body fluids and renal functions
DESCRIPTION
TRANSCRIPT
Body Fluids And Renal
Functions
Sudheerkumar kamarapu
Assistant Professor
Sri Shivani college of pharmacy
sudheerkumar kamarapu 1
Body Fluids And Renal
Functions
• The main channels of excretion in the body are kidneys, skin, lungs, digestive tract and salivary glands .
• Kidneys and partly the skin excrete soluble substances and water from the blood (maintain homeostasis of water and electrolyte concentrations within the body).
• Lungs excretes CO2 and water vapour, ammonia, ketone bodies, alcohol, aromatic oils etc.
sudheerkumar kamarapu 2
• Skins excretes water, salts, little urea etc.
• Liver excretes fatty substances through bile.
• Colon and salivary glands excretes heavy metals.
• The excretion of waste products done by the kidneys, that system will be called as Urinary system (or) renal system.
• Kidneys produce urine that contains metabolic waste products, including the nitrogenous compounds urea and uric acid, excess ions and some drugs.
sudheerkumar kamarapu 3
Functions of the kidneys
• Formation and secretion of urine
• Production and secretion of erythropoietin, the
hormone that controls the formation of red
blood cells
• Production and secretion of renin, an important
enzyme in the control of blood pressure.
• Ultimately the urine is stored in urinary bladder
and excreted by the process of micturition.
sudheerkumar kamarapu 4
• The urinary system is the main excretory
system and consists of the following structures:
• Two kidneys, which secretes urine
• Two ureters, which convey the urine from the kidneys to
the urinary bladder
• The urinary bladder, where urine collected and is
temporarily stored
• The urethra through which the urine is discharged from
the urinary bladder to the exterior.
sudheerkumar kamarapu 5
Anatomy of kidney
1. Kidneys produce
urine.
2. Ureters transport
urine.
3. Urinary bladder
stores urine.
4. Urethra passes
urine to outside.
renal
artery
renal
vein
aorta
inferior
vena
cava
sudheerkumar kamarapu 6
• The kidney lie on the posterior abdominal wall, one on each side of vertebral column, behind the peritoneum and below the diaphragm.
• They extend from the level of the 12th thoracic vertebra to the level of the 3rd lumbar vertebra.
• The right kidney is usually slightly lower than the left, probably because of the considerable space occupied by the liver.
• Kidneys are Bean shaped organs, about 11cm long, 6cm wide, 3cm thick and weight 150g.
• They are embedded in, and held in position by, a mass of fat called renal fat.
• Both the kidney and the renal fat is enclosed in a fibro elastic sheath called renal fascia.
sudheerkumar kamarapu 7
Organs associated with kidneys
• As the lie on either side of the vertebral column, each is associated with a different group of structures.
• Right kidney: • Superiorly – the right adrenal gland
• Anteriorly – the right lobe of the liver, the duodenum and the hepatic flexure of the colon.
• Posteriorly – the diaphragm, and muscles of the posterior abdominal wall.
• Left kidney • Superiorly – the left adrenal gland
• Anteriorly – the spleen, stomach, pancreas, jejunum and splenic flexure of the colon
• Posteriorly – the diaphragm, and muscles of the posterior abdominal wall
sudheerkumar kamarapu 8
Structure of kidney
• Areas of tissue:
• They are three areas of tissue that can be distinguished when the long section of the kidney, they are
• a fibrous capsule, surrounding the kidney
• The cortex, a reddish-brown layer of tissue present immediately below the capsule and outside the pyramids.
• The medulla is the innermost layer, consists of pale conical-shaped striations called pyramids.
sudheerkumar kamarapu 9
• Hilum:
• The hilum is the concave medial border of the
kidney, through this enters renal blood and
lymph vessels, the ureter and nerves.
• Renal pelvis:
• The renal pelvis is funnel-shaped structure that
act as a receptacle for the urine formed by the
kidney.
• It as a number of distal branches called
calyces, each calyces surrounds the apex of a
renal pyramid. sudheerkumar kamarapu 10
sudheerkumar kamarapu 11
sudheerkumar kamarapu 12
• Urine formed in the kidney passes trough a
papilla present at the apex of a pyramid, into a
minor calyx, then into a major calyx before
passing through the pelvis into the uterus.
• The walls of the pelvis contains smooth
muscles and are lined with transitional
epithelium.
• Peristalsis action of smooth muscle originating
in pacemaker cells in the walls of calyces,
propels urine through the pelvis and uterus to
the urinary bladder. sudheerkumar kamarapu 13
Microscopic structure of kidney
• The kidney is composed of about one million
functional units called the Nephrons and a
smaller number of collecting ducts.
• The collecting ducts appears as striped
striations, transport the urine through the
pyramids to the renal pelvis.
