2023 Lecture 29 Kidney Function & Glomerular Filtration PDF

Lecture 29 Kidney function and glomerular filtration BChD I HUB 105 2023 Dept. Medical Biosciences University of the Western Cape Introduction Urinary system maintains homeostasis by controlling the composition, volume and pressure of blood. This is achieve...

Lecture 29 Kidney function and glomerular filtration BChD I HUB 105 2023 Dept. Medical Biosciences University of the Western Cape Introduction Urinary system maintains homeostasis by controlling the composition, volume and pressure of blood. This is achieved by removing and restoring selected amounts of water and solutes. Major work is carried out by the nephrons, while the other parts form passageways and storage areas. Nephrons main role: 1. Control bld vol and [ ] 2. Regulate bld pH 3. Remove waste from bld Within the nephron the renal corpuscle is the site of fluid filtration. Blood enters the glomerulus and gets pushed through due to pressure gradients and the resulting fluid in the glomerular tubules is called filtrate. Kidney Functions 1. Excretion – filters blood & forms urine to remove: a) organic waste products generated by cells b) foreign substances e.g. drugs, pesticides and ingested chemicals 2. Regulation of: – blood volume & pressure by producing large volumes of diluted urine or small volumes of concentrated urine – concentration of solutes in the blood, e.g. Na+, Cl-, K+, Ca2+, HCO3- and HPO4-2 – pH of the extracellular fluid by secreting H+ or HCO3- into nephron 3. Hormonal function – synthesis of blood cells by secreting erythropoietin – synthesis of vitamin D (calcitriol), which plays NB role in controlling blood levels of Ca2+ – synthesis of the enzyme renin https://casweb.ou.edu/pbell/histology/outline/urine.html Internal Structure of the Kidney: Nephron principle organs = kidneys; accessory organs = ureters, urinary bladder, urethra (“conducting system”) Nephron = basic structural & functional unit of the kidney each kidney contains > 1 million nephrons, with a combined length of ±145 km!! nephron is composed of: 1. Renal corpuscle consists of a) enlarged end of nephron = Bowman’s capsule b) network of capillaries = Glomerulus 2. Renal tubule composed of proximal tubule, loop of Henle, distal tubule Internal Structure of the Kidney: Bowman’s capsule wall of Bowman’s capsule is indented to form a double layered chamber 1. outer layer = parietal layer 2. inner layer = visceral layer the parietal layer is composed of normal epithelial cells and plays no role in the production of the filtrate the visceral layer consists of specialized cells = podocytes podocytes have foot/cell processes that wrap around the glomerular capillaries the gaps between the cell processes = filtration slits the filtration slits allow the filtrate to enter the capsular space (inside of Bowman’s capsule) Internal Structure of the Kidney: Glomerulus the glomerular capillaries project into Bowman’s capsule endothelial cells of these capillaries are fenestrated = contain small openings through which filtration can take place blood enters glomerulus through the afferent arteriole & blood leaves through the efferent arteriole the structure of afferent & efferent arterioles cause pressure inside glomerulus to be higher than in normal capillaries – the efferent arteriole has a smaller diameter than the afferent arteriole – this creates a “bottleneck” effect inside the glomerulus and increases the pressure high pressure is NB for filtration to take place Glomerular Filtration Membrane Glomerular capsular space Efferent arteriole Proximal convoluted tubule Afferent arteriole Cytoplasmic extensions Glomerular capillary Parietal layer of podocytes covered by podocyte- of glomerular Filtration slits containing visceral capsule layer of glomerular Podocyte capsule cell body (a) Glomerular capillaries and the visceral layer of the glomerular capsule Fenestrations (pores) Glomerular capillary endothelium (podocyte covering and basement Foot processes membrane removed) of podocyte Figure 25.9a Glomerular Filtration Glomerular Filtration Membrane filtration involves passage across a filtration membrane. Structural components of Filtration membrane 1. Capillary endothelium: contains fenestrae 2. Basement membrane: lies sandwich From: Indu Khurana and Arushi (2009). Textbook of Anatomy and Physiology for Nurses and Applied Health between endothelium & podocytes Sciences, 1st Ed. 3. Podocytes of bowman’s capsule: form filtration slits Membrane prevents large solutes from passing thru into the filtrate. Eg plasma proteins, RBC. Filtrate composed of ions, water and small organic mol. Glomerular Filtration Principle of filtration, the force of moving fluids and dissolved substances through a membrane by pressure. occurs across the filtration membrane. How? Blood Pressure forces water and dissolved bld components thru the specifically structured membrane of the