15-02-23 - Glomerular filtration and its control Flashcards
Learning outcomes
- List the main functions of the renal system
- Describe (and be able to draw) the structure of the nephron
- Describe the structure of the glomerulus and its properties
- Explain how the glomerular filtrate is produced
- Describe how glomerular filtration rate is controlled
- Explain autoregulation of the GFR: both myogenic regulation and tubuloglomerular feedback
What are 3 key functions of the kidneys?
- 3 key functions of the kidneys:
1) They filter and excrete
* Remove metabolic waste products and toxins from the blood
* Excrete these into the urine
2) They regulate key homeostatic systems
* Body fluid status
* Body electrolyte balance
* Body acid-base balance
3) They produce hormones involved in:
* Erythrogenesis
* Ca2+ metabolism
* Regulation of blood pressure and blood flow
Describe the 9 divisions of the renal blood supply.
- 9 Divisions of the renal blood supply:
1) Renal artery to
2) Interlobar artery to
3) Arcuate artery to
4) Interlobular artery to
5) Afferent arteriole to
6) Glomerulus to
7) Efferent arteriole to
8) Peritubular capillaries to
9) Interlobular vein
What are nephrons?
How many nephrons are there in each kidney?
What 2 parts does each nephron consist of?
What is each part responsible for?
Can nephrons be regenerated?
When do nephrons reduce in number?
Why is renal failure often identified late?
Describe the structure of a nephron and identify which parts are located in the renal cortex and medulla (in picture).
- Nephrons are the functional unit of the kidney
- There are ~1 million nephrons in each human kidney
- 2 parts does each nephron consist of:
1) Glomerulus (filtration)
2) Tubule (reabsorption/secretion) - The kidney cannot regenerate nephrons
- Nephrons reduce in number with age
- Renal function remains until a drastic loss of nephrons, as remaining nephrons will compensate for the reduction in number, which is why renal failure can often be identified late
- Describe the structure of a nephron and identify which parts are located in the renal cortex and medulla (in picture).
What are the 2 different types of nephrons?
What 3 ways do they differ?
- 2 different types of nephrons:
1) Superficial (cortical) nephron
* Glomerulus is in the outer region of the cortex
* Loop of Henle is short, terminates in the Outer Medulla
* Efferent arteriole forms only the peritubular capillaries
2) Juxtamedullary nephron
* Glomerulus closer to the Medulla
* Loop of Henle is much longer, extending into the Inner Medulla
* Efferent arteriole forms peritubular capillaries and the vasa recta (supplies deep loop of Henle)
Describe the histology of the 2 types of nephrons (in picture)
Renal corpuscle cellular overview diagram (in picture)
What % of cardiac output is to the kidneys?
Describe the divisions of the renal artery. What happens to blood that enters the kidneys? What happens to the remaining blood? Describe the vessel divisions the remaining blood goes through
- 20% of cardiac output is to the kidneys via the renal arteries
- Renal artery > interlobar artery > arcuate artery > interlobular artery > afferent arteriole
- Blood flow to the kidneys is then filtered across the glomerular filter
- The rest of the blood then exits the glomerular capillaries via the efferent arteriole
- Efferent arteriole > peritubular capillaries > interlobular vein
What % of cardiac output is to the kidneys?
Describe the divisions of the renal artery.
What happens to blood that enters the kidneys?
What happens to the remaining blood?
Describe the vessel divisions the remaining blood goes through
- 20% of cardiac output is to the kidneys via the renal arteries
- Renal artery > interlobar artery > arcuate artery > interlobular artery > afferent arteriole
- Blood flow to the kidneys is then filtered across the glomerular filter
- The rest of the blood then exits the glomerular capillaries via the efferent arteriole
- Efferent arteriole > peritubular capillaries > interlobular vein
What are the 3 layers of glomerular filtration?
- 3 layers of glomerular filtration:
1) Endothelial cells of the glomerular capillaries
2) Basement membrane of the capillaries
3) Foot processes of the podocytes
- Think of 3 sieves with decreasing pore size
What is the Endothelial lining of the capillaries covered by?
What type of capillaries are these?
What is the pore size of the fenestrations in renal capillaries?
What does this barrier allow through and what does it block?
- The Endothelial lining of the capillaries is covered by a glycocalyx with negatively charged molecules (will repel positively charged molecule)
- Renal capillaries are fenestrated and contain many fenestrations (openings)
- The fenestrations have a pore size of ~ 70 nm
- These capillary fenestrations are not a barrier to H2O and small solutes (including proteins/large molecules)
- They mainly limit filtration of cellular elements e.g. erythrocytes
Where is the basement membrane of renal capillaries found?
