Renal Physiology

STRUCTURE OF KIDNEY
 1. Renal pyramid
 2. Interlobar artery
 3. Renal artery
 4. Renal vein
 5. Renal hilum
 6. Renal pelvis
 7. Ureter
 8. Minor calyx
 9. Renal capsule
 10. Inferior renal capsule
 11. Superior renal capsule
 12. Interlobar vein
 13. Nephron
 14. Minor calyx
 15. Major calyx
 16. Renal papilla
 17. Renal column
 Location of the Kidneys
 Dimensions
 Reddish-brown, bean shaped
 12cm long, 6cm wide, 3cm thick
 High on posterior abdominal wall
 at the level of T12 to L3- superior lumbar region
 Retroperitoneal & against the dorsal body wall
 The right kidney is slightly lower than the left ,convex
laterally
 Attached to ureters, renal blood vessels, and nerves
at renal hilus (medial indention)
 Atop each kidney is an adrenal gland
Coverings of the Kidneys
 Adipose capsule
 Surrounds the kidney
 Provides protection to the kidney
 Helps keep the kidney in its correct location against
muscles of posterior trunk wall
 Ptosis-kidneys drop to a lower position due to rapid
fat loss, creating problems with the ureters.
 Ptosis can lead to hydronephrosis, a condition
where urine backs up the ureters and exerts
pressure on the kidney tissue.

 Renal capsule
 Surrounds each kidney
Regions of the Kidney
 Three regions of kidneys
 Renal cortex – outer region, forms
an outer shell
 Renal columns – extensions of
cortex- material inward
 Renal medulla – inside the cortex,
contains medullary (renal) pyramids
 Medullary pyramids – triangular
regions of tissue in the medulla,
appear striated
 Renal pelvis – inner collecting tube,
divides into major and minor calyces
 Calyces – cup-shaped
structures enclosing the tips of
the pyramids that collect and
funnel urine towards the renal
pelvis
Functions of the Urinary System
 Elimination of waste products
 filtering gallons of fluid from the bloodstream every day
creating “filtrate”
 “filtrate” includes: metabolic wastes, ionic salts, toxins, drugs
 Maintenance of blood
 Red blood cell production- by producing hormone
erythropoietin to stimulate RBC production in bone
marrow
 Blood pressure (vessel size)- by producing renin which
causes vasoconstriction
 Blood volume (water balance)- ADH released from
Anterior Pituitary targets the kidney to limit water loss
when blood pressure decreases or changes in blood
composition
 Blood composition (electrolyte balance)- water follows
salt; aldosterone reclaims sodium to the blood
 Blood pH- regulates H+ ions and HCO3- ions
Blood Flow in the Kidneys
 Rich blood supply to filter blood and adjust blood composition
 ~¼ of blood supply passes through the kidneys each minute
 Blood enters the kidneys under extremely high pressure
 Renal artery arises from abdominal aorta, divides into Segmental
artery at hilus
 Inside renal pelvis, Segmental artery divides into Lobar artery, which
branch into Interlobar artery travelling thru the renal column to reach
the renal cortex
 At the medulla-cortex junction, the Interlobar artery curves over the
medullary pyramids as the Arcuate artery.
 Small Interlobular arterioles branch off of the Arcuate artery and
move away from the renal cortex and into the Nephron of the kidney
Blood Flow in the Kidneys
 The final branches of the interlobular arteries are called afferent
arterioles.
 Afferent arterioles lead to the glomerulus, a network of capillaries
that are involved in filtration.
 Leading away from the glomerulus, blood less filtrate travels through
the efferent arterioles and into the peritubular capillaries.
 From there, blood moves through similar veins that parallel the
arteries at their respective locations.
Nephrons
 The structural and functional units of the kidneys
 Over 1 million
 Responsible for forming urine
 Consist of renal corpuscle and renal tubule
 Renal corpuscle composed of a knot of capillaries
called the Glomerulus (a.k.a. Bowman’s Capsule)
 Renal tubule- enlarged, closed, cup-shaped end
giving rise to the PCT, dLOH, aLOH, DCT, and
CD.
PRESSURES IN RENAL CIRCULATION

