Renal Sodium Regulation

Front 1

Significance of Na transport

Back 1

•Na and water transport within the kidney are responsible for the maintenance of ECF and BP

Front 2

Function of the Kidneys

Back 2

Regulate the volume and composition of body fluids within narrow limits
–Total body water ie 58% of body mass
–Intracellular (5/8ths) and extracellular (3/8ths) body fluids

Front 3

Functions of the kidney in ion composition

Back 3

–Maintains electrolyte composition, Na, K, HCO3, Cl, Ca, PO4, and hence acid base status
–Regulates volume through regulation of Na reabsorption and secretion.
–Regulates ‘concentrations’ through regulation of water transport.
–Volume regulation (ie maintenance of BP) overrides regulation of electrolyte concentrations and acid base status.

Front 4

Hypovolaemia causes

Back 4

–GIT Na losses
–Sweating
–Renal Na losses – eg diuretics, mineralocorticoid deficiency, renal tubular disease

Front 5

Hypervolaemia causes

Back 5

–Iatrogenic – Na loading
–Renal Na retention in generalised oedema states (CCF, cirrhosis, nephrotic syndrome
–Renal Na retention in renal failure
–Primary mineralocorticoid excess

Front 6

•Glomerular filtration

Back 6

–is the process whereby a clear fluid is produced from the blood perfusing the glomerulus at each nephron. Blood, proteins and other macromolecules are excluded from the ultrafiltrate
–Produced largely because of hydrostatic pressure ie blood pressure (Hence if blood pressure falls below a critical perfusion pressure glomerular filtration stops!

Front 7

•Tubular Modification

Back 7

–Tubules alter the volume and composition of the glomerular ultrafiltrate
–Overall 99% of the filtrate is reabsorbed. However some organic molecules/drugs are secreted into the ultrafiltrate

Front 8

Filtration and Reabsorption in the Kidney

Back 8

Front 9

Blood flow and GFR

Back 9

•Kidneys receive 20% of the cardiac output
•CO about 5L/minute. Hence renal blood flow about 1000ml/min
•Assuming a Hct of 50%, then renal plasma flow is 500ml/min
•If filtration fraction is 20% then GFR is 100ml/min or 144L/24 hrs.
•Given 99% filtrate is reabsorbed 1L urine per 24 hrs

Front 10

Main task of the kidneys is to

Back 10

Main task of the kidney is to regulate body fluid composition and volume

•Volume regulation (I.e. ECF volume) is dependent on regulation of Na transport
•Osmolality (in effect serum Na) is dependent on regulation of water transport
•These two factors are independent

Front 11

Regulation of renal Na transport
•Dependent on

Back 11

–Delivery of Na to the kidney
»thus affected by BP, cardiac output, renal blood flow
–Renal function
»Including glomerular filtration rate (GFR), and intact tubular mechanisms for Na reabsorption
–Hormonal influences on tubular Na reabsorption
»Dominant influence is via the renin-angiotensin system on Na transport in the distal tubule

Front 12

RAAS acts mainly at the

Back 12

distal tubule
DOMINANT INFLUENCE IS HERE (idk if its the only input.. other slides saying it acts at the proximal tubules too)

•Whilst the proximal tubule is responsible for the bulk of Na transport, the distal tubule/CCD is the target of most regulation.

Front 13

Dysregulation of renal Na transport

Back 13

•Glomerular dysfunction
–Reduced delivery of Na to the tubule, thus if severe results in Na retention
•Tubular dysfunction
(due to primary renal disorders or secondary hormonal or haemodynamic influences on the tubule)
–May -> excess Na losses and volume depletion
–May -> excess Na reabsorption and increased ECFV, normally manifesting as hypertension
Normally 180 litres (each containing 140 mmol/l Na) are filtered by the glomerulus each day. Hence a 1% change in reabsorption results in large changes in Na and fluid homeostasis

Front 14

Proportion of Na reabsorption throughout the kidney tubules

Back 14

MAIN: proximal tubules

HOWEVER: (drugs) Na regulation is late distal tubule and collecting duct (seems counter intuitive but it is soo that the Na regulation is unaffected by tublues down track because thee is nothing down track)

Front 15

Macula Densa

Back 15

lies in close proximity to the glomerulus and feeds back to by producing renin (juxtaglomerulua apparutus)

•Macula densa located at this site which regulates tubuloglomerular feedback
–Ie - if increased Na delivery is sensed by the macula densa at the early distal tubule, a signal is transmitted to the glomerulus which reduces GFR.
–Signal most likely involves adenosine

Front 16

Regulation of renal Na transport Proximal tubule

Back 16

•Responsible for ‘bulk’ transport (50-75%)
•Glomerulotubular balance applies
–I.e if increased filtration, then increased reabsorption
–GT balance perturbed mainly by physical factors. Eg - high BP, increased ECF volume or low plasma oncotic pressure -> decreased proximal Na reabsorption
•Hormonal influences on PT Na reabsorption
–Angiotensin II -> increases PT Na reabsorption
–Dopamine inhibits Na reabsorption
•Increased sympathetic tone increases PT Na reabsorption
–Low BP or low ECF volume -> activates renal sympathetic nerves and Na reabsorption stimulated

