kidney- urine formation

Functions of kidney
• The main function of the kidneys is to regulate
the volume and composition of the extracellular
fluid
• Excrete metabolic waste products including
creatinine, urea, uric acid and some end
products of haemoglobin breakdown
• Excrete foreign substances and their derivatives,
including drugs, and food additives
• Function as endocrine organs, producing the
hormones renin, erythropoietin and calcitriol, the
active form of vitamin D.
Kidney Location and External
Anatomy
• The bean-shaped
kidneys lie in a
retroperitoneal
position in the
superior lumbar
region and extend
from the twelfth
thoracic to the third
lumbar vertebrae
• Renal capsule –
fibrous capsule that
prevents kidney
infection
• Adipose capsule –
fatty mass that
cushions the kidney
and helps attach it to
the body wall
• Renal fascia – outer
layer of dense fibrous
connective tissue that
anchors the kidney
• The lateral surface is
convex and the
medial surface is
concave, with a
vertical cleft called the
renal hilus leading to
the renal sinus
• Ureters, renal blood
vessels, lymphatics,
and nerves enter and
exit at the hilus
– Renal Hilum
• Opening to Kidney
– Renal Sinus
• Space within hilus
• Kidneys receive
blood vessels and
nerves.
 Internal anatomy
• Medulla divided in to
multiple cone shaped
masses called as
renal pyramid.
• It terminates in to
renal papilla which
projects in to the
space of renal pelvis
which continues as
ureter
Major calyx and minor calyx
Blood supply
 Nephron
• Each kidney is made up of 1 million
nephrons.
• It is a functional unit of kidney
• Kidney cannot regenerate nephrons
• After age of 40 nephron usually decreases
about 10 percent every 10 years
• At the age of 80 many people have 40
percent less nephrons
 The glomerulus and
juxtaglomerular apparatus
Regional differences in structure
 Urine formation
• A. Glomerular Filtration
• B. Tubular Reabsorption
• C. Tubular Secretion

• Expressed mathematically as:

• Urinary excretion rate = Filtration rate -
Reabsorption rate + Secretion
rate
 Renal handling of 4 hypothetical
substances
• A- creatinin
• B- many electrolytes
• C- amino acid and
glucose
• D- toxic products
Glomerular Capillary Membrane
1. The fenestrated endothelium of the capillary
which is the filtering membrane
2. The basement membrane of the Bowman’s
capsule contains mesangial cells that are both
phagocytic and contractile
3. The epithelial cells of the capsule. These are
known as podocytes because they have
numerous foot-like projections (pedicels) that
clasp the tubes of capillary endothelium.
 Glomerular Filtration - The first
Step in Urine Formation
• Composition of the Glomerular Filtrate
• - protein free and devoid of cellular
elements including red blood cells
• - calcium and fatty acids not freely
filtered because they are bound to
plasma proteins
• GFR = 125 ml/min or 180 L/day

Filterability of Solutes is inversely Related

to their size

Negatively Charged Large Molecules are

Filtered Less Easily Than Positively
Charged Molecules of Equal Membrane
Size
• In certain condition negative charge of
basement membrane is lost even before
change in histology called as minimal
change nephropathy
• As a result low molecular weight protein is
lost (albumin) and appear in urine called
as proeinurea
 Measurement of GFR
• GFR is not measured directly, but by
measurement of the excretion of a marker
substance
• GFR can be measured by using inulin, a
polymer of fructose, which is freely filtered and
neither secreted nor reabsorbed by the nephron
• Inulin does not occur naturally in the body and
must be given as a continuous intravenous
infusion to achieve a constant plasma
concentration
GFR =UX × V
PX
where PX = concentrations in plasma
UX = concentrations in urine of the substance
X,
V = urine flow as a volume per unit time.
 Clinically, creatinine is often used for the
measurement of GFR.
It is naturally occurring and is released
into plasma at a fairly constant rate by
skeletal muscle. Therefore there is no
need to give an infusion
 Determinants of the GFR
• The net filtration
pressure represents
sum of hydrostatic
and colloid osmotic
forces that either
favor or oppose the
filtration
 Renal blood flow
• Combined blood flow through kidney is about
1200ml/min or about 21% of cardiac output
• Purpose of high blood flow is to supply enough
plasma for high rate of glomerular filtration
 Measurement of renal blood flow

