Urinary 5&6 - GFR, Filtration, & Measurement of Kidney Function

Question 1

4 functions of the kidney

Answer 1

1. ) Regulation - controls concentration of key substances and volume of water in the ECF
2. ) Excretion - of waste products as urine
3. ) Endocrine - synthesis of renin, EPO, prostaglandins
4. ) Metabolism - active form of vit D, catabolism of insulin, PTH and calcitonin

Question 2

3 general features of the kidneys as a filter

Scale
Reabsorption
Secretion

Answer 2

1. ) Large Scale Filtration - 180L filtered per day, every L is filtered over ten times a day
   - produces only roughly 1.5L of urine a day (almost everything is recovered)
2. ) Reabsorption - majority of substances reabsorbed
   - 99% of water, 99% of NaCl, 100% of bicarbonate, 100% of glucose and AAs

3.) Active Secretion - some substances e.g. hydrogen ions are actively secreted so you lose more than was originally filtered

Question 3

4 features of the glomerulus as a filter

Location
Ultrafiltrate
Filtration Barrier
Net Filtration Pressure

Answer 3

1.) Location - renal cortex

2. ) Ultrafiltrate - end product of filtration
   - identical to blood plasma but just without the large proteins and cells (RBCs, WBCs, albumin etc.)
3. ) Filtration Barrier - consists of 3 layers
   - largest substance that can pass through is inulin (1.48nm radius)
4. ) Net Filtration Pressure - sum of the HP in the glomerular capillaries (Pgc), bowman’s capsule (Pbc), and oncotic pressure in the capillaries (Pigc)
   - Pgc favours filtration whilst Pbc and Pigc opposes filtration
   - NFP = Pgc - (Pbc + Pigc)

Question 4

What is glomerular filtration rate (GFR), renal plasma flow (RPF) and filtration fraction (FF)?

Answer 4

1. ) GFR - rate of filtration of blood by the glomerulus
   - approx 140-180L/day or 90-125ml/min (female-male)
   - determines kidney function
2. ) Renal Plasma Flow (RPF) - volume of blood that passes the kidneys
   - it is approx 800 ml/min
3. ) Filtration Fraction - proportion of blood reaching the kidneys that is filtered (passes into the renal tubules)
   - FF = GFR/RPF which is approx 20%
   - this means 80% of blood arriving exits the efferent arteriole
   - FF is the same in the cortical and juxtamedullary nephrons

Question 5

6 differences between the cortical nephron and the juxtamedullary nephron (JM)

Distribution
Size
Arteriole Diameter
Efferent Arteriole
Nerve Innervation
Renin Concentration

Answer 5

1. ) Distribution - cortical nephron is in the outer cortex whilst JM is inner cortex, next to the medulla
   - cortical makes up 90% of all the nephrons
2. ) Size - cortical has a smaller glomerulus and shorter loop of Henle
3. ) Arteriole Diameter - cortical has a wider afferent (x2) than efferent whilst JM has the same sized arterioles
4. ) Efferent Arteriole - cortical EA goes to form the peritubular capillary whilst JM EA forms vasa recta
5. ) Nerve Innervation - cortical has rich sympathetic innervation whilst JM’s quite poor
6. ) Renin Concentration - cortical has high conc. whilst JM has almost none

Question 6

3 features of autoregulation of the hydrostatic pressure in the capillaries (Pgc)

Physiological Limits
Afferent Arteriole
Myogenic Regulation

Answer 6

1.) Physiological Limits - maintains GFR when BP is within physiological limits (80-180 mmHg)

2. ) Afferent Arteriole - reacts to the BP to maintain HP and GFR
   - increase in BP –> constriction, decrease –> dilation
3. ) Myogenic Regulation - arterial smooth muscle responds to changes in vascular wall tension
   - occurs in the preglomerular resistance vessels (AA, interlobular, arcuate)

Question 7

5 stages in the further regulation of Pgc by tubuloglomerular feedback (TG-feedback) with an increase in GFR

