Excretion (my)

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 blood Osmoregulation 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!!

LIVER Wastes produce d

Breakdown of nucleic acids Deamination of amino acids

Waste s

Uric acid Urea

ALL Hemoglob CELLS in breakdow n Cellular respiration

Bile pigments

Wate r

Carbon dioxide

Organs of excretion KIDNEY

Excretio n

Urin e

DIGESTIV E SYSTEM Feces

SKIN

Swea t

LUNG S Exhaled air containing water vapor and carbon

Fig. 47-6b, p. 1016

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

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

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

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

Metabolic waste products: Water, CO2 and nitrogenous wastes

Nucleic acids

Proteins

Amino acids Nitrogenous bases –NH2 Amino groups

Many reptiles Most aquatic Mammals, most (including animals, including amphibians, sharks,birds), insects, most bony fishessome bony fishes land snails O

NH3 Ammonia

O

C

NH2 NH2 Urea

O

HN C

C

H C N

C O C N N H H Uric acid

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

Urea is excreted by amphibians and mammals • 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

Uric acid forms crystals and is excreted in a relatively dehydrated form • 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.

Amino acids

Nucleic acids

Deaminati on Keto acids

Ammoni a

Urea cycl e Ammoni a

15 steps

U rea

Purine s

The oxidized Uric purine acid structure

More energy needed to produce More water needed to

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 Fig. 47-1, p. 1013

Animals living on land Their environment is arid, and they face the threat of up. Adaptations: drying waxy cuticle in plants, waxy layers of insect exoskeletons, shells of land snails To conserve water, birds and mammals excrete very small volumes of concentrated urine, but HOW?

Right kidney Right renal vein

Adrenal gland Left renal artery Left kidney

Right and left ureters Urinary bladder Urethr a

Fig. 47-7, p. 1017

The Kidney structure

Renal pyramids (medulla) Capsul e Renal cortex Renal medulla Renal artery

Renal vein Renal pelvis Uret er

Internal structure of the kidney. Fig. 47-8a, p. 1018

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

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

Renal corpuscle OR

– A cluster of capillaries, glomerulus Malpighian – A cup-like Bowman’s capsule body – Long, coiled renal tubule (proximal convoluted tubule, the loop of Henle and distal convoluted tubule) Glomerulus (Sing.), Glomeruli (pl.) – Collecting duct

Proximal tubule

Bowman's capsule Glomerul us Efferent arteriole Afferent arteriole Peritubul ar capillarie Distal s tubule

From renal arter y

To renal vein

Loop of Henle

) Location and basic structure of a nephron

Fluid from several nephron s flow into Collectin To g duct renal pelvi s Fig. 47-9a, p. 1019

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

Originate closer to medulla, long loop of Henle

Distal Juxtamedulla convoluted ry nephron tubule

Renal cortex

Cortical nephron

Short loop of Henle

Capsul e Proximal convoluted tubule Glomerul us Bowman’s capsule Artery and vein Loop of Henle

Renal medulla

uxtamedullary and cortical nephrons.

Collecting duct Papill a Fig. 47-8b, p. 1018

Blood supply to nephron • 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,

Juxta- Cortical medullary nephron nephron

Blood route, to kidney

Afferent arteriole from renal Glomerulus artery Bowman’s capsule Proximal tubule Peritubula capillaries

Renal cortex

Collecting duct To renal pelvis

(c) Nephron

20 µm Renal medulla

SEM Efferent arteriole from glomerulus

Distal tubule

Collecting duct

Branch of renal vein Descending Loop limb of Ascending Henlelimb (d) Filtrate and blood flow

Vasa recta

“Countercurren t exchange”

How does the kidney regulate body fluids?? THREE PROCESSES: FILTRATION REABSORPTION SECRETION

• 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

REABSORPTION AND SECRETION

FILTRATION

Proximal tubule

Bowman's capsule Glomerulu s REABSORPTION AND SECRETION

REABSORPTION OF H2O; URINE CONCENTRATED Collecting duct

Distal tubule

Capillarie s

Renal artery Renal vein Loop of

To renal pelvis Fig. 47-10, p. 1020

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 wallsin ---HOW to The afferent arteriole is larger diameter achieve than thethis?? narrow efferent arteriole ----

provides a high rate of blood flow into the glomerulus, but a high resistance to blood

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

Blood cells restricted from passing through Red blood cell

Capillary pores

Endothelial cell of capillary

Nucleu s Podocyt e Filtratio n slits

Foot processesFig. 47-11b, p. 1021

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 platelets and Filtration isblood not cells, selective with plasma proteins. 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 • The hydrostatic blood pressure in the glomerular capillaries is abnormally high • Large surface area for filtration provided by the highly coiled glomerular capillaries • 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

1 Proximal tubule

4Distal tubule

NaCl Nutrients HCO3− H2O K+

H 2O NaCl HCO3−

H+

NH3

K+

H+

CORTEX Filtrate H2O Salts (NaCl and others) HCO3– H+ Urea Glucose; amino acids Some drugs