What 3 structures is the basement membrane of renal capillaries formed from?
What is their pore size?
What do they restrict?
- The basement membrane of renal capillaries is found between endothelium and podocytes (modified epithelial cells)
- 3 structures the basement membrane of renal capillaries is formed from:
1) Collagen
2) Laminin
3) Heparin sulphate
* Heparin sulphate contains negatively-charged proteoglycans
- The pore size of the basement membrane of renal capillaries is 12-14nm
- They restrict intermediate to large sized solutes (molecular weight >1kDa)
What are podocytes?
What are foot processes of podocytes?
How do they connect?
What structures do they contain?
What is their pore size?
- Podocytes are modified epithelial cells
- Foot processes of podocytes are interdigitating processes that cover the basement membrane
- These almost “zip” together via slit diaphragms
- Foot processes of podocytes contain negatively charged glycoproteins
- Their pore size 4-10 nm
What are 7 substances that are freely filtered through the glomerulus?
Which 2 substances can’t filter through the glomerulus despite being smaller than the slit diaphragms in podocyte foot processes?
Why is this?
How does charge affect filtration rate?
- 7 substances that are freely filtered through the glomerulus:
1) Na+
2) K+
3) Cl-
4) H2O
5) Urea
6) Glucose
7) Sucrose - Haemoglobin and serum albumin can’t filter through the glomerulus despite being smaller than the slit diaphragms in podocyte foot processes
- Serum albumin is negatively charged, so it will be repelled by the negative charged glycoproteins in the glomerulus (cant find reasons for Hb which is positively charged, but membrane of red blood cell is negatively charged)
- For any molecular radius, positively charged molecules are filtered much more readily than negatively charged molecules
- So large negatively charged proteins e.g. serum albumin are not filtered despite being small enough
What is renal blood flow (RBF)?
What is a normal value for RBF?
What is renal plasma flow (RPF)?
What is a normal value for RPF?
- Renal blood flow (RBF) is total volume of blood that traverses the renal artery/vein per unit time
- RBF is ~1100 ml/min (20% of total cardiac output)
- Renal plasma flow (RPF) is the total volume of plasma that traverses the renal artery/vein per unit time
- RPF = 55% x 1100 = 600 ml/min (if haematocrit is 45% - the ratio of the volume of red blood cells to the total volume of blood)
What is glomerular filtration rate (GFR)?
What is a normal value for GFR?
What is ultrafiltrate?
What is the ultrafiltrate produced a day?
How is urine formed from ultrafiltrate?
What volume of urine is produced a day?
- Glomerular filtration rate (GFR) is the volume of fluid filtered from the Glomerular capillaries to the Bowman’s capsule per unit time
- GFR is ~20 % of renal plasma flow (RPF), which is about 20% of about 625, equalling 120ml/min
- Ultrafiltrate is the filtered fluid entering the Bowman’s capsule (gone through the 3 filters)
- About ~180 L/day (avg. GFR/day) of ultrafiltrate from GFR is produced, with most of it being reabsorbed in the tubules
- Ultrafiltrate that is not reabsorbed travels along the tubule and will leave via ureter as urine
- About 1-1.5 litres of urine is produced a day
Generation of ultrafiltrate.
What Starling forces are present in glomerular capillaries?
Why is the hydrostatic pressure in glomerular capillaries very high?
What Starling forces are present in Bowman’s capsule (proximal tubule)?
Why is there no oncotic pressure in the kidney tubule?
What is the final net filtration pressure?
- Generation of ultrafiltrate
- Starling forces of blood in glomerular capillaries:
1) Hydrostatic – 55mmHg
* This is very high because the afferent arteriole moves into the efferent arteriole and not a vein
2) Oncotic – 30mmHg
- Starling forces in Bowman’s capsule (proximal tubule):
1) Hydrostatic pressure – 15mmHg
- There is no oncotic pressure in the kidney tubule because no proteins (e.g albumin) have crossed the glomerular filter to generate it
- The final net filtration pressure is 10mmHg in favour of pushing fluid out of the glomerular capillaries into Bowman’s capsule
What are 2 unique features of the renal microvasculature?
What are 3 consequences of this unique renal microvasculature?
