final study guide

PCB3702L Dr. Lisa Brinn Urinary System Lab

I. Overview of Renal Physiology – The kidneys do most of the work within the urinary system.

Other parts are mainly passageways and storage areas. The functions of the kidneys include

the following:

A. Excretion of wastes - By forming urine, kidneys help excrete wastes from body. Some

wastes excreted in urine result from metabolic reactions. These include urea and ammonia

from deamination of amino acids; creatinine from breakdown of creatine phosphate; uric

acid from catabolism of nucleic acids; and urobilin from breakdown of hemoglobin. These

products are collectively known as nitrogenous wastes because they are waste products

that contain nitrogen. Other wastes excreted in the urine are foreign substances that have

entered the body, such as drugs and environmental toxins.

B. Regulation of blood ionic composition - Kidneys help regulate the blood levels of several

ions by adjusting the of these ions that are excreted into urine, including sodium ions (Na+),

potassium ions (K+), calcium ions (Ca2+), chloride ions (Cl−), and phosphate ions (HPO4 2−).

C. Regulation of blood pH - Kidneys excrete a variable amount of hydrogen ions (H+) into the

urine and conserve bicarbonate ions (HCO3 −), which are an important buffer of H+ in blood.

Both activities help regulate blood pH.

D. Regulation of blood volume - Kidneys adjust blood volume by returning water to blood or

eliminating it in urine. An increase in blood volume increases blood pressure; a decrease in

blood volume decreases blood pressure.

E. Regulation of blood pressure - Kidneys help regulate blood pressure by secreting the

enzyme renin, which activates the renin–angiotensin–aldosterone pathway. Increased

renin causes increase in blood pressure.

F. Maintenance of blood osmolarity - By separately regulating loss of water and loss of

solutes in the urine, kidneys maintain a relatively constant blood osmolarity close to 300

milliosmoles per liter (mosmol/liter). (The osmolarity of a solution is a measure of the total

number of dissolved particles per liter of solution. The particles may be molecules, ions, or a

mixture of both. A similar term, osmolality, is the number of particles of solute/kg water.

Since it is easier to measure volumes of solutions than to determine the mass of water they

contain, osmolarity is used more commonly than osmolality).

G. Production of hormones - Kidneys produce two hormones. Calcitriol, the active form of

vitamin D, helps regulate calcium homeostasis, and erythropoietin stimulates the

production of erythrocytes.

II. Organization of the Kidneys

A. Kidneys

1. Paired bean-shaped organs just above the waist

2. Kidney structure

a. Contains an outer layer called the cortex

b. Contains an inner area called the medulla

c. Renal pyramids - Several cone-shaped structures located within the renal

medulla

d. Major and minor Calyces (singular is calyx)

e. Renal pelvis that leads urine into ureter

and then urinary bladder

3. Functional unit of the kidney is the nephron

a. Nephron parts:

1) Renal corpuscle - where blood plasma is filtered. The two components

of a renal corpuscle are the glomerulus (a capillary network) and

Bowman's capsule, or glomerular capsule, a double-walled epithelial

cup that surrounds the glomerular capillaries

2) Renal tubule - Once blood plasma is filtered at the renal corpuscle, the

filtered fluid passes into the renal tubule, which consists of a single

layer of epithelial cells that lines a lumen. The renal tubule has three

main sections: proximal tubule, loop of Henle, and distal tubule.

The renal corpuscle, proximal tubule, and distal tubule lie within the renal cortex; the loop of Henle

extends into the renal medulla, makes a hairpin turn, and then returns to the renal cortex. From the

renal corpuscle, filtered fluid first enters the proximal tubule. The term proximal denotes that this

part of the renal tubule is closest to the site where the renal tubule attaches to Bowman's capsule.

Most of the proximal tubule is convoluted, which means that it is coiled rather than straight. From the

proximal tubule, filtered fluid enters the loop of Henle, also known as the nephron loop. The first part

of the loop of Henle dips into the renal medulla, where it is called the descending limb. It then makes

that hairpin turn and returns to the renal cortex as the

ascending limb. From the loop of Henle, filtered fluid enters the

distal tubule. The term distal denotes that this part of the renal

tubule is farther away from the site where renal tubule attaches

to Bowman's capsule. The distal tubule is also convoluted.