• Arcuate artery = 100 mm Hg

• Glomerulus = 60 mm Hg

• Efferent arteriole = 13 mm Hg

• Peritubular capillaries = 13 mm Hg

• Venules = 10 mm Hg

• Final veins = 8 mm Hg Fig: Pressure profile of renal circulation. Ra, renal artery; Aa,
afferent arteriole; Glom, glomerular capillaries; Ea, efferent
arteriole; Pc, peritubular capillaries; V, venule; Rv, renal vein
 Glomerulus Capillaries
• Glomerular membrane has 3 major layers:
• Endothelial layer
• Basement membrane
• Epithelial cells
• Permeability is 100 t0 500 more than that of the ordinary capillaries
Endothelial cells:
Have thousands of small holes in the endothelium of capillaries called fenestrations
Basement membrane:
Composed of a meshwork of fibrillae having large spaces
Epithelial cells
Not continuous but in form of finger like projections that cover the basement
membrane
Slit pores:
The fingers of epithelial cells form slits called slit pores through which glomerular filterate filters
Although the filterate passes through 3 layers but each one is several hundred times
more permeable than ordinary capillaries
High degree of selectivity for the molecules:
Completely impermeable to all plasma proteins but highly permeable to essentially all other
dissolved substances in normal plasma
REASONS FOR MOLECULAR SELECTIVITY: Effect of
size & Charge
• First:
• Diameter of the capillary pores is enough to allow molecules
with diameters up to 8 nm
• The size of protein molecules  only about 6 nm (why they
cant pass through?)
• Second:
• Glomerular pores are lined with a complex of glycosylated
proteins with very strong negative charge
• Plasma proteins also have the negative charge 
electrostatic repulsion
Renal Tubule
 Glomerular (Bowman’s) capsule
enlarged beginning of renal tubule
 Proximal convoluted tubule- lumen
surface (surface exposed to filtrate) is
covered with dense microvilli to increase
surface area.
 The descending limb of the nephron -
Loop of Henle
 The ascending limb of the nephron coils
tightly again into the distal convoluted
tubule
 Many DCT’s merge in renal cortex to
form a collecting duct
 Collecting ducts not a part of nephron
 Collecting ducts receive urine from
nephrons and deliver it to the major
calyx and renal pelvis.
 CD run downward through the
medullary pyramids, giving them their
striped appearance.
Blood Supply of a Nephron
 Peritubular capillary
 Efferent arteriole braches into a second capillary bed
 Blood under low pressure
 Capillaries adapted for reabsorption instead of filtration.
 Attached to a venule and eventually lead to the interlobular
veins to drain blood from the glomerulus
 Cling close to the renal tubule where they receive solutes and
water from the renal tubule cells as these substances from the
filtrate are reabsorbed into the blood.
 Juxtaglomerular apparatus
 At origin of the DCT it contacts afferent and efferent arterioles
 Epithelial cells of DCT narrow and densely packed, called
macula densa
 Together with smooth muscle cells, comprise the
juxtaglomerular apparatus
 Control renin secretion & indirectly, aldosterone secretion
Types of Nephrons
 Cortical nephrons
 Located entirely in the cortex
 Includes most nephrons
 Juxtamedullary nephrons
 Found at the boundary of the cortex and medulla and
their LOH dip deep into the medulla.
Urine Formation Processes
 Filtration- Water & solutes
smaller than proteins are forced
through the capillary walls and
pores (of the glomerulus) into the
renal tubule (Bowman’s capsule).
 Reabsorption- Water, glucose,
amino acids & needed ions are
transported out of the filtrate into
the peritubular capillary cells and
then enter the capillary blood.
 Secretion- Hydrogen ions,
Potassium ions, creatinine & drugs
are removed from the peritubular
capillaries (blood) and secreted by
the peritubular capillary cells into
the filtrate.
Filtration
 Beginning step of urine formation
 Occurs at the glomerulus, nonselective passive process
 Water and solutes smaller than proteins are forced through
capillary walls of the glomerulus, which act as a filter.
 Fenestrations – (openings in glomerular walls) make
glomerulus more permeable than other arterioles.
