LECTURE NOTES ON THE RENAL

SYSTEM
• Renal system includes a pair of kidneys, Ureters, Urinary bladder,
urethra
• FUNCTIONS OF THE KIDNEY
• 1.Excretion of Metabolic Waste Products, Foreign Chemicals,
Drugs, and Hormone Metabolites including:
• urea (from the metabolism of amino acids),
• creatinine (from muscle creatine),
• uric acid (from nucleic acids),
• end products of hemoglobin breakdown (such as bilirubin), and
• metabolites of various hormones
• most toxins and other foreign substances that are either produced
by the body or ingested, such as pesticides, drugs, and food
additives.
General organisation of the kidneys
and urinary system
• 2.Regulation of water and Electrolyte
Balances.
• excretion of water and electrolytes must
precisely match intake.
• If intake exceeds excretion, the amount of that
substance in the body will increase.
• If intake is less than excretion, the amount of
that substance in the body will decrease.
 3.Regulation of Arterial Pressure.
• Long-term regulation of arterial pressure by
excreting variable amounts of sodium and
water.
• Short-term arterial pressure regulation by
secreting vasoactive factors or substances,
such as renin, that lead to the formation of
vasoactive products (e.g., angiotensin II).
• 4. Regulation of Acid-Base Balance:The
kidneys contribute to acid-base regulation,
along with the lungs and body
fluid buffers, by excreting acids and by
regulating the body fluid buffer stores.
5. Regulation of Erythrocyte Production.The
kidneys secrete erythropoietin, which
stimulates the production of red blood cells.
• 6.The Regulation of blood calcium level kidneys
produce the active form of vitamin D, 1,25-
dihydroxyvitamin D3 (calcitriol).
• Vitamin D is necessary for the absorption of
calcium from the intestine
• 7.Glucose Synthesis.The kidneys synthesize
glucose from amino acids and other precursors
during prolonged fasting - gluconeogenesis
 FUNCTIONAL ANATOMY
• Paired structures that lie on either side of the vertebral
column , retroperitoneal, a compound tubular gland
covered by a connective tissue capsule, each weighs
about 150g and is about 11cm long and 5 – 7 cm wide.
• On the medial border is a depression called a hilum
through which renal artery,vein,nerves and ureters
pass.
• LAYERS OF THE KIDNEY
• 2 major layers
Inner medulla
Outer cortex
 RENAL BLOOD SUPPLY
• The kidneys receive about 22 to 26% of CO(1100
to1300ml/min)
• The renal artery enters the kidney through the
hilum and then branches progressively to form
the interlobar arteries,arcuate arteries,
interlobular arteries (also called radial arteries)
and afferent arterioles, which lead to the
glomerular capillaries, where large amounts of
fluid and solutes (except the plasma proteins) are
filtered to begin urine formation.
• The distal ends of the capillaries of each glomerulus
coalesce to form the efferent arteriole, which leads to a
second capillary network, the peritubular capillaries, that
surrounds the renal tubules.
• The renal circulation is unique in that it has two capillary
beds, the glomerular and peritubular capillaries,which are
arranged in series and separated by the efferent arterioles,
which help regulate the hydrostatic pressure in both sets of
capillaries.
• High hydrostatic pressure in the glomerular capillaries
(about 60 mm Hg) causes rapid fluid filtration, whereas a
much lower hydrostatic pressure in the peritubular
capillaries (about 13 mm Hg) permits rapid fluid
reabsorption.
• The peritubular capillaries empty into the
vessels of the venous system, which run
parallel to the arteriolar vessels and
progressively form the interlobular
vein,arcuate vein, interlobar vein, and renal
vein, which leaves the kidney beside the renal
artery and ureter.
 NEPHRON
• The nephron is defined as the structural and functional unit of the
kidney.
• Each kidney consists of 1 to 1.3 millions of nephrons.
• Each nephron is formed by two parts
• 1. A blind end called a renal corpuscle. It is formed by glomerulus
and bowmans capsule.
The filtration of blood which forms the first phase of urine
formation occurs here.
Glomerulus : is a tuft of capillaries enclosed by bowmans capsule.
consists of a net work of glomerular capillaries which are connected
to an afferent arteriole on one end and an efferent arteriole on the
other end.
• 2. A tubular portion called called renal tubule
 TYPES OF NEPHRONS
• cortical nephrons:85% of neprons have their
corpuscles in the outer cortex of the kidney
near the periphery. Function in the production
of urine
• Juxtamedullary nephrons:have their
corpuscles in the inner cortex near the
medulla. Function in the production of urine
and concentration of urine.