• If a substance is completely removed from the

plasma passing through the kidney, leaving
none in the plasma in the renal vein, then the
clearance of that substance is equal to renal
plasma
• Para-aminohippuric acid (PAH) is a substance
that approaches this ideal.
 Physiologic Control of Glomerular
Filtration and Blood Flow
• Sympathetic nervous system Activation
Decreases GFR by constricting the renal
arterioles and decreasing the renal blood
flow
 Hormonal and Autocoid Control of
Renal Circulation
• Norepinephrine, epinephrine constrict
renal blood vessels and reduce GFR
• Angiotensin constricts efferent arteriole
which rise glomerular hydrostatic
pressure. It is secreted when arterial
pressure is decreased and helps to
maintain the filtration rate
 Contd
• Endothelial derived nitric oxide decreases
the vascular resistance and increase GFR
• Prostaglandin, bradykinin causes
vasodilation and increase in GFR, hence
NSAID like aspirin may cause reduction in
GFR under stressful condition
 Role of Tubuloglomerular
Feedback in Autoregulation of GFR
 Tubular processing of glomerular
filtrate
• Reabsorption
Primary Active reabsorption – by hydrolysis of
ATP (sodium)
Secondary Active reabsorption - energy
released during primary reabsorption is utilized
for to drive another sub (glucose)
symport and antiport.
Passive water reabsorption by osmosis
Reabsorption of chloride, urea by passive
diffusion
Reabsorption and secretion
along different part of
nephron
 PCT
• Na+/K+ ATPase pump located in basal and
lateral sides of cell membrane, creates gradient
for diffusion of Na+ across the apical membrane.
• Na+/K+ ATPase pump extrudes Na+.
• Creates potential difference across the wall of
the tubule, with lumen as –pole.
• Electrical gradient causes Cl- movement
towards higher [Na+].
• H20 follows by osmosis.
• Glucose reabsorption- It is cotransported
with sodium at the luminal membrane
• Amino acids- reabsorbed by cotransport with
sodium at the luminal membrane
• Potassium-The proximal tubule reabsorbs
about 80% of filtered potassium, reabsorbed
passively
Bicarbonate reabsorption
 Significance of PCT Reabsorption
• 65% Na+, Cl-, and H20 reabsorbed across
the PCT into the vascular system.
• 90% K+ reabsorbed.
• Reabsorption occurs constantly regardless
of hydration state.
• Not subject to hormonal regulation.
 Descending Limb LH
• Impermeable to passive
diffusion of NaCl.
• Permeable to H20.
• Hypertonic interstitial fluid
causes H20 movement out of
the descending limb via
osmosis, and H20 enters
capillaries.
• Fluid volume decreases in
tubule, causing higher [Na+]
in the ascending limb.
 Ascending Limb LH
• NaCl is actively extruded
from the ascending limb
into surrounding
interstitial fluid.
• Na+ diffuses into tubular
cell with the secondary
active transport of K+ and
Cl-.
• Occurs at a ratio of 1 Na+
and 1 K+ to 2 Cl-.
• Ascending walls are
impermeable to H20.
 Distal tubule
• First part of DCT forms the part of
juxtaglomerular complex that provides the
feedback control of GFR
• Called as diluting segment because it is
impermeable to water and actively
reasorbs most of the ion including sodium,
potassium and chloride
 Collecting Duct
- cortical
• Principle cell – reabsorbs sodium and
secretes potassium
• Intercalated cell- secretes hydrogen and
reabsorbs bicarbonates
• Permeable to H20 depends upon the
presence of ADH
 Medullary
• Medullary area impermeable to high [NaCl] that
surrounds it.
• Permeable to H20 depends upon the presence of
ADH.
– When ADH binds to its membrane receptors
on CD, it acts via cAMP.
• Stimulates fusion of vesicles with plasma
membrane.
– Incorporates water channels into plasma
membrane.
 Secretion
• Secretion of substances from the peritubular
capillaries into interstitial fluid.
• Then transported into lumen of tubule, and into
the urine.
• Allows the kidneys to rapidly eliminate certain
potential toxins.
Countercurrent mechanism
 The role of urea
• NaCl only accounts for about half (600
mOsm/kg H2O) of The total osmolality of
the interstitial fluid.
• The remaining 600 mOsm/kg H2O is due
to urea.
Osmolality of Different Regions of
the Kidney
Vasa Recta countercurrent exchanger