• The collecting tubules are supported by a small
amount of connective tissue, they containing
blood vessels, nerves and lymph vessels. sudheerkumar kamarapu 14
URINARY SYSTEM
KIDNEY (ORGANIZATION)
- RENAL HILUM, PELVIS, AND SINUS
- RENAL CAPSULE
GROSS STRUCTURE:
- RENAL CORTEX
- RENAL MEDULLA
M
C
sudheerkumar kamarapu 15
URINARY SYSTEM
KIDNEY (ORGANIZATION)
CORTEX
MEDULLA
- region immediately beneath renal capsule
- composed of two distinct regions:
(1) CORTICAL LABYRINTH
(2) MEDULLARY RAY
- located immediately beneath renal cortex
- consists of triangular blocks of tissue called the
PYRAMIDS
- RENAL COLUMNS are strands of cortical tissue that
extend down between adjacent pyramids
RC
P
P P
P
P
P
P
sudheerkumar kamarapu 16
URINARY SYSTEM
KIDNEY (ORGANIZATION)
P
P P
P
P
P
P
RENAL LOBE
- a single pyramid with its associated
overlying cortex
RENAL LOBULE
- defined within cortex and involves a
single medullary ray (central axis of
lobule) with adjacent adjacent cortical
labyrinth
- defined as a functional unit that consists
of a collecting duct and all the nephrons
that it drains
Cortical Labyrinth
with interdigitating
Medullary Rays
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URINARY SYSTEM
THE NEPHRON &
COLLECTING DUCTS
sudheerkumar kamarapu 18
URINARY SYSTEM
THE NEPHRON & COLLECTING DUCTS
1) THE NEPHRON
2) COLLECTING DUCTS
a) RENAL CORPUSCLE
- distributed throughout cortex and
various zones of medulla
BOWMAN’S CAPSULE + GLOMERULUS
b) PROXIMAL TUBULE
CONVOLUTED AND STRAIGHT PORTIONS
c) HENLE’S LOOP
THICK AND THIN PORTIONS
d) DISTAL TUBULE
STRAIGHT AND CONVOLUTED PORTIONS
sudheerkumar kamarapu 19
URINARY SYSTEM
THE NEPHRON & COLLECTING DUCTS
CORTICAL LABYRINTH
1- RENAL CORPUSCLES
2- PROXIMAL CONVOLUTED TUBULES
3- DISTAL CONVOLUTED TUBULES
MEDULLARY RAY
1- STRAIGHT PORTIONS OF PROXIMAL TUBULE
(THICK DESCENDING)
2- STRAIGHT PORTIONS OF DISTAL TUBULE
(THICK ASCENDING)
3- COLLECTING DUCTS
CORTEX:
sudheerkumar kamarapu 20
URINARY SYSTEM
THE NEPHRON & COLLECTING DUCTS
OUTER ZONE
INNER ZONE
MEDULLA:
1- STRAIGHT PORTIONS OF PROXIMAL TUBULE
(THICK DESCENDING)
2- STRAIGHT PORTIONS OF DISTAL TUBULE
(THICK ASCENDING)
4- COLLECTING DUCTS
3- THIN SEGMENTS OF LOOP OF HENLE
(DESCENDING & ASCENDING)
2- COLLECTING DUCTS
1- THIN SEGMENTS OF LOOP OF HENLE
(DESCENDING & ASCENDING)
sudheerkumar kamarapu 21
URINARY SYSTEM
BLOOD FLOW (KIDNEY)
AORTA
RENAL ARTERY
INTERLOBAR ARTERIES
INTERLOBULAR ARTERIES
ARCUATE ARTERIES
AFFERENT ARTERIOLES
GLOMERULAR CAPILLARY BED
EFFERENT ARTERIOLES
RENAL LOBULE
- run between lobes in medulla
- run parallel to bases of pyramids at
the corticomedullary junction
- delineate lateral limits of renal lobules
- supply blood to glomerulus
- drain blood from glomerulus and form
either peritubular capillary plexus (cortex)
or vasa recta system (medulla) sudheerkumar kamarapu 22
URINARY SYSTEM
BLOOD FLOW (KIDNEY)
VENA CAVA
RENAL VEIN
INTERLOBAR VEINS
INTERLOBULAR VEINS
ARCUATE VEINS
RENAL LOBULE
- run between lobes in medulla
- run parallel to bases of pyramids at
the corticomedullary junction
- delineate lateral limits of renal lobules
PERITUBULAR
CAPILLARY PLEXUS
VASA RECTA
SYSTEM sudheerkumar kamarapu 23
URINARY SYSTEM
G
aa
ea
IA
G
G
BLOOD FLOW (KIDNEY)
sudheerkumar kamarapu 24
URINARY SYSTEM
THE NEPHRON & COLLECTING DUCTS
1) THE NEPHRON
2) COLLECTING DUCTS
a) RENAL CORPUSCLE
- distributed throughout cortex and
various zones of medulla
BOWMAN’S CAPSULE + GLOMERULUS
b) PROXIMAL TUBULE
CONVOLUTED AND STRAIGHT PORTIONS
c) HENLE’S LOOP
THICK AND THIN PORTIONS
d) DISTAL TUBULE
STRAIGHT AND CONVOLUTED PORTIONS
HISTOLOGICAL STRUCTURE AND FUNCTION
sudheerkumar kamarapu 25
URINARY SYSTEM
THE NEPHRON & COLLECTING DUCTS
1) THE NEPHRON
2) COLLECTING DUCTS
a) RENAL CORPUSCLE
- distributed throughout cortex and
various zones of medulla
BOWMAN’S CAPSULE + GLOMERULUS
b) PROXIMAL TUBULE
CONVOLUTED AND STRAIGHT PORTIONS
c) HENLE’S LOOP
THICK AND THIN PORTIONS
d) DISTAL TUBULE
STRAIGHT AND CONVOLUTED PORTIONS
HISTOLOGICAL STRUCTURE AND FUNCTION
sudheerkumar kamarapu 26
URINARY SYSTEM
RENAL CORPUSCLE
BOWMAN’S CAPSULE + GLOMERULUS
1. BOWMAN’S CAPSULE:
- the beginning of the nephron that consists of
a blind sac lined with simple squamous
epithelium that is continuous with the PCT
- parietal layer & visceral layer (specialized)
2. GLOMERULUS:
- specialized tuft of capillaries which housed in
the capsular space (10-20 capillary loops)
- blood flowing through glomerulus capillaries
undergoes a filtration process to produce the
initial urine filtrate
FILTRATION APPARATUS OF KIDNEY
sudheerkumar kamarapu 27
URINARY SYSTEM
RENAL CORPUSCLE
BOWMAN’S CAPSULE + GLOMERULUS
FILTRATION APPARATUS OF KIDNEY
VASCULAR POLE
