OSMOREGULATION AND EXCRETION

OSMOREGULATION AND DISPOSAL OF METABOLIC WASTES

Read pg 1011

SUBTOPICS

Metabolic waste products: Ammonia, Urea, Uric acid

Osmoregulation and excretion in Vertebrates

Two processes help maintain fluid and osmotic

concentration in bloodOsmoregulation and

Excretion

Electrolyte/ salt homeostasis Disposal of

metabolic wastes

What is excretion?> The process of removal waste products of metabolism from the body/ body metabolic waste

What are the waste products?> Nitrogenous waste, eg. Urea, ammonia

> Waste products of metabolism, eg. CO2, bile pigments (breakdown of RBC by the liver into intestine)

> Toxic substances

Excretion NOT Secretion!!

Fig. 47-6b, p. 1016

ALL CELLS

LIVER

Wastes produce

d

Hemoglobin

breakdown

Breakdown of nucleic

acidsCellular

respirationDeamination

of amino acids

Uric acid

Wastes

Bile pigments

Water

Carbon dioxideUrea

Organs of excretion

KIDNEY

DIGESTIVE SYSTEM

SKIN LUNGS

Exhaled air containing water vapor and carbon

dioxide

Excretion

Urine

Feces Sweat

Osmoregulation?> Is maintaining the correct balance between the water and solutes in the body

> Concentration of water and salts

What are the solutes?> glucose, Na+, K+, etc

Which system of the body is responsible of osmoregulation?> Urinary system

> two kidneys, two ureters, the bladder and the uretha

BODY FLUID• ICF, Intracellular fluid (intra = inside)

– fluid within cells, accounts for the most body fluid

• ECF, Extracellular fluid (extra = outside; inter = between)– Fluid outside the cells, includes interstitial fluid,

lymph and blood plasma– Interstitial fluid forms from blood plasma and

bathes all the cells

• Electrolytes– Inorganic salts, acids and bases >>form ions in

body fluids

Important aspects of osmoregulation: Maintaining vol. and composition of body fluids

Body fluids• ECF differs, depending on where it

occurs in the body– within blood vessel, blood plasma– within lymphatic vessels, lymph– In and around the brain and spinal cord,

cerebrospinal fluid– In joints, synovial fluid– Of the eyes, aqueous humor and

vitreous body

Water, CO2 and nitrogenous wastes

Metabolic waste products:

Proteins Nucleic acids

Amino acids Nitrogenous bases

–NH2

Amino groups

Most aquaticanimals, includingmost bony fishes

Mammals, mostamphibians, sharks,some bony fishes

Many reptiles(includingbirds), insects,land snails

Ammonia Urea Uric acid

NH3 NH2

NH2O C

C

CN

CO N

H H

C ONC

HN

OH

Ammonia, a result of deamination of amino acids

• Ammonia (very toxic, soluble)– Ammonia is excreted directly by most aquatic

animals, – Easily permeates membrane since molecules are

small and very water soluble– In soft-bodied invertebrates, ammonia just

diffuses out.– In freshwater fishes, it is excreted as ammonium

ions (NH4+) across gill epithelium– Very toxic, excreted in very dilute solutions– In mammals, converted into a less toxic form

such as urea or uric acid

• Urea (less toxic, soluble)– Excreted by mammals and most adult amphibians– produce in liver by urea cycle combining ammonia

with CO2. It is transported to kidneys via the circulatory system.

– Amphibians that undergo metamorphosis and move as adults to land, switch from excreting ammonia to excreting urea

– Can be much more concentrated since it is much less toxic than ammonia; reduces water loss for terrestrial animals

– Advantage!! Can accumulate in higher conc. without causing tissue damage

– Disadvantage!! Animals must expend energy to produce urea from ammonia.

Urea is excreted by amphibians and mammals

• Uric acid (less toxic, insoluble in water)– Produced from ammonia and break down of

nucleotides from nucleic acid – Insects, land snails, reptiles, birds– excreted as semisolid paste (conserves water

>advantage for animals with little access to water)– Disadvantage!! Uric acid is even more energetically

expensive to produce than urea, require more ATP to produce/synthesis uric acid from ammonia.