• Tubular portion of the nephron- is a continuation
of the bowmans capsule. Consists of
• The proximal convulated tubule
• The loop of Henle-
the thin descending limb of the loop
The thin ascending limb of the loop
The thick ascending limb of the loop.
• The distal convulated tubule
JUXTAGLOMERULAR APPARATUS(JGA)
• This is a specialised organ situated near the
glomerulus of each nephron.
• It is formed by 3 structures:
• Macula densa
• Extraglomerular mesangial cells
• Juxtaglomerular cells.
M
• MACULA DENSA: is a specialized group of
epithelial cells in the terminal portion of the thick
ascending segment of the distal tubules that
comes in close contact with the afferent and
efferent arterioles of the same nephron.
• EXTRAGLOMERULAR MESANGIAL CELLS :also
called lacix cells or agranular cells. These cells are
situated in the triangular region bound by
afferent arteriole, efferent arteriole and macula
densa.
• JUXTAGLOMERULAR CELLS: the wall of the
afferent arteriole before entering the
Bowman’s capsule is thickened like a cuff.
• It is formed by juxtaglomerular cells(granular
cells) which are the specialised type of smooth
muscle cells derived from the wall of the
afferent arteriole.
 FUNCTIONS OF THE JGA

• SECRETION OF RENIN : the juxtaglomerular

cells secrete renin, a peptide.
• Factors that stimulate renin secretion:
– Fall in arterial blood pressure
– Reduction in the ECF volume
– Increased sympathetic activity
– Decreased load of sodium and chloride in macula
densa
 RENIN-ANGIOTENSIN SYSTEM
• Renin acts on angiotensinogen and converts it into
angiotensin I. Angiotensin I is converted into angiotensin II
by the activity of angiotensin converting enzyme (ACE)
secreted from the lungs.
• ACTIONS OF ANGIOTENSIN II.
• Acts on blood vessels and causes vasoconstriction
• Acts on the adrenal cortex to secrete aldosterone.
Aldosterone acts on renal tubule and increases retention of
sodium and raises blood pressure
• Regulates the glomerular filtration rate.(GFR)
• The extraglomerular mesangial cells secrete
prostaglandins.
• Macula densa secretes thromboxane A2
 URINE FORMATION
• Normally about 1 to 1.5 L of urine is produced
everyday.
• The kidneys secrete unwanted substances along with
water as urine.
• The urine formation includes 3 processes:
– Glomerular filtration by the glomerulus
– Tubular reabsorption and
– Tubular secretion by the tubular portion of the nephron
• These are regulated according to the needs of the
body.
 GLOMERULAR FILTRATION
• Glomerular filtration is the process by which the blood
that passes through the glomerular capillaries is
filtered through the filtration membrane.
• STRUCTURE OF THE GLOMERULAR FILTER
• This consists of
– Fenestrated glomerular capillary endothelium
– Basement membrane
– special cells of the visceral layer of the Bowman’s capsule.
These have foot processes known as podocytes which
connect to the basement membrane in an interdigitating
manner.
• GLOMERULAR FILTRATION RATE(GFR): is the total
quantity of filtrate formed in all the nephrons of both
kidneys in a given unit of time.
• The normal GFR is 125ml/min or 180L/day.
• FILTRATION FRACTION:is the fraction or percentage of
the renal plasma which becomes the filtrate.
• Resting renal plasma flow is 650ml/min,GFR is
125ml/min. the filtration fraction is given by
• Filtration fraction = GFR
Renal plasma flow
0.19 or 19%
 PRESSURES WHICH DETERMINE
FILTRATION
• Glomerular capillary pressure: about 60 mmHg.
Favours glomerular filtration
• Colloidal osmotic pressure or oncotic pressure exerted
by the plasma proteins in the glomeruli. 25mmHg. It
opposes filtration.
• Hydrostatic pressure in Bowman’s capsule,15mmHg.
Opposes filtration.
• Net filtration pressure is 20mmHg
• FILTRATION COEFFICIENT:is the GFR in terms of net
filtration pressure. Given as
GFR/ net filtration pressure =6.25ml/mmHg
 FACTORS AFFECTING GFR
• Renal blood flow: normal flow to the kidneys is about 1300ml/min..
GFR is directly proportional to renal blood flow.
• Systemic arterial pressure: abnormal increase in BP will increase
the GFR, while a decrease will reduce it. However When blood
pressure is altered between 80 and 180mmHg,renal blood flow and
GFR remain constant. This is called autoregulation.
• Afferent arteriolar constriction: reduces the blood flow and causes
a reduction in GFR.