Key Active transport Passive transport

2Descending limb of loop of Henle H 2O

Thick segment 3 of ascending limb NaCl

OUTER MEDULLA

NaCl 3Thin segment of ascending limb

5Collecting duct Urea

NaCl INNER MEDULLA

H 2O

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=

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

mosm/L= milliosmoles per liter – Solutes and NaCl more concentrated

Solute gradients and water conservation • 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

Afferent arteriole

Distal tubule

Bowman's capsule Proximal tubule 300

Efferent arteriole

100

300

100 200 CORTEX

Filtrate

300 100

300

300

400 200

400

400

600 400

600

600

600

Collecting duct

Interstitial fluid

1200

1200

MEDULLA

1200

Loop of Henle Fig. 47-13, p. 1023

Bowman's Afferen capsule t arteriol e Efferent arteriole Filtrat e

Distal tubule

Proximal tubule N aCl

H2 O

H2 O

CORTEX

NaCl

MEDULLA

NaCl H2 O

N aCl H2O

H2 O

NaCl U rea Ascendin g limb

Descendin g limb

Collectin g duct

Loop of Henle Fig. 47-12, p. 1022

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

Receptors in the hypothalamus

1. Fluid intake is low. 2. Blood volume decreases, and osmotic pressure increases. 6. Blood volume increases, and osmotic pressure decreases.

Posterior pituitary

7. ADH secretion 3. Posterior pituitary is inhibited. secretes ADH. Collecting duct Nephron

H2O H2O H2O 5. Water reabsorption increases. Lower urine volume

H2O H2O

Kidney

H2O 4. Collecting ducts become more permeable. Fig. 47-14, p. 1024

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

SO, (1) ADH increases water reabsorption (2) The renin-angiotensinaldosterone 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 urine + CO2 + H2O ↔ H2CO3 ↔ H + HCO3-

Recall the nephron unit: A: Renal arteriole B: Afferent arteriole C: Efferent arteriole D: Bowman's Capsule E: Glomerulus F: Proximal Tubule G: Loop of Henle H: 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

Osmoregulation and excretion in vertebrates What 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…………

CHALLENGES

Animals living in fresh water are continuously challenged with water balance problems. Their plasma has a high solute concentration (osmolarity) and tends to draw water by osmosis from its surroundings---hyperosmotic to their environment

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

By excreting large

• 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).

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

• 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

SHARKS DON’T DRINK SEAWATER!!

•

Marine cartilaginous fishes (chondrichthyans) – – – – –

Internal salt conc.
Animals that live in temporary waters? The incredible water bears!! OR tardigrades Is a tiny invertebrate

100 µm

100 µm

a) Hydrated tardigrade

(b) Dehydrated tardigrade

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

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

Blood water homeostasis (Osmoregulation) Homeostasis of blood volume and osmolarity

Blood water homeostasis (Osmoregulation) • 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

1

Osmoreceptors in hypothalamus

Thirst

Hypothalamus

ADH

Drinking reduces blood osmolarity to set point Increased permeability

Pituitary gland Distal tubule

STIMULUS: The release of ADH is triggered when osmoreceptor cells in the hypothalamus detect an increase in the osmolarity of the blood

H2O reabsorption helps prevent further osmolarity increase

Collecting duct

Homeostasis: Blood osmolarity

When body becomes dehydrated, the osmotic [ c ] OR Osmotic pressure of the blood ↑ Posterior lobe of the pituitary glandADH Figure 44.16a: Antidiuretic hormone (ADH) enhances fluid retention by making the kidneys reclaim more water

Low blood water potential (too little water) • 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, high osmotic concentration) • Osmolarity of the blood subside, – reduces the activity of osmoreceptor cells in the hypothalamus – and less ADH is secreted

What happen when low osmotic pressure detected?

Homeostasis: Blood pressure, volume

Increased Na+ and H2O reabsorption in distal tubules

Aldosterone Arteriole constriction

STIMULUS: The juxtaglomerular apparatus (JGA) responds to low blood volume or blood pressure (such as due to dehydration or loss of blood)

Adrenal gland

Angiotensin II

Distal tubule

Angiotensinogen JGA Renin production

Renin

Figure 44.16b

(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

Increase retention Aldosteroneof Na+ by the kidneys, greater fluid retention, increases blood vol.

Renin Angiotensinoge n (plasma protein)

Angiotensin II Vasoconstriction, increase blood pressure

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

• 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

Anatomical relations between the exocrine pancreas, liver and gall bladder Liver Right hepatic duct

Left hepatic duct

Cystic duct

Gallbladder Pancreas Sphincter of Oddi

Common bile duct

Pancreatic duct

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 • Regulation, Synthesis, and Secretion • Storage • Purification, Transformation, and Clearance • 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 • Ammonia products.

• • • •

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 ( ‘citrulineornithine 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 disease • Liver cancer – Primary cancer (cancer that starts in the liver) – Secondary cancer /Metastatic cancer (cancer that has spread from another part of the body)

END OF LECTURE