Uric acid forms crystals and is excreted in a relatively

dehydrated form

Fig. 47-1, p. 1013

Amino acids Nucleic acids

Deamination

Ammonia

Keto acids

Purines

Urea

cycle

15 steps

Ammonia

Urea

Uric acid

More energy needed to produceMore water needed to

excrete

As animal move to the land, natural selection will favour the evolution of structure and processes that conserve water

Uric acid and urea represent different adaptations for excreting nitrogenous wastes with minimal water loss.

The oxidized purine structure

Animals living on landTheir environment is arid,

and they face the threat of drying up.

To conserve water, birds and mammals excrete very small

volumes of concentrated urine, but HOW?

Adaptations: waxy cuticle in plants, waxy layers of insect exoskeletons,

shells of land snails

Fig. 47-7, p. 1017

Adrenal glandLeft renal artery

Right kidneyRight renal vein

Left kidney

Right and left ureters

Urinary bladder

Urethra

The Kidney structure

Fig. 47-8a, p. 1018

Renal pyramids (medulla)

CapsuleRenal cortexRenal medulla

Renal artery

Renal veinRenal pelvis

Ureter

Internal structure of the kidney.

Kidney Structure• Renal cortex

– outer portion • Renal medulla

– inner portion – contains 8 to 10 renal pyramids

• Renal pyramids – cone-shaped structures– tip of each pyramid is a renal

papilla

• Urine flows into collecting ducts– which empty through a renal papilla into

the renal pelvis (funnel-shaped chamber)

• Collecting ducts> renal papilla> renal pelvis> ureter> urinary bladder > urethra

• Nephrons – functional units of kidney – each kidney has more than 1 million

Learning Objective

• Describe (or label on a diagram) the structures of a nephron (including associated blood vessels)

• Give the functions of each structure

The nephron is the functional unit of the kidney

• Each kidney– > 1 million functional units, called

nephrons

• Nephron structure– A cluster of capillaries, glomerulus– A cup-like Bowman’s capsule – Long, coiled renal tubule (proximal

convoluted tubule, the loop of Henle and distal convoluted tubule)

– Collecting duct

Renal corpuscle OR

Malpighian body

Glomerulus (Sing.), Glomeruli (pl.)

Fig. 47-9a, p. 1019

Proximal tubule

Bowman's capsuleGlomerulusEfferent arterioleAfferent arteriolePeritubular capillariesDistal

tubule

Fluid from several nephrons flow into Collecting duct

From renal artery

To renal vein

To renal pelvis

Loop of Henle

(a) Location and basic structure of a nephron

2 types of Nephrons• Cortical nephrons (numerous, ~85%)

– located mostly within renal cortex – have small glomeruli, short loops of

Henle, confined to the renal cortex• Juxtamedullary nephrons (~15%)

– extend deep into medulla – have large glomeruli and long loops of

Henle, reach deep into the medulla– important in concentrating urine

Excretion of urine that is hypertonic to body fluids, an

important mechanism for conserving water

Fig. 47-8b, p. 1018

Juxtamedullary nephron

Distal convoluted

tubule

Cortical nephron

CapsuleProximal convoluted tubuleRenal

cortexGlomerulusBowman’s capsuleArtery and vein

Loop of Henle

Renal medulla Collecting

duct

Papilla

Juxtamedullary and cortical nephrons.