 Podocytes cover capillaries, make membrane impermeable to
plasma proteins.
 Blood cells cannot pass
out to the capillaries; filtrate
is essentially blood plasma
w/o blood proteins, blood cells.
 Filtrate is collected in the
glomerular (Bowman’s) capsule
and leaves via the renal tubule
Filtration pressure
 Hydrostatic pressure of blood forces substances through
capillary wall.
 Net filtration pressure normally always positive
 Hydrostatic pressure of blood is greater than the hydrostatic
pressure of the glomerulus capsule and the osmotic
pressure of glomerulus plasma
 If arterial blood pressure
falls dramatically, the glomerular
hydrostatic pressure falls below
level needed for filtration.
 The epithelial cells of renal
tubules lack nutrients and
cells die. Can lead to renal failure.
Determinants of 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.
Filtration rate
 Rate of filtration is directly proportional to net filtration pressure.
 Regulation of filtration rate
 Rate typically constant; may need to increase or
decrease to maintain homeostasis
 1. Sympathetic nervous system reflexes
 Respond to drops in blood pressure and blood volume
As pressure drops, sympathetic nerves cause
vasoconstriction of afferent arterioles.
Decreases rate of filtration
Less urine produced, water is conserved
As pressure rises, sympathetic nerves cause
vasodilation of efferent arterioles.
Increases rate of filtration
More urine produced, water is removed
Filtration rate
 2. Renin production by JGA
 Renin is an enzyme controlling filtration rate
 Juxtaglomerular cells secrete renin in response to 3 stimuli
 Sympathetic stimulation (fast response)
 Specialized pressure receptors in afferent arterioles
sense decrease in blood pressure
 Macula densa senses decrease in chloride, potassium,
and sodium ions reaching distal tubule
 Released renin reacts with angiotensinogen in bloodstream
to form angiotensin I  which is converted into angiotensin
II by the angiotensin I converting enzyme, ACE
 Angiotensin II acts to vasoconstriction efferent arteriole
 Blood backs up into glomerulus, increasing pressure and
maintains filtration rate
 Angiotension II also stimulates secretion of aldosterone
from adrenal glands
 Stimulates tubular reabsorption of sodium & H2O follows
RAAS (renin-angiotensin-aldosterone system)
Reabsorption
 The composition of urine is different than the composition of
glomerular filtrate.
 Tubular reabsorption returns substances to the internal
environment of the blood by moving substances through
the renal tubule walls into the peritubular capillaries (99%)
 Some water, ions, glucose, amino acids
 Some reabsorption is passive = water  osmosis
= small ions diffusion
 Most is active using protein carriers  by active transport
 Most reabsorption occurs in the proximal convoluted tubule,
where microvilli cells act as transporters, taking up needed
substances from the filtrate and absorbing them into the
peritubular capillary blood.
 Substances that remain in the renal tubule become more
concentrated as water is reabsorbed from the filtrate.
Reabsorption – sodium and water
 The sodium potassium pump reabsorbs 70% of sodium ions
in the PCT.
 The positive sodium ions attract negative ions across the
membrane as well
 Water reabsorption occurs passively across the membrane
to areas of high solute concentration
 Therefore, more sodium reabsorption = more water
reabsorption
 Active transport of sodium
ions occurs along remainder
of nephron and collecting duct
 Almost all sodium ions
and water are reabsorbed.
Materials Not Reabsorbed
 Nitrogenous waste products
 Urea – formed by liver; end product of
protein breakdown when amino acids are
used to produce energy
 Uric acid – released when nucleic acids are
metabolized
 Creatinine – associated with creatine
metabolism in muscle tissue
 Excess water
 Secretion – Reabsorption in Reverse
 Some materials move from the peritubular capillaries
into the renal tubules to be eliminated in urine.
 Example:
 Hydrogen ions; potassium ions
 Creatinine
 Drugs; penicillin; histamine
 Process is important for getting rid of substances not
