urine formation urinary physiology urine...

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Urinary PhysiologyUrinary Section pages 9-17

Urine Formation

• Filtrate

– Blood plasma minus most proteins

• Urine

– <1% of total filtrate

– Contains metabolic wastes and unneeded substances

Urine Formation

1. Glomerular filtration

2. Tubular reabsorption

� Returns components to blood

� Glucose, amino acids, water and salt

3. Tubular secretion

� Reverse of reabsorption

� Selective addition to urine

4. Water conservation

Figure 25.10

Cortical

radiate

artery

Afferent arteriole

Glomerular capillaries

Efferent arteriole

Glomerular capsule

Rest of renal tubule

containing filtrate

Peritubular

capillary

To cortical radiate vein

Urine

Glomerular filtration

Tubular reabsorption

Tubular secretion

Three major

renal processes:

Glomerular Filtration

�Occurs at renal corpuscle

� Passive process driven by hydrostatic pressure

�Glomerulus is a very efficient filter

�Permeable membrane

� Water and small solutes pushed through filter

� Large surface area

�Higher blood pressure

Figure 25.9a

Glomerular capillary

covered by podocyte-

containing visceral

layer of glomerular

capsule

Glomerular capillary

endothelium (podocyte

covering and basement

membrane removed)

Proximal

convoluted

tubule

Parietal layer

of glomerular

capsule

Afferent

arteriole

Glomerular capsular space

Fenestrations

(pores)

Efferent

arteriole

Podocyte

cell body

Foot processes

of podocyte

Filtration slits

Cytoplasmic extensions

of podocytes

(a) Glomerular capillaries

and the visceral layer of

the glomerular capsule

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• Filtration membrane

– 3 components

• Fenestrated capillary endothelium

• Basement membrane

• Podocytes

– Allows passage of water and small solutes

• Fenestrations prevent filtration of blood cells

• Negatively charged basement membrane repels large

anions

(c) Three parts of the filtration membrane

Fenestration

(pore)

Filtrate in

capsular

space

Foot processes

of podocyte

Filtration

slit

Slit

diaphragm

• Basement membrane

• Capillary endotheliumCapillary

Filtration membrane

• Foot processes of podocyte

of glomerular capsule

Plasma

(b) Filtration slits between the podocyte foot processes

Foot

processes

Filtration slits

Podocyte

cell body


• Net Filtration Pressure (NFP)

– Glomerular hydrostatic pressure (HPg)

– Capsular hydrostatic pressure (HPc)

– Blood osmotic pressure (OPg)


• Net Filtration Pressure (NFP)

– The pressure responsible for filtrate formation

NFP = HPg – (OPg + HPc)

Figure 25.11

Glomerular

capsule

Afferent

arteriole

10

mm

Hg

Net

filtration

pressure

Glomerular (blood) hydrostatic pressure

(HPg = 55 mm Hg)

Blood colloid osmotic pressure

(Opg = 30 mm Hg)

Capsular hydrostatic pressure

(HPc = 15 mm Hg)

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Net Filtration Pressure

NFP = HPG – (OPG + HPC)

= 55 mm Hg – (30 mmHg + 15 mmHg)

= 10 mmHg


• Glomerular Filtration Rate (GFR)

– 125 ml/min

1800 liters of blood through kidneys/day

= 1200 ml/min = about 180 liters filtrate/day


• Factors affecting GFR

– Kidney disease

• ↓ blood osmo>c pressure, ↑ capsular osmo>c pressure

– Hemorrhage

• ↓ glomerular blood hydrostatic pressure

– Hypotension

• Glomerular blood hydrostatic pressure = capsule hydrostatic and blood osmotic pressure = filtration stops!

– Termed renal suppression


• GFR is tightly controlled by two types of

mechanisms

– Intrinsic control (renal autoregulation)