The distal tubules of several nephrons empty into a single

collecting duct. Multiple collecting ducts in turn unite to form

larger ducts that drain into the minor calyces. Note that as fluid

passes through the nephron and collecting duct, it is referred to

as either filtrate, filtered fluid, or tubular fluid, and its composition can be modified. Once the fluid

exits the collecting ducts, it is referred to as urine, and its composition cannot be altered.

4. Types of nephrons

a. Cortical

1) 80% of the kidney's nephrons are cortical nephrons.

2) Their renal corpuscles lie in the outer portion of the renal cortex, and

they have short loops of Henle that lie mainly in the cortex and

penetrate only into the outer region of the renal medulla

b. Juxtamedullary

1) The other 20% of the nephrons are juxtamedullary nephrons.

2) Their renal corpuscles lie deep in the cortex, close to the medulla, and

they have a long loop of Henle that extends into the deepest region of

the medulla

3) Ascending limb of the

loop of Henle consists of

two portions: a thin

ascending limb followed

by a thick ascending limb

4) Nephrons with long loops

of Henle enable the

kidneys to excrete very

dilute or very

concentrated urine

5. Blood supply to kidney

a. Very extensive - as the kidneys remove wastes from the blood and regulate

its volume and ionic composition

b. Renal artery leads to the afferent arteriole, which:

c. Leads to glomerulus

d. Blood leaves glomerulus through efferent arteriole, which divides to form:

e. Peritubular capillaries that carry blood back to the renal veins and surround:

1) The tubular parts of both cortical and juxtamedullary nephrons that

are within the renal cortex.

2) Short loops of Henle of cortical nephrons.

f. Vasa recta – long loop-shaped capillaries that extend from some efferent

arterioles, that surround long loops of Henle of juxtamedullary nephrons

6. Juxtaglomerular apparatus

a. Important in regulating kidney function

b. Part of the distal tubule and afferent arteriole come in contact

c. Consist of:

1) Macula densa – specialized cells in this region

2) Juxtaglomerular cells (JG) – modified smooth muscle fibers

III. Overview of Renal Physiology

A. To produce urine you perform three basic tasks

1. Glomerular filtration - In the first step of urine production,

water and most solutes in blood plasma move across the wall of

glomerular capillaries into Bowman's capsule and then into the

renal tubule.

2. Tubular reabsorption - As filtered fluid flows through the renal

tubule and collecting duct, tubule and duct cells reabsorb about 99% of the filtered

water and many solutes. Reabsorption is the movement of substances from fluid in

the tubular lumen to blood in the peritubular capillaries. This process allows useful

substances to be returned to the bloodstream. The remaining 1% of filtered fluid

that is not reabsorbed contains substances that the body does not need (wastes,

drugs, excess ions, etc.) and will eventually be excreted into the urine.

3. Tubular secretion - As fluid flows through the renal tubule and collecting duct,

tubule and duct cells also secrete wastes and other substances that are not useful to

the body. Secretion is the transfer of substances from blood in the peritubular

capillaries to fluid in the tubular lumen. This process serves as an additional

mechanism for removing unneeded substances from the bloodstream.

IV. Glomerular Filtration

A. Occurs at the renal corpuscle

B. Consists of glomerulus and Bowman's capsule

1. Bowman’s capsule

a. Organized into two layers

1) Parietal layer - Single cell layer of epithelial cells

2) Visceral layer - Podocytes

2. Renal corpuscle

a. Contains filtration membrane

1) Made of glomerulus and visceral (podocyte) layer of Bowman’s capsule,

forming a leaky barrier

2) Permits filtration of:

i. Water and small solutes

3) Prevents filtration of:

i. Blood cells and nearly all plasma proteins

4) Substances filtered from the blood cross three barriers—the

endothelium of the glomerulus, the basement membrane of the

glomerulus, and the visceral layer of Bowman's

i. Endothelium of the glomerulus. Glomerular endothelial cells are

quite leaky because they have fenestrations (pores) that measure

70–100 nm in diameter. This size permits passage to water and all

solutes in blood plasma. However, the fenestrations are too small

to allow blood cells to filter through the endothelium. Located

among the glomerular capillaries and in the cleft between afferent

and efferent arterioles are mesangial cells.

