Renal Blood Flow and GFR

Question 1

Essentially, what is the kidney important in

Answer 1

Excretion and retention of nutrients

Question 2

What is GFR a key parameter in

Answer 2

Kidney failure

Question 3

What is meant by Glomerular filtration

Answer 3

Definition: formation of an ultrafiltrate of plasma in the glomerulus

Question 4

What is meant by renal failure

Answer 4

An abrupt fall in glomerular filtration is renal failure

Abnormalities in renal circulation lead to reduced glomerular filtration i.e. renal failure.

Question 5

What type of process is glomerular filtration

Answer 5

Passive process: fluid is ‘driven’ through the semipermeable (fenestrated) walls of the glomerular capillaries into the Bowmans capsule space by the hydrostatic pressure of heart.
Hydrostatic pressure of blood (generated by heart) drives blood through fenestrations

Question 6

Describe the movement of filtrate from the glomeruli to the Bowman’s Capsule

Answer 6

The filtration barrier (fenestrated endothelium of capillaries and semipermeable Bowman’s capsule)  is highly permeable to:
 fluids 
small solutes (these are “freely filtered”: same concentration in filtrate and plasma)

But impermeable to:
cells
proteins
drugs etc carried bound to protein

Question 7

What does this filtering produce

Answer 7

A clear fluid (ultrafiltrate), completely free from blood and proteins, is produced containing electrolytes and small solutes = ‘primary urine’
Ultrafiltrate= soluble components of plasma in the absence of cells or proteins.

Question 8

Do we excrete the primary urine

Answer 8

No -things will be reabsorbed

Question 9

If something is reabsorbed, what will its conc in the urine be

Answer 9

Low

Question 10

What is the space between the foot processes of the podocyte called

Answer 10

fenestration slits

Question 11

Why do we measure renal function in terms of flow

Answer 11

It is easier to measure than pressure

Question 12

Where do substances leaving the kidney leave

Answer 12

Renal vein and ureter

Question 13

What is the amount of something excreted equal to

Answer 13

Amount filtered + amount secreted - amount reabsorbed

Question 14

Where do the secretions come from

Answer 14

Peritubular capillaries (lead from efferent arteriole)
Don't go through filtering process

Question 15

What are the glomerular filtration pressures

Answer 15

Driving force = hydrostatic pressure in glomerular capillaries (due to blood pressure) (Pgc)

Opposing pressures: hydrostatic pressure of tubule (Pt)

osmotic pressure of plasma proteins in glomerular capillaries (πgc)
Together these determine the net ultrafiltration pressure (Puf)

Question 16

What is glomerular filtration pressure (net) equal to

Answer 16

Puf = Pgc- Pt- πgc

Normal GFP value = 10-20mmHg.

Question 17

Define GFR

Answer 17

GFR = The amount of fluid filtered from the glomeruli into the Bowmans capsule per unit of time (ml/min).
Sum of filtration rate of all functioning nephrons

Question 18

What is the formula for GFR

Answer 18

GFR = Puf x Kf
Where Kf is an ultrafiltration coefficient (membrane permeability and available for filtration).
Any changes in filtration forces or Kf will result in GFR imbalances.

Question 19

What can result in changes in Kf

Answer 19

o Kidney disease = reduce number of functioning glomeruli = reduce surface area = reduce Kf = reduce GFR.
o Dilation of glomerular arterioles by drugs/hormones = more surface area = increase Kf = increase GFR.

Kidney disease and inflammation will also increase permeability

Question 20

How do we get to the value for GFR

Answer 20

§ Renal blood flow (RBF) = approx. 1L/min – which is one fifth of cardiac output = 5.04L/min.
§ Renal plasma flow (RPF) = approx. 0.6L/min – just the plasma in the renal blood.
§ Filtration fraction (FF) = 0.2 – ratio between RPF and amount of filtrate filtered by glomerulus, which is normally 20%.

Glomerular filtration rate (GFR) = RPF x FF

Approx 120ml/min

Question 21

What does renal blood flow deliver

Answer 21

Delivers oxygen, nutrients and substances for excretion

Question 22

What does GFR depend on

Answer 22

Glomerular capillary pressure (Pgc)
Plasma oncotic pressure (πgc)
Tubular pressure (Pt)
Glomerular capillary surface area or permeability (Kf).

GFR is not a fixed value but is subject to physiological regulation. This is achieved by neural or hormonal input to the afferent/efferent arteriole resulting in changes in Puf.

Question 23

Why is autoregulation important

Answer 23

Exercise- hydrostatic pressure would increase- so would GFR- urinate more- this doesn’t make sense physiologically

Question 24

Describe myogenic autoregulation

Answer 24

Vascular smooth muscle constricts when stretched.
Keeps GFR constant when blood pressure rises.

