Physiological Mechanisms

Excretion

Dr Vani T Kurup BM-143 (first floor)

Shalimar Bagh (West) Delhi 110088

Contact: 27489591 Email: vani@edscientia.com

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Learning objectives

Structure and organization of the excretory system

• Kidneys

• Blood supply to the kidneys

• Functional unit of the kidney—Nephron

Urine formation

• Filtration in the glomerulus

o Factors causing filtration

o Glomerular filtration rate

• Reabsorption

• Secretion

• Physiology of urine formation

o Formation of very dilute urine and very concentrated urine

o Contribution of urea to the hyperosmolarity of the inner medullary interstitium

o Role of vasa recta in maintaining the hyperosmolarity of the medullary

interstitium

Acid-base balance

Disorders of the excretory system

External links 3D-model of urinary tract http://www.3dscience.com/3D_Models/Human_Anatomy/Urinary/index.phpAnimation link: Structure: http://www.nottingham.ac.uk/nursing/sonet/rlos/bioproc/kidneyanatomy/index.htmlPhysiology : http://www.nottingham.ac.uk/nursing/sonet/rlos/bioproc/kidneyphysiology/

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The function of eliminating nitrogenous and other wastes is performed mainly by the

excretory system (Fig. 1), which consists of two kidneys, two ureters, a urinary bladder

and a urethra that opens to the outside. The nitrogenous and other wastes are in the form

of a fluid called urine, which is formed by the kidneys, conveyed to the urinary bladder

(where it is temporarily stored) by the ureters and thrown out by the urethra through a

process called micturition.

Fig 1: Position of excretory system organs in the female body

Inferior vena cava

Right kidney

Right renal vein

Right ureter

In addition to forming

of the kidneys are liste

1. Homeostasis

Kidneys regulate the in

• Eliminating tox

(from breakdow

(derived from b

products of dru

• Maintaining the

Left kidney

urine the kidneys perform some other

d below:

ternal environment of the body by:

ic wastes, such as urea (from breakdo

n of nucleic acids), creatinine (from

ilirubin, a breakdown product of haem

gs.

pH of body fluids by secreting or ab

Left renal artery

Diaphragm

Abdominal aorta

Left ureter

Urinary bladder

Urethra

functions too. All functions

wn of amino acids), uric acid

muscle creatine), urobilin

oglobin) and breakdown

sorbing H+/HCO3-

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• Maintaining the osmotic balance in the body by excreting or retaining Na+ ions,

Cl- ions and water.

• Maintaining blood pressure by secreting renin <link to renin-angiotensin-

aldosterone system in circulation chapter>.

2. Metabolism

Kidneys contribute to the metabolic activities of the body by:

• Synthesizing glucose (gluconeogenesis) under conditions of fasting and

starvation.

• Secreting erythropoietin, which stimulates the synthesis of red blood cells.

• Participating in the synthesis of calcitriol, the active form of vitamin D.

Structure and organization of the excretory system Kidneys Each kidney is a bean-shaped organ lying outside the peritoneum (kidneys are

retroperitoneal) on the posterior side of the abdomen.

Each kidney consists of an outer cortex and inner medulla that contains pyramid shaped

structures (the renal pyramids – 8 to 18 in number) with their base lying at the junction of

the cortex and the medulla. The cortical tissue extends in between the renal pyramids

forming the renal columns of Bertini. Their apices face the inner cavity of the kidney, the

renal pelvis, from where the ureters arise. The apex of each renal pyramid (called the

renal papilla) empties into a cup-shaped structure, the minor calyx. Two or three adjacent

minor calyces join to form the major calyx which then empties into the renal pelvis. A

longitudinal fissure along the inner margin of the kidney through which the ureter leaves

and the blood vessels and nerves enter and leave is known as the hilum. It is continuous

with the renal pelvis.

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Each renal pyramid with its overlying cortex and half of the column of Bertini on each

side constitutes a renal lobe. So, the human kidney is a multilobar kidney. Medullary

material appears to be arranged in the form of vertical lines <link to nephrons> which

also extend into the cortical material above each renal pyramid and is known as a

medullary ray. Each medullary ray with its associated cortical material around it is known

as a lobule. (see figures 2, 3, 4)

Fig 2: Internal anatomy of the kidneys z

Renal columns of Bertini (cortex)

Major calyx

Renal pyramid

Renal papilla

Minor calyces

Renal sinus

Papillary ducts

Ureter

Renal pelvis

Renal medulla Renal cortex

Fig 3: Renal lobe and lobule

Renal lobule (each medullary ray with its associated cortical material)

Renal lobe (renal pyramid with its overlying

cortex and half of the column of Bertini)

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Fig 4: Internal structure of the right kidney

Types of nephrons

Renal pelvis

Renal vein

Renal artery

Renal medulla

Renal cortex

Ureter Juxtamedullary nephron

Cortical nephron

Renal cortex

Renal medulla

Collecting duct

All materials constituting the cortex and the medulla of the kidney is called the renal

parenchyma. The functional unit of the renal parenchyma is the nephron. Each nephron

consists of a renal corpuscle and the renal tubule. The renal corpuscle consists of a

glomerulus and Bowman’s capsule while the renal tubule consists of a proximal

convoluted tubule (PCT), loop of Henle with the descending and ascending limbs, distal

convoluted tubule (DCT) and collecting ducts (collecting ducts are formed by joining of

the terminal parts of the distal convoluted tubules of many nephrons). <see nephron in

fig 7>

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Fig 5: Histology of the renal cortex

Source: Courtesy: http://www.kumc.edu/instruction/medicine/anatomy/histoweb/urinary/urinary.htm ©1996 The University of Kansas

Fig: 5 Renal cortex. The numerous glomeruli (red arrows) identify the renal cortex. Medullary rays (between yellow arrows) and the interlobular artery, blue arrow)

The glomerulus consists of a bunch of capillaries arising from the afferent arteriole

beneath which is present a double-walled cup-like Bowman’s capsule that continues as

PCT. The glomerulus is the site of filtration where blood is filtered and the Bowman’s

capsule acts like a funnel in which the filtrate is collected.

There are two types of nephrons which differ in their location and function:

1. Short-loop nephrons or cortical nephrons: These nephrons lie in the outer regions of

the cortex with their short loops of Henle dipping into the upper parts of the medulla.