ii. Basement membrane of the glomerulus. a porous layer of acellular

material between the endothelium and the podocytes, consists of

collagen fibers and negatively charged glycoproteins. The pores

within the basement membrane allow water and most small

solutes to pass through. However, the negative charges of the

glycoproteins repel plasma proteins, most of which are anionic; the

repulsion hinders filtration of these proteins.

iii. Visceral layer of Bowman's capsule. Recall that the visceral layer of

Bowman's capsule consists of podocytes, and each podocyte

contains footlike processes called pedicels that wrap around

glomerular capillaries. The spaces between pedicels are the

filtration slits. A thin membrane, the slit membrane, extends

across each filtration slit; it contains pores that permit the passage

of molecules that have a diameter smaller than 6–7 nm, including

water, glucose, vitamins, hormones, amino acids, urea, ammonia,

and ions. Negatively charged glycoproteins that cover the slit

membrane oppose the filtration of plasma proteins. Because of the

negative charges associated with the podocyte layer and basement

membrane and the small size of the slit membrane pores, less than

1% of albumin, the smallest and most abundant plasma protein,

can pass through the filtration membrane and enter the

glomerular filtrate.

5) The principle of filtration—the use of pressure to force fluids and

solutes through a membrane—is the same in glomerular capillaries as

in capillaries elsewhere in the body. However, the volume of fluid

filtered by the renal corpuscle is much larger than in other capillaries of

the body for three reasons:

i. Glomerular capillaries present a large surface area for filtration

because they are long and extensive. Mesangial cells regulate how

much of this surface area is available for filtration. When

mesangial cells are relaxed, surface area is maximal, and

glomerular filtration is very high. Contraction of mesangial cells

reduces available surface area, and glomerular filtration decreases.

ii. Filtration membrane is thin and porous. Despite having several

layers, the thickness of the filtration membrane is only 0.1 mm

(100 µm). Glomerular capillaries also are about 50 times leakier

than capillaries in most other tissues, mainly because of their large

fenestrations.

iii. Glomerular capillary blood pressure is high. Because the efferent

arteriole is smaller in diameter than the afferent arteriole,

resistance to the outflow of blood from the glomerulus is high. As a

result, blood pressure in glomerular capillaries is considerably

higher than in capillaries elsewhere in the body.

C. Glomerular Filtration Is Determined by the Balance of Four Pressures

1. Glomerular capillary hydrostatic pressure (PGC) - is the blood pressure in

glomerular capillaries. Generally, PGC is about 55 mmHg. It promotes filtration by

forcing water and solutes in blood plasma through the filtration membrane.

2. Bowman’s space hydrostatic pressure (PBS) - is the hydrostatic pressure exerted

against the filtration membrane by fluid already in Bowman's space and renal

tubule. PBS opposes filtration and represents a “back pressure” of about 15 mmHg.

3. Plasma colloid osmotic pressure (πGC) - is due to the presence of proteins such as

albumin, globulins, and fibrinogen in blood plasma of glomerular capillaries. πGC

also opposes filtration and is typically about 30 mmHg.

4. Bowman’s space colloid osmotic pressure (πBS) - which is due to the presence of

proteins in the fluid in Bowman's space, promotes filtration. Under normal

conditions, the fluid in Bowman's space has very little protein, so πBS is 0 mmHg.

However, when the filtration membrane is damaged, protein can enter from blood

into Bowman's space, causing πBS to increase

D. Glomerular filtration rate (GFR)

1. Amount of filtrate formed per minute

2. A measure of kidney function

3. On average is about 180 L/day

4. Regulated many different ways

a. Autoregulation - The kidneys themselves help maintain a constant renal

blood flow and GFR despite normal, everyday changes in blood pressure, like

those that occur during exercise. Consists of two mechanisms that work

together to maintain nearly constant GFR over a wide range of systemic blood

pressures:

1) Myogenic mechanism - occurs when stretching triggers contraction of

smooth muscle cells in walls of afferent arterioles. As blood pressure

rises, GFR also rises because renal blood flow increases. However, the

elevated blood pressure stretches the walls of afferent arterioles. In

response, smooth muscle fibers in wall of afferent arteriole contract,

which narrows arteriole's lumen. As a result, renal blood flow

decreases, thus reducing GFR to its previous level. Conversely, when

arterial blood pressure drops, smooth muscle cells are stretched less

and thus relax. Afferent arterioles dilate, renal blood flow increases,

and GFR increases. The myogenic mechanism normalizes renal blood

flow and GFR within seconds after a change in blood pressure.

