Kidney

Most individuals are familiar with a key role of the kidneys - eliminating waste materials from the body
that are either ingested or produced by metabolic processes. The kidneys carry out this critical task by
filtering the plasma and selectively removing substances from the filtrate at varying rates, based on the
needs of the body. Ultimately, the kidneys "clean" unwanted substances from the filtrate (and thus from
the blood) by excreting them in urine while returning needed substances back to the bloodstream.

Additional kidney functions include:

 Excretion of metabolic waste products and foreign chemicals

 Regulation of water and electrolyte balance

 Regulation of body fluid osmolality and electrolyte concentrations

 Regulation of blood pressure

 Regulation of acid-base equilibrium

 Secretion, metabolism, and excretion of hormones

 Gluconeogenesis

Excretion of Metabolic Wastes, Foreign Chemicals, Drugs, and Hormone Byproducts.

The kidneys are the primary organ for eliminating unnecessary metabolic waste products from the body.
These wastes include urea (from amino acid metabolism), creatinine (from muscle creatine), uric acid
(from nucleic acids), end products of hemoglobin breakdown like bilirubin, and byproducts of various
hormones. These waste substances must be rapidly removed from the body as they are produced. The
kidneys also eliminate most toxins and foreign chemicals produced in or ingested by the body, such as
pesticides, pharmaceutical drugs, and food additives.

Renal Regulation of Water Balance

The kidneys play a vital role in regulating the body's water balance to maintain fluid homeostasis. This
regulation occurs through the following key processes:

Water is filtered along with solutes from the blood by the glomeruli into the renal tubules. Around 180
liters per day are filtered. - Most of the filtered water (~178 liters/day) is reabsorbed back into the
bloodstream along the tubules, mainly in the proximal convoluted tubule and loop of Henle.

The hypothalamus contains osmoreceptors that monitor the osmolality of the blood. If blood osmolality
increases, indicating dehydration, the hypothalamus in conjunction with the kidney triggers
compensatory mechanisms to retain water and increase water intake. The hypothalamus stimulates the
secretion ADH from the posterior pituitary gland when osmolality rises. ADH acts on the collecting ducts
in the kidneys to increase the number of aquaporin water channels, making the duct walls more
permeable to water. This allows more water to be reabsorbed from the filtrate back into the blood to
dilute the blood. The effects of ADH lead to the production of smaller volumes of more concentrated
urine, conserving body water. The retention of water causes blood osmolality to decrease back toward
normal levels, turning off the thirst center and decreasing ADH release.

Renal Regulation of Electrolyte balance

The kidneys precisely regulate electrolyte concentrations in the body through coordinated filtration,
reabsorption, and secretion of electrolytes along the nephron tubules. This allows the maintenance of
normal electrolyte composition of body fluids. Aldosterone, secreted by the adrenal cortex, plays a key
role in the renal regulation of sodium, potassium, and fluid balance. The stimulus for aldosterone
secretion dereased renal blood flow secondary to reduced blood pressure.

 Reduced blood flow/pressure to the kidneys activates the juxtaglomerular cells to secrete renin.

 Renin cleaves angiotensinogen to angiotensin I. ACE converts this to angiotensin II.

 Angiotensin II stimulates the adrenal cortex to synthesize and secrete the hormone aldosterone.

 In the collecting duct, aldosterone increases sodium reabsorption by stimulating insertion of

sodium channels (ENaC) into the luminal membrane.

 The increased sodium reabsorption creates an osmotic gradient that causes increased passive
reabsorption of water.

 The retention of sodium and water expands the extracellular fluid volume, increasing blood
volume.

 The increased sodium reabsorption also stimulates Na/K ATPase activity, leading to increased
potassium secretion into the tubule lumen.

 The expanded blood volume leads to increased blood pressure.

 The increased blood pressure inhibits renin release and angiotensin II production by the kidneys.

 With less angiotensin II, aldosterone synthesis/secretion decreases.

 This reduces sodium reabsorption, allowing more sodium excretion.

 Blood volume and pressure decrease back toward normal levels.

Regulation of Arterial Blood Pressure

The kidneys play a dominant role in longterm regulation of arterial pressure by excreting variable
amounts of sodium and water. It utilizes the mechanisms already described in water and electrolyte
balance to achieve longterm control of blood pressure. The kidneys also contributeto short-term arterial
pressure regulation by secreting hormones and vasoactive factors or substances (e.g.,renin) that lead to
the formation of vasoactive products(e.g., angiotensin II).