Originate closer to medulla, long loop of Henle

Short loop of Henle

• Blood route, to kidney– Renal artery> small branches of renal artery,

afferent arterioles > cluster of capillaries (1st), glomerulus > efferent arteriole > (2nd capillary network) peritubular capillaries, surround renal tubule (proximal and distal)

– Peritubular capillaries unite to form small veins, Leaves kidney through renal vein

– Vasa recta: Long, straight capillaries extend from the efferent arterioles of the juxtamedullary nephrons, capillaries that serve the loop of Henle, conveying blood in opposite directions, “ Countercurrent exchange”

Blood supply to nephron

Juxta-medullarynephron

Corticalnephron

Collectingduct

To renalpelvis

Renalcortex

Renalmedulla

20 µm

Afferentarteriolefrom renalartery

Glomerulus

Bowman’s capsuleProximal tubule

Peritubularcapillaries

SEM

Efferentarteriole fromglomerulus

Branch ofrenal vein

DescendinglimbAscendinglimb

Loopof

Henle

Distal tubule

Collectingduct

(c) Nephron

Vasarecta(d) Filtrate and

blood flow

Blood route, to kidney

“Countercurrent exchange”

How does the kidney regulate body fluids??

THREE PROCESSES:FILTRATION

REABSORPTIONSECRETION

• Key functions of most excretory systems are– Filtration, pressure-filtering of body

fluids producing a filtrate– Reabsorption, reclaiming valuable

solutes from the filtrate– Secretion, addition of toxins and other

solutes from the body fluids to the filtrate

– Excretion, the filtrate leaves the system

Fig. 47-10, p. 1020

REABSORPTION AND SECRETIONProximal

tubuleFILTRATION

Bowman's capsuleGlomerulus

REABSORPTION AND SECRETION

REABSORPTION OF H2O; URINE CONCENTRATEDDistal

tubule Collecting duct

Capillaries

Renal arteryRenal vein

To renal pelvis

Loop of Henle

FILTRATION: Blood is filtered from the glomerulus• Blood flows through the glomerular capillaries

(glomerulus) under high pressure, • Blood plasma forced out of the capillaries into

Bowman’s capsule• Fluid within Bowman’s capsule

– Is simply a filtrate of blood plasma– Fluid that is obtained from blood if it were strained through a

porous filter (porous walls of the glomerular capillary)

• Process is called ultrafiltration---Require high pressure, high permeability to achieve glomerular filtration—Fluid force through the walls ---HOW to achieve this??

The afferent arteriole is larger in diameter than the narrow efferent arteriole ----provides a high rate of blood flow into the glomerulus, but a high resistance to blood leaving the glomerulus.

Podocytes• The cells of the surface of the

Bowman’s capsule in contact with the glomerulus are permeable podocytes (specialized epithelial cells)

• Podocytes– Have numerous cytoplasmic extensions,

foot processes (pedicel)– Cover the surfaces of the glomerular

capillaries

Fig. 47-11b, p. 1021

Blood cells restricted from passing through

Endothelial cell of capillaryRed blood

cell

Capillary pores

Nucleus

Podocyte

Filtration slits

Foot processes

Filtration membrane

• Filtration membrane: – (1) the porous walls of the glomerular capillaries– (2) Filtration slits of the podocytes

• Permits fluid and small solutes dissolved in the plasma,– Such as glucose, amino acids, sodium, potassium,

chloride, bicarbonate, other salts, and urea to pass through

– BUT holds back blood cells, platelets and plasma proteins.

Filtration is not selective with regard to ions and small

molecules

• Cells lining the renal tubule– Simple epithelial cells– Abundant microvilli– Contain numerous mitochondria, energy

for active transport materials

The three barriers• Fluid that filters from the blood into

the lumen of the nephron must pass through three potential barriers

(1) The capillary endotheliums(2) The basement membrane

associated with the capillary(3) the epithelial cell layer making up

Bowman’s capsule

Qs

• What is the name of the fluid in Bowman’s capsule?

• What is the name of the fluid at the end of the collecting duct?

What are the factors contribute to the ultrafiltration?

