BIO5004A Introduction to the Kidney 2024 PDF

Human physiology BIO- 5004A/ 5104A Overview of Renal physiology Dr Tracey Swingler  Human physiology BIO- 5004A/ 5104A Lectures Lecture 1: Basic functions of the kidney An overview of nephron function Glomerular filtration Lecture 2: Urine production Lectur...

Human physiology BIO- 5004A/ 5104A Overview of Renal physiology Dr Tracey Swingler  Human physiology BIO- 5004A/ 5104A Lectures Lecture 1: Basic functions of the kidney An overview of nephron function Glomerular filtration Lecture 2: Urine production Lecture 3: Regulation of ion and water balanc Dr Tracey Swingler  Human physiology BIO- 5004A Learning outcomes Describe the structure and functions of the renal system Describe the process of filtration across the glomerulus Understand Glomerular filtration rate Describe the mechanisms that regulate GFR intrinsic and extrinsic Dr Tracey Swingler The kidney The kidney functions primarily role is a filter for blood. The body contains two "blood-filter" organs, the liver and the kidney Both organs remove unwanted materials from blood, but they do so by two very different methods BBC: Sort your life out Liver: identifies unwanted items and disposes of the them Kidney gets rid of everything and retrieves things it wants to keep he renal system Renal arteryAorta Filters 200 litres of fluid a day from the renal blood flow Toxins, metabolic waste products, and excess ions excreted while keeping essential substances in the blood The kidney is the principal organ The rest of the renal system is for transport, storage and elimination of the urine Urin e The kidneys do so much more…… e Renal system: Overview Waste elimination from blood Urea, uric acid, creatinine, Small peptides, toxins/ drugs Water and ion balance Regulation of extracellular volumes and osmolarity (Water and sodium in the blood) Regulation of electrolytes (Essential ions like: K+, Ca++, Mg++, Cl- , Pi, (Na+)) Control of acid-base balance (pH) (Regulation of levels of HCO3 - and H+) Blood pressure regulation Regulation by hormones: Renin, Angiotensin I & II, Aldosterone Acts as an endocrine gland ⁻ Secretion of erythropoietin, (EPO), Vitamin D conversion- active hormone controls calcium metabolism, renin production Gluconeogenesis ⁻ Anatomy of the kidney Structure determines function: The nephron NATOMY OF THE KIDNEY Cortex Interlobar vein and arteries Medulla Each kidney is supplied by a renal artery arising from the aorta Branches to form interlobar arteries Renal artery Medulla contains: Afferent arteriole 5-10 Pyramids Their tips Each afferent arteriole supplies one Renal vein project into the functional unit of the kidney- nephron renal pelvis The afferent arteriole lead into ball of Renal pelvis Calyx capillaries called the glomerulus Ureter NATOMY OF THE KIDNEY 1,000,000 nephrons in each Cortex kidney (Filtration unit) Interlobar vein and arteries Medulla Renal artery Medulla contains: 5-10 Pyramids Their tips Renal vein project into the renal pelvis Renal pelvis Calyx Ureter Two different types of nephron Juxtamedullary nephron Corticol nephron wo types of nephron Juxtamedullary nephron Corticol nephron 15% juxtameduallry nephron ⁻ Loop of Henle goes deep into the medulla and is responsible for generating the osmotic gradient- hypertonic (increased sodium levels), important for the reabsorption of water. 85% corticol nephron ⁻ Loop of Henle is in the cortex and responsible for the reabsorption and secretion and doesn’t Macul contribute to the hypertonic medulla a densa Macula densa: monitors filtrate osmolarity and blood pressure- helps keep the GFR steady Vasa recta in response to varying artery pressure Vasa recta: capillary networks that supply Hypertonic blood to the medulla, are highly permeable to solute and water. Form hair pin loops next to the loop of Henle he nephron: Overview The renal corpuscle The nephron: structural and functional unit Reabsorption Secretion Each segment performs specific Filtration transport functions 1. Filtration 2. Reabsorption 3. Secretion 4. Excretion Waste elimination, balance water Excretion volume/ pH/ osmolarity In the process, this creates urine he nephron: Overview The renal corpuscle The glomerulus The Bowmans capsule Vasa recta: capillary networks that supply blood to the medulla, are highly permeable to solute and water. Form hair pin loops next to the loop of Henle Movement of water and solutes Water through aquaporins- osmosis Interstitial fluid Solutes (Na+/Cl-/ K+/ HCO- Glucose, amino acids, creatinine, urea) - concentration gradient - ion channels - Specific transporters ell types in the kidney Epithelial cells ⁻ Tubule- One epithelial cell layer ⁻ 16 highly specialized epithelial cell types in the kidney ⁻ Podocytes (glomerular epithelial cell)- Filtration ⁻ Brush boarder cells