Physiology 12 Kidney and Fluid regulation Germann Ch: 17 &18

Roles of the Kidney Regulation of body fluid osmolarity and electrolytes Regulation of acidacid-base balance (pH) Excretion of natural wastes and foreign chemicals Regulation of arterial pressure Secretion of hormones (Epo (Epo)) Gluconeogenesis

Renal Physiology The Nephron and GFR Kidney Gross Anatomy The Nephron Glomerular Filtration Rate (GFR) Regulation of GFR

Physio 12 -Summer ‘02 - Renal Physiology - Page 1

Renal Arteries

Physio 12 -Summer ‘02 - Renal Physiology - Page 2

The Nephron

Cortical and Medullary Nephrons

Physio 12 -Summer ‘02 - Renal Physiology - Page 3

Physio 12 -Summer ‘02 - Renal Physiology - Page 4

Physio 12 -Summer ‘02 - Renal Physiology - Page 5

Glomerular Filtration Rate (GFR) Glomerular capillaries have higher filter rate than other capillaries – Due to higher hydrostatic pressure and leakier capillaries

GFR = 125 ml/min = 180 L/day Filtered fraction = GFR/Renal plasma flow = 20%

Figure 21-7: PNet

PNet

=

PG

-

PB

-

πG

Physio 12 -Summer ‘02 - Renal Physiology - Page 6

Influences on GFR GFR = Kf x PNet – Kf = leakiness of capillaries – PNet = net hydrostatic pressure = PG - PB - πG

Kf of glomerulus is 400400-fold higher than Kf of any other capillaries

Capillary Pressure (out) = 60 mmHg Bowmans Pressure (in) = 18 mmHg Plasma Colloidal (in) = 32 mmHg Bowman’s Colloidal (out) = 0 mmHg

10 mmHg outward pressure

↑ Afferent Constriction = ↓ Filtration

Physio 12 -Summer ‘02 - Renal Physiology - Page 7

↑ Efferent Constriction = ↑ Filtration

GFR Increases with: Increased glomerular blood flow Decreased afferent arteriolar resistance Increased efferent arteriolar resistance Sympathetic stimulation (extreme situations only) lowers GFR – NE and Epi lower GFR

Autoregulation of GFR GFR is relatively constant over arterial BPs of 8080-170 mm Hg Persists in isolated kidney – Independent of nervous system

No autoregulation would create 46 liters/day of urine if BP = 125 mm Hg – = 6 liters/day with autoregulation

Physio 12 -Summer ‘02 - Renal Physiology - Page 8

Figure 2121-9: Autoregulation of Renal Blood Flow and GFR

Normal

Pressure Diuresis

Autoregulation of GFR Mediated by Tubuloglomerular Feedback Low NaCl (flow) at Macula Densa: – Lowers afferent arteriolar resistance (?) – Raises efferent arteriolar resistance (AII)

Macula Densa also regulates renal BP via reninrenin-angiotensinangiotensin-aldosterone

Structure of Juxtaglomerular Apparatus

Renin Renin Secretion Secretion

Chemical Chemical Signal Signal from from MD MD

Physio 12 -Summer ‘02 - Renal Physiology - Page 9

Renal Physiology Filtration and Reabsorption 1o and 2o Active Transport – Passive diffusion of Cl, urea, water

Saturable reabsorption of glucose & AAs Tour of reabsorption and secretion along the tubule Renal Clearance

Two Paths for Reabsorption Basolateral

Apical

Physio 12 -Summer ‘02 - Renal Physiology - Page 10

Basolateral

Apical

Secondary Active Transport (Co(Co-Transport) Glucose and AA Active Reabsorption at Proximal Tubule

Physio 12 -Summer ‘02 - Renal Physiology - Page 11

Secondary Active Transport (Counter Transport) H+ Secretion

Filtration Filtration = PS x GFR, where PS is the plasma concentration of substance S This represent the tubular load or filtered load that must be handled Units: mg/ml x ml/min = mg/min

Figure 2121-15: Glucose Transport is Saturable: Diabetes mellitus PGlucose x GFR = Glucose 0.9 mg/ml x 125 ml/min = 112 mg/min

PGlucose x GFR =

Physio 12 -Summer ‘02 - Renal Physiology - Page 12

PGlucose GFR = Figure 21Glucose Transport is 21x-15: Glucose 3.2 mg/ml x 125 ml/min = mellitus Saturable: Diabetes 400 mg/min

Diabetes mellitus

PGlucose x GFR = Diabetes:

