urine Flow
 network of branching and

anastomosing glomerular
capillaries → Bowman’s capsule
→ proximal tubule (cortex) →
loop of Henle (medulla)
(descending and ascending limb;
thin and thick segment) →
macula densa → distal tubule
(cortex) → connecting tubule →
cortical collecting tubule
→cortical collecting duct → 8 to
10 cortical collecting ducts join to
form a single larger collecting
duct → medullary collecting duct
→ larger ducts → renal papillae
→ renal pelvis → ureter
 Tubular Processing

 Reabsorption – 99% of filtrate
 Secretion
 Urinary excretion = Glomerular filtration -Tubular
reabsorption +Tubular secretion
 Reabsorption

 Water and solutes
 (1) across the tubular epithelial membranes into the
renal interstitial fluid and then
 (2) through the peritubular capillary membrane back
into the blood
 Transport mechanisms
 Reabsorption varies according to the body's needs,
enabling the body to retain most of its nutrients.
 Transport Mechanism

 Transcellular route
 Passive diffusion
 Osmosis
 Active transport
 Paracellular route
 Tight junctions
 Ultrafiltration (bulk
flow)
Transport Mechanism

 Transport Mechanism

 Passive Water Reabsorption by Osmosis Is Coupled
Mainly to Sodium Reabsorption
 Reabsorption of Chloride, Urea, and Other Solutes
by Passive Diffusion (paracellular route)
 Pinocytosis
 proteins
 Counter Transport
 in Secretion
 Reabsorption and
Secretion Along
Different Parts of the

Nephron
 Proximal Convoluted Tubule

 Most of the volume (65%) of the fitrate solution is reabsobed
 Some water and most/all of the glucose (except in the case of
diabetics).
 Sodium - Most of the energy consumed by the kidneys is used in
its reabsorption
 Coupled with water molecules
 From tubular fluid into the cells of PCT mainly via active transport;
 Thru Symporters with glucose, amino acids, lactic acids, bicarbonate
ions → diffusion and/or other transport processes
 Solutes are selectively moved from the glomerular filtrate to the
plasma by active transport.
 Following the movement of solutes (including Na+ ), water is then
also reabsorbed by osmosis. As this part of the reabsorption
process is not controlled by the proximal tubule itself, it is
sometimes called obligatory water reabsorption.
 Proximal Convoluted
Tubule

 Concentrations of Solutes Along the Proximal Tubule.
 Sodium concentration remain relatively constant
 Organic solutes, such as glucose, amino acids, and bicarbonate
decrease
 Creatinine – increase concentration
 The total solute concentration - remains essentially the same all
along the proximal tubule because of the extremely high
permeability of this part of the nephron to water.
 Secretion of Organic Acids and Bases by the Proximal Tubule
 organic acids and bases such as bile salts, oxalate,urate,and
catecholamines
 many potentially harmful drugs or toxins
 para-aminohippuric acid (PAH)
 Loop of Henle

 The remaining water together with
the dissolved salts and urea passes
from the PCT into the descending
limb of Henle. It then passes along
the Loop of Henle, and up the
ascending limb of Henle.
 The different permeability
properties of the two limbs of the
Loop of Henle, together with their
counterflow arrangement, allows
a countercurrent multiplication to
generate a high solute
concentration in the tissue fluid of
the medulla.
 The highest solute concentrations
 Loop of Henle

 Descending Limb of Loop of Henle
 The epithelium lining of the descending limb of
Henle is relatively permeable to water - but much
much less permeable to the salts Na+ and Cl-, and to urea.
 Therefore water gradually moves from the
descending limb and into the interstitium as fluid
flows through this part of the system of renal
tubules.
Descending Limb of
Loop of
 Henle
 Loop of Henle