glomerular capsule forming filtrate. About 180L of filtrate enter the glomerular capsule each day. ~ 178 -179L return to the bloodstream by reabsorption in the renal tubules so only 1-2L are excreted as urine. Glomerular Filtration Membrane Lamina Podocyte Glomerulus cell Efferent Dense arteriole layer Capillary lumen (blood side) Afferent arteriole Filtration Podocyte slit Filtration of fluids thru glomerulus filtration membrane Pedicels Pore Capsular During filtration, blood pressure space (filtrate) forces water and solutes across this Filtration membrane and into the capsular spaces membrane The glomerular filtration membrane Glomerular Filtration Glomerular filtration occurs as fluids move across the glomerular capillaries in response to Glomerular hydrostatic pressure. The balance betw hydrostatic pressure (Fluid pressure) and colloid osmotic pressure (pressure due to materials in solutn) govern how fluid and solutes move across the membrane. Forces acting on filtration either promote filtration or oppose filtration Promote filtration: - Glomerular hydrostatic pressure (GHP): blood pressure arriving at glomerular capillaries via the afferent arteriole. (~50mmHg) Oppose filtration: - Capsular hydrostatic pressure (CsHP): pressure in capsule that pushes water and solutes back into plasma due to resistance of the capsule wall and filtrate inside. (~15mmHg) - Blood colloid osmotic pressure (BCOP): it draws water out of the filtrate and into the plasma due to the high [ ] of proteins in plasma. (~25mmHg) Glomerular Filtration Filtration Pressures allows the flow of filtrate thru glomerulus Afferent arteriole Glomerular capsule BCOP = 25 mm Hg GHP = 50 mm Hg CsHP= 15 mm Hg Glomerular (blood) hydrostatic pressure 10 (GHP = 50 mm Hg) mm Hg Blood colloid osmotic pressure (BCOP = 25 mm Hg) Filtration Capsular hydrostatic pressure (CsHP= 15 mm Hg) pressure Glomerular Filtration Filtration pressure (FP) is the average pressure inside the glomerulus that force water and dissolved material out the glomerular capillaries into the capsular space towards the tubule. FP = Promote Filtration – Oppose Filtration = GHP – (CsHP + BCOP) = 50 – (15 + 25) FP = 10mmHg Each kidney has 6m of filtration surfaces and filters about 125ml/min of fluid = Glomerular filtration rate (GFR) Regulation of Glomerular Filtration Filtration depends on adequate bld flow to glomerulus and on maintenance of normal filtration pressures. If filtration is not maintained, waste products wont be excreted, pH changes dramatically, this could be toxic to the body and cause damage to the glomerulus and kidneys. 3 mechanisms control GFR: 1) Autoregulation 2) Neural regulation 3) Hormonal regulation All mechanisms adjust the renal bld pressure and resulting blood flow. Regulation of Glomerular Filtration 1) Autoregulation Intrinsic regulation, kidneys automatically compensate for minor changes in BP for short periods of time. Regulated via negative-feedback mechanisms. ↑ BP → causes constriction of the afferent arterioles and dialate efferent arteriole. – Helps maintain normal GFR, by ↓ blood flow to glomerulus. – Protects glomeruli from damaging at high BP ↓ BP → causes dilation of afferent arterioles , the dilation of glomerular capillary and constricts efferent arteriole. – Helps maintain normal GFR, by ↑ BP and ↑ bld flow in glomerulus. Regulation of Glomerular Filtration Figure The Response to a Reduction in the GFR Autoregulation Immediate local response in the kidney HOMEOSTASIS Increased if sufficient RESTORED glomerular blood pressure Normal GFR Dilation of HOMEOSTASIS afferent arterioles DISTURBED Decreased GFR HOMEOSTASIS Contraction of mesangial cells resulting in Start Normal decreased filtrate glomerular Constriction of and urine filtration rate efferent arterioles production Regulation of Glomerular Filtration 2) Neural regulation At rest renal blood vessels are dilated and autoregulation mechanisms control minor changes. Under extreme stress (↓↓ BP /heart attack), Norepinephrine (NE) is released by the sympathetic nervous system and Epinephrine (E) is released by the adrenal medulla Both cause powerful constriction of afferent arterioles, inhibiting filtration Results: ↓GFR and slow filtrate production 3) Hormonal Mechanisms Involved in regulating the urine volume and concentration. GFR is regulated by these hormones: Renin-angiotensin Aldosterone Antidiuretic Atrial natriuretic peptide Revision Questions: 1. Define following: glomerular filtration, GHP, CsHP, BCOP, FP, intrinsic 2. Using a diagram to explain the process of forming filtrate. 3. List the kidney functions 4. Give the purpose of the filtration membrane and explain it’s structure. 5. What causes the filtration pressure in the glomerulus? 6. Name the 3 regulatory control of filtration and what significance do they have. 7. Explain the renin-angiotensin regulatory mechanism. 8. When would the neural regulation take effect.