body fluids and renal functions

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.


• 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.


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.


• 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.


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


• 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.


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


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.


• 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

• 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


URINARY SYSTEM


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


URINARY SYSTEM


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


URINARY SYSTEM

THE NEPHRON &

COLLECTING DUCTS


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


URINARY SYSTEM


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:


URINARY SYSTEM


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)


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)


URINARY SYSTEM


1) THE NEPHRON

2) COLLECTING DUCTS

a) RENAL CORPUSCLE




b) PROXIMAL TUBULE


c) HENLE’S LOOP


d) DISTAL TUBULE


HISTOLOGICAL STRUCTURE AND FUNCTION


URINARY SYSTEM

RENAL CORPUSCLE


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


URINARY SYSTEM

RENAL CORPUSCLE



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




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


URINARY SYSTEM

RENAL CORPUSCLE




1- fenestrated capillaries

2- continuous basal lamina

3- podocytes


PODOCYTE

1° process

2° pedicels


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


Glomerulus, a knot of capillaries



afferent

arteriole



afferent

arteriole

efferent arteriole



afferent

arteriole

efferent arteriole

venuole



afferent

arteriole

efferent arteriole

venuole

Bowman’s capsule



afferent

arteriole

efferent arteriole

venuole

Bowman’s capsule

proximal

tubule

distil

tubule



afferent

arteriole

efferent arteriole

venuole

Bowman’s capsule

proximal

tubule

distil

tubule

loop of Henle sudheerkumar kamarapu 40


afferent

arteriole

efferent arteriole

venuole

Bowman’s capsule

proximal

tubule

distil

tubule

loop of Henle

ascending loop

descending loop



afferent

arteriole

efferent arteriole

venuole

Bowman’s capsule

proximal

tubule

distil

tubule

loop of Henle

ascending loop

descending loop

Collecting duct



afferent

arteriole

efferent arteriole

venuole

Bowman’s capsule

proximal

tubule

distil

tubule

loop of Henle

ascending loop

descending loop

Collecting duct

to renal pelvis



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


• 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.


Bowman’s Capsule


Bowman’s Capsule

glomerulus


Bowman’s Capsule

glomerulus

afferent arteriole


Bowman’s Capsule

glomerulus

afferent arteriole

efferent arteriole


Bowman’s Capsule

glomerulus

afferent arteriole

efferent arteriole

distil convoluted tubule


Bowman’s Capsule

glomerulus

afferent arteriole

efferent arteriole


proximal convoluted tubule


Bowman’s Capsule

glomerulus

afferent arteriole

efferent arteriole


proximal convoluted tubule

capsular

space


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%.


• 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


3. Urine Formation


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

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.


Inulin clearance


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.


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.


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


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


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


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



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


Electrolyte Composition of Body

Fluids

Figure 26.2


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



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


Continuous Mixing of Body

Fluids


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%)


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)


Water Intake and Output


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


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


Regulation of Water Intake:

Thirst Mechanism


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


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


Figure 26.6

Mechanisms and Consequences of ADH Release


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


Figure 26.7a


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


• 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


Hypotonic Hydration


Figure 26.7b


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



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


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


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


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


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



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


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


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



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


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

InterActive Physiology®:

Fluid, Electrolyte and Acid/Base Balance: Water Homeostasis PLAY


../../Animations/InterActive_Physiology/systems/fluid_wathomeo.html


Aldosterone

Figure 26.8


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


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


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


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


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


Regulation of Calcium

• Ionic calcium in ECF is important for:

– Blood clotting

– Cell membrane permeability

– Secretory behavior

• Hypocalcemia:

– Increases excitability

– Causes muscle tetany


Regulation of Calcium

• Hypercalcemia:

– Inhibits neurons and muscle cells

– May cause heart arrhythmias

• Calcium balance is controlled by

parathyroid hormone (PTH) and calcitonin


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


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

InterActive Physiology®:

Fluid, Electrolyte, and Acid/Base Balance: Electrolyte Homeostasis PLAY


../../Animations/InterActive_Physiology/systems/elehomeo.html

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


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)


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


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)


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


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


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


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¯


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


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


Base Balance • Hydrogen ion secretion occurs in the PCT

and in type A intercalated cells

• Hydrogen ions come from the dissociation

of carbonic acid


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


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


• 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


body fluids and renal functions

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