Macula Densa
NKCC2
Adenosine
Arterioles

Answer 7

1.) Increase in GFR - more NaCl enters the tubules to be filtered

2. ) Macula Densa Cells - specialised epithelial cells in the DCT and thick ascending limb
   - detects the increase in NaCl and takes up more NaCl
3. ) NKCC2 Cotransporter - moves Na+, K+, 2Cl-, ions into the macula densa cells
   - increased intracellular conc of Na+ and Cl- ions triggers release of ATP
   - increased Na+, Cl- also inhibits renin release in JG
4. ) Adenosine - ATP –> AMP –> adenosine
   - binds to A1 on extraglomerular mesangial cells in the AA to activate G proteins
   - Gi causes inhibition of adenylate cyclase and Go leads to increase in intracellular Ca2+
   - adenosine can also bind to A2 receptors in the EA causing vasodilation
5. ) Vasoconstriction of AA - due to intracellular Ca2+
   - Ca2+ spread from the mesangial cells to the SMCs in the AA via gap junctions

Question 8

2 responses of the TG feedback if GFR decreases

2 substances
2 inhibitory drugs

Answer 8

1. ) Prostaglandins - released by the macula densa cells
   - causes vasodilation of AA –> increase in GFR
   - NSAIDs inhibits vasodilators so should not be given to patients with low kidney function (GFR)
2. ) Angiotensin II - causes vasoconstriction of the EA to increase GFR
   - ACE inhibitors blocks angII so should not be given to patients with poor GFR to prevent acute kidney failure

Question 9

5 individual factors affecting GFR

Age
Gender
Pregnancy
Size

Answer 9

1. ) Age - increases until you reach 30 years old
   - at birth, GFR is roughly 20 ml/min. Normal GFR is reached after 18 months
   - GFR starts declining after 30 years of age due to loss of functioning nephrons.
   - the kidneys enlarge to try and compensate with the cortex getting smaller and medulla getting larger

2.) Gender - GFR is naturally higher in males

3. ) Pregnancy - GFR increases by approx 50% and the kidneys enlarge (increased fluid)
   - it returns back to normal 6 months postpartum

4.) Size of Individual and Kidney

Question 10

What is clearance?

Definition
Formula
Renal Clearance

Answer 10

1. ) Definition - rate of volume of plasma cleared of a substance from the body (not just kidneys)
2. ) Formula - Clearance = amount of substance eliminated per unit time/ plasma concentration of substance
3. ) Renal Clearance (ml/min)
   - excretion rate (mg/min)/plasma conc (mg/ml)
   - excretion rate = amount in urine (mg/ml) x urine flow rate (ml/min)

Question 11

4 criterias needed to accurately measure kidney clearance of a substance

Answer 11

1. ) Produced at constant rate
2. ) Freely filtered across the glomerulus
3. ) Not be reabsorbed in the nephron
4. ) Not be secreted by the nephron

Question 12

3 exogenous markers for of measuring kidney clearance (GFR)

Inulin
51 Cr-EDTA
1 Other

Answer 12

1. ) Inulin - plant polysaccharide that is ingested into the body but is not produced by the body itself
   - it does match the rest of the criteria so accurately tells you the GFR
   - however, it is not used because it requires continuous monitoring and regular urine collections
2. ) 51 Cr-EDTA - radio-active labelled marker cleared exclusively by renal filtration
   - it approx has 10% lower clearance than inulin suggesting it is reabsorbed in the nephron
   - used clinically in children and where you need to know the exact GFR e.g. kidney transplant

3.) Iohexol

Question 13

5 features of using creatinine to estimate GFR

Estimate
Measurements
Normal Serum Creatinine
Usage
Factors Affecting Creatinine levels x7

Answer 13

1. ) Overestimate of GFR - creatinine is secreted by the nephron
   - it overestimates GFR by 10-20%
2. ) Creatinine Clearance - measured by using urine creatinine over 24 hours and serum creatinine
3. ) Normal Serum Creatinine - 70-150 micromoles/litre
4. ) Used in Pregnancy - because it is not radioactive
5. ) Factor Affecting Creatinine Levels
   - young, male, afro-caribbean, large muscle bulk
   - meat intake, creatinine supplements
   - drugs e.g. trimethoprim
   - in early childhood, serum creatinine is very high then decreases because the kidneys are not working during pregnancy so the mother’s creatinine levels are measured