The descending limb of the loop of Henle has a thin portion and a thick portion, the

latter continues as the ascending limb. <cortical nephron histology>

2. Long-loop or juxtamedullary nephrons (15-20% of the nephrons are of this type).

These nephrons have their glomeruli, PCT, and DCT lying just next to the medulla

(juxtamedullary). They have longer loops of Henle descending deeper into the

medulla. The tubules of these nephrons, in addition to the peritubular network of

capillaries, have U-shaped capillaries (called vasa recta (Fig. 6)) running parallel to

the loop of Henle. The loops of Henle have thick and thin portions in both the

ascending and descending limbs. These nephrons are responsible for forming very

dilute or very concentrated urine.<juxtamedullary nephron histology>

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Fig 6: Vasa recta

Vasa recta

Loop of Henle

The collecting ducts of many nephrons join to form the papillary ducts also known as

ducts of Bertini, which empty at the papilla of the renal pyramid into the minor calyces.

The fluid (urine) formed in the kidneys takes the following route (Fig. 7).

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Fig 7: Passage of filtrate from the nephron to outside the body

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Ascending limb of the loop of Henle (6)

Distal convoluted tubule (7)

Collecting duct (8)

Papillary duct (9) (now urine)

Minor calyx (10)

Major calyx (11)

Renal pelvis (12)

Ureter (13)

Urinary bladder (14)

Urethra (15)

Outside the body (16)

Glomerulus (1)

Bowman’s capsule (2)

Proximal convoluted tubule (3)

Descending limb of loop of Henle (4)

U-pin bend of the loop of Henle (5)

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1

2

8

6 4

5

9

10 13

11

12

13

14

15

16

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The afferent arteriole after forming the

capillaries of the glomerulus leaves the

glomerulus as the efferent arteriole which

further divides to form a capillary network,

the peritubular capillaries that surround the

PCT, loop of Henle, and DCT which then join

back to form the veins. In between the

glomerular capillaries are present special

types of cells called mesangial cells. Such

cells are also present in between the afferent

and efferent arteriole and are called the

extraglomerular mesangial cells (see box).

As the ascending limb traverses the cortex it

comes in contact with the afferent arteriole

(and sometimes efferent arteriole also) where the cells of the tubule and the afferent (and

efferent) arteriole are modified. The cells of the ascending limb of loop of Henle in

contact with the afferent arteriole are compactly arranged to form a region called macula

densa (the DCT starts some distance after the macula densa), which is sensitive to the

fluid volume and osmolarity of fluid in the ascending limb. Smooth muscle fibres beneath

the endothelial cells of the afferent (and efferent) arteriole in this region are modified to

form the juxtaglomerular cells which secrete renin <link to renin-angiotensin-aldosterone

system in chapters on circulation and hormonal control> and nitric oxide (see

autoregulation of GFR). The macula densa cells, the juxtaglomerular cells and the

extraglomerular mesangial cells together form the juxtaglomerular apparatus (JGA).

Functions of mesangial cells

Mesangial cells are supposed to have the

following functions:

• They contract to regulate the diameter

of the glomerular capillaries which in

turn regulates the glomeration

filtration rate (GFR).

• They phagocytose the trapped

residues and aggregated proteins from

the basal lamina of the glomerular

capillaries.

• They provide support to the

glomerular capillaries.

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Fig 8: The juxtaglomular apparatus

Macula densa

Bowman’s capsule

Glomerulus

Mesangial cells

Efferent arteriole

Afferent arteriole

Distal tubule

Endothelium

Juxtaglomerular cells

Proximal tubule

Juxtaglomerularapparatus

Blood supply to the kidneys The renal artery enters the kidney at the hilum which divides into branches, called

segmental arteries, which give rise to interlobar arteries that supply each lobe. The

interlobar artery divides into arcuate arteries that arch over the base of each renal pyramid

at the junction of the cortex and medulla. Each arcuate artery gives off branches, the

interlobular arteries, that supply each lobule. From the interlobular artery arises the

afferent arteriole which forms the glomerulus of the renal corpuscle.

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Fig 9: Blood supply of the kidney (left kidney, frontal section) Cortex

Interlobular artery and vein

Medulla

Renal artery Arcuate artery

Arcuate vein

Renal vein Interlobar artery

Interlobar vein

Segmental artery

Segmental vein

Ureter

Source: Courtesy, http://www.3dscience.com/ The glomerular capillaries join to form the efferent arteriole, which further divide to form

the peritubular capillaries (and vasa recta in long-loop nephrons). These join to form the

interlobular veins giving rise to arcuate veins and interlobar veins and finally the renal

vein that leaves the kidney through the hilum.

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Blood flow through the kidneys Renal artery (entering the kidney through the hilum)

branches into

Segmental arteries

branch into

Interlobar artery (supplying each lobe entering through the columns of

Bertini in the cortex of the kidneys)

branching into two (one going to each side)

Arcuate artery (arching over the base of the renal pyramid)

branching into the cortex

Interlobular artery (one going to each lobule)

branches into

Afferent arteriole

Glomerular capillaries

Efferent arteriole

Peritubular capillaries and vasa recta

Interlobular vein

Arcuate vein

Interlobar vein

Renal vein (leaves the kidney at the hilum)

Functional unit of the kidney—Nephron

The renal corpuscles of the nephrons are present in the cortex while the renal tubules

extend into the medulla giving it a striated appearance. Medullary rays extending into the

cortex consist of the descending limbs, ascending limbs and collecting ducts especially of

the short loop (cortical) nephrons. The renal corpuscle has the glomerulus and Bowman’s

capsule. The glomerulus is a bunch of capillaries with their walls made up of a single

layer of endothelial cells resting on a basal lamina. The Bowman’s (glomerular) capsule

is a double-walled cup with the outer wall, the parietal layer, made up of simple

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squamous epithelium. The inner wall, the visceral layer, is greatly modified and is closely

associated with the glomerular capillaries to form the filtration membrane. The modified

simple squamous cells of the visceral layer are called podocytes which have many foot-

like projections called pedicles that wrap around the capillaries of the glomerulus (Fig.

11). Pedicels from neighbouring podocytes interdigitate with one another. The gap

between these interdigitations, the filtration slits, have a thin membrane stretched across

called the slit membrane.

Fig 10: Histology of the glomerulus

Glomerulus: Three cell types of the glomerulus: endothelial (red), mesangial (blue) and the visceral eipithelial cell or podocyte (yellow). Squamous epithelial cells of the Bowman capsule (green). The macula densa (black) is part of the distal tubule.