• Act locally within the kidney

– Extrinsic controls

• Nervous and endocrine mechanisms that maintain

blood pressure and affect kidneys

Intrinsic Control

• Goal = Maintain a nearly constant GFR when

MAP is in the range of 80–180 mm Hg

– Renal autoregulation

• Mechanisms that cause vasoconstriction of afferent

arterioles in response to increased BP

• Reduces glomerular flow to keep

GFR the same

Extrinsic Controls

• Sympathetic nervous system

– At rest

• Renal blood vessels are dilated

• Renal autoregulation mechanisms prevail

• GFR maintained

– Extreme stress

• Norepinephrine and epinephrine released

• Both cause constriction of afferent arterioles

– Inhibits filtration

– Shunts blood to other vital organs

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Tubular Reabsorption

• 125 ml/min of filtrate produced

• Most of this fluid is reabsorbed

• A selective transepithelial process

• Includes active and passive process

• Most occurs in PCT


• PCT

– Site of most reabsorption

• 65% of Na+ and water

• All nutrients

• Ions

• Small proteins


• Transcellular route

Luminal membranes of tubule cells

Cytosol of tubule cells

Basolateral membranes of tubule cells

Endothelium of peritubular capillaries

Figure 25.13

Activetransport

Passivetransport

Peri-

tubular

capillary

2

4

4

3

31

1 2 43

Filtrate

in tubule

lumen

Transcellular

Paracellular

Paracellular

Tight junction Lateral intercellular space

Capillaryendothelialcell

Luminalmembrane

Solutes

H2O

Tubule cell Interstitial

fluid

Transcellular

Basolateralmembranes

1 Transport across the luminal membrane.

2 Diffusion through the cytosol.

4 Movement through the interstitial fluid and into the capillary.

3 Transport across the basolateral membrane. (Often involves the lateral intercellular spaces because membrane transporters transport ions into these spaces.)

Movement via thetranscellular route involves:

The paracellular routeinvolves:

• Movement through leaky tight junctions, particularly in the PCT.


• Paracellular route

– Between cells

– Limited to water movement and reabsorption of

Ca2+, Mg2+, K+, and some Na+ in the PCT where

tight junctions are leaky


• Sodium

– Most abundant cation in filtrate

– Primary active transport out of the tubule cell by

Na+-K+ ATPase in the basolateral membrane

– Na+ passes in through the luminal membrane by

secondary active transport or facilitated diffusion

mechanisms

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Figure 25.14

1 At the basolateral membrane,

Na+ is pumped into the

interstitial space by the Na+-K+

ATPase. Active Na+ transport

creates concentration gradients

that drive:

2 “Downhill” Na+ entry at the

luminal membrane.

4 Reabsorption of water by

osmosis. Water reabsorption

increases the concentration of

the solutes that are left

behind. These solutes can

then be reabsorbed as

they move down their

concentration gradients:

3 Reabsorption of organic

nutrients and certain ions by

cotransport at the luminal

membrane.

5 Lipid-soluble

substances diffuse by the

transcellular route.

6 Cl– (and other anions),

K+, and urea diffuse by the

paracellular route.

Filtrate

in tubule

lumen

Glucose

Amino

acids

Some

ions

Vitamins

Lipid-soluble

substances

Nucleus

Tubule cell

Paracellular

route

Interstitial

fluidPeri-

tubular

capillary

Tight junction

Primary active transport

Passive transport (diffusion)

Secondary active transport

Transport protein

Ion channel or aquaporin

Cl–, Ca2+, K+

and other

ions, urea

Cl–

3Na+

2K+

3Na+

2K+

K+

H2O

Na+

6

5

4

3

2

1


• Sodium

– Low hydrostatic pressure and high osmotic

pressure in the peritubular capillaries

• Promotes bulk flow of water and solutes (including Na+)

Tubular Maximum

– Transport maximum (Tm) reflects the number of

carriers in the renal tubules available

– When the carriers are saturated, excess of that

substance is excreted

– Example: too much glucose in the blood entering

glomerulus will cause glucosuria


• Reabsorption of nutrients, water and ions

– Blood becomes hypertonic to filtrate

– Water is reabsorbed by osmosis

– Cations and fat-soluble substances follow by

diffusion

Tubular Secretion

• Reabsorption in reverse

– K+, H+, NH4+, creatinine and organic acids move

from peritubular capillaries or tubule cells into

filtrate

– Involves active transport since no concentration

gradients in this case

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Figure 25.18a

Cortex

Outer

medulla

Inner

medulla

(a)

(b)

(c)

(e)

(d)

Na+ (65%)

Glucose

Amino acids

H2O (65%) and

many ions (e.g.

Cl– and K+)

300

Milliosmols

600

1200

Blood pH regulation

H+,

NH4+

HCO3–

Some

drugs

Active transport

(primary or

secondary)Passive transport

(a) Proximal convoluted tubule:

• 65% of filtrate volume reabsorbed

• Na+, glucose, amino acids, and other nutrients actively

transported; H2O and many ions follow passively

• H+ and NH4+ secretion and HCO3

– reabsorption to

maintain blood pH (see Chapter 26)

• Some drugs are secreted

Tubular Secretion

• Principle effects

– Rids body of

• Foreign substances (penicillin and other drugs)

• Nitrogenous wastes

• Excess K+

– Controls blood pH:

• Altering amounts of H+ or HCO3– in urine

Variations in Urine Formation

• Composition varies

– Fluid volume

– Solute concentration

Variations in Urine Formation

• Water intake must equal water loss

– Kidney regulates water loss by producing:

• Hypotonic urine (dilute)

• Hypertonic urine (concentrated)

Countercurrent Mechanism

• Role of countercurrent mechanisms

– Establish and maintain an osmotic gradient

– Creates hypertonic interstitial fluid within kidney

medulla

– Hypertonic interstitial fluid allows the kidneys to

vary urine concentration

Figure 25.16a

Loop of Henle

Osmolalityof interstitialfluid(mOsm)

Inner

medulla

Outer

medulla

CortexActive transport

Passive transport

Water impermeable

Countercurrent multiplierThe long loops of Henle of the

juxtamedullary nephrons

create the medullary

osmotic gradient.

