2017.12.06.

1

RENAL PHYSIOLOGY,

HOMEOSTASIS OF FLUID COMPARTMENTS (3)

Dr. Attila Nagy

2017

Protein-type reabsorption

Peptides with small molecular weight: carrier

mediated mechanism,

Proteins with large molecular weight are reabsorbed

with pinocytosis (endocytosis),

albumine, hemoglobine

2017.12.06.

2

Urea transport in the nephron

2017.12.06.

3

CO

RT

EX

OU

TE

RZ

ON

EIN

NE

R

ZO

NEM

ED

UL

LA

ACTIVE TRANSPORT

PASSIVE TRANSPORT

Urea transport in the nephronUrea-cycle

Uric acid

The filtrated uric acid will be totally reabsorbed in the proximal

tubulue.

In the 3. segment of the proximal tubule the uric acid will be secreted.

This secreted amout will then be excreted (approximately 10% of the

filtrated amount).

Gout

2017.12.06.

4

Mechanism of secretion in the proximal tubule

Organic acids and bases

K+ and H+

PAH-secretion, PAHTm,

Uric acid secretion (10 % of the filtrated amount

is excreted)

The filtrated uric acid entirely reabsorbes, the

excreted uric acid originates from the secreted

amount.

2017.12.06.

5

PAH secretion

excreted

secreted

filtrated

2017.12.06.

6

Tubular functions II.Loop of Henle and the distal nephron (Learning objectives: 57)

2017.12.06.

7

The loop of Henle

thin descending limb,

thin ascending limb,

squamous cells, few mitochondria, few microvilli

thick ascending limb (thick segment)

cuboid cells, many mitochondria, no microvilli

2017.12.06.

8

Loop of Henle

(30% isotonic fluid coming from the proximal tubulus)

Function

–Reabsorbs 20% of Na+ and 10%

of water

– lets hypotonic fluid into the distal

one

–Medullary gradient ( 50% NaCl,

50% urea).

Thin descending limb

1. Weakly permeable to solutes

2. Freely permeably to water

3. No active transport.

The osmolarity increases from 300 mosm/kg -to 1200 mosm/kg

in the long-looped nephrons and to 600 mosm/kg in the short

looped nephrons. The increase in the concentration is a

consequence of water reabsorption.

The predominant substance is Na+ és Cl- in the tubular lumen

and urea in the peritubular space.

2017.12.06.

9

Thin ascending limb

1. Impermeable to water,

2. Freely permeable to Na+- and Cl-

3. Moderately permeable to urea.

Na+ and Cl- diffuses into the peritubular space and urea

diffuses into the tubule.

The osmolarity decreases but the volume of the fluid

does not change.

Thick ascending limb

1. No water permeability

2. Actively reabsorbs Na+ and Cl- .

3. Weak urea permeability

The osmolality decreases in the tubular fluid, the

concentration of Na+ and Cl- concentration is lower.

The concentration of urea is unchanged because of the

low water permeability.

2017.12.06.

10

ATPase

2017.12.06.

11

NH4+-Transport in the loop of Henle

The Na+, K+, 2Cl– Symport can resorbe instead of K+

NH4+.

The fluid leaving the loop of Henle is:

1./ hypoosmotic,

2./ high urea concentration,

3./ unchanged volume.

The Na+ reabsorption is similar to that in the proximal

tubule, only the carrier is different on the apical surface.

The outward movement of one Na+ ion is bound to the

entry of 2 Cl- and one K+. (Na+/K+- 2Cl- symport).

Furosemide inhibits this transport.

2017.12.06.

12

CO

RT

EX

KÜ

LSŐ

ZÓ

NA

BE

LSŐ

Z

ÓN

A

ME

DU

LL

A

AKTÍV TRANSZPORT

PASSZÍV TRANSZPORT

Urea transport in the nephronUrea-cycle

Proximal tubule: passive transport, 50% of the filtrated amount will be reabsorbed

2017.12.06.

13

The distal nephron

In distal tubulus and collecting duct is the fine adjusting

of composition of urin.

High gradients can be built but the capacity of transport

is low.

It contains different segments and different kinds of

cells.

2017.12.06.

14

Distal nephron

Function:

active Na+ reabsorption,

weak water permeability,

weak urea permeability.

The distal nephron changes the tubular fluid into urine

Histological characteristics

Convoluted tubule

Cuboid cells, no interdigitation,

many mitochondria

no brush border

Collecting duct

cuboid-cylindrical cells.

Few cell organelle

No brush border

2017.12.06.

15

Active Na+ resorption

Distal convoluted tubule

The active Na+ transport is bound to Cl- carrier

(Na+/Cl- symport).

inhibited by thiazid

The osmolality and electrolyte concentration decrease

because of the Na+ reabsorption and low water

and urea permeability. The urea concentration is still

higher. The amount of tubular fluid is unchanged.

The distal tubule cell

Na+ resorption trough a Na+ Cl-- symporter. Cl– leaves the

cell through a K Cl – symporter of the basolteral membrane.