High pressure, high permeability ensure glomerular filtration

(1)The hydrostatic blood pressure in the glomerular capillaries is abnormally high

(2)Large surface area for filtration provided by the highly coiled glomerular capillaries

(3)Great permeability of glomerular capillaries, numerous small pores between the endothelial cells

The journey on how filtrate become urine

Proximal tubule• Cells of the transport epithelium

– Controlled secretion of H+, maintain a relatively constant pH in body fluids

– Synthesize and secrete ammonia, which neutralizes the acid

• Reabsorb– Buffer bicarbonate (HCO3

-), glucose, amino acids and potassium (K+), removed into peritubular capillaries

– Most of the NaCl (salt) and water into interstitial fluid, transfer of +ve charge is balanced by the passive diffusion of Cl-, water > osmosis

– Salt conc gradient is established, use to produced a concentrated urine

Proximal tubule

FiltrateH2OSalts (NaCl and others)HCO3

–

H+

UreaGlucose; amino acidsSome drugs

KeyActive transport

Passive transport

CORTEX

OUTERMEDULLA

INNERMEDULLA

Descending limbof loop ofHenle

Thick segmentof ascendinglimb

Thin segmentof ascendinglimb

Collectingduct

NaCl

NaCl

NaCl

Distal tubule

NaClNutrients

Urea

H2O

NaClH2O

H2OHCO3 K+

H+ NH3

HCO3

K+ H+

H2O

1 4

32

3 5

Descending limb of the loop of Henle

• Epithelium is freely permeable to water , BUT not permeable to sodium and urea

• The interstitial fluid has a high conc. of Na+, water moves out from the filtrate by osmosis– This process concentrates the filtrate insides

the loop of Henle

• Highly conc. Sodium chloride in the interstitial fluid of the medulla= hypertonic interstitial fluid

Ascending limb of the loop of Henle

• Two speacilized regions(1) a thin segment near the loop tip and(2) a thick segment adjacent to the distal tubule

• At the turn of the loop of Henle,– Walls become more permeable to salt, not permeable to

water

• Thin segment– NaCl became concentrated in the descending limb– Diffuses out into the interstitial fluid, increases the

osmalarity of the interstitial fluid in medulla

• Thick segment– Departure of salt from the filtrate continues, epithelium

actively transports NaCl into the interstitial fluid– By losing salt without giving out water, the filtrate is

progressively diluted

Distal tubule

• Plays a key role in regulating the K+ and NaCl conc. of body fluids, – by varying the amounts of the K+

secreted into the filtrate and – The amount of NaCl reabsorbed from

the filtrate

• Like the proximal tubule– pH regulation (secretion of H+ and

reabsorption of bicarbonate, HCO3-)

Collecting duct• Carries the filtrate through the medulla

renal pelvis• Actively reabsorbing NaCl, permeable to

water and urea• Filtrate becomes increasingly concentrated

as it loses more and more water by osmosis to the hyperosmotic interstitial fluid

• Degree of permeability is under hormonal control

• Final adjustment of urine vol. and conc.

Tubular transport maximum (Tm)• Substances useful to the body reabsorbed

– E.g. Glucose, a.a., solutes

• Maximum amount/rate of a substance that can be reabsorbed per unit time– Transport maximum (Tm)– Bonding sites are saturated on the membrane

proteins – Person with diabetes mellitus, the conc. of

glucose on the blood exceeds its Tm– The excess glucose cannot be reabsorbed,

excreted in the urine

Solute gradients and water conservation

Solute gradients and water conservation

• Filtrate passing from Bowman’s capsule to the proximal tubule has an osmolarity of about 300 mosm/L, SAME as blood, seawater has an osmolarity of 1000 mosm/L

• Proximal tubule: large amount of water and salt is reabsorbed– The vol. of filtrate decreases substantially, but

because of the salt loss, its osmolarity is the same• Filtrate flows from cortex to medulla,

descending limb of the loop of Henle, water move out, osmosis– Solutes and NaCl more concentrated

