Overview of Renal Physiology

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 </p

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