- 2 unique features of the renal microvasculature:
1) The vascular bed has 2 major sites of resistance control:
* Afferent arterioles
* Efferent arterioles
2) It has 2 capillary beds in series:
* Glomerular capillaries
* Peritubular capillaries
- 3 consequences of this unique renal microvasculature:
1) Significant pressure drops along both arterioles
2) Glomerular capillary pressure is relatively high
3) Peritubular capillary pressure is relatively low
How does can GFR be altered?
What 4 changes are seen when the afferent arteriole constricts?
- Constriction or relaxation of the afferent or efferent arteriole will change GFR
- 4 changes seen when the afferent arteriole constricts:
1) Hydrostatic pressure of blood in glomerular capillaries decreases
2) Oncotic pressure in blood remains stable
3) Net filtration pressure decreases
4) GFR decreases
What 3 changes are seen when the efferent arteriole constricts?
What 4 changes are then seen when the efferent arteriole constricts?
- 3 changes are seen when the efferent arteriole constricts:
1) Hydrostatic pressure of blood in glomerular capillaries increases
2) Net filtration pressure increases
3) GFR increases
- 4 changes then seen when the efferent arteriole constricts:
1) Hydrostatic pressure of blood in glomerular capillaries increases
2) Oncotic pressure in blood increases a lot
3) Net filtration pressure decreases
4) GFR will then decrease
What is the role of intrinsic feedback mechanisms in the kidney?
What are the 2 roles of autoregulation in most tissues?
What are the 2 roles of autoregulation in the kidneys?
- Feedback mechanisms intrinsic to the kidneys keep RBF and GFR relatively constant, despite marked changes in arterial BP
- 2 roles of autoregulation in most tissues:
1) Ensure delivery of O2 and nutrients
2) Ensures removal of waste products - 2 roles of autoregulation in the kidneys:
1) Also maintains RBF and GFR
2) Enables precise control of renal excretion of water and solutes
Describe the 5 steps in the renal myogenic mechanism for an increase in arterial BP.
- 5 steps in the myogenic mechanism for an increase in arterial BP:
1) Increase in arterial BP detected by stretch receptors in smooth muscle cells
2) Depolarisation results in contraction
3) Afferent arteriole constricts
4) Hydrostatic pressure in the glomerulus decreases
5) GFR decreases
Describe the 5 steps in the renal myogenic mechanism for a decrease in arterial BP.
- 5 steps in the myogenic mechanism for a decrease in arterial BP:
1) Decrease in arterial BP detected by stretch receptors in smooth muscle cells
2) Reduced depolarisation results in reduced contraction
3) Afferent arteriole dilates
4) Hydrostatic pressure int eh glomerulus increase
5) GFR increases
Where are the macula densa cells of the glomerulus located?
What are granular cells?
What do they contain?
Describe the 6 steps in the tubuloglomerular feedback for increased arterial BP.
What effects does this pathway have on the RAAS?
- Macula densa cells of the glomerulus are located in the tubular epithelium at the junction between the thick ascending limb of the Loop of Henle and the distal convoluted tubule
- Granular cells (juxtaglomerular cells) are specialised smooth muscle cells that
- Granular cells contain renin (part of the RAAS system)
- Macula densa cells are like the sensors while granular cells are the effectors
- 6 steps in the tubuloglomerular feedback for increased arterial BP:
1) Increased GFR/RBF due to increase arterial BP
2) Filtration fraction increases
3) More NaCl will move around tubule and if reabsorption processes remain stable, more will reach the macula densa before the distal convoluted tubule
4) More NaCl is reabsorbed by NKCC2 into the cell
5) Cell releases signalling molecules (e.g. adenosine) which act on neighbouring smooth muscle cells of afferent arteriole
6) Constriction of afferent arteriole therefore decreases GFR
- This pathway also inhibits the RAAS by inhibiting the release of renin from Granular cells (juxtaglomerular cells)
The tubuloglomerular feedback for increased arterial BP diagram
Describe the 6 steps in the tubuloglomerular feedback for decreased arterial BP.
How does this pathway affect the RAAS?
- 6 Steps in the tubuloglomerular feedback for decreased arterial BP:
1) Decreased GFR/RBF
2) Filtration fraction decreases
3) Less NaCl reaches macula densa
4) Less NaCl is reabsorbed by NKCC2 into the cell
5) Signalling molecules produced / released (e.g. prostaglandin E2, nitric oxide)
6) Vasodilation of afferent arteriole leading to increased GFR
- This pathway stimulates the RAAS through the release of renin