Source: Courtesy: http://www.kumc.edu/instruction/medicine/anatomy/histoweb/urinary/urinary.htm©1996 The University of Kansas

Fig 11: Podocyte

Podocyte

Capillary

Histology of the renal tubule

The renal tubule with its various parts, the PCT, the loop of Henle (with its ascending and

descending limbs), the DCT, and the collecting duct is lined with a single layer of

epithelial cells which are variously modified to suit the specific functions of that region.

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Region Figure 12 Structure Proximal convoluted tubule (PCT)

Simple cuboidal epithelial

cells with microvilli and

large elongate and

numerous mitochondria.

Thin segment of the descending limb of loop of Henle 1. In the short-loop nephrons

2. In the long-loop nephrons

(four types of cells have

been identified in different

animals). Though the

specific functions of these

four types of cells are not

known they may be

contributing to the counter-

current multiplier system

for the formation of very

dilute or concentrated

urine.

• Type I

• Type II

• Type III found in the lower

part of the descending limb

• Type IV cells found at the

U-pin bend of the long loop

nephron and the thin ascending

limb.

Short loop nephron Long loop nephron

Type I cells

Type II, III, IV cells

Type I: simple squamous

epithelium similar to that

found in the short-loop

nephrons.

Type II: Taller cells with

few short microvilli and

abundant cell organelles

Type III: Lower

epithelium with fewer

microvilli than Type I

cells

Type IV: Low, flattened

Type I

Type II

Type III

Type IV

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epithelium with few

microvilli, few organelles

but abundant

interdigitations between

neighbouring cells.

Thick ascending limb and distal

convoluted tubule (DCT)

Simple cuboidal

epithelium with small

apical microvilli in some

cells, large basal

mitochondria and apical

nuclei.

Last part of DCT and the

collecting duct (entire). Two

types of specialized cells are

present—Principal cells

Intercalated cells

Principal cells are low

cuboidal cells with no

microvilli.

Intercalated cells are

cuboidal cells with

microvilli.

Urine formation

Urine is formed as a result of three processes:

1. Filtration: Where blood is filtered at the glomerular level. Everything except proteins

and cells find their way into the filtrate.

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2. Reabsorption: All the material that is not supposed to be excreted but is present in the

filtrate, e.g. nutrients are absorbed back by the kidney tubules.

3. Secretion: All those substances that are not filtered at the glomerular level but have to

be excreted are added to the filtrate by the cells of kidney tubules by the process of

secretion. This type of secretion is different from that found elsewhere in the body.

Here the secreted substances are eliminated from the blood and not released into

blood.

Filtration in the glomerulus

The glomerular capillaries along with the visceral layer of the Bowman’s capsule form

the filtration membrane through which the filtrate passes into the Bowman’s space (the

space between the visceral and the parietal layers of the Bowman’s capsule). The

filtration membrane has the following three layers (Fig. 13):

1. The endothelial lining of the glomerular capillaries. This layer is fenestrated, with

large pores in the plasma membrane of the cells which allows the passage of solutes

and water in the plasma retaining the blood cells.

2. The basement membrane (basal lamina) beneath the endothelial layer consists of

collagen fibres and proteoglycans in a glycoprotein matrix. This layer prevents the

passage of large plasma proteins.

3. The slit membrane stretched across the filtration slits between the pedicels of the

podocyte prevents the passage of medium-sized plasma proteins.

Fig 13: Glomerulus-endolthelial-filtration membrane Podocyte

Slit membrane

Basement membrane

Endothelial lining of the glomerular capillaries

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Thus all the water, solutes, glucose, amino acids, small proteins, peptides, ammonia, urea

and ions are filtered through the filtration membrane to form the filtrate that comes into

the Bowman’s space.

Factors causing filtration

Glomerular hydrostatic pressure (GHP)

It is the pressure of blood in the glomerular capillaries. This causes movement of water

and solutes from the capillaries into Bowman’s space (Fig. 14).

Bowman’s capsule hydrostatic pressure (BHP)

Since some fluid is always present in the Bowman’s space it exerts some hydrostatic

pressure on the walls of the Bowman’s capsule causing the movement of water and

solutes out of the Bowman’s capsule into the capillaries.

Glomerular oncotic (colloidal osmotic) pressure (GOP)

This is caused by the proteins present in the blood which results in the movement of fluid

from the Bowman’s capsule into the capillaries. So while the glomerular hydrostatic

pressure favours filtration the other two factors (BHP and GOP) oppose it.

Fig 14: Glomerular hydrostatic pressure

Glomerular capillaries

Efferent arteriole Afferent aretriole

Bowman’s capsule

Net filtration pressure (NFP) =

GHP — (BHP + GOP)

GHP = 55 mmHg,

BHP = 15 mmHg

GOP = 30 mmHg

So, NFP = 55 – (15+30)

= 55 – 45 = 10 mmHg

NFP = 10 mmHg

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This net filtration pressure of 10 mmHg causes the filtration of 180 L of fluid every day,

out of which 1– 2 L forms the urine while 178–179 L of fluid is reabsorbed.

Glomerular filtration rate

Glomerular filtration rate (GFR) is defined as the amount of fluid filtered by all the

nephrons in both the kidneys every minute. Under normal conditions the average value of

GFR is 125 ml/minute in males and 105 ml/min in females. Such a large volume of fluid

is filtered by the nephrons because:

• The hydrostatic pressure in the glomerular capillaries is much higher than the

pressure in capillaries elsewhere in the body because the afferent arteriole is wider

than the afferent arteriole causing resistance to blood flow.

• The glomerular capillaries have a large surface area (as it is a bunch of capillaries).

• The glomerular capillaries are fenestrated, allowing a lot of fluid to leak through,

unlike the continuous capillaries found elsewhere in the body. (Link to type of

capillaries in circulatory system).

The GFR changes with change in blood pressure. But under normal conditions, the GFR

remains relatively constant even when the blood pressure is as low as 80 mmHg to as

high as 180 mmHg. This is achieved by the following regulatory mechanisms.

Autoregulation: Here the kidneys themselves regulate the GFR. This includes two

mechanisms:

1. Myogenic regulation: This operates by changes in the diameter of the glomerular

capillaries in response to changes in blood pressure. This is achieved by the smooth

muscle fibres in the capillaries which respond to oppose the change in their length

(i.e. they contract when stretched and relax when made to contract).