already in the filtrate or for controlling pH.
 Materials left in the renal tubule move toward the
ureter
 Formation of Urine
Summary:
• glomerular filtration of
materials from blood
plasma
•Reabsorption of
substances, including
glucose; water, sodium
•Secretion of substances,
including penicillin,
histamine, hydrogen and
potassium ions
The Link Between Water and Salt
 Changes in electrolyte balance causes water to move
from one compartment to another
 Alters blood volume and blood pressure (think of aldosterone)
 Can impair the activity of cells (swelling/edema)
 Water intake must equal water output
 Sources for water intake/output:
 Intake: Ingested foods and fluids, Water produced from
metabolic processes (glycolysis)
 Output: Vaporization out of the lungs, Lost in perspiration,
Leaves the body in the feces, Urine production
 Dilute vs. Concentrated Urine
 Dilute urine is produced if water intake is excessive
 Less urine (concentrated) is produced if large amounts of
water are lost
 Proper concentrations of various electrolytes must be present
Regulation of Water and Electrolyte Reabsorption
 Regulation is primarily by hormones
 Antidiuretic hormone (ADH) prevents excessive water
loss in urine
 Neurons in the hypothalamus produce ADH, which are
released by the anterior pituitary gland in response to a
decrease in blood volume or water concentration
 ADH increases the water permeability of the distal convoluted
tubule epithelium to the peritubular capillaries
Decreases volume of urine, increasing concentration
of solutes
Negative feedback control
 Aldosterone regulates sodium ion content of
extracellular fluid
 Triggered by the renin-angiotensin mechanism
 Stimulates the DCT to reabsorb sodium and excrete
potassium
 Cells in the kidneys and hypothalamus are active monitors
Maintaining Water and Electrolyte Balance
Potassium Regulation
• Potassium is filtered in the renal corpuscle and most of
it absorbed in the tubules.
• Any changes in potassium excretion, however, are
mainly due to changes in potassium secretion by
cortical collecting ducts.
• This secretion is associated with reabsorption of
sodium by Na, K-ATPase.
• Aldosterone-secreting cells are sensitive to potassium
concentration of their extracellular fluid and an
increased potassium concentration stimulates
aldosterone production, thereby increasing potassium
secretion and its excretion from the body.
Renal Water Regulation
• Water excreted = Water filtered – Water reabsorbed
Water excretion is regulated mainly at the level of reabsorption
by vasopressin.
• Baroreceptor control of vasopressin secretion
• Osmoreceptor control of vasopressin secretion
• Thirst
• Calcium Regulation
• Calcium is filtered in the renal corpuscle and most of it is reabsorbed.
There is no tubular secretion of calcium. Therefore, Calcium excreted
= Calcium filtered – Calcium absorbed Control of calcium excretion is
exerted mainly on reabsorption.
Hydrogen Ion Regulation
• Hydrogen ions can be redistributed in the body by binding
it reversibly with a buffer such as bicarbonates,
phosphates, proteins and Hb.
• Respiratory Mechanisms. Ventilation is altered by reflex
mechanisms in order to compensate for H+ ion imbalance.
• Renal Mechanisms. Kidneys compensate for H+ ion
imbalance by altering plasma HCO3– ion concentration. A
lowering of plasma H+ ion concentration results in
excretion of large quantities of HCO3– ions while a rise in
H+ ion concentration results in the production of
HCO3– ions and their addition to plasma by tubular cells.
 Maintaining Acid-Base Balance in
Blood
 Blood pH must remain between 7.35 and 7.45 to maintain
homeostasis
 Alkalosis – pH above 7.45
 Acidosis – pH below 7.35
 Most acid-base balance is maintained by the kidneys
 Excrete bicarbonate ions if needed
 Conserve / generate new bicarbonate ions if needed
 Excrete hydrogen ions if needed
 Conserve / generate new hydrogen ions if needed
 Regulation of these ions results in a urine pH range of 4.5 to 8.0
 Acidic urine: protein-rich diet, starvation, diabetes
 Basic urine: bacterial infections, vegetarian diet
Urine composition