• Efferent arteriolar constriction: has a biphasic effect on GFR. At
moderate levels of constriction , there is a slight increase in GFR,
but with severe constriction, there is a decrease in GFR.
• Hydrostatic pressure in Bowman’s capsule: this
normally opposes the hydrostatic filtering pressure.
Ureteric obstruction is a cause of a raised intracapsular
pressure.
• Surface area of capillary membrane: GFR is directly
proportional to the surface area.
• Permeability of the capillary membrane: GFR also
directly proportional to this.
• Hormones and secretory factors may increase the GFR
eg endothelial derived nitric oxide,prostaglandins while
some may decrease GFR eg noradrenaline, angiotensin
II.
 THE RENAL CLEARANCE TECHNIQUE
• Renal clearance is the ability of the kidneys to remove
molecules from the blood plasma by excreting them in
the urine
• The renal clearance of a substance is the volume of
plasma which contains the amount of the substance
excreted in the urine in one minute.
• Cₓ = Uₓ X V
Pₓ
Where Cₓ is the clearance of substance x
U ₓ is the concentration of x per ml of urine
V is the volume of urine produced in one minute
Pₓ is the plasma concentration of the substance x per ml of
plasma.
 Determination of GFR using clearance
technique
• GFR can be measured using clearance technique
• A substance used for measurement of GFR must have the following properties:
• Freely filtered
• Not reabsorbed
• Not secreted
• Not bound to plasma proteins
• Does not alter GFR
• Non toxic
• Not metabolised or stored in the kidney
• Can be easily measured in plasma and urine.
• A substance that satisfy the above criteria is inulin,
• It is a fructose polysaccharide ,which is hydrolysed in the gut, hence it is given iv
• A known amount of inulin is injected into the body, bladder is emptied, volume of
urine over an hour is collected and the concentration of inulin in the urine is
determined. A blood sample is taken midway of urine collection and its inulin
concentration is determined.
• In clinical practise , it is not used because already the patients renal
function is questionable.
• Instead creatinine clearance is determined.
• It is a normal plasma constituent derived from muscle creatine.
• Its plasma concentration is remarkably constant at about 1mg/dl.
• In man, some of it is secreted giving a false high value for UV.
• This is compensated for by the fact that the method of estimation
of creatinine in plasma also gives a false high value of P due to the
prescence of other chromogens in plasma.
• The two errors cancel out!
 TUBULAR REABSORPTION
• This is the process by which water and other
substances are transported from the renal
tubules back into the blood.
• The glomerular filtrate has the same
composition as plasma minus the plasma
proteins.
• Both quantitative and qualitative changes
occur. GFR is 180ml/day but only 1.5 L of urine
is produced daily.
 Threshold substances

• Depending on the degree of reabsorbtion, substances

are classed into
• High threshold substances: do not appear in the urine
in normal conditions but are completely reabsorbed.
They appear in urine only if their plasma
concentrations is abnormaly high or in renal disease.
They include glucose, aminoacids ,vitamins.
• Low threshold substances: appear in urine even under
normal conditions. Eg urea, uric acid, phosphates.
• Non threshold substances: are not absorbed at all and
excreted in urine eg creatinine
Four ways the body clears different
substances from the plasma
• Renal handling of four hypothetical substances
• A, The substance is freely filtered but not reabsorbed eg
creatinine,inulin.
• B, The substance is freely filtered,but part of the filtered
load is reabsorbed back in the blood eg sodium.
• C, The substance is freely filtered but is not excreted in the
urine because all the filtered substance is reabsorbed from
the tubules into the blood eg glucose,aminoacids.
• D, The substance is freely filtered and is not reabsorbed but
is secreted from the peritubular capillary blood into the
renal tubules eg paraminohippuric acid(PAH),diodrast.
REABSORPTION OF SOME IMPORTANT
SUBSTANCES
• REABSORPTION OF SODIUM
• In the proximal convulated tubule (PCT), two thirds of the sodium
load is actively reabsorbed and the other one third in the other
segments (except the descending limb). This is followed by passive
reabsorption of chloride along the electrochemical gradient.
• Sodium ions are transported from the lumen into the tubular cells
actively by two ways :
– In exchange for hydrogen ion by antiport
– Along with glucose and amino acid by symport
• Na is pumped into the interstitium by the Na-K ATPase. This pump
extrudes 3 Na in exchange for two K that are pumped into the cell.
• In the distal convulated tubule (DCT), Na reabsorption is under the
influence of aldosterone.
• REABSORPTION OF WATER
• This occurs from the PCT,DCT and CD.
• From the PCT, water reabsorption is secondary(obligatory)
to sodium reabsorption
• From the DCT and CD: these are impermeable to water
except in the presence of Antidiuretic hormone (ADH ).