• Highest osmolarity (1200 mosm/L), at the elbow of the loop of Henle

mosm/L= milliosmoles per liter

• Ascending limb, permeable to salt but not to water

• As the descending limb produces a progressively saltier filtrate, – NaCl diffuses from the ascending limb– maintain a high osmolarity in the

interstitial fluid of renal medulla

Solute gradients and water conservation

Fig. 47-13, p. 1023

Bowman's capsuleProximal tubule

Distal tubuleAfferent arteriole

300 300 100 100

200Efferent arteriole

CORTEX

Filtrate300 100 300 300

MEDULLA

400 200 400 400

600 400 600 600

600Interstitial

fluid

Collecting duct

1200 1200 1200

Loop of Henle

Fig. 47-12, p. 1022

Bowman's capsule Proximal

tubule

Distal tubule

Afferent arterioleEfferent arteriole

Filtrate

NaCl

MEDULLANaCl

CORTEX

NaCl

Collecting ductH2O NaC

l

NaCl Ure

aDescending limb Ascendin

g limbLoop of Henle

H2O

H2O

H2O H2O

Hormones regulate kidney function

Kidney function is regulated by hormones, ADH

• Urine vol. is regulated by the hormone, antidiuretic hormone (ADH), ADH increases water reabsorption

• ADH produced in the hypothalamus, stored and secreted by the posterior pituitary, targets the distal tubules and collecting ducts, making them more permeable to water, resulting in a > concentrated urine

• Secretion of ADH is stimulated by the hypothalamus• Receptors that are stimulated by osmotic changes

cause production of ADH, a thirst receptor causes increased fluid intake

• Diabetes insipidus – caused by lack of ADH and excrete a great vol. of urine

Fig. 47-14, p. 1024

1. Fluid intake is low.

Receptors in the hypothalamus

2. Blood volume decreases, and osmotic pressure increases.

Posterior pituitary

7. ADH secretion is inhibited.

6. Blood volume increases, and osmotic pressure decreases. Collecting duct

Nephron

H2O

Kidney

4. Collecting ducts become more permeable.Lower

urine volume

H2OH2O

H2O

H2O

H2O

3. Posterior pituitary secretes ADH.

5. Water reabsorption increases.

Kidney function is regulated by hormones, Aldosterone

• Aldosterone-produced by the adrenal cortex • stimulates the distal convoluted tubules and

collecting ducts to increase sodium reabsorption

• Aldosterone secretion is stimulated by a decrease in blood pressure – causing the cells of the juxtaglomerular apparatus

to produce renin, which activates the renin-angiotensin-aldosterone pathway

• Atrial natriuretic peptide (ANP) is produced by the walls of the atria of the heart, and inhibits aldosterone secretion and renin release

SO,(1) ADH increases water

reabsorption (2) The renin-angiotensin-

aldosterone pathway increases sodium

reabsorption

Urine is composed of water, nitrogenous wastes and

salts• Healthy urine is sterile, used to

wash battlefield wounds when clean water was not available

• Exposed to bacteria, urea rapidly decomposes to form ammonia

• Urinalysis (diagnostic tool): physical, chemical, and microscopic examination of urine, drug testing

How do the kidneys regulate pH?

• Regulation of pH is governed by hydrogencarbonate mechanism

• CO2 diffuse from blood into cells of the distal tubules---combines with water---produce carbonic acid---easily dissociates to form hydrogen ions and bicarbonate ions

• When blood too acidic, >H+ ions are secreted into the urineCO2 + H2O ↔ H2CO3 ↔ H+ + HCO3

-

Recall the nephron unit:

A: Renal arterioleB: Afferent arterioleC: Efferent arterioleD: Bowman's CapsuleE: GlomerulusF: Proximal TubuleG: Loop of HenleH: Distal Tubule

I: Collecting Tubule

Learning objective

Compare osmoconformers and osmoregulators

How do animals regulate their water intake in

different environment??Freshwater, marine and

terrestrial

Osmoconformers and Osmoregulators

• Osmoconformers (marine invertebrates)– Internal osmotic conc. is the same as the

surrounding env.– Do not need to expend much energy in

regulating the osmolarity of their body fluids

• Osmoregulators– Maintain an osmotic difference betw. their

body fluid and the surrounding environment

Osmoregulation and excretion in

vertebratesWhat is the main

osmoregulatory and excretory organ in

vertebrates??

• KIDNEY– Excrete nitrogenous wastes– Maintain fluid balance, HOW?– By adjusting the salt and water content

of the urine

• Skin, lungs or gills, and digestive system also helps…………

Animals living in fresh water are continuously challenged with water

balance problems.