2) Tubuloglomerular feedback - is so-named because part of renal

tubules—the macula densa—provides feedback to the glomerulus.

When GFR is above normal due to elevated systemic blood pressure,

filtered fluid flows more rapidly along renal tubules. As a result, the

proximal tubule and loop of Henle have less time to reabsorb Na+, Cl−,

and water. Macula densa cells are thought to detect the increased

delivery of Na+, Cl−, and water and to inhibit release of nitric oxide (NO)

from cells in the juxtaglomerular apparatus (JGA). Because NO causes

vasodilation, afferent arterioles constrict when level of NO declines. As

a result, less blood flows into glomerular capillaries, and GFR decreases.

When blood pressure falls, causing GFR to be lower than normal, the

opposite sequence of events occurs, although to a lesser degree.

Tubuloglomerular feedback operates more slowly than myogenic

mechanism.

b. Neural regulation - Like most blood vessels of the body, those of the kidneys

are supplied by sympathetic fibers of the autonomic nervous system (ANS)

that release norepinephrine. Norepinephrine causes vasoconstriction

through activation of α1 receptors, which are particularly plentiful in smooth

muscle fibers of afferent arterioles. At rest, sympathetic stimulation is

moderately low, the afferent and efferent arterioles are dilated, and renal

autoregulation of GFR prevails. With moderate sympathetic stimulation,

both afferent and efferent arterioles constrict to the same degree. Blood flow

into and out of the glomerulus is restricted to the same extent, which

decreases GFR only slightly. With greater sympathetic stimulation, however,

as occurs during exercise or hemorrhage, vasoconstriction of the afferent

arterioles predominates. As a result, blood flow into glomerular capillaries is

greatly decreased, and GFR drops. This lowering of renal blood flow has two

consequences: (1) It reduces urine output, which helps conserve blood

volume. (2) It permits greater blood flow to other body tissues.

c. Hormonal regulation - Two hormones contribute to regulation of GFR.

Angiotensin II reduces GFR; atrial natriuretic peptide (ANP) increases GFR.

Angiotensin II is a very potent vasoconstrictor that narrows both afferent and

efferent arterioles and reduces renal blood flow, thereby decreasing GFR.

Cells in the atria of the heart secrete atrial natriuretic peptide (ANP).

Stretching of atria, as occurs when blood volume increases, stimulates

secretion of ANP. By causing relaxation of the glomerular mesangial cells,

ANP increases the capillary surface area available for filtration. Glomerular

filtration rate rises as the surface area increases.

V. Tubular Reabsorption and Tubular Secretion

A. Filtration

1. Amount of filtrate that enters the proximal convoluted tubule is large

2. A volume greater than the plasma in half an hour

3. Because so much gets filtered many things must be taken back

B. Secretion

1. Transfer of material from blood to tubule

C. Reabsorption

1. Two routes

a. Paracellular

1) Substances travel between cells

b. Transcellular

1) Substances travel through cells

2) Uses transporters

2. Through transcellular pathway

a. Requires use of transport proteins

b. Much of it occurs through secondary

active transport using Na+

c. Important to have Na+/K+ pump which

will maintain concentration gradients

d. Water

1) Passive (obligatory) ~ 80%

i. Follows the solutes that get reabsorbed

ii. Occurs passively in all places

2) Facultative ~ 20%

i. Happens in the later parts of the kidney (distal convoluted

tubule and throughout collecting duct)

ii. Hormone regulated (antidiuretic hormone)

D. Reabsorption and secretion

1. Different substances are reabsorbed or secreted to varying degrees in different parts

of the renal tubule

a. Reabsorption and secretion – proximal convoluted tubule (PCT)

1) Largest amount of solute and reabsorption. The PCT contains a brush

border of microvilli along their apical membranes which increase the

surface area for reabsorption and secretion.