URINARY POLE
GLOMERULUS (FILTRATION MEMBRANE):
1- fenestrated capillaries;
discontinuous endothelium; fenestrae have a
diameter of 500-1000Å and lack a diaphragm
2- continuous basal lamina
3- podocytes of visceral layer; processes
contact basal lamina and are separated by
slits measuring approximately 250Å sudheerkumar kamarapu 28
URINARY SYSTEM
RENAL CORPUSCLE
BOWMAN’S CAPSULE + GLOMERULUS
FILTRATION APPARATUS OF KIDNEY
GLOMERULUS (FILTRATION MEMBRANE):
prevents RBC’s and large MW proteins
from leaving circulation, while most
other blood constituents pass easily
into the capsular space
MESANGIAL CELLS
- phagocytic cells with a surrounding
matrix that lend structural support
to the glomerulus
sudheerkumar kamarapu 29
URINARY SYSTEM
RENAL CORPUSCLE
BOWMAN’S CAPSULE + GLOMERULUS
FILTRATION APPARATUS OF KIDNEY
GLOMERULUS (FILTRATION MEMBRANE):
1- fenestrated capillaries
2- continuous basal lamina
3- podocytes
sudheerkumar kamarapu 30
PODOCYTE
1° process
2° pedicels
sudheerkumar kamarapu 31
Structure of the nephron
overview
• They consist of:
A cup-shaped Bowman’s capsule
Immediately below the capsule a twisted region called the proximal convoluted tubule. followed by the long hair-pin like loop of Henle, which runs deep into the medulla and then back into the cortex
This is followed by another twisted region called the distil convoluted tubule. This is joined to the collecting duct which carries urine through the medulla to the pelvis of the kidney
sudheerkumar kamarapu 32
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Glomerulus, a knot of capillaries
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Glomerulus, a knot of capillaries
afferent
arteriole
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Glomerulus, a knot of capillaries
afferent
arteriole
efferent arteriole
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Glomerulus, a knot of capillaries
afferent
arteriole
efferent arteriole
venuole
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Glomerulus, a knot of capillaries
afferent
arteriole
efferent arteriole
venuole
Bowman’s capsule
sudheerkumar kamarapu 38
Glomerulus, a knot of capillaries
afferent
arteriole
efferent arteriole
venuole
Bowman’s capsule
proximal
tubule
distil
tubule
sudheerkumar kamarapu 39
Glomerulus, a knot of capillaries
afferent
arteriole
efferent arteriole
venuole
Bowman’s capsule
proximal
tubule
distil
tubule
loop of Henle sudheerkumar kamarapu 40
Glomerulus, a knot of capillaries
afferent
arteriole
efferent arteriole
venuole
Bowman’s capsule
proximal
tubule
distil
tubule
loop of Henle
ascending loop
descending loop
sudheerkumar kamarapu 41
Glomerulus, a knot of capillaries
afferent
arteriole
efferent arteriole
venuole
Bowman’s capsule
proximal
tubule
distil
tubule
loop of Henle
ascending loop
descending loop
Collecting duct
sudheerkumar kamarapu 42
Glomerulus, a knot of capillaries
afferent
arteriole
efferent arteriole
venuole
Bowman’s capsule
proximal
tubule
distil
tubule
loop of Henle
ascending loop
descending loop
Collecting duct
to renal pelvis
sudheerkumar kamarapu 43
Glomerulus, a knot of capillaries
afferent
arteriole
efferent arteriole
venuole
Bowman’s capsule
proximal
tubule
distil
tubule
loop of Henle
ascending loop
descending loop
Collecting duct
to renal pelvis
capillary net
sudheerkumar kamarapu 44
sudheerkumar kamarapu 45
• Each nephron has a rich blood supply
• Each Bowman’s capsule is supplied with blood by an afferent arteriole
• This branches inside the Bowman’s capsule to form the glomerulus
• Taking blood away from the capsule is the efferent arteriole.
• The afferent arteriole is much wider than the efferent arteriole….. So there is more blood carried to the glomerulus than is carried away, and pressure is created in the glomerulus is high.
sudheerkumar kamarapu 46
Bowman’s Capsule
sudheerkumar kamarapu 47
Bowman’s Capsule
glomerulus
sudheerkumar kamarapu 48
Bowman’s Capsule
glomerulus
afferent arteriole
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Bowman’s Capsule
glomerulus
afferent arteriole
efferent arteriole
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Bowman’s Capsule
glomerulus
afferent arteriole
efferent arteriole
distil convoluted tubule
sudheerkumar kamarapu 51
Bowman’s Capsule
glomerulus
afferent arteriole
efferent arteriole
distil convoluted tubule
proximal convoluted tubule
sudheerkumar kamarapu 52
Bowman’s Capsule
glomerulus
afferent arteriole
efferent arteriole
distil convoluted tubule
proximal convoluted tubule
capsular
space
sudheerkumar kamarapu 53
FORMATION OF URINE
(Functions Of Nephron )
• The kidney forms the urine, which passes
through the ureters to the bladder for storage
prior to excretion.