CHALLENGES

> Subject to swelling by movement of water into their bodies owning to the osmotic gradient> Subject to the continual loss of body salts to the surrounding env.

Their plasma has a high solute concentration (osmolarity) and tends to draw water by osmosis from its surroundings---hyperosmotic to their environment

How do they cope??By excreting large

volumes of it!

• Freshwater fishes– Salt conc. of the body fluids is higher than

the surroundings– Hypertonic to the watery environment

(DANGER!! Water moves into body, waterlogged, oh dear!)

– Adaptation: Freshwater fishes covered with scales and a mucous secretion, retard the passage of water into the body

– BUT, water constantly enters through the mouth and gills (along with food). How? Huh?

Freshwater Fishes• Challenges?

– Constantly take in water from their hypoosmotic environment

– Lose salts by diffusion

• HOW? maintain water balance– excrete large volume of hypotonic, dilute urine

• Salts lost by diffusion– Are replaced by foods and – uptakes across the gills– Special gill cells, evolved actively transport

salts

• Marine fishes– Hypo-osmotic to the surrounding, lose water

osmotically and take in salts– Gills dispose of sodium chloride, specialized

chloride cells, actively chloride ion (Cl-) out, sodium ions (Na+) follow passively)

– Compensate for fluid loss, drink sea water– Very small or no glomeruli, very little urine

• Marine cartilaginous fishes (chondrichthyans)– Internal salt conc. <of the seawater, SO salt diffuse out– Marine sharks do not experience large , continuous osmotic water loss.– Osmoregulatory strategy? – Have high concentrations of urea , body fluids slightly hypertonic to

sea water, net inflow of water– Tissues are adapted to high concentrated urea (accumulated and

stored in the body), trimethylamine oxide (TMAO): protects proteins from damage by urea.

– Well-developed kidneys, excrete a large amount of urine

SHARKS DON’T DRINK SEAWATER!!

Animals that live in temporary waters?

The incredible water bears!! OR tardigrades

Is a tiny invertebrate

(a) Hydrated tardigrade(b) Dehydrated

tardigrade

100 µm

100 µm

Hydrate state: 85% water by weight

Adaptation: Anhydrobiosis

Allows organisms to survive dried up by replacing water with a sugar solution, trehalose (water that associated membranes and proteins) which keeps cells in a state of suspended animation until rehydration occurs

Animals living in harsh heat environments, e.g.

desert

• Kangaroo rats– Rodents, hopping around on

their hind legs, long tufted tail.

– Their body's ability to generate water, 10% from the seeds and vegetation they eat

– Recover 90% loss using metabolic water, derived from cellular oxidation

– They never have to drink liquid water their entire lives!

• Camels– The fur of the camel, reduce

sweating– Humps, a reservoir of fatty

tissue.

Blood water homeostasis (Osmoregulation)

Homeostasis of blood volume and osmolarity

• The water potential of the blood must be regulated to prevent loss or gain of water from cells.

• Osmoregulation– Regulates solute concentrations and balances the

gain and loss of water• Osmoregulation is based largely on controlled

movement of solutes– Between internal fluids and the external environment

• Blood water homeostasis (osmoregulation) is controlled by hypothalamus, which contains osmoreceptor cells, detect changes in the water potential of the blood passing through the brain.

Blood water homeostasis (Osmoregulation)

Osmoreceptorsin hypothalamus

Drinking reducesblood osmolarity

to set point

H2O reabsorption helps prevent further

osmolarity increase

STIMULUS:The release of ADH istriggered when osmo-receptor cells in the

hypothalamus detect anincrease in the osmolarity

of the blood

Homeostasis:Blood osmolarity

Hypothalamus

ADH

Pituitarygland

Increasedpermeability

Thirst

Collecting duct

Distaltubule

Figure 44.16a: Antidiuretic hormone (ADH) enhances fluid retention by making the kidneys reclaim more water

When body becomes dehydrated,

the osmotic [ c ] OR Osmotic pressure of the blood

Posterior lobe of the pituitary glandADH

1

• Hypothalamus controls the sensation of thirst and it also secretes the hormone ADH (antidiuretic hormone; a.k.a vasopressin).