Arterial pressure rises → afferent arteriole stretches →
arteriole contracts → (vessel resistance increases)→ blood flow reduces and GFR remains constant:

Question 25

What does freely filtered mean

Answer 25

"Freely filtered": solute found at same concentration in filtrate and plasma

Question 26

What is the effect of a severe haemorrhage on GFR

Answer 26

decreases Pgc so will decrease GFR

Question 27

What is the effect of an obstruction of a nephron tubule on GFR

Answer 27

increases Pt/decreases Kf so decreases GFR

Question 28

What is the effect of reduced plasma protein conc on GFR

Answer 28

decreases πgc so decreases GFR

Question 29

What is the effect of a small increase in blood pressure on GFR

Answer 29

no effect due to myogenic autoregulation

Question 30

How do we measure GFR

Answer 30

Renal clearance

Question 31

Describe renal clearance

Answer 31

As substances in the blood pass through the kidney they are filtered to different degrees. The extent to which they are removed from the blood is called clearance.

Question 32

Define renal clearance

Answer 32

Clearance is the number of litres of plasma that are completely cleared of the substance per unit time.

Question 33

What is the equation for renal clearance

Answer 33

(urine concentration x rate of urine production)/concentration in plasma UV/P ``` U = concentration of substance in urine P = concentration of substance in plasma V = rate of urine production ``` ml/min

Question 34

How can Renal clearance be used to measure GFR

Answer 34

If a molecule is freely filtered and neither reabsorbed nor secreted in the nephron then the amount filtered equals amount excreted. Thus GFR can be measured by measuring clearance of this molecule Has to be filtered, but cannot be absorbed or excreted

Question 35

Describe inulin

Answer 35

Inulin: - a plant polysaccharide - freely filtered and neither reabsorbed nor secreted - not toxic - measureable in urine and plasma. But not found in mammals so needs to be transfused therefore use an endogenous molecule with a similar clearance. clearance = 120ml/min.

Question 36

What is a practical measurement of GFR

Answer 36

GFR in humans is normally estimated from creatinine clearance. Creatinine: a waste product from creatine in muscle metabolism amount of creatinine released is fairly constant if renal function stable, amount creatinine in urine is stable low values of creatinine clearance may indicate renal failure high plasma creatinine may indicate renal failure

Question 37

If GFR decreases, what should happen to plasma creatinine

Answer 37

It's conc should increase

Question 38

List some values for renal clearance

Answer 38

``` Na 1.0ml/min K 11.0ml/min Ca 1.8ml/min Mg 3.6ml/min Phosphate 6.4ml/min Glucose 0.05ml/min Urea 17.0ml/min Inulin 120.0ml/min PAH 625.0ml/min ```

Question 39

When may plasma creatinine be high without any pathophysiology

Answer 39

In more muscular people

Question 40

How do we measure renal plasma flow

Answer 40

Measured by PAH (Para aminohippurate) clearance = 625ml/min Filtered and actively secreted in one pass of the kidney, thus can be used to measure RPF. In other words the all of the PAH is removed from the plasma passing through the kidney so its clearance equals the renal plasma flow What isn't filtered is actively secreted

Question 41

What does the amount of substance appearing in the urine reflect

Answer 41

The amount of substance appearing in the urine reflects the combined effects of filtration, reabsorption from nephron tubule to blood and secretion from blood into the tubular fluid, such that: Amount excreted = amount filtered - amount reabsorbed + amount secreted

Question 42

If a substance is reabsorbed what will its clearance be

Answer 42

Less than GFR

Question 43

If a substance is neither absorbed nor secreted what will its clearance be

Answer 43

= GFR

Question 44

If a substance is secreted and not reabsorbed what will its clearance be

Answer 44

> GFR

Question 45

Describe renal diagnostics

Answer 45

A fall in GFR is the cardinal feature of renal disease If GFR falls, excretory products will build up in the plasma. A raised plasma concentration of creatinine is diagnostic of renal disease.

Question 46

Why do we need to be careful about pharmacokinetics in renal failure

Answer 46

In acute kidney failure- GFR can decrease 4- fold Drugs will accumulate in the plasma 4-fold- potential overdose Drugs that treat AF partially bloc AV node- too much will kill you Excretion of many other substances will also be impaired in renal failure - including some drugs. This needs to be taken into account when calculating drug doses - PHARMACOKINETICS.

Question 47

Describe the excretion role of the kidney

Answer 47

Excretion of metabolic products e.g. urea, uric acid, creatinine Excretion of foreign substances (drugs)

Question 48

Describe the role of the kidney in homeostasis

Answer 48

Homeostasis of: body fluids (cell volume) electrolytes (cell volume) acid-base balance

Question 49

Describe the role of the kidney in regulating BP

Answer 49

``` Regulate blood pressure - Secrete hormones (renin, erythropoietin) - ```

Question 50

What factors can affect net ultrafiltration

Answer 50

Arterial blood pressure: if increases, will increase Pgc and hence Puf and GFR Plasma protein concentration: if increases, will increase πgc and hence decrease Puf and GFR Ureteral obstruction: will increase Pt, hence decreasing Puf and GFR