S2: the glomerulus

Question 1

Describe the function of the glomerulus

Answer 1

Found in the cortex

Glomerular filtration = passive process that involves the flow of a solvent through a filter

Question 2

What is glomerular filtration rate?

Answer 2

Amount of filtrate that is produced from the blood flowing through the glomerulus per unit time
-normal GFR = 90-120mL/min/1.73m2
Glomerular filtrate normally:
-contains no blood cells or platelets
-contains virtually no proteins
-composed mostly of organic solutes with a low molecular weight & inorganic ions

Question 3

Describe the process of glomerular filtration

Answer 3

Driven by Starling’s forces
Glomerular capillary hydrostatic pressure pushes fluid out of the arteriole, forming filtrate
This is opposed by the hydrostatic pressure in Bowman’s capsule and the colloid oncotic pressure within the capillary
Fluid is reabsorbed into the peritubular capillaries as a result of high colloid oncotic pressure & low hydrostatic pressure -> this reabsorption causes a fall in oncotic pressure as plasma proteins become diluted

Question 4

What are the two mechanisms involved in regulating renal blood flow and GFR?

Answer 4

1) Myogenic mechanism

2) Tubuloglomerular feedback mechanism

Question 5

Explain the tubuloglomerular feedback mechanism in response to high tubular flow

Answer 5

1) Macula densa cells of the DCT epithelium detect osmolality/rate of movement of Na+ or Cl- movement into the cells – higher the flow of filtrate the higher the Na+ concentration in cells
2) Signal is sent via the juxtaglomerular cells, triggered by an increase in NaCl conc. of distal tubular fluid
3) ATP released, converted to adenosine, binds with A1 receptor on afferent arteriole
4) Further vasoconstriction of smooth muscles of the adjacent afferent arterioles & therefore decrease in RPF -> decrease in GFR (renin synthesis also inhibited)

Question 6

Explain the tubuloglomerular feedback mechanism in response to low BP

Answer 6

1) Release of prostaglandins – attenuate constriction of afferent arteriole
2) Renin is released by juxtaglomerular cells (3 stimuli responsible for release – sympathetic nerve stimulation, decreased stretch of afferent arteriole, signals generated by macula densa cells in response to decreased NaCl delivery)

Question 7

List factors which can modulate the sensitivity of the tubuloglomerular feedback mechanism

Answer 7

ANP and NO = decrease sensitivity

Angiotensin II = increase sensitivity

Question 8

Define clearance

Answer 8

Clearance is the volume of plasma that is cleared of a substance in a unit time
Measure of the kidney’s ability to remove a substance from the plasma and excrete it

Question 9

Describe how clearance and GFR are related

Answer 9

Clearance of a substance will provide an accurate estimate of the GFR if that substance ‘follows’ the filtrate without being altered by the kidney (i.e. is not reabsorbed, secreted, synthesised or metabolised by the kidney)

Question 10

Describe inulin

Answer 10

Introduced into the body into the body by injection or IV
All inulin filtered by the glomerulus is excreted in the urine – can be used to assess glomerular function in disease
-inulin clearance is equal to GFR
-cannot be used to assess GFR in routine clinical practice

Question 11

Describe eGFR and the use of creatinine

Answer 11

Creatinine is found in the body – produced during muscle metabolism
Like inulin, creatinine is filtered freely & is not affected/produced by the kidney except a small contribution to the clearance comes from tubular secretion (overestimates GFR by 10-20%)
Therefore, it is eGFR (estimated GFR – calculated by an equation)
Plasma creatinine is commonly used as a marker of renal function

Question 12

List factors that effect the relationship between GFR and creatinine

Answer 12

Age
Sex
Muscle mass
Certain drugs
(NB: plasma creatinine levels alone cannot be used as an accurate predictor of renal function – GFR may be estimated from the plasma creatinine using the MDRD equation)

Question 13

Explain the myogenic mechanism in response to high blood pressure

Answer 13

Vasoconstriction of the afferent arteriole
Prevents transmission of increased BP to glomerular capillary -> maintains normal glomerular capillary pressure
Maintains GFR and RBF

Question 14

Explain the myogenic mechanism in response to low BP

Answer 14

Vasoconstriction of efferent arteriole if BP is low
Increases GFR
Maintains GFR and RBF

Question 15

What is the formula for clearance?

Answer 15

Clearance of x = (urine concentration of x * urine flow rate)/plasma concentration of x

Question 16

What is the formula for filtration rate?

Answer 16

Filtration rate = plasma concentration of x * GFR

Question 17

What is the formula for excretion rate?

Answer 17

Excretion rate = urine concentration of x * urine flow rate

Question 18

Why can inulin be used to give an accurate measurement of GFR?

Answer 18

Inulin is freely filtered, not secreted or reabsorbed

Can therefore provide an accurate measurement of GFR

Question 19

Is creatinine clearance an accurate way of measuring GFR?

Answer 19

Not an ideal marker for GFR
Although it is freely filtered and not reabsorbed, creatinine is also secreted into the nephron
Approximately 10% of all creatinine excreted in the urine reflects this secretory component

Question 20

Why is creatinine clearance used clinically as a measure of GFR?

Answer 20

Creatinine is used clinically to measure GFR because it is produced endogenously by skeletal muscle and does not require infusion
Best and most practical marker we have
Easy to calculate creatinine clearance, because the patient can collect their urine at home and a single blood sample is required