2) Water, Na+, K+, Ca++

i. 65%

3) Organic solutes

i. 100%

4) Bicarbonate

i. 80-90%

5) Most occurs through Na+ cotransport

b. Reabsorption and secretion – loop of Henle

1) Chemical composition of filtrate is different but still isosmotic

2) Reabsorption continues

3) Water – only in descending limb

i. 15%

4) Ions – only in ascending limb

i. 20-30%

5) Bicarbonate

i. 10-20%

c. Reabsorption and secretion – early distal tubule

1) Little reabsorption takes place

2) Mostly Na+ and Cl-

3) Carried out but the Na+/Cl- symporters

d. Reabsorption and secretion – late distal tubule and collecting duct

1) Two different cell types present

i. Principal cells

1. Reabsorb Na+

2. Secrete K+

ii. Intercalated cells

1. Reabsorb HCO3 -

2. Secrete H+

E. Hormonal control of secretion and absorption

1. Antidiuretic hormone (ADH)

a. Also known as vasopressin

b. ADH is produced by neurons in the hypothalamus and is stored and released

from the posterior pituitary gland

c. Secreted in response to increased plasma osmolarity and decreased blood

volume

d. Stimulates facultative water reabsorption. Promotes water reabsorption by

inserting aquaporins into the collecting duct

2. Other hormones

a. Renin-angiotensin-aldosterone system

1) Triggered when blood pressure and blood volume decrease

2) Decreased filtration

3) Stimulates reabsorption of Na+ which facilitates reabsorption of water

4) Renin secreted by juxtaglomerular cells

5) Angiotensin converting enzyme secreted by lungs

6) Aldosterone produced and secreted by adrenal cortex

i. Secreted in response to low blood volume and increased

plasma potassium

ii. Targets the late distal tubule and collecting duct

iii. Increases sodium reabsorption

iv. Increases potassium and hydrogen secretion

b. Atrial natriuretic peptide (ANP)

1) Inhibit reabsorption of Na+

2) Increases urine output

c. Parathyroid hormone

1) Stimulates the reabsorption of Ca++

Summary of filtration, reabsorption, and secretion in the nephron and collecting duct.

VI. Regulating Blood Pressure: The Renin Angiotensin Aldosterone System (RAAS)

A. A structure associated with the nephron—the juxtaglomerular apparatus (JGA), which is

located adjacent to the efferent and afferent arterioles at the transition point between the

ascending limb of the nephron loop and the distal tubule. It plays an important role in

regulating blood pressure. The JGA consists of two groups of cells: the juxtaglomerular

cells of the afferent arteriole and the macula densa cells of the distal tubule. When blood

pressure in the renal corpuscle drops, the cells of the JGA release the enzyme renin. The

level of renin increases in the blood which will then convert angiotensinogen (a plasma

protein produced by the liver), into angiotensin I. This now circulates around the body and

once blood arrives at the capillaries, particularly the ones of the lungs, the enzyme:

angiotensin- converting enzyme converts angiotensin I into the hormone angiotensin II.

B. A series of subsequent reactions in the blood plasma results in the production of

angiotensin II, which has three major effects: (1) It directly stimulates blood vessels to

constrict; (2) it stimulates the posterior pituitary to release antidiuretic hormone (ADH),

which stimulates the reabsorption of water by the kidneys; and (3) it stimulates the

adrenal cortex to release aldosterone, which induces the kidneys to reabsorb sodium (and

thus water via the resulting osmosis). The constriction of blood vessels raises blood

pressure directly; the reabsorption of water resulting from the action of ADH and

aldosterone increases blood volume, which also increases blood pressure. When blood

pressure rises to within its homeostatic range, the JGA stops releasing renin.

VII. Production of Dilute and Concentrated Urine

Even though your fluid intake can be highly variable, the total volume of fluid in your body

normally remains stable. Homeostasis of body fluid volume depends in large part on the ability of

the kidneys to regulate the rate of water loss in urine. Normally functioning kidneys produce a

large volume of dilute (hypoosmotic) urine when fluid intake is high, and a small volume of

concentrated (hyperosmotic) urine when fluid intake is low or fluid loss is large. ADH controls

whether dilute urine or concentrated urine is formed. In the absence of ADH, urine is very dilute.

However, a high level of ADH stimulates reabsorption of more water into blood, producing a

concentrated urine.