Basolateral Apical

Increased Increased by by AII

Reabsorption

Ca++

PAH, many drugs

Secretion

Processes at Proximal Tubule

← ←H H22O O

20%

NaCl NaCl → →

Processes at Thin Loop of Henle

Physio 12 -Summer ‘02 - Renal Physiology - Page 13

Increased Increased by by Aldosterone Aldosterone Blocked Blocked by by Lasix

no no H H22O O→ → 25%

Processes at Thick Loop of Henle

Increased Increased by by Aldosterone Aldosterone Blocked Blocked by by Amiloride Variable % Hypoosmotic

no no H H22O O→ →

++]] Reabsorption [Ca [Ca++ Reabsorption Increased Increased by by PTH PTH

Processes at Early Distal Tubule

Calcium Homeostasis 90% dietary Ca excreted in feces, 10% in urine Low [Ca] in plasma causes parathyroid cells to secrete PTH – ↑ Ca reabsorption from distal tubule – ↑ Ca reabsorption from intestine – ↑ Release of Ca stored in bone Can eventually strip bone of Ca supply

Physio 12 -Summer ‘02 - Renal Physiology - Page 14

Blocked Blocked by by Amiloride 90 % of cells

Increased Increased by by Aldosterone Aldosterone Decreased Decreased by by ANP ANP Variable %

10 % of cells

Processes at Late Distal Tubule and Collecting Duct

90 % of cells Increased Increased by by ADH ADH

H2 O Decreased Decreased by by ANP ANP Variable %

10 % of cells

Processes at Late Distal Tubule and Collecting Duct

90 % of cells

Variable %

Location Location of of [K+] [K+] Control Control

10 % of cells

Processes at Late Distal Tubule and Collecting Duct

Physio 12 -Summer ‘02 - Renal Physiology - Page 15

Potassium Homeostasis Most K+ is inside cells (140 mM), not outside (4.2 mM) ↑ plasma [K+] causes ↑ K+ secretion from principal cells: – Direct ↑ Na/K pump – ↑ Aldosterone secretion => ↑ Na/K pump

90 % of cells

Variable %

Location Location of of AcidAcidBase Base Control Control

10 % of cells

Processes at Late Distal Tubule and Collecting Duct

Acid-Base Homeostasis Diet usually generates an excess of acid Most HCO3- is reabsorbed by PT (85%), remainder by TAL and CD Controlled by tubule cells, which sense pH and [CO2] – Secrete more H+ if pH too low – Secrete less H+ if pH too high

Physio 12 -Summer ‘02 - Renal Physiology - Page 16

Acid-Base Homeostasis Excess H+ is secreted by Intercalated Cells in DT and CD – Urinary H+ is buffered by phosphate and ammonia so that pH ≥ 4.5

Relative Concentrations of Substances along Tubule

Glucose & AAs

Relative Concentrations of Substances along Tubule Inulin

H2 O

Physio 12 -Summer ‘02 - Renal Physiology - Page 17

Relative Concentrations of Substances along Tubule H+

HCO3-

Relative Concentrations of Substances along Tubule

Relative Concentrations of Substances along Tubule

PAH

K

Cl Na

HCO3-

Physio 12 -Summer ‘02 - Renal Physiology - Page 18

Renal Clearance Renal Clearance (CS) is the volume of plasma completely cleared of a substance (S) per minute – Units are ml/min

CS = (US x V)/PS – US is [S] in urine, V is urine flow rate, PS is [S] in plasma

Renal Clearance FilteredFiltered-Only substances (no secretion or reabsorption) have CS = GFR – Example: Inulin

Secreted substances have CS > GFR – Example: PAH

Reabsorbed substances have CS < GFR – Example: glucose

Renal Clearance Renal clearance of inulin allows clinical determination of GFR – GFR = (UI x V)/PI

PAH is 90% secreted. Renal clearance of PAH allows clinical determination of Renal Plasma Flow – RPF = (UPAH x V)/(PPAH x 0.9)

Physio 12 -Summer ‘02 - Renal Physiology - Page 19

Renal Physiology: Renal Exchange Mechanisms

Excrete excess solutes And/or Concentrating the Urine

Create a very high osmotic pressure in the interstitial fluid • Created by active transport of ions. • Increase the interstitial fluid Osmolarity.

Physio 12 -Summer ‘02 - Renal Physiology - Page 20

Physio 12 -Summer ‘02 - Renal Physiology - Page 21

Physio 12 -Summer ‘02 - Renal Physiology - Page 22

Create a very high osmotic pressure in the interstitial fluid • Created by active transport of ions. • Increase the interstitial fluid Osmolarity. • Arteriole and Capillary system transports ions to medullary areas of the kidney.

Physio 12 -Summer ‘02 - Renal Physiology - Page 23

Kidney Dialysis

Physio 12 -Summer ‘02 - Renal Physiology - Page 24