Regulation of Acid-Base Balance. In addition to the lungs and body fluid buffers, the kidneys help
regulate acid-base balance by excreting acids and regulating the body's buffer stores. The kidney
achieves this through various mechanisms including

 Filter H+ ions - H+ ions are filtered out of the blood into the renal tubules to help regulate pH.

 Excrete acids - The kidneys eliminate acids that cannot be excreted by the lungs, including
sulfuric acid and phosphoric acid from protein metabolism.

 Reabsorb filtered HCO3- - Filtered bicarbonate is reabsorbed by the renal tubules to conserve
plasma buffers.

 Generate new HCO3- - Renal tubular cells produce new bicarbonate from carbonic acid to
replace plasma buffers lost in urine.

 Secrete H+ - Renal tubular cells secrete H+ ions into the tubule, which combine with filtered
HCO3- to form carbonic acid and CO2. The CO2 exits in the urine.

 Excrete ammonium - Renal glutaminase converts glutamine to ammonia and ammonium ions.
Ammonium binds with H+ and is excreted, reducing acidity.

 Adapt to changes - The kidneys adjust rates of acid excretion and new bicarbonate generation to
match changes in acid-base status and buffer needs.

Regulation of Red Blood Cell Production. The kidneys secrete erythropoietin, which spurs red blood cell
production from hematopoietic stem cells in the bone marrow,. A key trigger for erythropoietin
secretion by the kidneys is hypoxia. Under normal conditions, the kidneys account for nearly all
erythropoietin secreted into the circulation. In people with severe kidney disease or who have had their
kidneys removed and are on hemodialysis, severe anemia develops due to decreased erythropoietin
production.

Regulation of Calcitriol Production. The kidneys produce the active form of vitamin D, 1,25-
dihydroxyvitamin D3 (calcitriol), by hydroxylating this vitamin at the "number 1" position. Calcitriol is
essential for normal calcium deposition in bone and calcium reabsorption by the gastrointestinal tract.
The kidneys play an essential role in regulating the production of 1,25-dihydroxyvitamin D3, also known
as calcitriol, the biologically active form of vitamin D. Calcitriol is synthesized in the kidneys by
hydroxylation of vitamin D at the 1-position by the enzyme 25-hydroxyvitamin D-1-alpha-hydroxylase.
This enzymatic conversion of vitamin D into its active form is tightly regulated by the kidneys in response
to the body's needs for calcium and phosphate absorption and bone mineralization.

When plasma calcium levels begin to decline, calcitriol production is upregulated by the kidneys.
Calcitriol enhances intestinal absorption of calcium and phosphate by increasing the expression of
epithelial calcium channels and phosphate transporters. In the bones, calcitriol stimulates osteoblasts
and promotes mineralization of the bone matrix. Together, these effects help restore plasma calcium
concentrations back toward normal. The rise in blood calcium then provides negative feedback to the
parathyroid glands, decreasing the secretion of parathyroid hormone (PTH). PTH normally stimulates
calcitriol synthesis, so reduced PTH decreases the production of calcitriol when calcium levels are
adequate.

Glucose Synthesis. The kidneys play an important role in glucose homeostasis through their ability to
perform gluconeogenesis, which is the generation of glucose from non-carbohydrate precursors such as
lactate, glycerol, and amino acids. During prolonged fasting when glycogen stores are depleted, renal
gluconeogenesis serves as a critical source of glucose production to help maintain blood glucose levels.

The kidneys receive a high load of lactate and amino acids like glutamine and alanine which can serve as
substrates for renal gluconeogenesis. The kidneys contain all the necessary enzymes to convert these
precursors into glucose through a series of reactions analogous to hepatic gluconeogenesis. The glucose
that is synthesized de novo can then be released into the circulation via glucose transporters expressed
in the renal vein, supplementing the glucose produced by the liver.

During fasting conditions, hormones like glucagon and glucocorticoids stimulate the kidneys to increase
the rate of gluconeogenesis, while insulin inhibits renal glucose production. The capacity for glucose
synthesis by the kidneys approaches that of the liver during prolonged fasting. ATP generated from renal
oxidative metabolism provides energy for the gluconeogenic reactions. Therefore, the kidneys play an
essential role, along with the liver, in maintaining glucose homeostasis through hormonally-regulated
gluconeogenesis, preventing life-threatening hypoglycemia during fasting.