Increase in blood presssure Walls of the afferent arteriole stretch

Smooth muscle fibres of the arteriole wall contract

Decrease in blood pressure Walls of the afferent arteriole do not stretch (i.e. they are contracted to some extent)

Smooth muscle fibres of the arteriole relax

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Diameter of the afferent arteriole reduces Reduced (restored to normal) GFR

Diameter of the afferent arteriole increases Increased (restored to normal) GFR

2. Glomerular feedback. Here the cells

of the macula densa sense the amount

of Na+ and Cl– ions and water in the

fluid in the ascending limb of loop of

Henle and causes the JGA cells to

release or inhibit the release of NO

(nitric oxide) which is a vasodilator.

Vasodilation in the afferent arteriole

increases the blood flow into the

glomerulus causing an increased GFR.

Increased release of NO occurs when

the GFR decreases due to reduced

blood pressure to cause vasodilation in the afferent arteriole to increase (restore) the

GFR.

Neural regulation: In most of the blood vessels in the body the afferent and efferent

arterioles undergo vasoconstriction by moderate sympathetic stimulation (which causes

the GFR to remain the same as both afferent and efferent arterioles have the same degree

of constriction keeping the blood flow through the glomerulus constant).

But under conditions of exercise or haemorrhage the following occurs:

Increased sympathetic stimulation

Greater vasoconstriction in the afferent arteriole than in the efferent arteriole

Reduced blood flow through the glomerular capillaries

Reduced GFR Increased blood flow to other tissues like the skeletal muscle and

heart (where there is a vasodilation in response to sympathetic stimulation) <link to circulation chapter>

Increased blood pressure Increased GFR

Increased flow of fluid in the tubules Less Na+, Cl– and water is reabsorbed Increased Na+, Cl– and water in the ascending limb of loop of Henle Macula densa cells stimulated Release of NO inhibited from the JGA cells Vasoconstriction in the afferent arteriole Reduced (restored to normal) GFR

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Hormonal regulation:

Renin–angiotensin system

A reduced blood pressure causing reduced GFR is sensed by the JGA cells which release

renin. Renin acts in the following manner:

Reduced blood pressure

Reduced GFR

JGA cells get stimulated

Angiotensinogen in blood

Renin Angiotensin I Angiotensin II

Vasoconstriction in efferent arterioles

Increased (restored to normal) GFR

* ACE : angiotensin converting enzyme

ACE* in lungs

Reabsorption

Reabsorption in the PCT

Reabsorption of Na+ ions

Reabsortion of water

Reabsorption of solutes

Reabsorption in the loop of Henle

Reabsorption in the DCT and the collecting duct

Most of the reabsorption occurs in the PCT where all the glucose, amino acids and

vitamins, most of Na+, K+, HCO3– ions, water and half of Cl– ions are reabsorbed. Here

water is reabsorbed passively (as it follows the absorption of solutes). This type of

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Paracelluar and transcellular absorption

The cells of the kidney tubules have tight

junctions between them which make them

virtually impermeable to specific molecules.

These tight junctions, however, allow significant

diffusion of water and small ions especially in

the PCT. Water and solutes can be transported

from the lumen into the interstitium through the

junctional spaces between the cells (paracellular

route) or across the tubular cell through the cell

membrane (transcellular route) .

Transcellular route

Paracellular route

Tight junction

reabsorption is called obligatory

reabsorption. Ions are also absorbed

in the thick ascending limbs of loop

of Henle.

Some reabsorption occurs in the loop

of Henle, the distal part of the DCT

and the collecting ducts. The

reabsorption of water and salts in the

distal parts of DCT and collecting

ducts is known as facultative

reabsorption because the amount of

water and salts reabsorbed or

excreted is dependent on the needs

of the body to maintain the osmotic

balance.

Reabsorption in the PCT

Reabsorption of Na+ ions. Na+ ions are reabsorbed in the PCT by three mechanisms:

1. Absorption of Na+ ions through leak channels and their active transport into the

interstitium

2. Co-transport with glucose or amino acids by secondary active transport

3. Counter transport with H+ ions (with the aim of secreting H+ ions for maintaining the

acid-base balance <link to acid-base balance>).

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Absorption of Na+ ions through leak channels and their active transport into the

interstitium.

The concentration of Na+ ions in the filtrate in the PCT is much higher than that inside

the tubular cells which facilitates the diffusion of Na+ ions through leak channels in the

apical membrane of these cells. Once inside the cells, Na+ ions are actively transported

into the interstitium by the Na+-K+-ATPase pump. From the interstitium Na+ ions diffuse

into peritubular capillaries.

Fig 15: Active reabsorption of sodium in PCT cell

Interstitial fluid

Na+Na+

Fluid in tubule lumen

Reabsorbed into the peritubular capillary

K+

Na+Na+

K+

Proximal convoluted tubule cell

ATP ADP

Leak channel

Na+-K+-ATPase pump Active transport

Passive diffusion

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Co-transport with glucose or amino acids by secondary active transport.

There are symporters (protein molecules) present in the apical membrane of the PCT

cells. These symporters transport Na+ ions with one glucose or amino acid molecule.

(The Na+ ions are transported down their concentration gradient and this energy is used

for the transport of another molecule like glucose). While glucose or amino acid

molecules diffuse across the basal membrane into the interstitial fluid (by facilitated

diffusion) and from there into the peritubular capillaries (by passive diffusion), the Na+

ions have to be pumped out by the Na+ -K+ -ATPase pump which utilizes energy in the

form of ATP. This type of transport is known as secondary active transport (as energy is

utilized not primarily for transporting the glucose or amino acid molecule but for

transporting the Na+ ions out).

Fig 16: Glucose reabsorption by secondary active transport in PCT cell

K+

Fluid in tubule lumen

Reabsorbed into the peritubular capillary

Na+ Na+ Na+Na+

Proximal convoluted tubule cell

ATP ADP

Interstitial fluid

Active transport

Passive diffusion

Na+-K+-ATPase pump

Glucose Glucose Glucose Glucose

Facilitated diffusion

Secondary active transport

Na+-glucose symporter

K+

Glucose facilitated diffusion transporter (carrier)

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Counter transport with H+ ions.

Na+ ions are also transported from the lumen into the PCT cell by an antiporter (a

protein) that exchanges one Na+ ion (brought inside the cell) with one H+ ion (secreted

into the lumen) <see acid–-base balance> This is also a form of secondary active

transport because the Na+ ions then have to be transported out into the interstitial fluid

(which then diffuse into the peritubular capillaries) by the Na+-K+-ATPase pump which

utilizes ATP. This mechanism is used for secreting H+ ions into the lumen.