• The composition of urine reflects exchange of
substances between the nephron and the blood
in the renal capillaries.
• Composition of urine:
– Water – 96% Urea – 2%
– Creatinine, ammonia, sodium, potassium, chlorides,
phosphates, sulphates, oxalates – 2%.
sudheerkumar kamarapu 54
• Use of excretion of urine:
– Waste products of protein metabolism are
excreted
– Electrolyte levels are controlled
– pH (acid-base balance ) is maintained by
excretion of hydrogen ions.
• Formation of urine involves three process: • Filtration
• Selective reabsorption
• secretion
sudheerkumar kamarapu 55
3. Urine Formation
sudheerkumar kamarapu 56
Functions of Nephron When blood is delivered in to glomerulus by afferent arteriole many of its
components are filtered off through the pores in the glomerular capillary loops.
The components which are filtered off include amino acids, salts, water and
those with molecular mass of below 50,000 Da. RBC and plasma proteins are
not readily filtered because their molecular mass is above 50,000 Da. The
glomerular filtration rate (GFR) of plasma components is directly dependent on
the hydraulic pressure in renal vasculature, which tends to drive water and
solutes out of the glomerular capillaries into bowman’s capsule.
20% of the renal blood flow is filtered off from by the glomerular capillaries of
kidneys i.e., each minute 650 mL of blood flows through kidneys and
approximately 130 mL of its components are filtered and remaining 520 mL is
directed out by efferent arterioles. But each minute 1 mL of urine is formed from
130 mL filtered and more than 99% of the blood components filtered is
reabsorbed.
There are four major sites along the nephron which involve in active absorption
of sodium which include
Site 1: The convoluted and straight part of proximal tubule
Site 2: the thick ascending limb of Henle loop
Site 3: Distal convoluted tubule and
Site 4: The collecting tubule. sudheerkumar kamarapu 57
sudheerkumar kamarapu 58
Site 1
It is responsible for the reabsorption of about 65% - 70% of the
filtered loads of sodium, chloride, water and calcium, 80% - 90%
of the filtered loads of bicarbonate, phosphate and urate and
100% filtered loads of glucose, amino acids and low molecular
mass proteins.
The mechanism by which sodium is reabsorbed include
In exchange of H+ Sodium is reabsorbed. H+ is produced by
degradation of H2CO3 to H+ and HCO3- and the enzyme
responsible for this degradation is carbonic anhydrase. Inhibition
of this enzyme prevents the sodium reabsorption.
Cotransportation of sodium along with glucose, amino acids
and phosphate.
Along with chlorine as sodium chloride.
Collectively site 1 is responsible for 65 – 70% reabsorption of
sodium. sudheerkumar kamarapu 59
Site 2
Here sodium is reabsorbed by the concentration gradient and
Na+,K+-ATPase pump and Na+-K+-2Cl- cotransport system involve
actively in the absorption of sodium. Site 2 accounts for nearly 20
– 25% of the sodium reabsorption.
Site 3
Site 3 accounts for 5 – 8% of sodium reabsorption. Here
sodium is reabsorbed in exchange of potassium, and Na+,K+-
ATPase pump involve actively in the absorption of sodium in
exchange of potassium.
Site 4
Site 4 accounts for 2 – 3% of sodium reabsorption. Here also
sodium is reabsorbed in exchange of potassium, and Na+,K+-
ATPase pump involve actively in the absorption of sodium in
exchange of potassium. The amount of sodium reabsorbed is
modulated by mineralocorticoids like aldosterone, the higher the
levels of circulating aldosterone greater the reabsorption of
sodium and excretion of potassium and Hydrogen ions.
sudheerkumar kamarapu 60
Inulin clearance
sudheerkumar kamarapu 61
sudheerkumar kamarapu 62
sudheerkumar kamarapu 63
Proximal Convoluted
Tubule:
Initiate concentration of
glomerular filtrate.
About 75% of sodium
removed by active
transport here, and
chlorine follows
passively.
Remaining fluid in
nephron tube is about
same concentration as
that of surrounding
interstitial fluid.
Remaining fluid reduce
to about 25% original
volume sudheerkumar kamarapu 64
Loop of Henle:
Acts in manner of counter
current exchanger. Note
that each limb of loop has
fluid moving in opposite
directions (even though
connected at one end).
Further concentrates
urine.
Also means that salt
concentration will be
highest near bend in the
loop.
sudheerkumar kamarapu 65
DESCENDING LOOP OF HENLE: No active
transport of salt out of the descending loop of Henle.
ASCENDING LOOP OF HENLE: Chlorine ions
actively transported out of loop into the interstitial
space. Oppositely charged sodium ions follow.
However, water does not move out of the ascending
loop.
A concentration gradient IN THE INTERSTITIAL
SPACE has been set up by the chlorine ( plus
sodium) transport. sudheerkumar kamarapu 66
Distal Convoluted
Tubule:
In addition to sodium-
chloride, potassium,
ammonia, and carbonate
removed from filtrate here.
These are retained as
needed by the body.
At this point, nephron has
used materials IN the
glomerular filtrate to set up
a concentration gradient in
the interstitial space of the
kidney.
sudheerkumar kamarapu 67
Collecting Duct:
Receives many proximal
convoluted tubules.