Front 17

Proximal tubule Pumps

Back 17

MOST Na and water via the shunt pathway; isotonic

Front 18

Regulation of renal Na transport Loop of Henle

Back 18

•Responds to delivered load of Na
•Prostaglandins -> inhibit Na reabsorption in the loop

Front 19

LOH Pumps

Back 19

Shunt is WATER IMPERMEABLE

Front 20

Regulation of renal Na transport Distal convoluted tubule

Back 20

•Responds to delivered load of Na
•Macula densa located at this site which regulates tubuloglomerular feedback
–Ie - if increased Na delivery is sensed by the macula densa at the early distal tubule, a signal is transmitted to the glomerulus which reduces GFR.
–Signal most likely involves adenosine

Front 21

Tubuloglomerular feedback

Back 21

Front 22

Early Distal Tubule Pumps

Back 22

- also water impermeable
- hypercalcaimic
- main reason due to proximal reabsorption (due to dec. Na levels.. )
- INC ca reabsorption
- Ca

Front 23

Regulation of renal Na transport Collecting Duct

Back 23

•Main site of regulation of Na transport
•Main regulators are:
–Delivered Na load
–Activation of the renin angiotensin system -> Increased action of aldosterone
–Atrial natriuretic hormone.
»Released from the atria under conditions of volume expansion and inhibits Na reabsorption in the distal tubule
–Other glucocorticoids
–Prostaglandins

Front 24

Main Regulators of Na

Back 24

–Activation of the renin angiotensin system -> Increased action of aldosterone
–Atrial natriuretic hormone.
»Released from the atria under conditions of volume expansion and inhibits Na reabsorption in the distal tubule
–Other glucocorticoids
–Prostaglandins

Front 25

RAAS

Back 25

Front 26

Aldosterone in distal tubule

Back 26

Net effect of Aldosterone is to increase Na entry into cell -> facilitates Na reabsorption -> K losses (hypokalaemia -> H losses (alkalosis) -> increase ECFV, BUT over the course of a few days Na excretion becomes normal, but at the expense of increased ECF and BP

Front 27

Cortical Collecting Duct Pumps

Back 27

Order of events:
1. Na reabsorbed
2. -ve lumen drives K+ out

PRINCIPAL CELL
1. Na/K/ATPase
2. Na channel (lumen to cell)
3. -ve INC. in lumen, drives K out of the cell
AND drives Cl- away

INTERCALATED CELL
reabsorbs -ve ions and secretes H+
- H+ loss is increased with aldosterone usage too (countering the -ve lumen)

Front 28

Summary Slide of Renal Tubule

Back 28

Front 29

Mechanisms to deal with volume change

Back 29

Front 30

Endocrine Function of the Kidneys

Back 30

EPO
activation of VitD (1OH to 25OH vit D)
renin

Front 31

Priority of Functions within the Kidney

Back 31

volume> osmolality > potassium & acid‐base

Front 32

Kidney Overview

Back 32

Front 33

Tubular Cells

Back 33

Front 34

Reabsorption, Secretion and excretion

Back 34

Front 35

"Shunt" pathway

Back 35

Front 36

Renal Sodium Transporters

Back 36

Front 37

Reabsoption of Proteins

Back 37

in proximal tubule
- specific receptors (eg megalin, cubilin, AMN)

Front 38

Proximal tubular disorders

Back 38

low MW proteinuria
renal glycosuria
aminoaciduria
phosphaturia
uricosuria
hypokalaemia
proximal RTA

Front 39

Loop of Henle (thick ascending limb)
transport lesions

Back 39

salt wasting and hypovolaemia
hypokalaemia
high renin and aldosterone
JGA hypertrophy
metabolic alkalosis
hypomagnesaemia (+/-)
hypocalcaemia (Hypercalciuria)
impaired urine concentration
BP normal or low

Front 40

Juxtaglomerular Cells

Back 40

this apparatus produces renin

Front 41

Early distal tubule transport lesions

Back 41

mild salt wasting and hypovolaemia
hypokalaemia
metabolic alkalosis
hypomagnesaemia
hypocalciuria (hypercalcaemia)*
impaired urine dilution*
BP normal or low

* differences between it and the LOH

Front 42

Cortical collecHng duct transport
lesions

Back 42

A. IMPAIRED Na TRANSPORT ‐
salt wastng
hypovolaemia
hypotension
hyperkalaemia
metabolic acidosis (RTA type IV)
B. ENHANCED Na TRANSPORT ‐
salt retenHon
hypertension
hypokalaemia (K wasHng)
metabolic alkalosis
low renin and aldosterone
C. IMPAIRED H+ SECRETIONRenal
tubular acidosis

Front 43

RTA Type 1

Back 43

renal tubular acidosis
- abnormality in H+ excretion

Front 44

RTA 4

Back 44

defect in principal cell
- thus the lumen is no longer -ve and thus harder to secrete H+ ions into the lumen
and alos
harder to secret K+