Fig 17: Sodium reabsorption with H+ ion secretion in PCT cell

Na+

Fluid in tubule lumen

Reabsorbed into peritubular capillary

Na+ Na+Na+

K+

Proximal convoluted tubule cell

ATP ADP

Interstitial fluid

Active transport

Passive diffusion

Na+-K+-ATPase pump

Secondary active transport

K+

H+ H+

Na+- H+- antiporter

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Reabsortion of water

As Na+ ions are absorbed from the lumen into the tubular cell, then into the interstitial

fluid and finally into peritubular capillaries, the osmotic concentration of the fluid

increases in the cell, then in the interstitial fluid and finally in the peritubular capillaries.

Water moves into the peritubular capillaries following this osmotic gradient.

Fig 18: Passive reabsorption of water following sodium reabsorption in PCT cell

Interstitial fluid

Fluid in tubule lumen

Reabsorbed into the peritubular capillary

Na+ Na+ Na+Na+

Proximal convoluted tubule cell

ATP

H2O H2O H2O

K+ K+

H2O

ADP

Na+-K+-ATPase pump Active transport

Leak channel Passive diffusion

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Reabsorption of solutes

As water and Na+ are reabsorbed, the concentration of other ions and solutes like K+,

Ca2+, Mg2+, Cl– and urea increases especially in the latter part of the PCT. These

substances are then absorbed by passive diffusion both via the paracellular and

transcellular routes. This mechanism of absorption specially favours the diffusion of Cl–

ions, because there is an electrochemical gradient favouring the absorption of negatively

charged ions as there is a slight positive charge created in the peritubular capillaries due

to the absorption of Na+ ions. Along with other ions and solutes some urea is also lost

from the lumen into the blood (in the peritubular capillaries) by this mechanism, though

not intentionally. Small proteins and peptides are absorbed in the PCT by pinocytosis.

Fig 19: Passive reabsorption of water and solutes in the PCT cell

Interstitial fluid

Fluid in tubule lumen

Reabsorbed into the peritubular capillary

Na+ Na+ Na+Na+

ATP

H2O

Cl–

HCO3–

Urea

H2O H2O

Cl– Cl–

HCO3– HCO3

–

Urea Urea K+ K+

ADP

Proximal convoluted tubule cell

Na+-K+-ATPase pump Active transport

Leak channel Passive diffusion

Transport maximum (Tm) and gradient–time transport

There is a fixed number of carrier protein molecules (symporters or antiporters) that can

carry a specific number of molecules inside the tubular cells. The maximum rate of

absorption of a particular solute is known as its transport maximum (Tm). If the

concentration of the solute in the tubular fluid is higher than its Tm it starts appearing in

the urine. The plasma concentration of a substance at which it starts appearing in the

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urine (because it reaches its Tm and some of it cannot be reabsorbed) is known as its

renal threshold, e.g. the renal threshold for glucose is 200 mg per 100 ml that is if the

concentration of glucose in the plasma is more than 200 mg per 100 ml of blood it starts

appearing in urine (glucosuria) as all of it cannot be reabsorbed by the kidney tubules.

There is no transport maximum for solutes that diffuse passively but the rate at which

they are reabsorbed depends upon:

• The electrochemical gradient that facilitates their reabsorption

• The permeability of the membrane to that solute

• The time for which the fluid containing this solute remains in that part of the

tubule where it can be reabsorbed.

Hence this type of transport is known as the gradient–time transport.

Reabsorption in the loop of Henle

By the time the fluid reaches the loop of Henle—

• 100% of nutrients have been reabsorbed

• 80–90% of HCO3– ions have been reabsorbed (link to acid-base balance)

• 65% of Na+, K+ and water have been reabsorbed

• 50% of Cl– ions have been reabsorbed

In the loop of Henle

• 35% of filtered K+ ions are reabsorbed

• 25% of filtered Na+ and Cl– ions are reabsorbed

• 15% of water is reabsorbed.

The loop of Henle consists of three functionally different parts:

1. Thin descending limb: It is permeable to water and moderately permeable to Na+ ions

and urea.

2. Thin ascending limb. It is impermeable to water and has no reabsorption capacity for

solutes, permeable to urea.

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3. Thick ascending limb. It is impermeable to water but has a large reabsorptive capacity

for solutes. Na+, K+ and Cl– ions are actively transported across the cell by symporters

(Fig. 20).

Most of the reabsorption takes place in the ascending limb of loop of Henle by secondary

active transport but the symporters here are different from those in the PCT.

The cells of the thick ascending limb have symporters that carry 1 Na+, 1 K+ and 2 Cl–

ions into the tubular cell. From here chloride and K+ diffuse into the peritubular

capillaries by passive diffusion while Na+ is thrown across the basolateral membrane by

the Na+-K+ -ATPase pump (secondary active transport). From the interstitium, Na+ and

Cl– ions diffuse into the peritubular capillaries. While K+ ions redistribute themselves

across the membrane as the membrane is leaky to K+ ions; so the net result is the

absorption of Na+ and Cl– ions. Na+ ions are also reabsorbed in this part of the tubule in

exchange with H+ ions (by Na+ / H+ antiporters) with the primary aim of secreting H+

ions (see acid–base balance).

Fig 20: Sodium-potassium-chloride symporters in the thick ascending limb cell

Apical membrane is impermeable to water

Cl–

Na+

Fluid in tubule lumen

Reabsorbed into peritubular capillaries or vasa recta

Na+

Na+

Na+

Interstitial fluid

ATP ADP

2Cl–Cl–2Cl–

K+

K+K+

K+

Thick ascending limb cell

Na+-K+-ATPase pump Na+-K+-2Cl– symporter Active transport

Leak channel Passive diffusion

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Reabsorption in the DCT and the collecting duct

The early part of DCT reabsorbs some more solutes and ions by active transport (Na+-K+-

Cl– symporters) but is virtually impermeable to water and urea. The latter part of DCT

and the collecting duct are permeable to water only under the influence of the antidiuretic

hormone (ADH). The principal cells of these parts of the tubule become highly

permeable to water in the presence of ADH and permeable to Na+ ions (in exchange with

K+), in the presence of aldosterone; so Na+ and water are reabsorbed in these regions to

maintain the osmotic balance in the body only when ADH and aldosterone are present.

Secretion

Various substances (e.g. H+, K+ and NH4+ ions, creatinine and drugs like penicillin) are

added to the tubular fluid by secretion. K+ ions are secreted by the principal cells of the

collecting duct in exchange of Na+ ions that are reabsorbed (under the influence of

aldosterone).

