Transcript (Renal haemodynamic and GFR).

Renal Physiology 2:
Renal Haemodynamic &
Glomerular Filtration Rate
Dr Ahmad Ahmeda
[email protected]
Mobile No: 0536313454
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Learning Objectives
• Describe that the mechanism of urine formation include
three basic processes; glomerular filtration, tubular
reabsorption and tubular secretion.
• Define GFR and quote normal value.
• Identify and describe the factors controlling GFR in terms
of starling forces, permeability with respect to size, shape
and electrical charges and ultra-filtration coefficient.
• Describe Intrinsic and extrinsic mechanism that regulate
GFR.
• Describe autoregulation of GFR & tubuloglomerular
feedback mechanism.
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Blood supply to the kidney
• Approximately one-fourth (1200 ml) of systemic
cardiac output flows through the kidneys each minute
• Arterial flow into and venous flow out of the kidneys
follow similar paths
• The cortex receives more than 90% of the blood that
perfused into the kidney, which is perfused at a rate of
about 500 ml/min per 100 gm tissue.
(100 times greater than resting muscle blood flow)
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Blood supply to the kidney
• The remainder of the renal blood supply goes to the
capsule and the renal adipose tissue.
• Some of the cortical blood then passes to the
medulla, the outer medulla has a blood flow of
100ml/min per 100 g tissue, and the inner medulla a
flow of 20 ml/min per 100 g tissue.
• Due to high blood flows to the cortex so, more oxygen
than required and that lead to the arterio-venous
oxygen difference is only 1-2 %
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Blood supply to the kidney
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1= interlobar arteries
1a= interlobar vein
2= arcuate arteries
2a= arcuate vein
3= interlobular arteries
3a= interlobular vein
4= stellate vein
5= afferent arterioles
6= efferent arterioles
7a,7b= glomerular
capillary network
8,8a = descending vasa
recta
9= ascending vasa recta
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Capillary Beds of the Nephron
• Every nephron has two capillary beds
– Glomerulus
– Peritubular capillaries
• Each glomerulus is:
– Fed by an afferent arteriole
– Drained by an efferent arteriole
• Blood pressure in the glomerulus is high because:
– Arterioles are high-resistance vessels
– Afferent arterioles have larger diameters than efferent
arterioles
• Fluids and solutes are forced out of the blood
throughout the entire length of the glomerulus
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Capillary Beds
• Peritubular beds are low-pressure, porous
capillaries adapted for absorption that:
– Arise from efferent arterioles
– adhere to adjacent renal tubules
– Empty into the renal venous system
• Vasa recta – long, straight efferent arterioles of
juxtamedullary nephrons
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Vascular Resistance in
Microcirculation
• Afferent and efferent arterioles offer high resistance
to blood flow
• Blood pressure declines from 95mm Hg in renal
arteries to 8 mm Hg in renal veins
• Resistance in afferent arterioles:
– Protects glomeruli from fluctuations in systemic blood
pressure
• Resistance in efferent arterioles:
– Reinforces high glomerular pressure
– Reduces hydrostatic pressure in peritubular capillaries
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Measurement of renal blood flow
1)
Clearance methods:
Use of a substance which is filtered, secreted but
not reabsorbed by the nephrons and apply the
clearance formula.
An example is para-amino-hippuric acid (PAH)
which is freely filtered, secreted by the organic
pumps of the proximal tubule and is 100%
removed on passage through the kidney.
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Measurement of renal blood flow
• Direct dynamic measurements:
Electromagnetic flowmeter
• Ultrasound flowmeter
• Laser-Doppler flowmetry : Intrarenal
haemodynamics
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Proximal convoluted tubule
Bowman’s capsule
Afferent arteriole
Peritubular capillaries
Efferent arteriole
Glomerular capillary bed
High pressure vascular bed,
increasing oncotic pressure
Peritubular capillary bed,
Low pressure vascular bed,
high oncotic pressure.
Good for filtration
Good for re-absorption
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Mechanisms of Urine Formation
• The kidneys filter the body’s entire plasma volume
40 times each day.
• The filtrate:
– Contains all plasma components except protein
– Loses water, nutrients, and essential ions to
become urine
• The urine contains metabolic wastes and unneeded
substances
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Mechanisms of Urine Formation
• Urine formation and
adjustment of blood
composition involves
three major
processes
– Glomerular
filtration
– Tubular
reabsorption
– Secretion
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Glomerular Filtration
• The first step in urine formation
• Blood flows through the glomerulus, allowing
protein-free plasma to be filtered through the
glomerular capillaries into the Bowman’s capsule.
