Session 2 ILOs - Glomerulus and Clearance and kidney function

Question 1

Briefly describe the process of glomerular filtration

Answer 1

Filtration at the glomerulus primarily occurs due to the high hydrostatic pressure in the capillary (opposed by the lesser forces of hydrostatic pressure in BC and oncotic pressure)

• High hydrostatic pressure pushes fluid plasma (and everything dissolved within it) through the capillaries and into the BC

Question 2

Briefly describe what happens upon hypoperfusion and hyperperfusion (think arteriole pressure!) in the kidneys

Answer 2

Hypoperfusion:

• Decreased afferent arteriole pressure
• Reduced GFR
• Dilation of afferent arteriole
• Constriction of efferent arteriole

Hyperperfusion:

• Increased afferent arteriole pressure
• Increased GFR
• Constriction of afferent arteriole
• Dilation of efferent arteriole

Question 3

Describe myogenic regulation and glomerular tubular feedback (forms of autoregulation)

Answer 3

Myogenic regulation:
- Automatic response of glomerulus to maintain pressure/perfusion via smooth muscle contraction
INCREASED BLOOD FLOW
- Detected by afferent arteriole
- Stretch of the afferent arteriole leads to opening of stretch-activated Na+ channels in the smooth muscle membranes leading to release of Na+ leading to cell depolarisation
- This opens voltage-gated Ca2+ channels and then that Ca2+ initates smooth muscle contraction, leading to afferent arteriole constriction
- Reduce flow and maintain GFR

Glomerular tubular feedback:
INCREASED BLOOD FLOW
- Detected by macula densa cells
- Macula densa cells contain NaKATPase on the basement membrane and NaKCL transporter on the apical membrane
- If there is high blood flow then the NaKATPase can’t keep up therefore a high conc. of Na and Cl occurs in the cells
- This increases the osmolarity and water moves into the macula densa cells causing them to swell
- Swelling of the macula densa cells leads to ATP release
- ATP is converted to Adenosine which binds to A1 receptors on the afferent arteriole
- Afferent arteriole constricts to reduce flow and maintain GFR

Question 4

L2

Answer 4

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Question 5

Describe clearance and how you would calculate clearance (triangle equation)

Answer 5

Clearance = volume of plasma that is cleared of a substance, per unit of time

Clearance is a measurement of the kidney’s ability to remove a substance from the plasma and excrete it

Clearance of a substance = (urine conc. of substance X urine flow rate) / plasma conc. of substance

Question 6

Describe how GFR and clearance are related

Answer 6

Clearance of a substance (x) that is NOT reabsorbed and NOT secreted by the tubules is equal to the GFR

Otherwise, clearance and GFR are different processes/concepts!

Question 7

Understand the idea of eGFR and clinical implications to make explicit differences to GFR

Answer 7

GFR would be best measured by injecting inulin (non-naturally occurring substance
- Inulin is not reabsorbed or secreted therefore it is a direct measure of GFR (by definition)

However, in reality it is very difficult to use inulin as patients would need to be continuously infused with inulin and regular urine collection/anaylsis which is expensive and impractical

Instead in practice, we have 2 methods:

1. Inject Radioactive labelled marker Chromium EDTA
   - Exogenous
   - Approx 10% lower clearance than inulin (reabsorption?)
   - Generally used in children or for knowing the specific renal function
2. Use creatinine
   - Endogenous (end product of muscle breakdown)
   - Can measure serum creatinine or urine samples over 24 hrs
   - However overestimates GFR by 10-20% due to creatinine secretion

Question 8

Outline how much the kidney filters (what fluid this is) and roughly how much is recovered, including the amount urine that is produced

Answer 8

Kidney filters 180L/day of ECF

Of that, nearly all of it is recovered

Only 1.5L/day urine produced

Question 9

Outline how much of the following substance are recovered: water, sodium and chloride ions, bicarbonate, glucose, amino acids

Outline one substance that is actively secreted:

Answer 9

Water - 99% recovered
Sodium and chloride ions - 99% recovered
Bicarbonate - 100% recovered
Glucose - 100% recovered
Amino acids - 100% recovered

Actively secreted: H+ ions

Question 10

Describe glomerular filtration rate (GFR) and how you work out filtration fraction (FF) with approximate values

Answer 10

Glomerular filtration rate = reflects the flow of plasma from the glomerulus into Bowman’s space over a specified period, fluid produced is termed the ‘ultrafiltrate’

Chief measure of kidney function

Approx. 125mL/min

Filtration Fraction/percentage = glomerular filtration rate / renal plasma flow (aka. how much is filtered from the blood flow) approx. 20%

Question 11

Describe the composition of the ultrafiltrate produced at the glomerulus

Answer 11

Contains:

• Organic solutes with low mr
• Inorganic ions
• Glucose, urea, creatinine

Does not contain:

• RBC
• Platelets
• Protein e.g. haemoglobin or albumin

Question 12

Describe the composition of the ultrafiltrate produced at the glomerulus

Answer 12

Contains:

• Organic solutes with low mr
• Inorganic ions

Does not contain:

• RBC
• Platelets
• Protein
• Glucose