Physiologic Analysis of the Kidney

The two kidneys are located on the back wall of the abdomen, outside the peritoneal cavity. In adults,
each kidney weighs about 150 grams and is roughly the size of a fist. The indented region on the inner
side of each kidney is called the hilum, through which pass the renal artery and vein, lymph vessels,
nerves, and the ureter that carries urine from the kidney to the bladder for storage until urination. The
kidney is enveloped by a tough fibrous capsule that protects the delicate interior structures.

When bisected from top to bottom, two main regions are visible - the outer cortex and the inner
medulla. The medulla consists of 8 to 10 cone-shaped tissue masses called renal pyramids. The base of
each pyramid lies at the border of the cortex and medulla, and terminates at the papilla which projects
into the renal pelvis. The pelvis is a funnel-shaped continuation of the upper end of the ureter. The
outer border of the pelvis divides into pouches called major calyces, which branch into minor calyces
that collect urine from the tubules of each papilla. The walls of the calyces, pelvis and ureter contain
muscle fibers that propel the urine into the bladder for storage until it is emptied by urination.

Renal Blood Flow

Under normal conditions, approximately 22% of cardiac

output, or 1100 mL/min, flows to the two kidneys. The renal artery enters each kidney through the
hilum and progressively branches into interlobar arteries, arcuate arteries, interlobular arteries (also
called radial arteries), and afferent arterioles, which supply the glomerular capillaries. It is at the
glomerular capillaries where large volumes of fluid and solutes, except for plasma proteins, are filtered
from the blood to begin the process of urine formation.

After passing through the glomerular capillaries, the blood enters efferent arterioles, then flows into a
second capillary network surrounding the renal tubules called the peritubular capillaries. This allows
reabsorption and secretion between the peritubular capillaries and tubular fluid. The peritubular
capillaries converge into venules then veins, finally exiting the kidney as the renal vein through the renal
hilum.
The renal circulation is unique in having two capillary beds - glomerular and peritubular - arranged in
series and separated by the efferent arterioles. The efferent arterioles help regulate the hydrostatic
pressure in both capillary systems. High pressure (≈60 mm Hg) in the glomerular capillaries causes rapid
fluid filtration, while much lower pressure (≈13 mm Hg) in the peritubular capillaries allows rapid
reabsorption. By adjusting resistance of the afferent and efferent arterioles, the kidneys can regulate
pressure in the glomerular and peritubular capillaries, thereby altering the rates of filtration and
reabsorption to meet homeostatic needs. Precise regulation of renal blood flow and glomerular filtration
is critical for proper kidney function.

Diagram showing the Major Vessel Supplying the Kidney

The Nephron

Each human kidney contains about 800,000 to 1 million nephrons, which are the functional units
capable of forming urine. The kidneys cannot regenerate new nephrons, so kidney injury, disease, or
aging leads to a gradual decrease in nephron number. After age 40, the number of functioning nephrons
declines around 10% per decade. By age 80, many people have 40% fewer working nephrons than at age
40. This loss is not life-threatening because the remaining nephrons undergo adaptive changes to
excrete proper amounts of water, electrolytes, and wastes, as discussed in Chapter 31.

Each nephron is composed of (1) a tuft of glomerular capillaries called the glomerulus, where large
volumes of fluid are filtered from the blood, and (2) a long tubule in which the filtrate is converted to
urine as it flows toward the renal pelvis.
The glomerulus contains intertwining glomerular capillaries with high hydrostatic pressure (≈60 mm Hg)
compared to other capillaries. The glomerular capillaries are surrounded by epithelial cells and encased
in Bowman's capsule.

Fluid filtered from the glomerular capillaries enters Bowman's capsule then the proximal tubule in the
renal cortex. It then flows into the loop of Henle, which dips into the medulla, consisting of a descending
and ascending limb. The walls of the descending limb and lower ascending limb are very thin and called
the thin segment. After the ascending limb returns partway to the cortex, its walls thicken, becoming the
thick ascending limb.

At the end of the thick ascending limb is the macula densa, a plaque of specialized cells that helps
control nephron function. Fluid then enters the distal tubule in the cortex, followed by the connecting
tubule, cortical collecting tubule, and collecting ducts, which empty urine into the renal pelvis through
the papillae. The kidneys contain two main types of nephrons - cortical and juxtamedullary - which differ
in their structures and locations.

Although all nephrons contain the same components, there are structural differences depending on the
nephron's depth within the kidney. Nephrons with glomeruli in the outer cortex are cortical nephrons.
They have short loops of Henle that extend only a small distance into the medulla.

