Glomerular Filtration Lecture Slides PDF

Glomerular Filtration Dr Mark Richards [email protected] Acknowledgements to Dr Nick Hopcroft & Dr Jamie Roebuck Learning Outcomes By the end of this session, you should be able to: 1. Explain how glomerular filtrate is produced and its role in uri...

Glomerular Filtration Dr Mark Richards [email protected] Acknowledgements to Dr Nick Hopcroft & Dr Jamie Roebuck Learning Outcomes By the end of this session, you should be able to: 1. Explain how glomerular filtrate is produced and its role in urine formation 2. Describe the structures that form the glomerular filtration barrier and explain how these influence which molecules cross into the filtrate 3. Describe the factors that determine glomerular filtration rate 4. Describe autoregulation of glomerular filtration rate 5. Explain how GFR is used as a clinical assessment of renal function (part 2)  Urine Formation 1 The nephron is the functional unit of the kidney Three main processes performed by the nephron:- 1. Filtration 2. Reabsorption 3. Secretion Urinary excretion of any substance reflects the sum of these processes Urinary excretion rate = Filtration rate + Secretion rate – Reabsorption rate LO: 1 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323597128000266#hl00003 Image: Guyton & Hall Textbook of Medical Physiology (13e) - Hall  Urine Formation 2 Different substances handled in different ways by the kidney Processes can be altered according to needs of body to either lose or retain a substance Filtration is first step in process of urine formation High rate of filtration needed to help clear waste products efficiently LO: 1 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323597128000266#hl00003 Image: Guyton & Hall Textbook of Medical Physiology (13e) - Hall Filtration Filtration requires good blood flow to kidney Kidneys receive ~20% cardiac output ∴ Renal blood flow ~1 litre / min (haematocrit ~0.4) ∴ Renal plasma flow ~600ml / min ~20% of renal plasma flow passes through filtration barrier to form filtrate i.e. ~120 mL/min – filtration fraction LO: 1 Clinicalkey: ∴ ~180 litres / day of filtrate https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702073373000146#hl00017 67 Image: Netter’s Essential Histology (2e) - Ovalle  Filtration Barrier Glomerular filtration barrier formed from: 1. Glomerular capillary endothelium (fenestrated) 2. Basement membrane (negative charge) 3. Epithelial cells (podocytes) (interdigitating foot processes and filtration slits) Limits passage of substances based on their size, charge and shape Blood cells and most plasma proteins (including substances bound to them) are excluded from Disease processes may alter the properties of the filtrate barrier allowing protein to appear in the filtrate Filtrate has similar composition to LO: plasma 2 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00034 Image: Guyton & Hall Textbook of Medical Physiology (13e) - Hall  Factors Determining Filtration Glomerular filtration rate (GFR) is:- The volume of filtrate formed by all the nephrons in both kidneys per unit time Determined by: 1. Glomerular capillary filtration coefficient, Kf 2. Net filtration pressure (NFP) GFR = Kf x NFP LO: 3 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00035 Image: Guyton & Hall Textbook of Medical Physiology (13e) - Hall Filtration Coefficient, Kf Glomerular capillary filtration coefficient, Kf reflects the: 1. Surface area available for filtration 2. Hydraulic conductivity (‘permeability’) of the filtration barrier Changes in Kf aren’t the major part of the physiological regulation of GFR but may be affected in disease processes e.g. reduced number of nephrons or processes which damage the filtration barrier will ↓surface area or ↓permeability, ∴ decrease GFR LO: 3 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00035  Net Filtration Pressure (NFP) Net filtration pressure is given by the sum of the PG pressures acting across πG the filtration barrier (Starling forces) 1. hydrostatic pressures Bowman’s capsule colloid osmotic 2. colloid osmotic pressure (0 mm Hg) NFP = PG pressures (oncotic) – PB – π G + πB PB πB NFP = 60 – 18 – 32 + 0 Disease processes can alter these components LO: ∴ 3 typical NFP = 10 mmHg Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00035 33 Image: Guyton & Hall Textbook of Medical Physiology (12e) - Hall  Regulation of GFR 1 GFR = Kf x NFP Where NFP = PG – PB – πG + πB Most physiological regulation of GFR occurs due to changes in glomerular hydrostatic pressure (PG) PG depends on: 1. Arterial pressure 2. Afferent arteriole resistance 3. Efferent arteriole resistance Can vary PG independently of arterial pressures by varying the resistance of the afferent and efferent arterioles LO: 3 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00037 Image: Medical Physiology (2e) - Boron Leaky hose analogy Can vary PG independently of arterial pressures by varying the resistance of the afferent and efferent arterioles LO: 3 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00037 Regulation of GFR 2 Balance of afferent (AA) and efferent arteriole (EA) resistances help determine GFR General rule: AA dilation and/or EA constriction increases GFR AA constriction and/or EA dilation reduces GFR LO: 3 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00037 Regulators of GFR The presence or absence of vasoactive substances can all have an effect on PG and thus GFR. Examples include: Angiotensin II preferentially constricts EA – thus increasing PG Prostaglandins and atrial natriuretic peptide (ANP) vasodilate AA – thus increasing PG Noradrenaline (sympathetic nervous system), adenosine and endothelin tend to vasoconstrict AA – thus reducing PG LO: 3 