H+ ions are secreted by the PCT cells and the intercalated cells of the collecting duct

while NH4+ ions are secreted by the PCT cells (see acid–base balance).

Physiology of urine formation Formation of very dilute and very concentrated urine

Kidneys can adjust the volume of water excreted with urine according to the needs of the

body. If a person drinks a lot of water, very dilute urine (about 65 mOsm/L which is

about five times more dilute than plasma) is excreted. When there is a shortage of water,

kidneys can excrete very concentrated urine (1200 mOsm/L to 1400 mOsm/L which is

four to five times more concentrated than plasma). The ability to excrete concentrated

urine is especially important for survival in places like a desert or in the sea where

drinking water is scarce.

Formation of dilute urine

The following sequence of events results in the formation of dilute urine.

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Glomerular filtrate entering the PCT has the same concentration (osmolarity) as that of

plasma (300 mOsm/L).

As this fluid moves down the PCT and the descending limb of loop of Henle it keeps

losing solutes and water in equal proportion so the fluid in the initial portion of the

descending limb has the same osmolarity as plasma (300 mOsm/L).

In the latter part of the descending limb, water is lost from the fluid into the hypertonic

interstitium of the medulla (Why is the medullary interstitium hypertonic?).

The tubular fluid at the U-pin bend of the loop of Henle becomes hypertonic; could be as

concentrated as 1200 mOsm/L.

As this fluid moves up the thick ascending limb of loop of Henle it loses ions like Na+,

K+ and Cl– by the Na+-K+ -Cl– symporters by secondary active transport.

Since only ions are lost and not water, by the time this fluid reaches the early part of the

DCT it becomes very dilute (100 mOsm/L).

In the absence of ADH, the principal cells of the late DCT and the collecting ducts are

impermeable to water. In these regions again, solutes are reabsorbed while water is

retained in the tubular fluid.

By the time the fluid reaches the papillary ducts its concentration is as low as 65

mOsm/L.

Very dilute urine is excreted.

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Fig 21: Formation of dilute urine

Formation of concentrated urine

A person with an average weight needs to excrete 600 mOsm/L of solutes (including

urea, uric acid etc.) every day. The maximum concentration of urine that can be formed

by the kidney tubules is 1400 mOsm/L, i.e. at.least 1 L of water is required to dissolve

1400 mOsm solutes. So, everyday a person needs 600 /1400 L of water to dissolve 600

mOsm of solutes, i.e. at least, 0.444 L of water is required to excrete the wastes everyday.

This is known as obligatory water loss. This is in addition to the water lost from other

regions of the body, e.g. as sweat, as water vapours during breathing, water lost with

feces, etc.

The following factors facilitate achievement of urine concentration (1400 mOsm/L) in

the kidney tubules.

• The loop of Henle of the long loop nephrons dip down deep into the medulla.

• The descending and the ascending limbs of loop of Henle run parallel to one another

and the fluid in it runs in opposite directions.

• The collecting ducts are also parallel to the ascending and descending limbs.

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• The descending and the ascending limbs of the loop of Henle and the collecting ducts

are surrounded by the same interstitium.

• The loop of Henle is surrounded by U- shaped capillaries, the vasa recta, which have

a sluggish blood flow.

• The lower portions of the descending and ascending limbs are permeable to urea

while the DCT is not.

• The medullary interstitium is made progressively hyperosmotic from upper medulla

to deeper medulla.

• Antidiuretic hormone makes the principal cells of the late DCT and collecting duct

highly permeable to water.

The basic principle in the formation of concentrated urine is to make the medullary

interstitium highly hypertonic and the fluid in the collecting ducts highly dilute so that in

the presence of ADH a lot of water is lost to the hypertonic interstitium (which is then

carried away by the capillaries) making the fluid in the collecting duct (urine) highly

concentrated. This is achieved by a counter-current multiplier system which utilizes

the following functional features:

• The descending limb of loop of Henle is permeable to water.

• The ascending limb (especially the thick part) is impermeable to water but it can

transport solutes from the tubular fluid into the interstitium.

The following steps elaborate the working of the counter-current multiplier system

(though actually many of these steps may be occurring simultaneously and not

sequentially).

Fluid in the upper part of PCT has the same osmolarity as plasma (300 mOsm/L)

This fluid keeps losing solutes and water in the same proportion as it moves down the

PCT to maintain the same osmolarity (300 mOsm/L).

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As this fluid moves up the ascending limb, the Na+-K+-2Cl– symporters transport Na+, K+

and Cl– into the tubular cells

Na+ and K+ are thrown out into the interstitium by the Na+-K+-ATPase pump while Cl–

diffuses out passively.

Concentration of solutes in the interstitium keeps increasing while the concentration of

solutes in the fluid keeps decreasing as it moves up the ascending limb. The Na+-K+-

ATPase pump and the Na+-K+-2Cl– symporters can maintain a difference of 200 mOsm/L

between the tubular fluid in the ascending limb and the interstitium.

If the concentration of tubular fluid in the ascending limb is 200 mOsm/L the

concentration of interstitial fluid surrounding it would be 400 mOsm/L.

Since the descending limb has a fluid with the concentration of 300 mOsm/L (same as

plasma) and the interstitium surrounding it has a concentration of 400 mOsm/L and the

descending limb is permeable to water, fluid in the descending limb keeps losing water

till it gets equilibrated with the interstitium. More solutes are simultaneously being added

to the interstitium by the thick ascending limb.

Fluid in the descending limb with a concentration of 400 mOsm/L keeps moving down

and as more and more solutes are added to the interstitium, fluid in the descending limb

keeps becoming more and more hypertonic.

New fluid is added to the PCT which also keeps becoming hypertonic.

The concentration of solutes in the descending limb gets multiplied because the

concentration of solutes in the interstitium keeps increasing and the fluid in the

descending limb keeps losing water. Fluid in the ascending limb keeps losing solutes and

becomes more and more dilute as it moves up towards the DCT.

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By the time the fluid reaches the U- pin bend of the loop of Henle the concentration of

solutes inside as well as the interstitium surrounding it could be as high as 1400 mOsm/L,

while the concentration of fluid in the early parts of DCT is around 100 mOsm/L which

further reduces to about 70 mOsm/L in the early DCT.

The late DCT and the collecting ducts have principal cells which are permeable to water

under the influence of ADH.