• ADH is stored in pituitary gland, – and its target cells are the distal tubules and collecting

ducts of the kidney nephrons.

• ADH increases the permeability of the epithelium to water.

• Increased water reabsorption, reduces urine volume.

Low blood water potential (too little water)

• Osmolarity of the blood subside, – reduces the activity of osmoreceptor cells

in the hypothalamus – and less ADH is secreted

Low blood water potential (too little water, high osmotic

concentration)

What happen when low osmotic pressure

detected?

Figure 44.16b

Increased Na+

and H2O reabsorption indistal tubules

Homeostasis:Blood pressure,

volume

STIMULUS:The juxtaglomerular

apparatus (JGA) respondsto low blood volume or

blood pressure (such as dueto dehydration or loss of

blood)

Aldosterone

Adrenal gland

Angiotensin II

Angiotensinogen

Reninproduction

Renin

Arterioleconstriction

Distal tubule

JGA

(b) The renin-angiotensin-aldosterone system (RAAS) leads to an increase in blood volume and pressure.

In response to low blood pressure OR blood vol.,

READ pg 936

AldosteroneIncrease retention of Na+ by the kidneys, greater fluid retention, increases blood vol.

Angiotensin II

Vasoconstriction, increase blood

pressure

ReninAngiotensinoge

n (plasma protein)

• A second regulatory mechanism involves juxtaglomerular apparatus (JGA), located near the afferent arteriole that supplies blood to the glomerulus.

• When the blood pressure/blood volume in the afferent arteriole drops, enzyme renin initiates the conversion of angiotensinogen (a plasma protein) to angiotensin II (a peptide).

High blood water potential (low osmotic concentration) > low blood

pressure

• Angiotensin II – raises blood pressure by constricting arterioles,

decreasing blood flow to many capillaries (including those in the kidney)

– Stimulates the proximal tubules of the nephrons to reabsorb more NaCl and water.

– Stimulates the adrenal glands to release aldosterone (hormone), that acts on the nephrons distal tubule, reabsorb more sodium and water

• This reduces the amount of salt and water excreted in the urine and consequently raises blood volume and pressure

High blood water potential (low osmotic concentration) > low blood

pressure

• The renin-angiotensin-aldosterone system (RAAS)– Is part of a complex feedback circuit that

functions in homeostasis

Liver

Structure of the liver• Liver: the LARGEST gland in the body.

– Accessory digestive gland – 60% of the liver---hepatocytes– The rest---biliary system– Ability to regenerate itself– Massive damage, 75% --dysfunction, scar tissue (fibrosed)

known as cirrhosis

• liver has two blood vessels supplying it with blood – (1) hepatic portal vein (~75% of the blood supply), blood

transport nutrients from intestines, – (2) arterial blood supplies oxygen, through the hepatic artery

(~25% of the blood supply)

• functions as an exocrine gland, secretes bile• The pear-shaped gallbladder stores and conc. bile----

release into duodenum• Hepatocytes absorb nutrients, detoxify and remove

harmful substances from blood

Liver

Anatomical relations between the exocrine pancreas, liver and gall bladder

Right hepatic

ductLeft

hepatic duct

Gallbladder

Cystic duct

Common bile ductPancreas

Pancreatic ductSphincter of Oddi

Portal triad

Liver lobules

Oxygenated blood from hepatic

artery

Nutrient-rich, deoxygenated blood from hepatic portal

vein

Liver sinusoids

Central vein

Hepatic vein

Vena cava

Liver: Four basic functions

1. Regulation, Synthesis, and Secretion

2. Storage3. Purification, Transformation, and

Clearance4. Fighting infections

(1) Regulation, Synthesis, and Secretion

• Hepatocytes – take up glucose, minerals and vitamins

from the blood and store them– produce important substances needed

by the body, • such as blood clotting factors, transporter

proteins, cholesterol, and bile components

– regulating blood levels of substances such as cholesterol and glucose, maintain body homeostasis 

•Glucose – STORAGE SITE: A role in the homeostatic control

of blood glucose, by storing or releasing in response to the pancreatic hormones insulin and glucagon

• Proteins– Most blood proteins (except antibodies) are

synthesized and secreted by the liver, e.g. albumin, proteins responsible for blood clotting, clotting factors

– Decreased amounts of serum albumin >>oedema (swelling due to fluid accumulation in the tissues.)

