6.

Regulation of blood flow - Kidney

6. Regulation of blood flow - Kidney

afferent arterioles renal artery afferent arterioles

cortical glomerulus

efferent arterioles

peritubular capillaries venule

juxtamedulary glomerulus

efferent arterioles

peritubular capillaries

vasa recta

6. Regulation of blood flow - Kidney

1. Autoregulation

- keep Q constant over a range of pressures

Q (ml/min)

50

180

MAP (mmHg)

2. Control of radius of resistance vessels i) Nervous direct SNS innervation Vasoconstrictor - afferent > efferent
can constrict the upstream one better than the downstream one

(therefore decrease PG)

ii) Local (paracrine and autocrine) NO - Vasodilator - afferent and efferent equally ET-1 Vasoconstrictor afferent and efferent equally (Adenosine)ADO Vasoconstrictor afferent ATP Vasoconstrictor afferent iii) Endocrine

Epi Vasoconstrictor afferent > efferent AII Vasoconstrictor efferent > afferent ANP Vasodilate afferent, vasoconstrict efferent (letting more in, letting less out) ADH-VP Vasoconstrictor afferent > efferent
6. Regulation of blood flow - Kidney 4

If something affects both Aff and Eff then redirection of blood flow will occur, if one more than the other then the PG will be effected.

6. Regulation of blood flow - Kidney

Control of vasculature:

( AFF and Eff)

6. Regulation of blood flow - Kidney

Silverthorn Fig 19-2

Proximal Tubule

Lumen of tubule Symport - glucose - aa lumenal - phosphate side will - lactate be stacked - bicarb with these transporters 2K+

3Na+ Glu Na+ K+ Cl-

PTC Lumen of blood vessel

the glucose transporter only exists on the proximal tubule

we will come back to HCO3this

Antiport

ClH+ Na+ H2CO3 CA CO2 + H2O H+ + HCO3-

Glu, aa, phosphate, lactate, bicarb

secretion

3Na+ cation organic cation organic anion Diffusion - Na+, Cl-, H2O - K+, urea, Ca++ - CO2 Ionic capture NH3 + H+ 2NH3 anion (Cl-) organic anion
solvent drag - when H2O moves, solutes move with it

2K+ organic cation carboxylate

anions bile salts cAMP penicillin cations epi norepi morphine

ammonia

bicarb

Blood flow

2HCO3glutamine 2K+
H2O moves by osmosis and H2O channels (aquaporins)

once bound to a 4th NH+4 H ion, ammonium is too big to come back in and it then gets excreted

3Na+

Endocytosis - proteins - polypeptides

6. Regulation of blood flow - Kidney

SEE NOTES NOV. 7th Pt. 1

6. Regulation of blood flow - Kidney

HCO3-

Loop of Henle: Thin descending limb - H2O permiable - Na+ impermiable Thin ascending limb - H2O impermiable - Na+ permiable thick ascending limb - H2O impermiable

lumen H+ Na+ H+ + HCO3H2CO3 CA CO2 + H2O

2K+ 3Na+ HCO3-

ISS
6. Regulation of blood flow - Kidney
5

Diffusion (Ca++, Na+, K+, Mg+) K+ 2ClNa+

2K
+

3Na+ ClK+

symporters (cells we care about)

Regulation: 1. Neural - direct SNS (NE) - increase Na+ reabsorption 2. Hormonal - ALDO - acts to increase # of symporters and Na+K+ATPases therefore increase Na+ reabsorption. - Epi - increase reabsorption of Na+.
hormonally regulated -can make them work harder if needed

6. Regulation of blood flow - Kidney

impermeable

Early distal tubule - H2O permiable - Na+Cl- symport Late distal tubule and collecting duct: principle cells
TWO DIFF CELL TYPES

intercalated cells
ATP
we will revisit these

Regulation: 1. Neural - direct SNS (NE) - Na+ and H2O reabsorption 2. Hormonal - ADH-VP * principle cells - can be regulated hormonally ADH-VP - # H2O channels (aquaporins) on apical and Anti-diurectic hormone basolateral membranes - increase H2O permiability increases aquaporins ADH-VP - # H2O channels (aquaporins) on apical and basolateral membranes - decrease H2O permiability - ALDO - Na+ reabsorption therefore H2O to follow - ANP and urodilantin - inhibits Na+ and H2O reabsorption. central control local Urodilantin - local hormonal production - stimulation from (at kidney) MAP and blood volume - secreted by cells of the distal tubule and collecting duct.
Urodilantin does same thing as ANP

6. Regulation of blood flow - Kidney

SEE NOTES NOV. 7 th Pt. 2

6. Regulation of blood flow - Kidney

B & L pg 703

6. Regulation of blood flow - Kidney

Summary of tubule characteristics

Permeability Water Loop of Henle Thin decending loop Thin ascending loop Thick ascending loop Distal Convoluted Tubule Early Late Collecting duct Cortical Medullary * increased in the presence of ADH-V high 0 0 0 0* 0* low* NaCl low high low low low low low Urea low low 0 0 0 0 moderate Active NaCl Transport 0 0 high low low low low

