dr Dedy

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Basic Physiology The Urinary System Overview of Functions Glomerular Filtration The Nephron Hormonal Control Renin-Angiotensin System Micturition Reflex

Transcript of dr Dedy

Page 1: dr Dedy

Basic Physiology

The Urinary System

• Overview of Functions

• Glomerular Filtration

• The Nephron

• Hormonal Control

• Renin-Angiotensin System

• Micturition Reflex

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Overview of Functions

• The basic function of the urinary system is

the formation of urine.

• What is urine:

– Filtrate of blood plasma

– Vehicle for secretion of waste products:

• Filtered: drugs, pesticides, food additives.

• Secreted: ammonia, potassium, hydrogen ions.

– High salt concentration (4 x more concentrated

than plasma).

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Overview of Functions

• High salt concentration results from

reabsorption of water.

• Ability to recycle water is a major

advantage to land-based organisms

such as humans (amniotes).

– able to go without water for extended

periods of time.

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Overview of Functions

• The kidneys therefore have two major

obvious roles:

– Elimination of waste products

– Reabsorption of nutrients/water.

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Overview of Functions

• But there are other less obvious but important functions:

– Regulation of blood pressure

– Regulation of fluid composition

– Regulation of fluid pH

– Hormone secretion:

• Renin and erythropoietin

– Activation of vitamin D

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twelfth rib

ureters

urinary bladder

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SECTION THROUGH A KIDNEY

medulla

cortex

capsule

ureter

renalpyramids

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BLOOD VESSELS IN THE KIDNEY

renal artery

renal vein

interlobularartery and vein

arcuateartery and vein

interlobar artery

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FEATURES IN A RENAL PYRAMID

interlobulararteries and

veinscortex

medulla

interlobarartery and

vein

arcuateartery and

vein

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NEPHRONS

medulla

cortex

loop ofHenle

collectingtubule

corpuscles

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RENAL CORPUSCLE

juxtaglomerularapparatus

sphincterof afferentarteriole

glomeruluscovered withpodocytes

outer layer ofBowman’scapsule

capsularspace

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Components:-

1. Afferent arteriole - carries blood to the glomerulus

2. Glomerulus - a tuft of capillaries that filters a protein

free plasma into the Bowman’s capsule

3. Bowman’s capsule - collects the glomerular filtrate

180 Litres are filtered each day!!!

Glomerula Filtration

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GLOMERULAR CAPILLARIES

The glomerular capillaries are fenestrated (riddled with pores)

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podocyte

pedicelof podocyte

filtration slitsin betweenpedicels

ELECTRON MICROGRAPH OF GLOMERULAR SURFACE

Covering the capillaries are podocytes (the visceral layer)

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GLOMERULAR FILTRATION

blood solutemolecules

basement lamina

pedicel

filtration slits

fenestration

capsular space

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BLOOD HYDROSTATIC PRESSURE

Hydrostatic pressure forces fluid out of the glomerulus.

Normal blood pressure in the glomerulus is around 55 mm Hg.

This is the major force driving glomerular filtration.

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BLOOD OSMOTIC PRESSURE

The osmotic (oncotic) pressure is due to plasma proteins and

attracts water into the glomerulus.

Normally about 30 mm Hg

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HYDROSTATIC PRESSURE IN THE BOWMAN’S CAPSULE

Hydrostatic pressure forces fluid out of the Bowman’s capsule.

Normal pressure in the capsular space is around 15 mm Hg.

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NET FILTRATION PRESSURE

Driving pressure minus opposing pressures = net filtration pressure

= 55 - (30 + 15) = 10

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GLOMERULAR FILTRATION RATE

- kidneys normally receive 20 to 25% of cardiac output

- average GFR is about 125 ml/minute (180 litres urine/day)

- GFR is dependent on the diameter of the afferent arteriole

Diameter is under sympathetic control

- Vasoconstriction of the afferent arterioles decreases

GFR

- Therefore baroreceptors and mean arterial blood pressure will

affect GFR

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ARTERIOLE DIAMETER CONTROLS GLOMERULAR PRESSURE

1. Smooth muscle tends to contract when it is stretched-autoregulation

2. Smooth muscle is under control of the sympathetic system- receptors

3. Smooth muscle is influenced by chemicals (from the macula densa)α

Glomerular hydrostatic pressure remains relatively constant - 55 mm Hg

sphincterof afferentarteriole

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The Nephron

• Basic functional unit of the kidney.