 Composition differs considerably based upon diet,
metabolic activity, urine output.
 ~95% water, contains urea and uric acid,
electrolytes and amino acids (trace amount)
 Volume produced ranges from 0.6-2.5 liters per day
(1.8L average).
 Depends on fluid intake, body and ambient air
temperature, humidity, respiratory rate, emotional
state
 Output of 50-60ml per hour normal, less than 30ml
per hour may indicate kidney failure
 Ureters
 Slender tubes attaching the kidney to the bladder 10-12” long & ¼”
diameter
 Superior end is continuous with the renal pelvis of the kidney
 Mucosal lining is continuous with that lining the renal pelvis and
the bladder below.
 Enter the posterior aspect of the bladder at a slight angle
 Runs behind the peritoneum
 Peristalsis aids gravity in urine transport from the kidneys to the
bladder.
 Smooth muscle layers in the ureter walls contract to propel urine.
 There is a valve-like fold of bladder mucosa that flap over the ureter
openings to prevent backflow.
 Renal calculi= calculus means little stone; result of precipitated uric
acid salts created by bacterial infections, urinary retention, and
alkaline urine. Lithotripsy or surgery are common treatments.
Urinary Bladder
 Smooth, collapsible, muscular sac
 Temporarily stores urine
 Located retroperitoneally in the pelvis
posterior to the pubic symphysis.
Urinary Bladder
 Trigone – three openings
 Two from the ureters (ureteral orifices)
 One to the urethra (internal urethral orifice) which drains the
bladder.
 Common site for bacterial infections
 In males, prostate gland surrounds the neck of the bladder where it
empties into the urethra.
Urinary Bladder Wall
 Three layers of smooth muscle (detrusor muscle)
 Mucosa made of transitional epithelium
 Walls are thick and folded in an empty bladder 2-3” long
 Bladder can expand significantly without increasing
internal pressure
 As it fills, the bladder rises superiorly in the abdominal
cavity becoming firm and pear shaped.
 A moderately full bladder can hold ~500mL (1 pint) of
urine.
 A full bladder can stretch to hold more than twice that
amount.
 Urethra
 Thin-walled tube that carries urine from the bladder to
the outside of the body by peristalsis
 Release of urine is controlled by two sphincters
 Internal urethral sphincter (involuntary) – a thickening
of smooth muscle at the bladder-urethra jxn. keeps
urethra closed when urine is not being passed.
 External urethral sphincter (voluntary) --
skeletal muscle that controls urine as the
urethra passes through the pelvic floor.
Urethra Gender Differences
 Length
 Females – 3–4 cm (1-1.5 inches)
 Males – 20 cm (7-8 inches)
 Location
 Females – along wall of the vagina
 Males – through the prostate and penis
 Function
 Females – only carries urine
 Males – carries urine and is a passageway for
sperm cells
 Estimation of
glomerular filtration
rate
Clearance:

The clearance of a substance is the volume of

plasma from which the substance was completely
cleared by the kidneys per unit time, (units = vol.
plasma/time),
CX = UX V
PX
Clearance of ‘X’, CX = GFR when the
substance ‘X’ meets the following criteria,
i. freely filterable at the glomerulus
ii. not reabsorbed by tubules
iii. not secreted by tubules
iv. not synthesised by tubules
v. not broken-down by tubules
Creatinine

is formed from muscle creatine and is released

at approximately a constant rate. Therefore
blood [Cr] changes little per 24 hrs.
However, Cr is secreted by the tubules and
overestimates GFR by small amount.
for freely filterable substances, when,
a. CX < CIN  net tubular reabsorption
b. CX > CIN  net tubular secretion
 Creatinine clearance:
In clinical practice creatinine clearance may be
used to estimate GFR for the following
reasons.
1. Inulin is not produced endogenously.
Therefore, it must be infused intravenously if it is to be
used in renal function tests.
It is much more convenient to use a substance that is
normally present in plasma that is freely filtered, but
neither secreted, nor reabsorbed.
2. Creatinine, a normal breakdown product of creatine, is
an endogenous compound that fulfils these criteria.
Endocrine functions of Kidney