6. Regulation of blood flow - Kidney

10

Low ADH
Cortex 300 300
Na-290 U-10

Na+

100
Na-10 U-90

100
Na-5 U-90 X-5

320

300

Na+

Outer Medulla
H2O

2Cl+ K+

Na+

900
Na-810 U-90

800
H2O

95
Na+ Na+

900

700

800
Na-760 U-30

Inner H2O Medulla 1400

H2O

1400 1000 1400

U-50 Na-1350

Na+

H2O Urea 150

1400 1000
X-25 U-125

1400 Large volume of dilute urine - up to 18 L/day!!

700 Na+ 700 Urea

Urea

6. Regulation of blood flow - Kidney

11

Countercurrent theory
300 300 300 300 300 300 300 300 300 300 300 300 300 300 300 300 400 400 400 400 200 200 200 200 300 400 400 400 400 400 400 200 200 200 200

300 300 400 400

300 300 400 400

200 200 400 400

300 300 400 400 350 500 500

150 150 300 300

300 350 500 500

300 350 500 500

150 150 300 300

6. Regulation of blood flow - Kidney

12

High ADH
Cortex 300 300
Na-290 U-10

100
Na-10 U-90

300
Na-5 U-90 X-250

H2O

320

300

Na+

H2O Na+ H2O

Outer Medulla
H2O

2Cl+ K+

800
H2O

900
Na-810 U-90

H2O Na+
U-600 X-200

900 800
H2O

800
Na-760 U-30

800

Na+

Inner Medulla 1400

1400
H2O

Na+ H2O Urea 1400 Urea

X-700 U-700

H2O

1400 1000 1400

1000 1400
U-50 Na-1350

H2O

700 Na+ 700 Urea

Small volume of concentrated urine

6. Regulation of blood flow - Kidney 13

ADH - released by post. pit.

we live here
*

Two stimulus for ADH: 1 . Hemodynamic stimulus - high and low pressure baroRc -> brainstem->hypothal. -> synapse onto ADH secreting cells tonic signals from baroRc inhibit ADH release Therefore if decrease bl vo. (decrease MAP) -> decrease AP freq of sensors -> decrease inhibition -> increase ADH secretion

6. Regulation of blood flow - Kidney

14

3. ANP product of volume sensor in right atria stretch volume venous return right atria i) vasodilate afferents, vasoconstrict efferents

ANP release

ii) inhibit ADH release

iii) inhibit renin

iv) decrease ALDO

6. Regulation of blood flow - Kidney

14

6. Regulation of blood flow - Kidney

15

Angiotensinogen

renin AI Angiotensin Converting Enzyme AII

6. Regulation of blood flow - Kidney
6. Regulation of blood flow - Kidney 15

Adrenal Glands

ALDO

16

4. Renin AII - ALDO

Stimulus for renin release: 1. Perfusion pressure afferent arterioles have high pressure baroRc

[renin]

2. SNS innervation of afferent and efferent arterioles

[renin]

SNS activity

3. Delivery of NaCl (by distal tubule) to the macula densa

[renin]

NaCl in MD

6. Regulation of blood flow - Kidney

16

6. Regulation of blood flow - Kidney

Afferent arteriole Pressure and/or volume

17

ADH IN HUMAN KIDNEY FUNCTION The purpose of this experiment was to study urine production as a function of the nature and volume of fluid intake. Protocol: Two hours before the laboratory, bladders were emptied but no sample taken. At the start of the laboratory, the bladder was completely emptied into a beaker. This was the control sample. The urine osmolarity and the rate of urine production (volume of sample/time between samples) were determined. Subjects were placed in one of the following groups: 1. Control - followed usual fluid intake pattern 2. Sudden water load - drank 642 ml of water as quickly as possible immediately after the control sample. 3. Continuous water load - drank 400 ml as quickly as possible immediately after the control sample and drank 200 ml every 30 min for 1 hour. 4. Substance eX-ethanol boosted beverage - drank 642 ml as quickly as possible after the control sample. At 30 min intervals after the control sample bladders were emptied and the rate of urine production (V) and osmolarity were determined.
9 8 7 6 V/V control 5 4 3 2 1 0
0.00

Osmolarity/control osmolarity

Control Sudden H2O Continuous H2O Substance "eX"

1.25

1.00

0.75

0.50

0.25

10

20

30

40

50

60

70

80

90

10

20

30

40

50

60

70

80

90

Time (min)

Time (min)

6. Regulation of blood flow - Kidney

18

6. Regulation of blood flow - Kidney

19

Central - endocrine

ANP heart

ADH-V posterior pituitary Aldosterone adrenal cortex

Reff MAP PGC Raff

AIIlocal renin

AIIcentrall

MD osmolarity

Osm

GFR Qtubule Autoregulation - paracrine

Local - paracrine
6. Regulation of blood flow - Kidney 20

Interhormonal relationships OsmBl

H2O reabsorption

ADH-V ANP MD osm Aldosterone Na+K+ ATPase Na+ channels AII

BV MAP
renin VC Raff, Reff GFR SNS

Urodilatin
6. Regulation of blood flow - Kidney 21