• Consists of:

• Bowmans Capsule.

• Proximal convoluted tubule

• Site of most reabsorption.

• Loop of Henle

• Site of “Counter-current Multiplier System”

• Sodium/water reabsorption

• Distal convoluted tubule

• Adjustment of extracellular sodium levels

• Enter into collecting ducts

• Formation of concentrated urine by water reabsorption

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proximalconvoluted

tubule

ascending loop

descending loop

distalconvolutedtubule

collectingtubule

THE NEPHRON- TUBULAR COMPONENTS

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peritubular

capillary

network

vasa recta

CAPILLARIES AROUND THE NEPHRON

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TUBULAR REABSORPTION

Some substances are not reabsorbed or are reabsorbed incompletely

because they lack carriers or do not pass through the membrane

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TUBULAR REABSORPTION

Most takes place in the proximal tubule.

In general waste products are not reabsorbed

- water 99% reabsorbed (180 litres → 1.8 litres urine)

- sodium 99.5% reabsorbed

- glucose 100% reabsorbed

- aminoacids 100% reabsorbed

- water soluble vitamins 100% reabsorbed

- urea 44% reabsorbed

Two types of uptake by the epithelial cells

1. active transport

2. passive transport

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TUBULAR SECRETION

Some substances such as hydrogen and potassium ions

are secreted into the urinary filtrate

Water soluble drugs such as penicillin and morphine

are also secreted

The secretory systems also rids the body of pesticides

and food additives

Ammonia diffuses into the urine

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THE LOOP OF HENLE

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THE LOOP OF HENLE

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DIFFERENCES IN THE NEPHRON LOOP

The descending limb:-

1. Highly permeable

to water

2. Relatively

impermeable to

sodium

The ascending limb:-

1. Impermeable

to water

2. Actively transports

sodium out of the

filtrate

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OSMOTIC GRADIENT

In the medulla there is a vertical osmolality gradient.

Osmolality is greatest in the apices of the pyramids

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ESTABLISHING THE OSMOTIC GRADIENT 1

(“COUNTERCURRENT MULTIPLIER SYSTEM”)

300

300

300

300

300

300

300

300

descendinglimb

ascendinglimb

Filtrate entering the loop of Henle is iso-osmotic with plasma

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ESTABLISHING THE OSMOTIC GRADIENT 2

Salt is pumped out of the ascending limb and

water leaves the descending limb passively until

the osmotic difference is 200 mosm/L

NaCl

NaCl

NaCl

NaClwater

water

water

water400

400

400

400

400

400

400

400

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ESTABLISHING THE OSMOTIC GRADIENT 3

More filtrate comes in from the proximal convoluted tubule

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ESTABLISHING THE OSMOTIC GRADIENT 4

NaCl

NaCl

NaCl

NaClwater

water

water

water350

350

350

350

500

500

500

500

The 200 mosm/L gradient is re-established at each level

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ESTABLISHING THE OSMOTIC GRADIENT 5

More fluid enters from the proximal tubule

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ESTABLISHING THE OSMOTIC GRADIENT 6

The 200 mosm/L gradient is re-established at each level

NaCl

NaCl

NaCl

NaClwater

water

water

water325

325

425

425

425

425

600

600

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THE FINAL OSMOTIC GRADIENT

300

450

600

750

900

1050

1200

1200

The final osmotic gradient is maintained. Blood flow

through the medulla is specialised so that osmolytes

forming the gradient are not removed.

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“Countercurrent Multiplication System”

• Summary:

– “Countercurrent” refers to opposite directions of flow within the descending and ascending loop of Henle.

– “Multiplication” refers to the multiplied increase in osmolarity towards apex of medullary pyramids as filtrate continues to flow into nephron.

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“Countercurrent Multiplication System”

• Summary:

– Results in the formation of an osmotic

gradient.

– Enables formation of a hypotonic filtrate

by the nephron.

– Assists of osmosis of water into the

ascending limb (loop of Henle) and into

collecting ducts (requires ADH).

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vasa recta

1200

300

600

Vasa recta follow the loops of Henle into the medulla.