A. Production of dilute urine allows the kidneys to get rid of excess water

1. Glomerular filtrate has the same ratio of water and solute particles as blood; its

osmolarity is about 300 mosmol/liter. As previously noted, fluid leaving the proximal

tubule is still isoosmotic to blood plasma. When dilute urine is being formed, the

osmolarity of the fluid in the tubular lumen increases as it flows down the descending

limb of the loop of Henle, decreases as it flows up the ascending limb, and decreases

still more as it flows through the rest of the nephron and collecting duct. These

changes in osmolarity result from the following conditions along the path of tubular

fluid:

a. Because the osmolarity of the interstitial fluid of the renal medulla becomes

progressively greater, more and more water is reabsorbed by osmosis as

tubular fluid flows along the descending limb toward the tip of the loop. As a

result, the fluid remaining in the lumen becomes progressively more

concentrated.

b. Cells lining the thick ascending limb of the loop of Henle have symporters

that actively reabsorb Na+, K+, and Cl− from the tubular fluid. The ions pass

from the tubular fluid into thick ascending limb cells, then into interstitial

fluid, and finally some diffuse into the blood inside the vasa recta.

c. Although solutes are being reabsorbed in the thick ascending limb, water

permeability of this portion of the nephron is always quite low, so water

cannot follow by osmosis. As solutes—but not water molecules—are leaving

the tubular fluid, the osmolarity of the tubular fluid drops to about 150

mosmol/liter. Fluid entering distal tubule is thus more dilute than plasma.

d. While the fluid continues flowing along the early distal tubule, more solutes,

but only a small number of water molecules, are reabsorbed. The cells of the

early distal tubule are not very permeable to water and are not regulated by

ADH.

e. Finally, the principal cells of the late distal tubule and collecting duct are

impermeable to water when the blood concentration of ADH is very low.

Because additional solutes but very few water molecules are reabsorbed in

these regions when there is a very low blood ADH level, tubular fluid becomes

progressively more dilute as it flows onward. By the time the tubular fluid

drains into the renal pelvis, its concentration can be as low as 65–70

mosmol/liter. This is four times more dilute than blood plasma or glomerular

filtrate.

B. Mechanism of concentrated urine production - When water intake is low or water loss

is high (such as during heavy sweating), the kidneys must conserve water while still

eliminating wastes and excess ions. Under the influence of ADH, the kidneys produce a

small volume of highly concentrated urine. Urine can be four times more concentrated

(up to 1200 mosmol/liter) than blood plasma or glomerular filtrate (300 mosmol/liter).

a. The ability of ADH to cause excretion of concentrated urine depends on the presence

of an osmotic gradient of solutes in the interstitial fluid of the renal medulla.

b. The three major solutes that contribute to this high osmolarity are Na+, Cl−, and urea.

c. Two main factors contribute to building and maintaining this osmotic gradient:

i. differences in solute and water permeability and reabsorption in different

sections of the long loops of Henle and the collecting ducts and

ii. the countercurrent flow of fluid through tube-shaped structures in the renal

medulla. Countercurrent flow refers to the flow of fluid in opposite directions.

This occurs when fluid flowing in one tube runs counter (opposite) to fluid

flowing in a nearby parallel tube. Two types of countercurrent mechanisms

exist in the kidneys: countercurrent multiplication and countercurrent

exchange.

• countercurrent multiplication - process by which a progressively

increasing osmotic gradient is formed in the interstitial fluid of the

renal medulla because of countercurrent flow.

o Production of concentrated urine by the kidneys occurs in the

following way:

i. Symporters in thick ascending limb cells of the loop of Henle cause a buildup of Na+ and

Cl− in the renal medulla. In the thick ascending limb of the loop of Henle, the Na+–K+–

2Cl− symporters reabsorb Na+ and Cl− from the tubular fluid. Water is not reabsorbed in

this segment, however, because the cells are impermeable to water. As a result, there is

a buildup of Na+ and Cl− ions in the interstitial fluid of the medulla.

ii. Countercurrent flow through the descending and ascending limbs of the loop of Henle

establishes an osmotic gradient in the renal medulla. Because tubular fluid constantly

moves from the descending limb to the thick ascending limb of the loop of Henle, the

thick ascending limb is constantly reabsorbing Na+ and Cl− ions. Consequently, the

reabsorbed Na+ and Cl− become increasingly concentrated in the interstitial fluid of the

medulla, which results in the formation of an osmotic gradient that ranges from 300

mosmol/liter in the outer medulla to 1200 mosmol/liter deep in the inner medulla. The

descending limb of the loop of Henle is very permeable to water but impermeable to

solutes except urea. Because the osmolarity of the interstitial fluid outside the

descending limb is higher than the tubular fluid within it, water moves out of the

descending limb via osmosis. This causes the osmolarity of the tubular fluid to increase.

