Glomerular Filtration and Renal Blood Flow

Question 1

2 potential outcomes for plasma when it enters the glomerulus?

Answer 1

20% is filtered

80% is not filtered and leaves via the efferent arteriole

Question 2

Steps in the creation of urine?

Answer 2

1. Glomerular filtration
2. Tubular reabsorption
3. Tubular secretion
4. Excretion

Question 3

Barriers to glomerular filtration?

Answer 3

1. Glomerular capillary endothelium - barrier to RBCs
2. Basement membrane - barrier to plasma proteins, which are repelled by the -ve charge
3. Slit processes of podocytes (AKA glomerular epithelium) - barrier to plasma proteins

Question 4

Collective name for the three barriers?

Answer 4

These make up the GLOMERULAR MEMBRANE

Question 5

What Starling forces comprise the net filtration pressure?

Answer 5

Glomerular capillary BP - 55 mmHg (exerted from the capillary into the tubule)

Bowman’s capsule hydrostatic (fluid) pressure (exerted from the tubule to the capillary) - 15 mmHg

Capillary oncotic pressure (exerted from the tubule to the capillary) - 30 mmHg

Bowman’s capsule oncotic pressure - 0 mmHg

Question 6

What is the net filtration pressure?

Answer 6

(55 + 0) - (15 + 30) = 10 mmHg

Question 7

Define the GFR?

Answer 7

Rate at which protein-free plasma is filtered from the glomeruli into the Bowman’s capsule PER UNIT TIME

Question 8

Calculating the GFR?

Answer 8

Kf x net filtration pressure

Kf = filtration coefficient (refers to how permeable/”holey” the glomerular membrane is)

Question 9

Normal GFR?

Answer 9

125 ml/min

Question 10

What is the major determinant of GFR?

Answer 10

Glomerular capillary fluid (blood) pressur e

Question 11

2 methods to regulating renal blood flow and GFR?

Answer 11

1. EXTRINSIC regulation of GFR:
   • Sympathetic control via baroreceptor reflex
2. INTRINSIC auto-regulation of GFR:
   • Myogenic mechanism
   • Tubuloglomerular feedback mechanism

Question 12

Describe the direct effect of arterial BP on GFR

Answer 12

If arterial BP increases, there is increased blood flow into the glomerulus thus:
• Glomerular capillary BP increases
• Net filtration pressure increases
This results in an increased GFR

If glomerular capillary BP decreases (following constriction of the afferent arteriole), the GFR decreases

Question 13

What happens to GFR when vasoconstriction occurs?

Answer 13

Decreases blood flow into the glomerulus so there is a decreases in glomerular capillary BP and net filtration pressure

Thus, there is a decreased GFR

Question 14

What happens to GFR when vasodilatation occurs?

Answer 14

Increases blood flow into the glomerulus so there is an increase in glomerular capullary BP and in net filtration pressure

Thus, there is an increased GFR

Question 15

How is GFR controlled by alterations in arterial BP?

Answer 15

1. Fall in blood volume, e.g: haemorrhage, decreases arterial BP (detected by aortic and carotid-sinus baroreceptors)
2. Increased sympathetic activity causes generalised arteriolar vasoconstriction and constriction of afferent arterioles
3. Glomerular capillary BP decreases and so does GFR
4. Decreased urine volume and this helps to compensate for the fall in blood volume

Question 16

Why is it that changes in systemic arterial BP do not necessarily result in changes in GFR?

Answer 16

Auto-regulation prevents short-term changes in systemic arterial BP affecting GFR

Question 17

2 components in auto-regulation of GFR?

Answer 17

1. Myogenic - if vascular smooth muscle is stretched, i.e: arterial pressure is increased, it contracts and constricts the arteriole
2. Tubuloglomerular feedback:
   • Inv. the juxtaglomerular apparatus (mechanism remains unclear)
   • If GFR rises, more NaCl flows through the tubule leading to constriction of afferent arterioles

Question 18

Which area of the juxtaglomerular apparatus is salt-sensitive?