Blood flow through these capillaries is sluggish.

VASA RECTA

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Vasa recta are also freely permeable to salt and water.

As blood flows slowly there is ample time for diffusion to occur.

SALT AND WATER EXCHANGE IN VASA RECTA

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CONCENTRATING URINE

Urine enters the

distal convoluted

tubule with an

osmolality of

100 mosm/L

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CONCENTRATING URINE

Urine passes down

the collecting

tubule back into

the medulla through

a concentration

gradient

300

450

600

750

900

1050

1200

1200

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ANTIDIURETIC HORMONE

– Osmoreceptors in hypothalamus monitor osmotic pressure

of extracellular fluid

– ADH is released when osmotic pressure increases

– Produced in hypothalamus

– Secreted from posterior pituitary

– Increases reabsorption of water in distal tubule and

collecting tubule (opening of channels in the cells)

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ANTIDIURETIC HORMONE AND TISSUE OSMOLALITY

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The collecting tubules are normally impermeable to water.

ADH causes water channels to be inserted in the plasma membrane

ANTIDIURETIC HORMONE AND COLLECTING TUBULES

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EFFECT OF ADH

The distal convoluted tubule and the collecting tubules are

normally impermeable to water.

- ADH causes them to become permeable

- Water will then move into the medullary fluid by osmosis

- The urine becomes more concentrated

- Maximum urine concentration is 1200 mosm/L

- Minimum urine concentration is 100 mosm/L

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REABSORBING MORE WATER

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SODIUM BALANCE - SENSORS

juxtaglomerularapparatus

maculadensa cells

juxtaglomerularcells

Macula densa cells are part of the distal convoluted tubule and are

osmoreceptors. JG cells are smooth muscle and contain renin granules.

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SODIUM BALANCE - EFFECTORS

Fine tuning of sodium balance occurs in the distal convoluted

tubules and collecting ducts. Sodium is exchanged for potassium

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REABSORBING MORE SODIUM

Aldosterone targets the DCT and collecting ducts:-

sodium channels opened

more sodium transporters synthesised

more potassium channels synthesised

An indirect effect of aldosterone is the promotion of water

absorption because water follows sodium if it can.

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REABSORBING MORE SODIUM

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MAINTAINING SODIUM BALANCE

THROUGH THE RENIN-ANGIOTENSIN SYSTEM

ANGIOTENSINOGEN ANGIOTENSIN I ANGIOTENSIN II

RENIN

CONVERTING

ENZYME

ARTERIOLE

VASOCONSTRICTION

liver kidney lungs

adrenalcortex

kidney

ALDOSTERONE

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ALDOSTERONE PRODUCTION

– Osmoreceptors in the juxtaglomerular apparatus monitor

the volume of extracellular fluid

– Renin is released when the volume decreases

– Renin acts on angiotensinogen

– Angiotensin I is formed in the blood stream

– Angiotensin II is formed in the lungs

– Aldosterone is released from the adrenal cortex

– Sodium is reabsorbed by the distal tubules

– Water follows by osmosis

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Increased blood volume causes

increased atrial stretch

atrial myocardial cells stretch

and release

atrial natriuretic peptide (factor)

hypothalamus kidney adrenal cortex

inhibits ADH decreases renininhibits

aldosterone

increases NaCl and water excretion

EXCRETING MORE SODIUM

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ERYTHROPOIETIN

peritubular

capillary

network

Interstitial cells of the kidney peritubular capillary bed produce EPO

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OXYGEN, EPO AND THE KIDNEY

EPO is also made, to a lesser extent, by cells in the liver.

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ACID AND THE KIDNEY

pH homeostasis depends on buffers, the lungs and the kidneys

fatty acids

amino acids

carbon dioxide

lactic acid

Plasma pH 7.35 - 7.45

Buffers (proteins, haemoglobin

bicarbonate and phosphate)

carbon dioxide

lactic acidacid

diet

metabolism

ventilation

renal

acid input

acid output

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BLADDER

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MICTURITION REFLEX

Bladder fills

Stretch receptors

Parasympathetic

nerve

Bladder contractsInternal urethral

sphincter opens

Only the external urethral sphincter is controlled voluntarily

+

+

Spinal Cord