Na+ will be transported out of the cell through

Na+/K+ -ATPase. Accumulated K+ leaves the cell through

K+ chanels.

These cells can Ca2+ also resorbe. Luminale Ca2+

Channels and basolteral Na+/Ca2+ exchanger.

2017.12.06.

16

Transport in the distal tubule cell

Principal (main) cell

In late distal tubulus and in the collecting duct can be found

these cells.

Luminal Na+ und K+- channels

The cells resorbe Na+ and secrete K+

Increased Na+-Resorption

Increased K+-Sekretion und K+-Excretion

2017.12.06.

17

Principal cell

Intercalated cell

Typ A

Intercalated cell

Typ B

Na+ household

Na+ intake

Na+ content of drinks and food between 10 and 600 mmol

Na+ (100-400 mmol/day in general ).

No physiological mechanism of Na+ intake

Na+ loss

Sweat

Stool

Urine (100-400 mmol/day).

Regulation of salt household

Through salt loss.

2017.12.06.

18

Effector mechanisms

1./ GFR

2./ Renin-Angiotensin-Aldosterone system

Adrenal cortex glomerular zone (mineralocorticoid)

Na+ and K+ ion exchange in the distal tubule and

collecting duct

3./ “third factor”

Renin-angiotensin-aldosteron system

A juxtaglomerular apparatus

myoepithel cells of vas afferents,

macula densa in distal tubulus,

mesangial connective tissue,

Renin ( 66500 d)

angiotensinogen (alfa2-globulin, liver),

Angiotensine I (10 amino acid (ACE, angiotensine

converting enzyme)

Angiotensine II (8 amino acid)

Angiotensine III

2017.12.06.

19

JUXTAGLOMERULAR APPARATUS

endfeet of

podocytes

capillary

mesangial cell

podocyte

mesangial cell

2017.12.06.

20

Renin secretion increased by

1. decreased renal blood flow

2. amount and chemical composition of tubular

fluid at macula densa,

3. stimulation of renal sympatethic nerve,

4. extracellular hypovolemia (bleeding)

Renin secretion decreased by:

1. prostaglandines ( PGE2, PGD2, PGI2)

2. atrial natriuretic factor (ANF)

2017.12.06.

21

Control of renin secretion

Angiotensine II effects

1/ Blood pressure

vasoconstrictor (systolic and diastolic RR increases)

2/ Aldosteron

3/ Central effects (hypothalamus)

2017.12.06.

22

Factors increasing aldosterone secretion:

angiotensine II

decreased atrial natriuretic factor,

increased plasma K+,

ACTH,

2017.12.06.

23

Regulation of Aldosterone secretion

Atrial natriuretic factor (ANF)

Right atrium

28 (21 - 73) amino acid (2800-13.000 dalton).

126 amino acid precursor (pro-ANF (atriopeptinogen).

ANF secreted

Increased atrial stretch (hypervolemia)

ADH

adrenalin

2017.12.06.

24

Effects of ANF

1. Vasodilatation

2. increased GFR

(dilatation of the afferent arteriole)

3. inhibition of renin secretion

4. decreased in aldosterone secretion

5. inhibition of ADH

6. natriuresis and water diuresis

decreased cardiac output

Mechanisms of Na+-resorption in the whole nephron

Na/H antiporter

Na/S symporter

Paracellular transport

Na/K/2Cl symporter

Paracellular transport

Na/Cl Symporter

Na channels

Proximal Tubule

(acetazolamide inhibits)

Loop of Henle

(furosemide inhibits)

Distal Nephron

(thiazide inhibits)

2017.12.06.

25

Intercalated cells

Intercalated cells secrete either H+ (Typ A) or

HCO3- (Typ B).

In intercalated cells Typ A can be observed the H+ Sekretion

through H+-ATPase or in K+-deficit through H+/K+

ATPase.

In intercalated cells Typ B HCO3- secretion is through

Cl-/HCO3- antiporter. The accumulated Cl- leaves the cell

through basolateral Cl- channels.

Paracellular Cl- resorption is also possible.

Principal cell

Intercalated cell

Typ A

Intercalated cell

Typ B

2017.12.06.

26

Potassium household

Factors determining K+ content of the body

1. K+ intake and output,

2. distribution of potassium between the intracellular and

extracellular space.

INTAKE OUTPUT

Drinks, food 50-100 mmol/day Sweat, Stool 5-10 mmol/day

Urine 45-90 mmol/day

Sum 50-100 mmol/day 50-100 mmol/day

Distribution of K+ between the intracellular and extracellular fluids

2017.12.06.

27

K+ reabsorption

proximal nephron 1. and 2. segments

thick segment

K+ secretion

proximal tubule 3. segment

thin descending limb

distal tubule

regulation: aldosterone, (insuline)

2017.12.06.

28

secretion

Potassium transport in the loop of Henle

2017.12.06.

29

Potassium transport in the distal tubule cell

Principal cell

(aldosteron effect)

Intercalated cell

Typ A

Intercalated cell

Typ B

Potassium transport in the principal and intercalated cells