• The ADH acts by regulating the aquaporin 2 which are
membrane proteins which act as water channels.
• REABSORPTION OF GLUCOSE
• This is completely reabsorbed in the PCT. Na and glucose
bind to a common carrier sodium dependant glucose
transporter 2(SGLT 2) in the luminal membrane.
• The renal threshold for glucose is 180mg/dl.
Above this level, the reabsorption of glucose is
not complete and glucose appears in the urine
–glycosuria.
• REABSORPTION OF AMINO ACIDS: occurs
completely in the PCT along with sodium.
• REABSORPTION OF BICARBONATES is actively
reabsorbed mostly in the PCT in the form of
carbon dioxide.
 TUBULAR SECRETION
• Is the process by which substances are transported
from the blood into the renal tubules.
• Potassium is secreted actively by the sodium –
potassium pump in the PCT,DCT and the CD
• Ammonia is secreted in the PCT
• Hydrogen ions are secreted in the PCT ,DCT.
• Many waste products of metabolism such as bile salts,
oxalate, uric acid, harmful toxins, drugs such penicillin
and salicylates are secreted by the PCT and thus
removed from the body.
• Whatever is left in the tubular lumen at the end of the
collecting duct passes out as urine.
 FORMATION OF DILUTE URINE

• The mechanism for the formation of urine is the same for both
dilute and concentrated urine till the fluid reaches the DCT.
• FORMATION OF DILUTE URINE:
• When the water content in the body increases, the kidneys excretes
dilute urine.
• This is achieved by the inhibition of ADH and there is no
reabsorption of water from the DCT and CD leading to dilute urine
excretion.
• The stimulus for ADH is decreased body fluid volume or increased
sodium concentration.
• ADH increases water reabsorption from the DCT and CD resulting in
the concentration of urine.
` 1t
 FORMATION OF CONCENTRATED
URINE
• When the water content in the body decreases,
kidneys excretes concentrated urine.
• The human kidney can produce a urine concentration
of 1200mOsm/L which is four times that of plasma
300mOsm/L
• The ability to produce concentrated urine depends on
three factors:
• Possession of U shaped nephrons which act as
countercurrent multipliers.
• Possession of U shaped vasa recta which act as counter
current exchangers.
• Presence of ADH
• COUNTERCURRENT FLOW:
• A countercurrent flow is a system of U shaped
tubes in which the flow of fluid is parallel to, in
opposite direction in two limbs of the U shaped
tubules and in close proximity.
• COUNTERCURRENT MULTIPLIER
• The loop of Henle functions as the multiplier. It is
responsible for the development of the
hyperosmolarity of the medullary interstitial
fluid.
• The descending limb is freely permeable to water, the thin
ascending limb is relatively permeable to sodium and urea and
impermeable to water.
• The thick ascending limb is impermeable to water , and vigorously
transports Nacl from the lumen into the interstitial space.
• The major cause of this hyperosmolarity is the active reabsorption
of sodium chloride and other solutes from the ascending limb of
the loop of Henle into the medullary interstitium.
• Due to the concentration gradient, the sodium and chloride ions
diffuse from the medullary interstitium into the descending limb of
Henle’s loop and reach the ascending limb again via hairpin bend.
• This occurs repeatedly leaving a small amount to be excreted in the
urine.
• Also, there is addition of more new sodium and
chloride ions into the descending limb by constant
filtration.
• Recirculation of urea also increases the osmolarity in
the medullary interstitium.
• Urea is completely filtered and not reabsorbed. The
concentration of urea increases in the collecting duct
and diffuses down the concentration gradient into the
medullary interstitium. The urea then diffuses down
the gradient into the ascending limb,DCT and CD
• This occurs repeatedly.
n
COUNTER CURRENT EXCHANGER
• The vasa recta functions as the counter current exchanger.
It maintains the the hyperosmolarity of the medullary
interstitial fluid.
• The blood flow through the medulla is very low, only about
8 to 10 % of renal blood flow perfuses the medulla.
• The hairpin configuration of the vasa recta means that as
the isosmotic blood in it descends into the hypertonic
medulla, it loses water and gains salt and therefore
becomes hypertonic but as it ascends into the cortex,
which is isosmotic,it loses salt and gains water.
• In this way, the blood circulation does not wash away the
hypertonicity but takes away the excess salt gradually.
• PRESENCE OF ADH: the final concentration of
the urine is achieved by ADH secretion.
• The DCT and CD become permeable in the
presence of ADH leading to reabsorption of
large volumes of water and formation of
concentrated urine.