As the fluid continues along the descending limb, its osmolarity increases even more: At

the hairpin turn of the loop, the osmolarity can be as high as 1200 mosmol/liter in

juxtamedullary nephrons. As you have already learned, the ascending limb of the loop is

impermeable to water, but its symporters reabsorb Na+ and Cl− from the tubular fluid

into the interstitial fluid of the renal medulla, so the osmolarity of the tubular fluid

progressively decreases as it flows through the ascending limb. At the junction of the

medulla and cortex, osmolarity of tubular fluid has fallen to about 100 mosmol/liter.

Overall, tubular fluid becomes progressively more concentrated as it flows along the

descending limb and progressively more dilute as it moves along the ascending limb.

iii. Cells in the collecting ducts reabsorb more water and urea. When ADH increases the

water permeability of the principal cells, water quickly moves via osmosis out of the

collecting duct tubular fluid, into the interstitial fluid of the inner medulla, and then

into the vasa recta. With loss of water, the urea left behind in the tubular fluid of the

collecting duct becomes increasingly concentrated. Because duct cells deep in the

medulla are permeable to it, urea diffuses from the fluid in the duct into the interstitial

fluid of the medulla.

iv. Urea recycling causes a buildup of urea in the renal medulla. As urea accumulates in the

interstitial fluid, some of it diffuses into the tubular fluid in the descending and thin

ascending limbs of the long loops of Henle, which are also permeable to urea. However,

while the fluid flows through the thick ascending limb, distal tubule, and cortical

portion of the collecting duct, urea remains in the lumen because cells in these

segments are impermeable to it. As fluid flows along collecting duct, water reabsorption

continues via osmosis because ADH is present. This water reabsorption further

increases the concentration of urea in the tubular fluid, more urea diffuses into the

interstitial fluid of the inner renal medulla, and the cycle repeats. The constant transfer

of urea between segments of the renal tubule and the interstitial fluid of the medulla is

termed urea recycling. In this way, reabsorption of water from the tubular fluid of the

ducts promotes the buildup of urea in the interstitial fluid of the renal medulla, which in

turn promotes water reabsorption. The solutes left behind in the lumen thus become

very concentrated, and a small volume of concentrated urine is excreted.

• countercurrent exchange - is the process by which solutes and water

are passively exchanged between the blood of the vasa recta and

interstitial fluid of the renal medulla because of countercurrent flow.

Note that the vasa recta also consists of descending and ascending

limbs that are parallel to each other and to the loop of Henle. Just as

tubular fluid flows in opposite directions in the loop of Henle, blood

flows in opposite directions in the descending and ascending parts of

the vasa recta. Because countercurrent flow between the descending

and ascending limbs of the vasa recta allows for exchange of solutes

and water between the blood and interstitial fluid of renal medulla,

the vasa recta is said to function as a countercurrent exchanger.

• Blood entering the vasa recta has an osmolarity of about 300

mosmol/liter. As it flows along the descending part into the renal

medulla, where the interstitial fluid becomes increasingly

concentrated, Na+, Cl−, and urea diffuse from interstitial fluid into the

blood, and water diffuses from the blood into the interstitial fluid. But

after its osmolarity increases, the blood flows into the ascending part

of the vasa recta. Here, blood flows through a region where the

interstitial fluid becomes increasingly less concentrated. As a result,

Na+, Cl−, and urea diffuse from the blood back into interstitial fluid,

and water diffuses from interstitial fluid back into the vasa recta. The

osmolarity of blood leaving the vasa recta is only slightly higher than

the osmolarity of blood entering the vasa recta. Thus, the vasa recta

provides oxygen and nutrients to the renal medulla without washing

out or diminishing the osmotic gradient. Whereas the long loop of

Henle establishes the osmotic gradient in the renal medulla by

countercurrent multiplication, the vasa recta maintains the osmotic

gradient in the renal medulla by countercurrent exchange.

VIII. Evaluation of Kidney Function

A. Routine assessment of kidney function involves evaluating both the quantity and quality of

urine and the levels of wastes in the blood.