H2O

H2O

H2O

H2O

H2O

H2O

H2O

NaCI

NaCI

NaCI

NaCI

NaCI

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Formation of Concentrated Urine

• Depends on the medullary osmotic gradient and the ability to alter permeability of the collecting tubules

� osmolarity of extracellular fluid (also � plasma volume)

� ADH release

� aquaporins in collecting duct

� H2O reabsorption in collecting duct

Small volume of concentrated urine

Figure 25.17b

Active transport

Passive transport

Small volume of

concentrated urine

Cortex

NaCI

NaCI

NaCI Urea

Urea

H2O

H2O

H2O

H2O

H2O

H2O

H2O

Outer

medulla

Inner

medulla

(b) Maximal ADH

DCT

Descending limb

of loop of Henle

Collecting duct

H2O

H2O

Formation of Dilute Urine

• Filtrate is diluted in the ascending Loop of Henle

• In the absence of ADH, dilute filtrate continues into the renal

pelvis as dilute urine

� osmolarity of extracellular fluid

� ADH release

� aquaporins in collecting duct

� H2O reabsorption in collecting duct

Large volume of dilute urineFigure 25.17a

Active transport

Passive transport

(a) Absence of ADH Large volume

of dilute urine

Collecting duct

Cortex

NaCI

NaCI

NaCI

Urea

Outer

medulla

Inner

medulla

DCT

H2O

H2O

Descending limb

of loop of Henle

Acid-Base Balance

• pH affects all functional proteins and biochemical reactions in the body– Regulation prevents changes in body’s internal environment

• Alkalosis or alkalemia: arterial blood pH >7.45

• Acidosis or acidemia: arterial pH < 7.35

Acid-Base Balance

• Concentration of hydrogen ions is regulated by

1. Chemical buffer systems in blood

• Rapid, first line of defense

2. Brainstem respiratory centers

• Acts within 1–3 minutes

3. Renal mechanisms

• Most potent

• Requires hours to days to affect pH changes

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Acid-Base Balance

– Blood

• CO2 + H2O ↔ H2CO3↔ HCO3- + H+

– Lungs

• Regulate carbonic acid levels by CO2 manipulation

– Kidneys

• Selectively secrete and reabsorb to maintain pH

Acid-Base Balance

• Most important renal mechanisms:

– Conserving (reabsorbing) HCO3–

– Excreting HCO3–

– Secretion of H+

• H+ secretion occurs in the PCT and in collecting tubules

Acid-Base Balance

• Examples

– Respiratory Acidosis

• Lungs are unable to eliminate CO2 adequately

• Kidneys reabsorb HCO3–, secrete H + (and NH4 +)

– Respiratory Alkalosis

• CO2 levels are low

• Kidneys secrete HCO3–, retain H + (and NH4 +)

Figure 26.12

1 CO2 combines with water within the tubule cell, forming H2CO3.

2 H2CO3 is quickly split, forming H+ and bicarbonate ion (HCO3

–).

3aH+ is secreted into the filtrate.

3bFor each H+ secreted, a HCO3– enters the

peritubular capillary blood either via symport with Na+ or via antiport with CI–.

4 Secreted H+ combines with HCO3– in the

filtrate, forming carbonic acid (H2CO3). HCO3–

disappears from the filtrate at the same rate that HCO3

– (formed within the tubule cell) enters the peritubular capillary blood.

5 The H2CO3

formed in the filtrate dissociates to release CO2

and H2O.

6 CO2 diffuses into the tubule cell, where it triggers further H+

secretion.

* CA

CO2CO2

+

H2O

2K+2K+

*

Na+ Na+

3Na+3Na+

Tight junction

H2CO3H2CO3

PCT cell

NucleusFiltrate intubule lumen

Cl–Cl–HCO3– + Na+

HCO3–

H2O CO2

H+ H+ HCO3–

HCO3–

HCO3–

ATPase

ATPase

Peri-tubular

capillary

1

2

4

5

6

3a 3b

Primary activetransport

Simple diffusion

Secondary activetransport

Carbonic anhydrase

Transport protein

Variations in Blood Pressure

• Activity of kidney related to variations in blood

pressure

– Blood pressure and blood volume are related

– Blood volume is controlled by

• Solute concentration

• Water regulation

Variations in Blood Pressure

• Renal mechanisms influencing blood pressure

– ADH

• Water

– Renin-angiotensin mechanism

• Sodium

• Potassium

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Antidiuretic Hormone (ADH)

• Plasma osmolarityIncreases (what could cause this?)