•Bile – a greenish fluid synthesized by

hepatocytes–

– secreted into the bile duct; stored in the gallbladder, emptied into the duodenum.

– Bile is both excretory and secretory

– BILE: bile salts, cholesterol, phospholipids, and bilirubin (from the breakdown of haemoglobin).

– Bile salts act as "detergents" that aid in the digestion and absorption of dietary fats

•Lipids

– Cholesterol, essential component of cell membranes

– circulates in the body to be used or excreted into bile for removal

– Increased cholesterol conc. in bile ---lead to gallstone formation, crystallization of cholesterol

– synthesizes lipoproteins, circulate in the blood and shuttle cholesterol and fatty acids between the liver and body tissues.

(2) Storage

• Stores glucose in the form of glycogen,

• fat-soluble vitamins (A, D, E and K), • Vitamins B6, and B12, and • minerals such as copper and iron. However, EXCESSIVE accumulation

of certain substances can be harmful !!

(3) Purification, Transformation, and Clearance

Removes harmful substances from the blood--- HOW?

>Breaks them down into less harmful compounds

>Converts most hormones and drugs less active products. • Ammonia

• Bilirubin• Hormones• Drugs• Toxins

• Ammonia– Liver converts ammonia > urea-- excreted in

urine by the kidneys. Process is called deamination

– convert one amino-acid into a keto acid to form a different amino acid (NOT ‘essential’ amino-acids), a process called transamination ( ‘citruline-ornithine pathway’)

– In adult humans only 11 of 20 amino acids can be made by transamination.

• Bilirubin – a yellow pigment formed, a breakdown

product of RBC haemoglobin– The spleen, destroys old red cells,

releases bilirubin into the blood, where it circulates to the liver which excretes it in bile.

– Excess bilirubin results in jaundice, a yellow pigmentation of the skin and eyes

• Hormones– A role in hormonal modification and

inactivation, e.g. the steroids testosterone and oestrogen are inactivated by the liver.

– Men with cirrhosis (chronic inflammation of the liver, results from chronic alcoholism or severe chronic hepatitis), ---especially those who abuse alcohol, --have increased circulating oestrogen, --may lead to body feminization.

• Drugs

– Nearly all drugs are modified or degraded in the liver

– oral drugs are absorbed by the gut and transported to the liver, where they may be modified or inactivated before they enter the blood.

– Alcohol, broken down by the liver, and long-term exposure to its end-products --lead to cirrhosis.

• Toxins. – The liver is generally responsible for

detoxifying chemical agents and poisons.

(4) Fighting infections

The liver contains macrophages

(known as Kuppfer cells),

which destroy any bacteria that they come into contact

with

Liver disease• Most liver disease is symptomless and

when there are symptoms they are often vague. – Jaundice (a yellow discoloration of the skin and

the whites of the eyes).– Hepatitis (cause by virus)

• Hepatitis A, spread by food and drinking water• Hepatitis B, spread by blood-to-blood contact and

also sexually• Hepatitis C, by blood borne

– Cholestasis (reduction or stoppage of bile flow)– Cirrhosis (results from infection with hepatitis

B and C, alcohol misuse)– Liver enlargement, portal hypertension

(abnormally high blood pressure in the veins that bring blood from the intestine to the liver)

– Gall bladder disease (gallstone)– Paracetamol poisoning

• Liver cancer– Primary cancer (cancer that starts in

the liver)– Secondary cancer /Metastatic cancer (cancer that has spread from another

part of the body)

Liver disease

END OF LECTURE