Regulation of kidneys work.
Role of kidneys in homeostasis
maintenance.
Balancing role of the kidney
• Water balance
• Sodium / potassium / chloride intake and
excretion balanced
• Average daily requirements:
• Water : 25 - 35 ml/kg/day
• Sodium : 1 - 1.4 mmol/kg/day
• Potassium: 0.7 - 0.9 mmol/kg/day
• Chloride : 1.3 - 1.9 mmol/kg/day
Urine formation results from Glomerular filtration,
Tubular reabsorption, and Tubular secretion
Filtration only
GFR = C in
Filtration, reabsorption
Filtration, secretion
C sub. ˂ C in.
C sub.
in.
Urine
Urine
˃C
Urine
Urinary excretion rate = Filtration rate – Reabsorption rate + Secretion rate
Glomerular Filtration Rate - Determinants
This is simplification of Starlings principle for
movement across capillaries
Net Filtration = Kf  NFP
Kf is Filtration co-efficient
Incorporates surface area  membrane permeability
NFP= Net filtration pressure in mmHg:
NFP = Glomerular capillary hydrostatic pressure –
Bowman’s capsule hydrostatic pressure – Glomerular
capillary oncotic pressure
Glomerular filtration rate (GFR)
Kf affected by:
– Mesangial cell contraction  ↓ area
– Causes - angiotensin II
- ADH
- bradykinin
– Membrane permeability relatively constant
Think about the effects of each of the determinants of net
filtration pressure –
GCHP
e.g: if afferent arteriole constriction, efferent arteriole dilatation,
GCHP falls. This leads to a fall in GFR
BCHP
e.g: ureteric obstruction causes ↑BCHP and ↓GFR
GCOP
e.g: fluid overload with low oncotic pressure - ↑GFR
Net Filtration Pressure along glomerulus
Drop along capillary due to
Decreased glomerular capillary hydrostatic pressure
Increased glomerular capillary oncotic pressure
Glomerular capillary NFP:
NFP = GCHP – BCHP – GCOP
Numbers:
Afferent end:
24 = 60 - 15 – 21
Efferent end:
10 = 58 – 15 - 33
Factors affecting GFR - summary
1. Mean Hydrostatic driving force
(pressure in GC-BC)
2. Kf (filtration coefficient)
3. Oncotic pressure gradient
Measuring GFR
Ideal is CLEARANCE of a substance that is freely filtered by
the glomerulus but not secreted or reabsorbed. Also not
stored, metabolised in kidney, not toxic, does not alter GFR
and easy to measure.
INULIN is gold standard
Would need constant infusion to maintain a constant plasma
concentration
Creatinine – not ideal – formed by muscle, released at
reasonably constant rate, BUT – overestimates GFR by
approx 10% due to SECRETION in tubules
Plasma Clearance
Plasma clearance is defined as the
amount of plasma that is cleared or
“cleansed” of a particular substance
in one minute. The kidneys will carry
out this clearance process through the
use of filtration, reabsorption and
secretion
Filtration will directly affect clearance. As
filtration increases, more material will be
removed from the blood plasma.
Reabsorption will indirectly affect
clearance. As reabsorption increases, less
material will be removed from the blood
plasma. Secretion will directly affect
clearance. As secretion increases, more
material will be removed from blood
plasma.
Plasma Clearance
The formula used to calculate plasma clearance is:
C = V x U/P
C = plasma clearance rate in ml/min
V = urine production rate in ml/min
U = the concentration of a substance in the urine in
mg/ml
P = the concentration of a substance in the plasma
in mg/ml
As you track the units in the equation, you will notice that
mg/ml cancel out, leaving ml/min.
Let us practice calculating plasma clearance
using the clearance equation. In all your
calculations, assume that the urine
production rate (V) is 2 ml/min. Let’s start
with the substance inulin (not insulin!). If
after a dose of inulin, your urine has 30
mg/ml and your plasma has 0.5 mg/ml of
this substance, what is the inulin clearance
rate? If you got 120ml/min, you are
correct!
120 ml/min = 2 ml/min x 30 mg/ml/ 0.5 mg/ml
Renal Blood Flow (RBF)
Very high – 20% cardiac output at rest, (1200ml
blood/min or 600ml of plasma/min). Kidneys <1%
body wt
Tightly autoregulated (similar to heart, brain)
Why the high blood flow:
High O2 consumption –
6ml/100g/min (C/W heart 8-10, Brain 3.5)
Second highest behind heart (per gram tissue)
Most blood flow and O2 consumption goes to cortex
Oxygen extraction quite low – 1.5vol% c/w 5vol% for
body as whole
Related mainly to active Na+ reabsorption and H+
ATPase pumps. Linked to GFR. (↑ GFR ↑02
consumption.)
Regulation of RBF
SYSTEMIC and LOCAL (=autoregulation)
SYSTEMIC effects blood flow to more than just kidneys
Neural – sympathetic/noradrenergic
Vasoconstriction – ↓ RBF. Small ↓ GFR (partially offset by
increased oncotic pressure in glomerular capillaries)
Increased renin secretion (direct effect on 1 receptors). Causes
angiotensin II release Afferent and efferent V/C and also action
on mesangial cells  ↓ GFR (but ↓ RBF more so filtration
fraction increases)
Increased sensitivity of juxtaglomerular cells
Humoral
Noradrenaline – V/C
Prostaglandins – PGI2, PGE2. Cause renal
arteriole V/D
Renin (as per prev page)
Other – e.g. exercise, diet
Renin – Angiotensin system
Autoregulation of RBF
• MYOGENIC and
METABOLIC components
• Metabolic component here
is tubuloglomerular
feedback, that also
regulates GFR
• RBF relatively constant
between approx MBP 75
and 170 mmHG
Reabsorption of sodium
Mechanisms of reabsorption