Osmoreceptors stimulated

Thirst & ADH secretion

Water reabsorption (decreased urine output)

Increased blood volume

Increased blood pressure

Aldosterone

• Produced in adrenal cortex in response to…

– Low blood volume

– Low blood pressure

– Low plasma Na +

– High plasma K +

• Stimulates K+ secretion and Na+ reabsorption

• Changes in plasma sodium levels affect…

– Plasma volume

– Blood pressure

Aldosterone

• Regulation of sodium balance

– Na+ reabsorption

• 65% is reabsorbed in the proximal tubules

• 25% is reclaimed in the Loops of Henle

– Aldosterone causes active reabsorption of

remaining Na+ in DCT and collecting ducts

– Water follows Na+

– How would this affect blood volume and blood

pressure?

Aldosterone

• Renin-angiotensin mechanism is the main

trigger for aldosterone release

– Granular cells of JGA secrete renin in response to

• Sympathetic nervous system stimulation

• ↓ Filtrate osmolality (decreased sodium)

• ↓ Stretch (due to ↓ blood pressure)

Figure 25.8

Glomerulus

Glomerular capsule

Afferent arteriole

Efferent arteriole

Red blood cell

Podocyte cell body (visceral layer)

Foot processesof podocytesParietal layer

of glomerularcapsule

Proximaltubule cell

Lumens of glomerularcapillaries

Endothelial cellof glomerularcapillary

Efferent arteriole

• Macula densa cellsof the ascending limbof loop of Henle

• Granular cells

• Extraglomerularmesangial cells

Afferent arteriole

Capsularspace

Renal corpuscleJuxtaglomerularapparatus

Mesangial cellsbetween capillaries

Juxtaglomerularapparatus

Aldosterone

• Renin catalyzes the production of angiotensin

II

– Prompts aldosterone release from the adrenal

cortex

• Targets cells of DCT and collecting ducts

• Initiates sodium reabsorption

– Causes systemic vasoconstriction

– Effect on BP?

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Figure 26.8

K+ (or Na+) concentration

in blood plasma*

Stimulates

Releases

Targets

Renin-angiotensin

mechanism

Negative

feedback

inhibits

Adrenal cortex

Kidney tubules

Aldosterone

Effects

Restores

Homeostatic plasma

levels of Na+ and K+

Na+ reabsorption K+ secretion

Blood Pressure Control

• 3 main mechanisms

– Renin-angiotensin system

– Neural regulation (sympathetic control)

– ADH release

Figure 26.10

Stretch in afferent

arterioles

Angiotensinogen

(from liver)

Na+ (and H2O)

reabsorption

Granular cells of kidneys

Renin

Posterior pituitary

Systemic arterioles

Angiotensin I

Angiotensin II

Systemic arterioles

Vasoconstriction Aldosterone

Blood volume

Blood pressure

Distal kidney tubules

Adrenal cortex

Vasoconstriction

Peripheral resistance

(+)

(+)

(+)

(+)

Peripheral resistance

H2O reabsorption

Inhibits baroreceptors

in blood vessels

Sympathetic

nervous system

ADH (antidiuretic

hormone)

Collecting ducts

of kidneys

Filtrate NaCl concentration in

ascending limb of loop of Henle

Causes

Causes

Causes

Causes

Results in

Secretes

Results in

Targets

Results in

Releases

Release

Catalyzes conversion

Converting enzyme (in lungs)

(+)

(+)(+)

(+)

(+)

(+)

(+) stimulates

Renin-angiotensin system

Neural regulation (sympathetic

nervous system effects)

ADH release and effects

Systemic

blood pressure/volume Factors Affecting Urine Volume

• Increased temperature

– Increases vasodilation and perspiration

– Decreases blood flow to kidneys

• Decreased temperature

– Increases blood flow to kidneys

Diuretics

• Chemicals that increase urine output

– Osmotic diuretics

• Substances not reabsorbed

– Glucose in a diabetic patient

– ADH inhibitors

• Alcohol and water

– Substances that inhibit Na+ reabsorption

• Caffeine, thiazides (class of medications), loop diuretics (inhibit Na+-K+-Cl- symport proteins)

– Potassium levels are affected by some diuretics

• Can be extremely dangerous

Factors Affecting Urine Output

• ↑ blood pressure

• ↑ blood solute concentration

• ↓ plasma proteins

• Psychological factors

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