As this dilute tubular fluid (70 mOsm/L) comes in contact with the hypertonic

interstitium around it down the collecting duct, it keeps losing water to the interstitium

through the principal cells under the influence of ADH.

At the end of the collecting ducts, deep into the medulla, where the interstitium has a

concentration of 1200 mOsm/L the fluid gets equilibrated with it by losing water.

Concentrated (1200 mOsm/L) urine is excreted.

Fig 22: Counter-current multiplier system for producing concentrated urine

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Contribution of urea to the hyperosmolarity of the inner medullary

interstitium

The descending and the early ascending limbs of the loop of Henle are permeable to urea

while the upper part of the ascending limb of the loop of Henle, the DCT and the upper

collecting ducts are impermeable to urea. The medullary portions of the collecting ducts

become permeable to urea under the influence of ADH.

So when water is being absorbed from the collecting ducts under the influence of ADH

urea also diffuses out into the interstitium to make it more hyperosmotic. Some of this

urea finds its way into the thin descending limb and early part of ascending limb from

where it goes up into the thick ascending limb and DCT (from where it cannot diffuse

out) and some of it is excreted. This recycling of urea contributes in making the

medullary interstitium hypertonic and also facilitates the excretion of urea. People with a

higher protein intake have a better ability to concentrate the urine in the kidney tubules

because of the presence of larger amounts of urea in the filtrate.

Role of vasa recta in maintaining the hyperosmolarity of the medullary

interstitium

Since the vasa recta are also U-shaped

capillaries present in the medulla with

blood in the two limbs of the capillaries

running in opposite directions, they also

have a counter-current system that

contributes to the maintenance of the

hyperosmolarity of the medullary

interstitium.

Fig 23: Exchange of solutes between the

blood in vasa recta and medullary interstitium

Vasa recta

As blood flows from the vasa recta in the

upper medulla it starts losing water and

gaining solutes because the interstitium

keeps becoming hyperosmotic as blood flows down. So at the U-pin bend of the vasa

36

recta where the interstitium has the maximum osmolarity, blood becomes hyperosmotic.

As this blood moves up in the ascending limb of the vasa recta it keeps losing solutes and

gains water to emerge from the medulla at only a slightly higher concentration (320

mOsm/L) than plasma and does not carry away the solutes from the medullary

interstitium. This is facilitated by a sluggish blood supply through the vasa recta so that

blood gets enough time to get equilibrated with its surrounding interstitium.

Acid–base balance

Kidneys contribute to the acid–base balance in the body by regulating the amount of H+

ions or HCO3– ions lost from the body. Under normal conditions of metabolism, there is a

higher concentration of H+ ions (non-volatile acids from protein metabolism) than HCO3–

ions in the body. These extra H+ ions have to be removed. Also all the HCO3– ions that

are filtered by the glomerular capillaries have to be reclaimed. H+ ions are secreted by the

kidney tubule cells both in order to reabsorb filtered HCO3– ions and to remove the

excess H+ ions formed. If still there is an excess of H+ ions in the body (metabolic

acidosis) new HCO3– ions are added to the blood.

H+ ion secretion and HCO3– ion reabsorption occurs in the PCT, thick ascending limb,

DCT and collecting duct cells.

H+ ion secretion in the PCT, the thick ascending limb of loop of Henle, and early

DCT

The HCO3– ions filtered by the glomerulus cannot be reabsorbed directly through the

tubular cells as the cell membrane of these cells is not permeable to HCO3– ions. For each

filtered HCO3– ion in these parts of the kidney tubule a new HCO3

– ion is generated and

absorbed in the peritubular capillary and one H+ ion is secreted which combines with the

filtered HCO3– ion to form H2CO3 by the action of the enzyme carbonic anhydrase

associated with the apical membrane of the tubular cell. The sequence of events is as

follows.

CO2 formed within the tubular cell or generated from H2CO3 in the lumen (see below)

diffuses into the cell.

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CO2 combines with H2O in the cell to form H2CO3 (catalyzed by the enzyme carbonic

anhydrase in the cell)

H2CO3 dissociates into H+ and HCO3– ions in the cell

HCO3– ion is absorbed by the At the cell surface H+ ion is secreted in

peritubular capillaries along exchange of a Na+ ion that is reabsorbed

with the reabsorbed Na+ which is into the cell by a Na+-H+ antiporter

pumped into the interstitium by

the Na+-K+-ATPase pump

This secreted H+ ion combines with the filtered HCO3– ion to

form H2CO3 (by enzyme carbonic anhydrase

associated with the apical membrane of the cell)

H2CO3 dissociates into H2O and CO2

CO2 diffuses into the tubular cell (first step in this flow chart)

Fig 24: Secretion of H+ ions in the PCT cell

K+ K+

CO2Carbonic anhydrase

H2O

H2CO3

Fluid in tubule lumen

Peritubular capillary

Na+

Na+ Na+Na+

HCO3–

reabsorbed

H2O

Carbonic anhydrase

H2CO3

CO2

Proximal convoluted tubule cell

ATP ADP

Interstitial fluid

Primary active transport

Passive diffusion

H+

HCO3– HCO3

–H+

(filtered)

Secondary active transport

Na+-K+-ATPase pump

Na+- H+- antiporter

38

H+ secretion in the late DCT and collecting duct

Here the mechanism of H+ secretion is different because there are not enough Na+ ions in

the tubular fluid to be exchanged with H+ (at least not reabsorbed obligatorily, only under

the influence of aldosterone). Here H+ ions are secreted by the intercalated cells of the

late DCT and the collecting ducts by the following mechanism.

CO2 diffuses into the intercalated cell either from the lumen or is generated by metabolic

activities within the cell.