Collecting duct now passes
through the concentration
gradient set up by many
adjacent nephrons.
So, as glomerular filtrate
passes down collecting
tubule, it moves through
higher and higher
concentration of sals that
were set up by loops of
Henle.
Direction of
fluid flow
through
collecting
tubule.
By process of osmosis, water wants to move from region of higher
water concentration to lower. This pulls water from filtrate, leaving
behind a more concentrated “urine”. sudheerkumar kamarapu 68
sudheerkumar kamarapu
Fluid, Electrolyte, and Acid-Base
Balance
69
Body Water Content
• Infants have low body fat, low bone mass, and are 73% or more water
• Total water content declines throughout life
• Healthy males are about 60% water; healthy females are around 50%
• This difference reflects females’: – Higher body fat
– Smaller amount of skeletal muscle
• In old age, only about 45% of body weight is water sudheerkumar kamarapu 70
Fluid Compartments
• Water occupies two main fluid compartments
• Intracellular fluid (ICF) – about two thirds by volume, contained in cells
• Extracellular fluid (ECF) – consists of two major subdivisions
– Plasma – the fluid portion of the blood
– Interstitial fluid (IF) – fluid in spaces between cells
• Other ECF – lymph, cerebrospinal fluid, eye humors, synovial fluid, serous fluid, and gastrointestinal secretions
sudheerkumar kamarapu 71
Fluid Compartments
Figure 26.1 sudheerkumar kamarapu 72
Composition of Body Fluids
• Water is the universal solvent
• Solutes are broadly classified into:
– Electrolytes – inorganic salts, all acids and
bases, and some proteins
– Nonelectrolytes – examples include glucose,
lipids, creatinine, and urea
• Electrolytes have greater osmotic power
than nonelectrolytes
• Water moves according to osmotic
gradients sudheerkumar kamarapu 73
Electrolyte Concentration
• Expressed in milliequivalents per liter
(mEq/L), a measure of the number of
electrical charges in one liter of solution
• mEq/L = (concentration of ion in [mg/L]/the
atomic weight of ion) number of
electrical charges on one ion
• For single charged ions, 1 mEq = 1 mOsm
• For bivalent ions, 1 mEq = 1/2 mOsm
sudheerkumar kamarapu 74
Extracellular and Intracellular
Fluids • Each fluid compartment of the body has a
distinctive pattern of electrolytes
• Extracellular fluids are similar (except for
the high protein content of plasma)
– Sodium is the chief cation
– Chloride is the major anion
• Intracellular fluids have low sodium and
chloride
– Potassium is the chief cation
– Phosphate is the chief anion sudheerkumar kamarapu 75
Extracellular and Intracellular
Fluids • Sodium and potassium concentrations in
extra- and intracellular fluids are nearly
opposites
• This reflects the activity of cellular ATP-
dependent sodium-potassium pumps
• Electrolytes determine the chemical and
physical reactions of fluids
sudheerkumar kamarapu 76
Extracellular and Intracellular
Fluids • Proteins, phospholipids, cholesterol, and
neutral fats account for:
– 90% of the mass of solutes in plasma
– 60% of the mass of solutes in interstitial fluid
– 97% of the mass of solutes in the intracellular
compartment
sudheerkumar kamarapu 77
Electrolyte Composition of Body
Fluids
Figure 26.2
sudheerkumar kamarapu 78
Fluid Movement Among
Compartments • Compartmental exchange is regulated by
osmotic and hydrostatic pressures
• Net leakage of fluid from the blood is picked up
by lymphatic vessels and returned to the
bloodstream
• Exchanges between interstitial and intracellular
fluids are complex due to the selective
permeability of the cellular membranes
• Two-way water flow is substantial
sudheerkumar kamarapu 79
Extracellular and Intracellular
Fluids
• Ion fluxes are restricted and move selectively by active transport
• Nutrients, respiratory gases, and wastes move unidirectionally
• Plasma is the only fluid that circulates throughout the body and links external and internal environments
• Osmolalities of all body fluids are equal; changes in solute concentrations are quickly followed by osmotic changes
sudheerkumar kamarapu 80
Continuous Mixing of Body
Fluids
Figure 26.3 sudheerkumar kamarapu 81
Water Balance and ECF
Osmolality • To remain properly hydrated, water intake
must equal water output
• Water intake sources
– Ingested fluid (60%) and solid food (30%)
– Metabolic water or water of oxidation (10%)
sudheerkumar kamarapu 82
Water Balance and ECF
Osmolality • Water output
– Urine (60%) and feces (4%)
– Insensible losses (28%), sweat (8%)
• Increases in plasma osmolality trigger
thirst and release of antidiuretic hormone
(ADH)
sudheerkumar kamarapu 83
Water Intake and Output
Figure 26.4 sudheerkumar kamarapu 84
Regulation of Water Intake
• The hypothalamic thirst center is
stimulated:
– By a decline in plasma volume of 10%–15%
– By increases in plasma osmolality of 1–2%
– Via baroreceptor input, angiotensin II, and
other stimuli
sudheerkumar kamarapu 85
Regulation of Water Intake
• Thirst is quenched as soon as we begin to
drink water
• Feedback signals that inhibit the thirst
centers include:
– Moistening of the mucosa of the mouth and
throat
– Activation of stomach and intestinal stretch
receptors
sudheerkumar kamarapu 86
Regulation of Water Intake:
Thirst Mechanism