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00028  Autoregulation of GFR Renal blood flow and GFR stay relatively constant across a range of systemic blood pressures (~80–180 mm Hg) Prevents large changes in renal excretion of water and solutes TWO mechanisms of autoregulation: 1. Myogenic response 2. Tubuloglomerular feedback LO: 4 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00029 45 Image: Guyton & Hall Textbook of Medical Physiology (12e) - Hall Myogenic Autoregulation Myogenic response Inherent ability of Increase in arterial blood pressure smooth muscle in ↓ afferent arterioles to Increased renal blood flow and increased GFR respond to changes in ↓ vessel circumference ↑stretch of afferent arteriole (AA) smooth muscle cells by contracting or ↓ relaxing Opens Ca2+ channels ↓ Reflex contraction of AA smooth muscle ↓ Vasoconstriction of AA ↓ ↑Resistance to flow ↓ Prevents changes in renal blood flow and GFR LO: 4 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00029 45  Tubuloglomerular Feedback (TGF) Tubuloglomerular feedback mechanism links changes in [NaCl] in tubule lumen to control of own afferent arteriole resistance (glomerulus) in same nephron Utilises juxtaglomerular apparatus (JGA) LO: 4 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00029 45 Image: Guyton & Hall Textbook of Medical Physiology (13e) - Hall Juxtaglomerular Apparatus Distal tubule Macula Macula densa cells in early Lacis cells densa part of distal tubule sense [NaCl] Afferen t Effere When arterial blood arteriol nt pressure is increased, Granulare arteri cells ole causes a transient ↑GFR which increases flow and [NaCl] delivered to distal tubule When arterial blood pressure is reduced, causes a transient ↓GFR which decreases flow and [NaCl] delivered to distal tubule Glomerula r LO: 4 capillaries Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00029 Image: Medical Sciences (2e) – Naish TGF Mechanism - ↑BP Increase in arterial blood pressure (BP) ↓ Increased renal blood flow and increased GFR ↓ Increased [NaCl] delivered to macula densa cells ↓ Release of paracrine factors (e.g. adenosine) ↓ Constriction of AA smooth muscle ↓ Vasoconstriction of AA ↓ ↑Resistance to flow ↓ Restores renal blood flow and GFR LO: 4 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00029 Image: Medical Sciences (2e) – Naish  TGF Mechanism - ↓BP Mechanism shown for tubuloglomerular feedback following a fall in arterial pressure Note release of renin which will have systemic as well as the local effects illustrated here (covered in future session) LO: 4 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00029 45 Image: Guyton & Hall Textbook of Medical Physiology (13e) - Hall Test your knowledge 1. Write the equation used to calculate Net Filtration Pressure (NFP). What is a typical value for NFP? 2. Which pressure in the glomerulus most strongly opposes filtration? 3. Constriction of which glomerular arteriole leads to decreased renal plasma flow and increased glomerular filtration rate? 4. In regulation of GFR, where is an increased filtration rate detected for tubuloglomerular feedback? 5. An increase in filtration rate leads to constriction of which glomerular arteriole? Image: Guyton & Hall Textbook of Medical Physiology (13e) - Hall The Kidney Headlines! Kf represents the properties of the filtration barrier: GFR is determined by Kf Fenestrated vascular x NFP endothelium Negatively charged basement NFP is the sum of membrane hydrostatic and colloid Specialised epithelium - osmotic pressures Podocytes Glomerular filtration acting across the rate is maintained at a filtration barrier relatively constant level despite changes NFP = PG – PB – πG + in mean arterial πB pressure GFR is regulated via GFR is maintained by afferent and efferent autoregulation via the arteriole resistance myogenic response and tubuloglomerular feedback This Photo by Unknown Author is licensed under CC BY-SA  Take a break! Feedback by Ojos de Brujo https://www.youtube.com/watch?v=l2pqH Z0s4VU Answers 1 1. Write the equation used to calculate Net Filtration Pressure (NFP). What is a typical value for NFP? The equation to calculate NFP is the sum of the pressures at the glomerulus: NFP = PG – PB – πG + πB The typical value for NFP is 10mmHg 2. Which pressure in the glomerulus most strongly opposes filtration? Starling forces determine filtration at the glomerulus and the colloid osmotic pressure due to the proteins in the plasma most strongly oppose filtration 3. Constriction of which glomerular arteriole leads to decreased renal plasma flow and increased glomerular filtration rate? Constriction of the efferent arteriole will reduce the renal blood flow by increasing resistance to blood flow into the peritubular capillaries. Increased resistance through the efferent arteriole will also increase the hydrostatic pressure of the plasma in the Image: Guyton & Hall Textbook of Medical Physiology (13e) - Hall Answers 2 4. In regulation of GFR, where is an increased filtration rate detected for tubuloglomerular feedback? Macula Densa. This is an area of cells in the distal convoluted tubule that detects sodium and chloride concentration and communicates this to cells in the juxtaglomerular apparatus 5. An increase in filtration rate leads to constriction of which glomerular arteriole? The increased filtration rate will lead to more filtered NaCl and this will be detected by the macula densa. The macula densa secretes vasoactive substances that signal to the afferent arteriole to constrict and reduce renal blood flow into the glomerular capillaries, reducing glomerular hydrostatic pressure and GFR, to restore filtration to normal levels Image: Guyton & Hall Textbook of Medical Physiology (13e) - Hall