CO2 + H2O H2CO3 H+ + HCO3–

Carbonic anhydrase

H+ is secreted by the intercalated cells by HCO3– is reabsorbed by the peritubular

the H+-ATPase pump which utilizes capillaries in exchange of a Cl– ion

energy for secreting this H+ ion by the HCO3–/ Cl– ion antiporter (as

here very few Na+ ions are

H+ ion in the lumen combines with the reabsorbed to facilitate the diffusion of

remaining HCO3– ions to form H2CO3 HCO3

– ions)

H+ + HCO3–

H2CO3 H2O + CO2 (filtered)

Diffuses into the cell (first step in this flow chart)

While all the filtered HCO3– ions are reabsorbed by combining with the secreted H+ ion

(for which one HCO3– ion is added to the blood) the extra H+ ions that are to be

eliminated from the body (for which there are no filtered HCO3– ions to be reabsorbed)

combine with other buffering ions in the tubular fluid. The secreted H+ ion (for which one

new HCO3– ion is added to the blood here again) combines with other substances like

39

HPO42– or NH3 to form H2PO4

– and NH4+ ions, respectively, that are excreted in the

urine. Fig 25: Addition of new bicarbonate ions to the blood when there are no filtered bicarbonate

ions to be reabsorbed

Na+-K+-ATPase pump

Passive diffusion

Primary active transport

Or

HPO42– + H+

H2PO4–

HCO3–

new

CO2 + H2O

ATP ADP

H+ + HCO3–

2Cl–

HCO3–

HCO3–

2Cl–

NH3 + H+

NH4+

Interstitial fluid

Intercalated cell in collecting duct

Absorbed into peritubullary capillary

Fluid in tubule lumen

HCO3+ / Cl– antiporter

New HCO3– ions can also be added to the blood by deamination of glutamine in the

PCT, the thick ascending limb and early DCT cells

When there are no HCO3– ions to be reabsorbed new HCO3

– ions can be added by another

mechanism.

Glutamine generated in the liver by deamination of proteins

Glutamine transported into the tubular cell

A series of reactions

Glutamine forms 2NH4+ and 2HCO3

– ions

2NH4+ ions are secreted by the tubular

cell in exchange of 2Na+ ions by the

Na+/NH4+ antiporter where the NH4

+ ions

are excreted with Cl– ions in the fluid

Na+ ions are transported into HCO3– ions are absorbed by

40

the interstitium by Na+-K+-ATPase facilitated diffusion (facilitated

pump from where they diffuse into by the absorption of Na+ ions into

the peritubular capillaries the capillaries which have been pumped

by the Na+-K+-ATPase pump)

Fig 26: New bicarbonate ions can be added to blood by deamination of glutamine

Na+-K+-ATPase pump

K+

Na+

Cl–

HCO3–

Glutamine

Active transport

Glutamine

2HCO3–2NH4

+

NH4+

Na+

ATP ADP

K+

Na+

Cl– + NH4+

Glutamine

Proximal tubular cell Peritubular capillary Fluid in tubule

lumen

Na+-NH4+ antiporter Passive diffusion

Under conditions of alkalosis e.g. in vomiting where excess H+ ions are lost from the

body, less H+ ions are secreted from the tubular cells so that less HCO3– ions are

reabsorbed. This results in the loss of HCO3– ions in the urine (or addition of H+ ions in

the body) which restores the acid–base balance.

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Disorders of the excretory system

Glomerulonephritis

Urinary tract infection

Renal failure

Renal calculi or kidney stones

Glomerulonephritis

It is the inflammation of the kidneys caused by an allergic reaction due to an infection in

the body especially by streptococcal bacteria. The glomerulus gets affected where the

filtration membrane gets damaged so that protein and blood cells start appearing in the

urine.

Urinary tract infection

It is caused by bacteria that may infect any part of the urinary system. It is more common

in females because they have a shorter urethra. Symptoms include burning sensation

while urinating, frequent urge to urinate and lower back pain.

Renal failure

It is a reduction or complete cessation of glomerular filtration. It is of two types:

• Acute renal failure

• Chronic renal failure

Acute renal failure

It is a sudden, usually reversible, loss of kidney function. It can be classified into three

types depending on the causes.

i) Pre-renal acute failure. Where the cause of renal failure occurs in the body before the

kidneys, e.g. haemorrhage, diarrhoea, burns, cardiac failure, hypotension caused by

peripheral vasodilation (such as anaphylactic shock, anaesthesia, sepsis, severe

infections). Abnormalities in blood vessels going to the kidneys e.g. renal artery

stenosis, embolism or thrombosis of the renal artery can also result in renal failure.

42

ii) Intra-renal acute renal failure. Where the factor causing the failure is within the

kidneys, e.g. glomerular or vessel injury, or tubular epithelial injury caused by toxins

or ischemia, renal interstitial injury etc.

iii) Post-renal acute renal failure. Where the causative factor originates in the structures

after the kidneys, e.g., obstruction of the urinary collecting system (from the calyces

to the bladder) as caused by kidney stones.

Chronic renal failure

It is a progressive and irreversible loss of functional nephrons. Normal functioning of the

kidneys is maintained till 70–75% of nephrons are lost but when the number of functional

nephrons decreases below 25%, the composition of body fluids is affected. Causes of

chronic renal failure include metabolic disorders e.g. diabetes mellitus, hypertension,

infections, immunological disorders like systemic lupus erythematosus, nephrotoxins like

analgesics and heavy metals, urinary tract obstructions and congenital disorders.

Renal calculi or kidney stones

It is the deposition of crystals of salts like calcium oxalate, uric acid or calcium phosphate

in the excretory system. Conditions resulting in kidney stone formation include excessive

calcium intake, low water intake, abnormally acidic or alkaline urine and overactivity of

parathyroid gland (which causes increased Ca2+ ion levels in plasma).

For hormones (renin-angiotensioin-aldosterone system, antidiuretic hormone and antinatriuretic

factor) in osmoregulation, see chapter on Hormonal Control <link to Hormonal Control>

Dialysis (see box below)

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Dialysis

It is the process of removing wastes (small molecules) from blood through a semi

permeable membrane that retains the larger molecules and cells. When a person’s, kidneys

fail to perform their function because of some injury or disease the wastes from the blood

are removed artificially by dialysis. The method of haemodialysis involves circulation of the

person’s blood through a dialyzer (an artificial kidney) which has a semi permeable

membrane that separates the blood from the surrounding dialyzate. (Blood clotting is

prevented by adding an anticoagulant, e.g. heparin.) Blood loses the waste molecules (urea,

uric acid, creatinine and excess ions like phosphate, sulphate, etc.) to the dialyzate while it

acquires useful solutes, e.g. glucose, HCO3–, ions, etc. The blood is then returned to the

body after passing it through a bubble trap to remove any bubbles from the blood. Care is

taken to maintain the temperature of the dialyzate by first passing it through a temperature

bath. This artificial kidney cannot perform other functions, like secretion of erythropoetin,

activation of vitamin D, and acid–base balance.

Figure 27: Principle of dialysis (Courtesy: Karnataka Nephrology And Transplant Institute,

Bangaluru, India). Source: http://www.kanti.com/subpage/knowyourkidney/dialysis.html

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