Figure 26.5 sudheerkumar kamarapu 87
Regulation of Water Output
• Obligatory water losses include:
– Insensible water losses from lungs and skin
– Water that accompanies undigested food
residues in feces
• Obligatory water loss reflects the fact that:
– Kidneys excrete 900-1200 mOsm of solutes
to maintain blood homeostasis
– Urine solutes must be flushed out of the body
in water
sudheerkumar kamarapu 88
Influence and Regulation of
ADH • Water reabsorption in collecting ducts is proportional to
ADH release
• Low ADH levels produce dilute urine and reduced
volume of body fluids
• High ADH levels produce concentrated urine
• Hypothalamic osmoreceptors trigger or inhibit ADH
release
• Factors that specifically trigger ADH release include
prolonged fever; excessive sweating, vomiting, or
diarrhea; severe blood loss; and traumatic burns
sudheerkumar kamarapu 89
Figure 26.6
Mechanisms and Consequences of ADH Release
sudheerkumar kamarapu 90
Disorders of Water Balance:
Dehydration • Water loss exceeds water intake and the body is
in negative fluid balance
• Causes include: hemorrhage, severe burns, prolonged vomiting or diarrhea, profuse sweating, water deprivation, and diuretic abuse
• Signs and symptoms: cottonmouth, thirst, dry flushed skin, and oliguria
• Prolonged dehydration may lead to weight loss, fever, and mental confusion
• Other consequences include hypovolemic shock and loss of electrolytes
sudheerkumar kamarapu 91
Figure 26.7a
Disorders of Water Balance:
Dehydration
Excessive loss of H2O from
ECF
1 2 3 ECF osmotic
pressure rises Cells lose H2O
to ECF by
osmosis; cells
shrink
(a) Mechanism of dehydration
sudheerkumar kamarapu 92
• Renal insufficiency or an extraordinary amount of water ingested quickly can lead to cellular overhydration, or water intoxication
• ECF is diluted – sodium content is normal but excess water is present
• The resulting hyponatremia promotes net osmosis into tissue cells, causing swelling
• These events must be quickly reversed to prevent severe metabolic disturbances, particularly in neurons
Disorders of Water Balance:
Hypotonic Hydration
sudheerkumar kamarapu 93
Figure 26.7b
Disorders of Water Balance:
Hypotonic Hydration
Excessive H2O enters
the ECF
1 2 ECF osmotic
pressure falls
3 H2O moves into
cells by osmosis;
cells swell
(b) Mechanism of hypotonic hydration
sudheerkumar kamarapu 94
Disorders of Water Balance:
Edema • Atypical accumulation of fluid in the
interstitial space, leading to tissue swelling
• Caused by anything that increases flow of fluids out of the bloodstream or hinders their return
• Factors that accelerate fluid loss include:
– Increased blood pressure, capillary permeability
– Incompetent venous valves, localized blood vessel blockage
– Congestive heart failure, hypertension, high blood volume
sudheerkumar kamarapu 95
Edema
• Hindered fluid return usually reflects an
imbalance in colloid osmotic pressures
• Hypoproteinemia – low levels of plasma
proteins
– Forces fluids out of capillary beds at the
arterial ends
– Fluids fail to return at the venous ends
– Results from protein malnutrition, liver
disease, or glomerulonephritis
sudheerkumar kamarapu 96
Edema
• Blocked (or surgically removed) lymph
vessels:
– Cause leaked proteins to accumulate in
interstitial fluid
– Exert increasing colloid osmotic pressure,
which draws fluid from the blood
• Interstitial fluid accumulation results in low
blood pressure and severely impaired
circulation
sudheerkumar kamarapu 97
Electrolyte Balance
• Electrolytes are salts, acids, and bases, but electrolyte balance usually refers only to salt balance
• Salts are important for: – Neuromuscular excitability
– Secretory activity
– Membrane permeability
– Controlling fluid movements
• Salts enter the body by ingestion and are lost via perspiration, feces, and urine
sudheerkumar kamarapu 98
Sodium in Fluid and Electrolyte
Balance • Sodium holds a central position in fluid and
electrolyte balance
• Sodium salts: – Account for 90-95% of all solutes in the ECF
– Contribute 280 mOsm of the total 300 mOsm ECF solute concentration
• Sodium is the single most abundant cation in the ECF
• Sodium is the only cation exerting significant osmotic pressure
sudheerkumar kamarapu 99
Sodium in Fluid and Electrolyte
Balance • The role of sodium in controlling ECF
volume and water distribution in the body
is a result of:
– Sodium being the only cation to exert
significant osmotic pressure
– Sodium ions leaking into cells and being
pumped out against their electrochemical
gradient
• Sodium concentration in the ECF normally
remains stable sudheerkumar kamarapu 100
Sodium in Fluid and Electrolyte
Balance • Changes in plasma sodium levels affect:
– Plasma volume, blood pressure
– ICF and interstitial fluid volumes
• Renal acid-base control mechanisms are
coupled to sodium ion transport
sudheerkumar kamarapu 101
Regulation of Sodium Balance:
Aldosterone • Sodium reabsorption
– 65% of sodium in filtrate is reabsorbed in the
proximal tubules
– 25% is reclaimed in the loops of Henle
• When aldosterone levels are high, all
remaining Na+ is actively reabsorbed
• Water follows sodium if tubule permeability
has been increased with ADH
sudheerkumar kamarapu 102
Regulation of Sodium Balance:
Aldosterone • The renin-angiotensin mechanism triggers
the release of aldosterone
• This is mediated by the juxtaglomerular
apparatus, which releases renin in
response to:
– Sympathetic nervous system stimulation
– Decreased filtrate osmolality
– Decreased stretch (due to decreased blood
pressure) • Renin catalyzes the production of angiotensin II, which prompts
aldosterone release sudheerkumar kamarapu 103
Regulation of Sodium Balance:
Aldosterone
• Adrenal cortical cells are directly
stimulated to release aldosterone by
elevated K+ levels in the ECF
• Aldosterone brings about its effects
(diminished urine output and increased
blood volume) slowly
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sudheerkumar kamarapu 104
Regulation of Sodium Balance:
Aldosterone
Figure 26.8
sudheerkumar kamarapu 105
Regulation of Potassium
Balance • Relative ICF-ECF potassium ion
concentration affects a cell’s resting
membrane potential
– Excessive ECF potassium decreases
membrane potential
– Too little K+ causes hyperpolarization and
nonresponsiveness
sudheerkumar kamarapu 106
Regulation of Potassium
Balance • Hyperkalemia and hypokalemia can:
– Disrupt electrical conduction in the heart
– Lead to sudden death
• Hydrogen ions shift in and out of cells
– Leads to corresponding shifts in potassium in
the opposite direction
– Interferes with activity of excitable cells
sudheerkumar kamarapu 107
Regulatory Site: Cortical
Collecting Ducts • Less than 15% of filtered K+ is lost to urine
regardless of need
• K+ balance is controlled in the cortical collecting ducts by changing the amount of potassium secreted into filtrate
• Excessive K+ is excreted over basal levels by cortical collecting ducts
• When K+ levels are low, the amount of secretion and excretion is kept to a minimum
• Type A intercalated cells can reabsorb some K+ left in the filtrate
sudheerkumar kamarapu 108
Influence of Plasma Potassium
Concentration • High K+ content of ECF favors principal
cells to secrete K+
• Low K+ or accelerated K+ loss depresses
its secretion by the collecting ducts
sudheerkumar kamarapu 109
Influence of Aldosterone
• Aldosterone stimulates potassium ion secretion by principal cells
• In cortical collecting ducts, for each Na+ reabsorbed, a K+ is secreted
• Increased K+ in the ECF around the adrenal cortex causes:
– Release of aldosterone
– Potassium secretion
• Potassium controls its own ECF concentration via feedback regulation of aldosterone release
sudheerkumar kamarapu 110
Regulation of Calcium
• Ionic calcium in ECF is important for:
– Blood clotting
– Cell membrane permeability
– Secretory behavior
• Hypocalcemia:
– Increases excitability
– Causes muscle tetany
sudheerkumar kamarapu 111
Regulation of Calcium
• Hypercalcemia:
– Inhibits neurons and muscle cells
– May cause heart arrhythmias
• Calcium balance is controlled by
parathyroid hormone (PTH) and calcitonin
sudheerkumar kamarapu 112
Regulation of Calcium and
Phosphate • PTH promotes increase in calcium levels
by targeting:
– Bones – PTH activates osteoclasts to break down bone matrix
– Small intestine – PTH enhances intestinal absorption of calcium
– Kidneys – PTH enhances calcium reabsorption and decreases phosphate reabsorption
• Calcium reabsorption and phosphate excretion go hand in hand
sudheerkumar kamarapu 113
Regulation of Calcium and Phosphate
• Filtered phosphate is actively reabsorbed in the proximal tubules
• In the absence of PTH, phosphate reabsorption is regulated by its transport maximum and excesses are excreted in urine
• High or normal ECF calcium levels inhibit PTH secretion – Release of calcium from bone is inhibited
– Larger amounts of calcium are lost in feces and urine
– More phosphate is retained sudheerkumar kamarapu 114
Influence of Calcitonin
• Released in response to rising blood calcium
levels
• Calcitonin is a PTH antagonist, but its
contribution to calcium and phosphate
homeostasis is minor to negligible
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sudheerkumar kamarapu 115
Regulation of Anions
• Chloride is the major anion accompanying
sodium in the ECF
• 99% of chloride is reabsorbed under
normal pH conditions
• When acidosis occurs, fewer chloride ions
are reabsorbed
• Other anions have transport maximums
and excesses are excreted in urine
sudheerkumar kamarapu 116
Acid-Base Balance
• Normal pH of body fluids
– Arterial blood is 7.4
– Venous blood and interstitial fluid is 7.35
– Intracellular fluid is 7.0
• Alkalosis or alkalemia – arterial blood pH
rises above 7.45
• Acidosis or acidemia – arterial pH drops
below 7.35 (physiological acidosis)
sudheerkumar kamarapu 117
Sources of Hydrogen Ions
• Most hydrogen ions originate from cellular
metabolism
– Breakdown of phosphorus-containing proteins
releases phosphoric acid into the ECF
– Anaerobic respiration of glucose produces
lactic acid
– Fat metabolism yields organic acids and
ketone bodies
– Transporting carbon dioxide as bicarbonate
releases hydrogen ions sudheerkumar kamarapu 118
Hydrogen Ion Regulation
• Concentration of hydrogen ions is
regulated sequentially by:
– Chemical buffer systems – act within seconds
– The respiratory center in the brain stem – acts
within 1-3 minutes
– Renal mechanisms – require hours to days to