1. Urinalysis - analysis of the physical, chemical, and microscopic properties of urine

a. Blood urea nitrogen (BUN) - which measures the blood nitrogen that is part

of the urea resulting from catabolism and deamination of amino acids. When

glomerular filtration rate decreases severely, as may occur with renal disease

or obstruction of the urinary tract, BUN rises steeply. One strategy in treating

such patients is to minimize their protein intake, thereby reducing the rate of

urea production.

b. Plasma creatinine - which results from catabolism of creatine phosphate in

skeletal muscle. Normally, the blood creatinine level remains steady because

the rate of creatinine excretion in the urine equals its discharge from muscle.

A creatinine level above 1.5 mg/dL (135 mmol/liter) is usually an indication of

poor renal function.

2. Renal plasma clearance – indicates how effectively the kidneys are removing a

substance from blood plasma.

a. Even more useful than BUN and blood creatinine values in the diagnosis of

kidney problems is an evaluation of how effectively the kidneys are removing

a given substance from blood plasma and excreting it into urine.

3. Renal failure - occurs because of inadequate kidney function

a. Acute renal failure (ARF)

1) When the kidneys almost completely stop working

2) Main feature is suppression of urine flow

3) Causes include low blood volume (for example, due to hemorrhage),

decreased cardiac output, damaged renal tubules, kidney stones, and

certain drugs.

4) Causes a multitude of problems:

i. There is edema due to salt and water retention

ii. Acidosis due to an inability of the kidneys to excrete acidic

substances

iii. In the blood, urea builds up due to impaired renal excretion of

metabolic waste products and potassium level rises, which can lead

to cardiac arrest.

iv. Often, there is anemia because the kidneys no longer produce

enough erythropoietin for adequate erythrocyte production.

v. Because the kidneys are no longer able to produce calcitriol, which

is needed for adequate calcium absorption from the small

intestine, osteomalacia (softening of bones) also may occur.

b. Chronic renal failure (CRF)

1) Progressive and irreversible decline in kidney function

2) may result from other kidney disorders or from traumatic loss of kidney

tissue.

3) develops in three stages

i. Diminished renal reserve - nephrons are destroyed until about 75%

of the functioning nephrons are lost. At this stage, a person may

have no signs or symptoms because the remaining nephrons

enlarge and take over the function of those that have been lost.

ii. Renal insufficiency – Occurs once 75% of the nephrons are lost.

Characterized by a decrease in glomerular filtration rate (GFR) and

increased blood levels of nitrogen-containing wastes and

creatinine. Also, the kidneys cannot effectively concentrate or

dilute the urine.

iii. End-stage renal failure - Final stage, occurs when about 90% of

the nephrons have been lost. At this stage, GFR diminishes to 10–

15% of normal, oliguria is present, and blood levels of nitrogen-

containing wastes and creatinine increase further. People with

end-stage renal failure need dialysis therapy and are possible

candidates for a kidney transplant operation.

IX. Urine Transportation, Storage, and Elimination

A. Urine transportation

1. Once urine is formed in the kidneys, it drains into the minor and major calyces and

then into the renal pelvis.

2. From the renal pelvis, urine drains into the ureters

3. Ureters carry urine to the urinary bladder

4. Bladder store urine

5. Excreted through the urethra.

B. Micturition reflex

1. Micturition – also known as urination or voiding

a. Discharge of urine from the bladder

b. occurs via a combination of involuntary and voluntary muscle contractions.

2. Coordinated events controlled by spinal cord micturition centers

a. When the volume of urine in the urinary bladder exceeds 200–400 mL,

pressure within the bladder increases considerably, and stretch receptors in

its wall transmit action potentials into the spinal cord.

b. Simultaneously, the micturition center inhibits somatic motor neurons that

innervate skeletal muscle in the external urethral sphincter.

c. Upon contraction of the urinary bladder wall and relaxation of the sphincters,

urination takes place.

d. Urinary bladder filling causes a sensation of fullness that initiates a conscious

desire to urinate before the micturition reflex actually occurs.

3. Urethra conveys urine out to the environment

a. Opening of the urethra to the exterior is called the external urethral orifice,

which is located between the clitoris and vaginal opening in a female and at

the tip of the penis in males

b. In both males and females, the urethra is the terminal portion of the urinary

system and the passageway for discharging urine from the body.