About 20-30% of nephrons are juxtamedullary nephrons, which have glomeruli deep in the cortex near
the medulla. Their long loops of Henle dip far into the medulla, sometimes all the way to the renal
papilla tips.

The blood supply also differs between cortical and juxtamedullary nephrons. Cortical nephrons are
surrounded along their entire tubular system by an extensive peritubular capillary network. For
juxtamedullary nephrons, long efferent arterioles from the glomeruli extend into the outer medulla,
then divide into specialized peritubular capillaries called vasa recta.

The vasa recta run downward alongside the long loops of Henle into the deeper medulla, then return to
the cortex and empty into cortical veins. This unique capillary network in the medulla is essential for
concentrating urine. The differences in loop of Henle length and vasa recta blood supply allow
juxtamedullary nephrons to concentrate urine more than cortical nephrons.

The Bladder

The urinary bladder is a smooth muscle chamber composed of two main parts - the body, which collects
urine, and the neck, a funnel-shaped extension that connects to the urethra.

The smooth muscle of the bladder body is called the detrusor muscle. Its fibers extend in all directions
and can generate pressures up to 60 mm Hg when contracted, which empties the bladder. Detrusor
muscle cells are electrically coupled, allowing action potentials to spread rapidly throughout the muscle.
On the posterior bladder wall above the neck lies the trigone, a triangular area where the two ureters
enter the upper angles and the bladder neck opens at the lower apex into the posterior urethra. The
trigone mucosa is smooth, unlike the rugae of the bladder body.

The ureters tunnel obliquely through the detrusor muscle before entering the bladder subsurface. The
2-3 cm long bladder neck/posterior urethra is composed of detrusor muscle and elastic tissue called the
internal sphincter. Its tonic contraction prevents bladder emptying until pressure in the main bladder
rises sufficiently.

Beyond the posterior urethra, the urethra passes through the urogenital diaphragm, containing a layer
of voluntary skeletal muscle called the external sphincter. This muscle is consciously controlled to
prevent urination even when involuntary systems attempt to empty the bladder.

Innervation of the Bladder

The principal nerve supply to the bladder is through the pelvic nerves connecting with the sacral spinal
cord, mainly segments S2-S3. The pelvic nerves contain sensory fibers that detect bladder wall stretch,
especially from the posterior urethra, which initiates reflexes for bladder emptying.

Pelvic nerves also contain parasympathetic motor fibers that synapse with ganglion cells in the bladder
wall. Short postganglionic nerves then innervate the detrusor muscle.

Two other innervations are important. Voluntary skeletal motor fibers passing in the pudendal nerve
control the external sphincter. Also, the hypogastric sympathetic nerves, connecting with the lumbar
cord, stimulate mainly the bladder blood vessels, with some sensory fibers involved in fullness and pain
sensations.

Therefore, the pelvic nerves provide the main sensory signals to initiate urination and parasympathetic
motor input to the detrusor muscle, while the pudendal nerve controls the external sphincter, and the
hypogastrics have a minor role in bladder blood flow and sensation.

Micturition

As the bladder fills, many small micturition contractions appear. These result from a stretch reflex
initiated by sensory receptors in the bladder wall, especially in the posterior urethra as it fills at higher
pressures. Sensory signals from the stretch receptors are conducted by the pelvic nerves to the sacral
cord and reflexively back to the bladder via parasympathetic fibers, causing contraction.

When the bladder is partially filled, these micturition contractions often relax spontaneously after a
short time as the detrusor muscle stops contracting and pressure falls. As the bladder continues filling,
the micturition reflexes become more frequent and vigorous.

Once a micturition reflex begins, it is "self-regenerative" - initial bladder contraction activates the stretch
receptors, increasing sensory signals and causing greater reflexive contraction. This cycle repeats,
intensifying the contraction over seconds to a minute until the reflex fatigues and the regenerative
process ceases, allowing bladder relaxation. The micturition reflexes provide an intrinsic means for the
bladder to empty itself at appropriate times.

Micturition Reflex

Sensory signals from bladder stretch receptors travel via pelvic nerve sensory fibers to the sacral spinal
cord. In response, efferent motor impulses are generated in the cord and conducted by pelvic nerve
motor fibers back to the bladder and internal sphincter. These motor signals cause contraction of the
detrusor muscle and relaxation of the internal sphincter, allowing urine to enter the urethra from the
bladder.