effect pH changes
sudheerkumar kamarapu 119
Chemical Buffer Systems
• Strong acids – all their H+ is dissociated
completely in water
• Weak acids – dissociate partially in water
and are efficient at preventing pH changes
• Strong bases – dissociate easily in water
and quickly tie up H+
• Weak bases – accept H+ more slowly
(e.g., HCO3¯ and NH3)
sudheerkumar kamarapu 120
Chemical Buffer Systems
• One or two molecules that act to resist pH
changes when strong acid or base is
added
• Three major chemical buffer systems
– Bicarbonate buffer system
– Phosphate buffer system
– Protein buffer system
• Any drifts in pH are resisted by the entire
chemical buffering system sudheerkumar kamarapu 121
Bicarbonate Buffer System
• A mixture of carbonic acid (H2CO3) and its
salt, sodium bicarbonate (NaHCO3)
(potassium or magnesium bicarbonates
work as well)
• If strong acid is added:
– Hydrogen ions released combine with the
bicarbonate ions and form carbonic acid (a
weak acid)
– The pH of the solution decreases only slightly
sudheerkumar kamarapu 122
Bicarbonate Buffer System
• If strong base is added:
– It reacts with the carbonic acid to form sodium
bicarbonate (a weak base)
– The pH of the solution rises only slightly
• This system is the only important ECF
buffer
sudheerkumar kamarapu 123
Phosphate Buffer System
• Nearly identical to the bicarbonate system
• Its components are:
– Sodium salts of dihydrogen phosphate
(H2PO4¯), a weak acid
– Monohydrogen phosphate (HPO42¯), a weak
base
• This system is an effective buffer in urine
and intracellular fluid
sudheerkumar kamarapu 124
Protein Buffer System
• Plasma and intracellular proteins are the
body’s most plentiful and powerful buffers
• Some amino acids of proteins have:
– Free organic acid groups (weak acids)
– Groups that act as weak bases (e.g., amino
groups)
• Amphoteric molecules are protein
molecules that can function as both a
weak acid and a weak base sudheerkumar kamarapu 125
Physiological Buffer Systems
• The respiratory system regulation of acid-
base balance is a physiological buffering
system
• There is a reversible equilibrium between:
– Dissolved carbon dioxide and water
– Carbonic acid and the hydrogen and
bicarbonate ions
CO2 + H2O H2CO3 H+ + HCO3¯
sudheerkumar kamarapu 126
Physiological Buffer Systems
• During carbon dioxide unloading, hydrogen ions are incorporated into water
• When hypercapnia or rising plasma H+ occurs: – Deeper and more rapid breathing expels more
carbon dioxide
– Hydrogen ion concentration is reduced
• Alkalosis causes slower, more shallow breathing, causing H+ to increase
• Respiratory system impairment causes acid-base imbalance (respiratory acidosis or respiratory alkalosis) sudheerkumar kamarapu 127
Renal Mechanisms of Acid-
Base Balance • Chemical buffers can tie up excess acids or
bases, but they cannot eliminate them from the
body
• The lungs can eliminate carbonic acid by
eliminating carbon dioxide
• Only the kidneys can rid the body of metabolic
acids (phosphoric, uric, and lactic acids and
ketones) and prevent metabolic acidosis
• The ultimate acid-base regulatory organs are the
kidneys sudheerkumar kamarapu 128
Renal Mechanisms of Acid-
Base Balance • The most important renal mechanisms for
regulating acid-base balance are:
– Conserving (reabsorbing) or generating new
bicarbonate ions
– Excreting bicarbonate ions
• Losing a bicarbonate ion is the same as
gaining a hydrogen ion; reabsorbing a
bicarbonate ion is the same as losing a
hydrogen ion sudheerkumar kamarapu 129
Renal Mechanisms of Acid-
Base Balance • Hydrogen ion secretion occurs in the PCT
and in type A intercalated cells
• Hydrogen ions come from the dissociation
of carbonic acid
sudheerkumar kamarapu 130
Reabsorption of Bicarbonate
• Carbon dioxide combines with water in tubule
cells, forming carbonic acid
• Carbonic acid splits into hydrogen ions and
bicarbonate ions
• For each hydrogen ion secreted, a sodium ion
and a bicarbonate ion are reabsorbed by the
PCT cells
• Secreted hydrogen ions form carbonic acid;
thus, bicarbonate disappears from filtrate at the
same rate that it enters the peritubular capillary
blood sudheerkumar kamarapu 131
Ammonium Ion Excretion
• This method uses ammonium ions
produced by the metabolism of glutamine
in PCT cells
• Each glutamine metabolized produces two
ammonium ions and two bicarbonate ions
• Bicarbonate moves to the blood and
ammonium ions are excreted in urine
sudheerkumar kamarapu 132
Developmental Aspects
• Water content of the body is greatest at birth (70-80%) and declines until adulthood, when it is about 58%
• At puberty, sexual differences in body water content arise as males develop greater muscle mass
• Homeostatic mechanisms slow down with age
• Elders may be unresponsive to thirst clues and are at risk of dehydration
• The very young and the very old are the most frequent victims of fluid, acid-base, and electrolyte imbalances
sudheerkumar kamarapu 133
• Occur in the young, reflecting:
– Low residual lung volume
– High rate of fluid intake and output
– High metabolic rate yielding more metabolic
wastes
– High rate of insensible water loss
– Inefficiency of kidneys in infants
Problems with Fluid, Electrolyte,
and Acid-Base Balance
sudheerkumar kamarapu 134