 Thin Ascending Limb of Loop of Henle
 The thin ascending limb of Henle differs from the
descending limb in that it is impermeable to water (so the
water that is inside the tubule at this stage generally remains
inside it), but is highly permeable to Na+ and Cl-, and somewhat
permeable to urea.
 Therefore while the tubular fluid flows back towards the
renal cortex, Na+ and Cl- (which are more concentrated in
the tubular fluid than in the interstital fluid)
diffuse from the tubules into the interstitium.
 Some urea also enters the tubules at this stage - but the
loss of NaCl from the tubular fluid greatly exceeds the
gain in urea.
Thin Ascending Limb of
Loop of
 Henle
 Loop of Henle

 Thick Ascending Limb of
Loop of Henle
 The thick ascending limb
of Henle (and its
continuation into the first
part of the DCT),
reabsorbs NaCl from the
tubular fluid via a
different transport process
from that of the thin
ascending limb of Henle.
 Loop of Henle

 The overall effect of the processes outlined above is
that the concentration of the fluid inside the renal
tubules that form the Loop of Henle is highest at the
deepest part of the renal medulla, and is less
concentrated in the renal cortex.
 This is what is meant by the "concentration gradient"
of the Loop of Henle.
 The term "counter-current" is also used in
descriptions of the Loop of Henle - and refers to the
tubular fluid flowing in opposite directions along the
descending and ascending limbs.
 Distal Convoluted Tubules

 The water, urea, and salts contained within the
ascending limb of Henle eventually pass into
the distal convoluted tubule (DCT).
 The DCT reacts to the amount of anti-diuretic
hormone (ADH) in the blood:
 The more ADH is present in the blood, the more water
is re-absorbed into it. This happens because the
presence of ADH in the blood causes the cells in the
last section of the DCT (and associated tubules and
collecting ducts) to become more permeable to water,
therefore they allow more water to pass from the
tubular fluid back into the blood.
 This results in more concentrated urine.
 Distal Convoluted Tubule

 The opposite is also true, i.e. if the level of ADH in
the blood is reduced then the cells in the latter
sections of the DCT (and associated tubules and
collecting ducts) becomes less permeable to water
 therefore less water is able to pass from the tubular
fluid back into the blood - which results in less
concentrated urine.
 The amount of ADH in the blood may be affected
by conditions such as diabetes insipidus, or by
consumption of diuretics* in the diet (*substances that
occur in some foods and drinks).
Juxtaglomerular complex

 Tubular Secretion

 The third process by which the kidneys clean blood
(regulating its composition and volume) is
called tubular secretion
 and involves substances being added to the tubular
fluid.
 This removes excessive quantities of certain
dissolved substances from the body, and also
maintains the blood at a normal healthy pH (which is
typically in the range pH 7.35 to pH 7.45).
 Tubular Secretion

 The substances that are secreted into the tubular
fluid (for removal from the body) include:
 Potassium ions (K+),
 Hydrogen ions (H+),
 Ammonium ions (NH4+),
 creatinine,
 urea,
 some hormones, and
 some drugs (e.g. penicillin).
 Tubular Secretion

 Tubular secretion occurs from the epithelial cells that
line the renal tubules and collecting ducts.
 It is the tubular secretion of H+ and NH4+ from the
blood into the tubular fluid that helps to keep blood
pH at its normal level.
 The movement of these ions also helps to conserve
sodium bicarbonate (NaHCO3).
 The typical pH of urine is about 6.

 Urine excretion

 Urine formed via the three
processes trickles into the
kidney pelvis.
 At this final stage it is only
approx. 1% of the originally
filtered volume but
includes high
concentrations of urea and
creatinine, and variable
concentrations of ions.
 The typical volume of urine
produced by an average
adult is around ? per day.
 Urine output
Solutes in Urine

 Urine Output

 Normal output
 800ml – 2000ml in 24 hrs
 Oliguria
 <500ml in 24 hrs
 Polyuria
 >2000ml in 24 hrs
 Formula:
 UO = 1-2ml/kg/hr
End of Lecture

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