Once urine stretches the urethral receptors, sensory signals are sent via pelvic nerves to the spinal cord.
Impulses generated in the cord then inhibit the pudendal nerve, causing the external sphincter to relax
so that micturition can occur.

The micturition reflex is self-regenerative - initial bladder contraction further activates stretch receptors,
increasing sensory signals from the bladder and urethra. The greater sensory input causes stronger
reflexive bladder contraction. This cycle continues, intensifying contraction until urine is fully voided.

During micturition, urine flow is facilitated by increased abdominal pressure from voluntary contraction
of the abdominal muscles. The elegant coordination of parasympathetic excitation of the detrusor
muscle and simultaneous inhibition of the internal and external sphincters allows complete bladder
emptying.
Abnormalities of micturition

Atonic Bladder and Incontinence from Sensory Loss

Destruction of the sensory nerve fibers from the bladder to the spinal cord prevents transmission of
stretch signals, causing atonic bladder and urinary incontinence despite intact efferent and central
pathways. The bladder simply fills to capacity and leaks small amounts, called overflow incontinence.
This can result from spinal cord trauma or diseases damaging the dorsal root fibers.

Automatic Bladder After Upper Spinal Cord Damage

If the spinal cord is damaged above the sacral segments but the sacral cord remains intact, micturition
reflexes still occur but without brain control. For days to weeks after the damage, reflexes are
suppressed by spinal shock. However, periodic catheterization prevents overstretching until the reflexes
recover and uncontrolled bladder emptying begins. Scratching the genital region can elicit the reflex in
some patients.

Uninhibited Neurogenic Bladder from Loss of Inhibition

Lack of inhibitory signals from the brain due to partial spinal/brain stem lesions causes frequent, poorly
controlled urination from highly excitable sacral micturition centers. Even small urine volumes elicit
unstoppable reflexes due to constant facilitative signals without inhibition. Thus, interruption of central
inhibition can lead to neurogenic bladder problems.

Urine Formation

The rate of urinary excretion of a substance represents the sum of three renal processes:

1. Glomerular filtration

2. Tubular reabsorption from the tubules into blood

3. Tubular secretion from blood into the tubules

This can be expressed as:

Excretion rate = Filtration rate - Reabsorption rate + Secretion rate

Urine formation begins with filtration of large volumes of protein-free fluid from the glomerular
capillaries into Bowman's capsule. Concentrations of most plasma solutes, except proteins, are almost
equal in the glomerular filtrate and plasma due to free filtration.

As the filtrate flows through the tubules, it is modified by reabsorption of water and specific solutes
back into the bloodstream or by secretion of other substances from the peritubular capillaries into the
tubules.
For each solute, the combination of its filtration, reabsorption, and secretion rates determines its rate of
urinary excretion. Therefore, urine composition reflects the relative rates of these three processes for
each constituent.

Glomerular Filtration

Urine formation begins with filtration of large volumes of fluid across the glomerular capillaries into
Bowman's capsule. Similar to most capillaries, the glomerular capillaries are relatively impermeable to
proteins, so the resulting glomerular filtrate contains no proteins or cells, including red blood cells.

The concentrations of most salts and small organic molecules in the glomerular filtrate are almost equal
to their plasma concentrations, since these substances are freely filtered. However, some low molecular
weight substances like calcium and fatty acids are partially bound to plasma proteins, so only their free,
unbound portions are filtered through the glomerular capillaries. For instance, about half of the plasma
calcium and most plasma fatty acids are protein-bound, so their concentrations in the filtrate are lower
than in plasma.

In summary, the glomerular filtrate formed is protein-free and has similar concentrations of freely
filtered substances as plasma, except for protein-bound solutes whose filtration is restricted. This filtrate
flowing into Bowman's capsule represents the initial stage of urine formation

The glomerular filtrate formed by filtration across the glomerular capillaries is protein-free and lacks
cells, similar to plasma except for proteins. Concentrations of most small solutes like salts and organics
match plasma. Exceptions include some substances like calcium and fatty acids that are partially plasma
protein-bound, so only the free portion is filtered.

Glomerular Filteration Rate (GFR)

The GFR is determined by the balance of hydrostatic and colloid osmotic forces and the capillary
filtration coefficient Kf, a measure of permeability and surface area. Glomerular capillaries have a very
high filtration rate due to the high hydrostatic pressure and large Kf.