• Vasa recta maintains hypertonicity by

countercurrent exchange.
• NaCl and urea diffuse into descending
limb and diffuse back into medullary tissue
fluid.
• Walls are permeable to H20, NaCl and
urea.
• Colloid osmotic pressure in vasa recta >
interstitial fluid.
Countercurrent exchanger
Summary
 Glucose and Amino Acid
Reabsorption
• Filtered glucose and amino acids are
normally reabsorbed by the nephrons.
• In PCT occurs by secondary active
transport with membrane carriers.
• Renal transport threshold:
• Renal plasma threshold for glucose = 180-
200 mg/dl.
 Electrolyte Balance
• Kidneys regulate Na+, K+, H+, Cl-, HC03-,
and PO4-3.
• Control of plasma Na+ is important in
regulation of blood volume and pressure.
• Control of plasma of K+ important in proper
function of cardiac and skeletal muscles.
– Match ingestion with urinary excretion.
 Renal Acid-Base Regulation
• Kidneys help regulate blood pH by excreting H+ and
reabsorbing HC03-.
• Most of the H+ secretion occurs across the walls of the
PCT in exchange for Na+.
• proximal tubule - H+ secretion mainly occurs via the
Na+/H+ countertransporter
• distal tubule and collecting duct - bicarbonate
reabsorption is linked to H+ secretion
• Normal urine normally is slightly acidic because the
kidneys reabsorb almost all HC03- and excrete H+.
• Returns blood pH back to normal range.
 Renal
regulation
• Renin–angiotensin system
Renin

angiotensin I from angiotensinogen

angiotensin
converting enzyme
(ACE)

angiotensin II
• It stimulates sodium reabsorption by the
proximal tubule, and chloride and water
follow passively.
• It stimulates aldosterone secretion by
the adrenal cortex.
• It stimulates antidiuretic hormone (ADH)
secretion from the posterior pituitary
gland.
• It stimulates thirst
 Aldosterone
• Aldosterone released by the adrenal cortex.
• stimuli
3. Increase in the concentration of angiotensin II
4. increase in plasma K+ concentration.
• Aldosterone acts to stimulate Na+ absorption
and K+ secretion by the principal cells of
• the distal tubule and collecting duct
• increasing the number of Na+ and K+
channels in the luminal membrane and in
increasing the activity of Na+/K+ ATPase
• Atrial natriuretic peptide – secreted by
cells of atria when distended by excess
volume
• Inhibits sodium and water reabsorption
• Parathyroid – calcium regulating hamone
• Increases reabsorption of calcium from
DCT and loop of henle
Role of ADH
Regulation of body fluid volume
 Production
of calcitriol.
• Vitamin D3 is present in diet and that can be
synthesized in the skin in the presence of ultraviolet light.
• Converted to 25-hydroxycholecalciferol in the liver
• Then to the active metabolite calcitriol in the kidney
(mainly in the proximal tubule).
• The conversion to calcitriol is stimulated by PTH and
is therefore indirectly stimulated by a reduction in
Ca2+.
• Calcitriol increases Ca2+ and phosphate absorption by
the gut and it enhances bone resorption
 Applied physiology
• Acute renal failure:
• Ability of kidneys to excrete wastes and regulate
homeostasis of blood volume, pH, and electrolytes
impaired.
• Types
4. Prerenal renal failure - due to a failure of renal
perfusion.
5. Renal’ renal failure - the cause of the renal failure lies
within the kidneys
6. Postrenal renal failure problem lies distal to the
kidneys. Obstruction to the renal tract can occur in one
ureter and lead to loss of function of the corresponding
kidney
• Effects
• (a) fluid and electrolyte balance;
• (b)excretion
• (c) endocrine functions
• Glomerulonephritis:
• Inflammation of the glomeruli.
• Autoimmune disease by which antibodies have
been raised against the glomerulus basement
membrane.
• Leakage of protein into the urine.
• Renal insufficiency:
• Nephrons are destroyed.
• Clinical manifestations:
• Salt and H20 retention.
• Uremia.
• Elevated plasma [H+] and [K+].
 Diuretics
• Increase urine volume excreted.
– Increase the proportion of glomerular filtrate that is
excreted as urine.
• Loop diuretics:
– Inhibit NaCl transport out of the ascending limb of the
LH.
• Thiazide diuretics:
– Inhibit NaCl reabsorption in the 1st segment of the
DCT.
• ACE inhibitors
• Osmotic diuretics:
– Increase osmotic pressure of filtrate