• ~20% of plasma entering the glomerulus is filtered
• 125 ml/min filtered fluid
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Tubular Reabsorption
• Movement of substances from tubular lumen back
into the blood
• Reabsorbed substances not lost in the urine, but
are carried by the peritubular capillaries to the
venous system
• Most of the filtered plasma is reabsorbed
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Tubular Secretion
• The selective transfer of substances from the
peritubular capillary into the tubular lumen
• Allows for rapid elimination of substances from the
plasma via extraction of the 80% of unfiltered
plasma in peritubular capillaries and adding it to
the substances already in tubule as result of
filtration
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Urine Excretion “The end
product”
• The elimination of substances from the body in the
urine
• All plasma constituents filtered or secreted, but not
reabsorbed remain in the tubules and pass into the
renal pelvis to be excreted as urine and eliminated
from the body
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Types of Tubular Reabsorption
• Reabsorption can be transcellular (across the cell)
or paracellular (between the cells)
• Once the substance has moved pass the tubular
epithelium cell into the interstitial space bulk flow
then accounts for its movement back into the
peritubular capillaries
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Passive Reabsorption
• Bulk flow results
from the imbalance
of osmotic or
hydrostatic forces
at the peritubular
capillary. Exactly
the same as at the
peripheral capillary
or the glomerulus
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Active Reabsorption
• Major substances are reabsorbed via active
transport. These are substances that are needed by
the body (e.g. Na+, glucose, aas, other electrolytes)
• Sodium reabsorption-99.5% of filtered sodium is
absorbed
– Proximal tubules (67%)
– Loop of Henle (25%)
– Distal/Collecting tubules (8%)
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Active Reabsorption
• Active reabsorption is via primary active transport
based on ATP hydrolysis (e.g. Na+) or secondary
active transport based on an ion gradient (e.g.
glucose)
• Known transporters:
– Na+/K+ ATPase
– H+ ATPase
– H+/K+ ATPase
– Ca++ ATPase
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Net Filtration Pressure (NFP)
• The pressure responsible for filtrate formation
• NFP equals the glomerular hydrostatic pressure
(HPg) minus the oncotic pressure of glomerular blood
(OPg) combined with the capsular hydrostatic
pressure (HPc)
NFP = HPg – (OPg + HPc)
Or
NFP = PGC – PBS - OGC
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Glomerular Filtration Rate
• Glomerular filtration rate (GFR) is the rate of
production of filtrate at the glomeruli from plasma
– Typically 80 – 140 ml/min depending on age, sex
etc
– Sum of the filtration rates of all functioning
nephrons
– Index of kidney function
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GFR
• Factors governing filtration rate at the
capillary bed are:
– Total surface area available for filtration
– Filtration membrane permeability
– Net filtration pressure
• GFR is directly proportional to the NFP
• Changes in GFR normally result from
changes in glomerular blood pressure
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GFR
• If the GFR is too high:
– Needed substances cannot be reabsorbed
quickly enough and are lost in the urine
• If the GFR is too low:
– Everything is reabsorbed, including wastes that
are normally disposed of
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Filtration:
glomerular hydrostatic pressure (GHP)
push fluid out of vessels
capsular hydrostatic pressure (CsHP)
push fluid back into vessels
net hydrostatic pressure
(NHP)
NHP = GHP - CsHP
35 =
50
- 15
mm Hg
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Filtration:
blood colloid osmotic pressure (BCOP)
proteins in blood (hyperosmotic)
draw water back into blood
~ 25 mm Hg
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Filtration:
FP = NHP - BCOP
10 =
35 - 25
mm Hg
importance of blood pressure
20% drop in blood pressure
50mm Hg to 40mm Hg
filtration would stop
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•
•
Driven by Starling forces
Pressure inside capillaries >
Pressure outside
 movement of fluid from blood
• Forces in capillaries: hydrostatic
pressure PGC = + 60mmHg
• oncotic pressure GC = - 29 mmHg
 net outward pressure = 60 – 29
= 31mmHg
• Forces in capsule: hydrostatic
pressure PBS = -15mmHg
• oncotic pressure GBS = 0 mmHg
• Overall: 31 – 15 = 16 mmHg
outward
• Male adults GFR: ~ 90 – 140
ml/min
• Female: 80 – 125 ml/min
• 125 ml/min usually good average
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