In average adults, the GFR is about 125 mL/min or 180 L/day. About 20% of the renal plasma flowing
through the kidneys is filtered into the nephron tubules - this filtration fraction of 0.2 means GFR/renal
plasma flow is about 1/5. The high glomerular pressure, filtration coefficient, and large surface area
allow large volumes of filtrate formation while preventing protein loss.

Glomerular Capillary Membrane

The glomerular capillary membrane has three major layers that together act as a filtration barrier:

1. Capillary endothelium - This layer contains numerous fenestrations, or small pores, that allow
high permeability while the cell's negative charges hinder protein filtration.
 2. Basement membrane - This consists of a meshwork of collagen and proteoglycan fibrils with
large spaces that allow easy passage of water and small solutes but block proteins, partly due to
the strong negative charges of proteoglycans.

3. Podocytes - Epithelial cells line the outer surface with interdigitating foot processes that encircle
the capillary. Slit pores between these processes allow filtration while preventing protein loss.

This unique three-layered structure, especially the fenestrated endothelium and podocyte slit
membranes, allows the glomerular capillaries to have both a filtration rate hundreds of times higher
than other capillaries and a selectively high permeability to water and small solutes over proteins. This
allows the formation of large volumes of protein-free filtrate.

Size and charge are some of the major factors that determine the filterability of solutes in plasma
Despite having a molecular diameter of only ~6 nm, the plasma protein albumin is normally prevented
from filtering through the ~8 nm pores of the glomerular membrane. This restriction of albumin
filtration is due to its negative charge and electrostatic repulsion by the negatively charged
proteoglycans of the glomerular capillary wall.

In some kidney diseases, negative charges on the basement membrane are lost even before other
histological changes can be observed, called minimal change nephropathy. This loss of the basement
membrane's negative charges allows increased filtration of some small proteins like albumin, leading to
proteinuria or albuminuria.

Therefore, the negative charges of the basement membrane play a key role in blocking filtration of
negatively charged plasma proteins like albumin, which are smaller than the physical pore size.
Neutralization of these charges can lead to abnormal plasma protein filtration and excretion before
other signs of glomerular damage are present.

The GFR is determined by:

1. The net filtration pressure - the sum of hydrostatic and colloid osmotic forces across the
glomerular membrane

2. The glomerular capillary filtration coefficient (Kf)

The GFR equation is:

GFR = Kf x Net Filtration Pressure

The net filtration pressure is determined by forces favoring filtration:

 Glomerular hydrostatic pressure (PG) - promotes filtration

 Bowman's capsule colloid osmotic pressure (πB) - promotes filtration

And forces opposing filtration:

 Bowman's capsule hydrostatic pressure (PB) - opposes filtration

 Glomerular capillary colloid osmotic pressure (πG) - opposes filtration

The net filtration pressure is calculated as:

PG - PB - πG + πB

Normally πB ≈ 0 mmHg because proteins in the filtrate are very low.

For example: PG = 60 mmHg (favoring filtration) PB = 18 mmHg (opposing filtration) πG = 32 mmHg

(opposing filtration) πB = 0 mmHg Net Filtration Pressure = 60 - 18 - 32 = +10 mmHg

Therefore, the GFR is determined by the balance of hydrostatic and colloid osmotic forces across the
glomerular capillary membrane as well as the permeability and surface area represented by Kf.

The GFR is determined by:

1. The net filtration pressure - the sum of hydrostatic and colloid osmotic forces across the
glomerular membrane

2. The glomerular capillary filtration coefficient (Kf)

The GFR equation is:

GFR = Kf x Net Filtration Pressure

The net filtration pressure is determined by forces favoring filtration:

 Glomerular hydrostatic pressure (PG) - promotes filtration

 Bowman's capsule colloid osmotic pressure (πB) - promotes filtration

And forces opposing filtration:

 Bowman's capsule hydrostatic pressure (PB) - opposes filtration

 Glomerular capillary colloid osmotic pressure (πG) - opposes filtration

The net filtration pressure is calculated as:

PG - PB - πG + πB

Normally πB ≈ 0 mmHg because proteins in the filtrate are very low.

For example: PG = 60 mmHg (favoring filtration) PB = 18 mmHg (opposing filtration) πG = 32 mmHg

(opposing filtration) πB = 0 mmHg Net Filtration Pressure = 60 - 18 - 32 = +10 mmHg

Therefore, the GFR is determined by the balance of hydrostatic and colloid osmotic forces across the
glomerular capillary membrane as well as the permeability and surface area represented by Kf.