Answer 18

Macula densa cells sense NaCl content of tubular fluid

Question 19

Pathologies affecting GFR?

Answer 19

Kidney stones increase Bowman’s capsule fluid pressure; this decreases GFR

Diarrhoea increases capillary oncotic pressure; this decreases GFR

Severe burns decrease capillary oncotic pressure; this increases the GFR

Change in the surface area available for filtration decreases the Kf; this decreases GFR

NOTE: GFR = Kf x net filtration pressure

Question 20

Define plasma clearance?

Answer 20

A measure of how effectively the kidneys can clean the blood of a substance; each substance handled by the kidneys has its own plasma clearance value

It is equal to the volume of plasma completely cleared of a particular substance

Question 21

Calculating clearance of substance X?

Answer 21

Rate of excretion of X / plasma concentration of X

Question 22

What are the UNITS OF PLASMA CLEARANCE?

Answer 22

ml/min

Question 23

What is inulin?

Answer 23

NOT the same as insulin; it is freely filtered at the glomerulus and is:
• Not absorbed nor secreted, i.e: inulin enters urine via filtration alone
• Not metabolised by kidney
• Not toxic

It is also easily measure in urine and blood

Question 24

Uses of inulin?

Answer 24

Measurement of inulin clearance can be used clinically to determine GFR, as inulin clearance = GFR

i.e: 125ml of inulin-free plasma is returned to the circulation per minute

Question 25

In terms of clearance, what can be used instead of inulin?

Answer 25

Creatinine clearance

Question 26

For which substances does clearance = 0?

Answer 26

Those that are filtered, completely reabsorbed and thus not secreted, e.g: glucose Also applies to a substance that is not filtered and not secreted

Question 27

For which substances is clearance < GFR?

Answer 27

Those that are filtered, partly reabsorbed and not secreted, e.g: urea i.e: only a portion of the plasma is cleared

Question 28

For which substances is clearance > GFR?

Answer 28

Those that are filtered, secreted but not reabsorbed, e.g: H+ i.e: all of the filtered plasma is cleared of a substance, as is the peritubular plasma from which the substance is secreted

Question 29

Depending on the comparison of proportion of clearance and GFR, does tubular reabsorption or secretion occur?

Answer 29

If clearance < GFR (inulin clearance) then substance is REABSORBED If clearance = GFR then the substance is neither reabsorbed nor secreted If clearance > GFR then the substance is secreted into the tubule

Question 30

What can be used to measure renal plasma flow?

Answer 30

Para-amino hippuric acid (PAH) is an exogenous organic anion used clinically to measure renal plasma flow (which is = 650 ml/min)

Question 31

Why is PAH used to measure renal plasma flow?

Answer 31

1. Freely filtered at glomerulus 2. Secreted into the tubule (not reabsorbed) 3. Completely cleared from the plasma i. e: all the PAH in the plasma that escapes filtration is secreted from the peritubular capillaries

Question 32

Example clearance values?

Answer 32

C(glucose) = 0 C(inulin) - 125 ml/min C(creatinine) - 125 ml/min (same as GFR and is easier to measure than insulin clearance) C(PAH) - 650 ml/min

Question 33

Properties of substances used as a clearance marker?

Answer 33

1. Non-toxic 2. Inert, i.e: not metabolised 3. Easy to measure A GFR marker should be filtered freely (NOT secreted or reabsorbed) An RPF marker should be filtered completely and completely secreted

Question 34

What is the filtration fraction?

Answer 34

Fraction of plasma flowing through the glomeruli that is filtered into the tubules Filtration fraction = GFR / renal plasma flow i.e: 20% of the plasma that enters the glomeruli is filtered; the remaining 80% moves on to the peritubular capillaries

Question 35

How is renal blood flow (RBF) calculated?

Answer 35

RPF x (1 / 1-HCT) 650 x 1.85 1200 ml/min (Hct = haematocrit)