for absorption in Proximal tubule ⁻ Cells that express different channels and transporters Immune cells ⁻ Range of immune cells- e.g. macrophages, lymphocytes Renal interstitium ⁻ Fibroblasts, myofibroblasts, erythropoietin- renin- producing juxtaglomerular cells Endothelial cells ⁻ Kidney has a complex vascular system ⁻ he nephron: Overview Renal corpuscle Filtration Plasma is 300mOs Water and small molecules enter the bowmans space and into the bowmans capsule Filtrate is 300mOs concentration H2O glucose Na+, Cl-, HCO-, K+ urea Amino acids creatinine he nephron: Overview Proximal tubule Proximal convoluted tubule epithelial cell Reabsorption back into the blood stream 100% glucose/ amino acids 90% HCO- (Blood pH) 65% Na+ 65% H20 Movement of sodium down it concentration gradient drives the reabsorption he nephron: Overview Loop of Henle Concentration of the filtrate Hyperosmotic medulla Permeable to H2O, Impermeable to Na + Impermeable to H O, Na+ actively 2 pumped Hyperosmotic gradient HYPEROSMOSTIC Medullary interstitial fluid COUNTERCURRENT MULTIPLIER SYSTEM Hyperosmotic he nephron: Overview Distal convoluted tubule Macula densa Responsive to hormones (aldosterone) Reabsorption of sodium/ water Regulation of blood volume/ pressure Regulation of blood pH- Reabsorption/ secretion of H+ and HCO3- he nephron: Overview Pituitary gland Collecting duct Subject to a lot of Osmoreceptors (hypothalamus/ arteries) control Detect osmotic changes ADH (antidiureti c hormone) Dehydrated ⁻ ADH released from pituitary gland ⁻ Increased aquaporins (water channel) ⁻ H2O reabsorbed passively by osmosis Over-hydrated ⁻ Conc. Urine (hyperosmotic) ⁻ ADH decreased Aquaporin H2 O channel ⁻ Decreased aquaporins ⁻ Dilute urine (hypo-osmotic) Urine Baroreceptors- change in blood volume- RAAS ey points so far…..  1 million nephrons in the kidney  Structural and function unit  Three main processes: FILTRAATION, REABSORPTION, SECRETION  Main function is to produce urine to regulate: ⁻ Extracellular volume ⁻ Osmolarity ⁻ pH ⁻ Eliminate waste products  The renal corpuscle: Filtration The formation of urine begins with the process of filtration at the filtration membrane. GFR is determined by net pressure, permeability of the membrane and the surface area he nephron: Ultrafiltration Afferent arteriole glomerulus  efferent arteriole 1 litre of blood/ min passes through the kidneys Renal corpuscle: Ultrafiltration- creates filtrate Glomerular capillaries increase surface area and 300mOsm/L has a specific structure that creates a ‘sieve’ 300mOsm/L Small molecules are filtered: Water, glucose, amino acids, ions Contains no blood cells/ proteins, chemically similar to serum Many of the useful chemical constituents of this filtrate are reabsorbed Urine: mainly water, with some salts and urea he nephron: Ultrafiltration The GFR: volume of plasma filtered by the glomerulus per unit of time. It is the most important laboratory indicator of kidney function. Glomerular filtration rate (GFR) is kept constant despite fluctuations (within a normal range) of blood pressure Crucial for maintaining stable kidney function and constant elimination of waste GFR is defined by: 1. Glomerular filtration pressure 2. Permeability of the filtration membrane 3. Surface area of filtration STARLINGS FORCES 1. Hydrostatic 2. Osmotic he nephron: Ultrafiltration STARLINGS FORCES Favouring filtration: 1. Glomerular capillary blood pressure (hydrostatic)(PGC) 60 Opposing filtration 2. Fluid in Bowmans capsule (hydrostatic) (PBS) 15 mmHg GC BS 3. Osmotic force due to protein in plasma (Pp) 29mmHg Pp Net glomerular pressure = PPG – PBS – Pp Net glomerular pressure= + 16mmHg Normal GFR = 90 - 125 mL/min in healthy people Glomerular filtration rate (GFR) Varies with age, sex, and muscle mass, Volume of fluid filtered into Bowman’s Sum of all filtration rates in all functioning space 180L/day (125ml/min) nephrons: ‘rough’ assessment of the number of functioning nephrons ↓ GFR indicates renal disease. al corpuscle: flitration membrane cells AA: Afferent arteriole EA: Efferent arteriole Blood ‘IN’ Blood ‘OUT’ DT: Distal tubule Blood pressure drives the filtration Macula densa Glomerular capillary is formed by a Parietal layer of endothelial cells Epithelial cells Specialised epithelial cells of the Podocytes Bowmans capsule- Foot processes of Endothelial cells PODOCYTES cover the outside of the glomerular capillary. Mesangial cells Epithelial cells of the nephron Primary filtrate Mesangial cells (MC) - excitable renal is collected in pericytes that regulate filtration by Bowman‘s space modulating capillaries (BS) Primary filtrate ration membrane: Three layers Capillary 1. Endothelial cells of the capillary: many perforations called fenestrae- more permeable than other capillaries 2. Glomerular basement membrane: negatively charged repel proteins GLYCOCALYX 3. Podocytes: specialised epithelial cells of Bowman’s capsule. Foot-like BASEMEN processes project from these podocytes T pedicels and interdigitate to form filtration slits MEMBRAN FILTRATION and slit diaphragm (a cell-cell junction E SLITS between the foot processes of renal podocytes) Injury to any of these components can result in the development of proteinuria ltration membrane The membrane is selectively permeable: only small and positively charged molecules pass freely. Glomerular capillary wall; fenestrations allow passage of small and medium-sized molecules- blood cells blocked Basement membrane allows positively charged molecules only. Podocytes allow passage of only smallest molecules through filtration slit and slit diaphragm. Small molecules (water, glucose, amino acids, nitrogenous wastes); pass freely through filtration membrane to become part of ultrafiltrate. ases associated with filtration A major role for the GBM is to restrict the passage of plasma proteins into Bowman’s space Alports syndrome- Mutation in type IV collagen Found in Lamina densa in basements membranes (Glomerulas, eyes, cochlea) Collagen IV- important to support cells and form barriers Alport's syndrome- the BM becomes thin and porous- RBC and protein are filtered (haematuria/ proteinuria) GBM undergoes sclerosis Renal insufficiency/ failure  The renal corpuscle: Glomerular filtration The volume ofrate fluid filtered from the glomeruli into the Bowmans space per unit time ~180L/day (125ml/min) Several mechanisms control the rate of filtration Regulation of GFR GFR is kept constant despite fluctuations (within a normal range) of blood pressure Crucial for maintaining stable kidney function and constant elimination of waste Problems: Normal Very low blood pressure (due to heart diseases/Circulation deficits) > Insufficient filtration > Insufficient elimination of waste > Dialysis may be needed Too high blood pressure: > Increased filtration > Increased loss of solutes GFR is tightly regulated through several mechanisms to protect the kidneys from Regulation of GFR: Several mechanisms 1. Intrinsic control within the kidney Autoregulation: the kidneys adjust their own blood flow and GFR a) myogenic response b) tubuloglomerular feedback mechanisms (JGA) 2. Extrinsic control that originates outside of the kidney 1. Hormonal regulation: Hormones such as ANGIOTENSIN II/ Atrial natriuretic peptide (ANP) play a role in regulating GFR 2. Neural regulation: The sympathetic nervous system can influence GFR, causing vasoconstriction of renal blood vessels, decreasing GFR Work together to maintain a relatively constant GFR even when arterial blood pressure changes Regulation of GFR Decreased GFR Increased GFR Blood pressure in Constriction glomerulus GFR 1. of afferent capillariescapillaries decreased decreased 2. of efferent capillaries increased increased Dilation 1. of afferent capillaries increased increased 2. of efferent capillaries decreased decrease INTRINSIC Regulation of GFR: 1. Myogenic response Despite changes in BP, GFR will change very Autoregulati little. on Arteriole walls comprise vascular smooth muscle cells Increased renal blood flow  increased BP increases BP decreases hydrostatic capillary pressure on the walls stretch receptors are activated and induce vasoconstriction. When blood pressure drops, the same smooth muscle cells relax to lower resistance, increasing blood flow. Maintains normal net filtration pressure (NFP) and GFR Maintains fluid, electrolyte, acid-base balance, remove waste INTRINSIC Regulation of GFR: 2. Tubuloglomerular feedback Autoregulation The tubuloglomerular feedback mechanism involves juxtaglomerular apparatus (JGA) and a paracrine signalling Juxtaglomerular cells: modified, smooth muscle cells lining the afferent arteriole Contract or relax in response to the paracrine secretions released by the macula densa As GFR increases  less time for solutes to be absorbed  higher osmolarity  activates macula densa cells to respond by releasing ATP acts locally as a paracrine factor to stimulate JG cells to constrict  decreases GFR Juxtaglomerul ar apparatus GFR decreases, less NaCl is in the filtrate (reabsorbed) decreased ATP arteriole dilates INTRINSIC Regulation of GFR: Effects on Urine Volume and Composition  Both the myogenic and tubuloglomerular feedback mechanisms help stabilize GFR which in turn stabilizes urine volume and composition.  When GFR is too high, these mechanisms reduce it, allowing more time for reabsorption of water and solutes  Conversely, when GFR is too low, they increase it, reducing the time for reabsorption and resulting in more dilute urine.  EXTRINSIC Regulation of GFR: Neural and hormonal control mpathetic nervous system ivated by decreased blood volume (baroreceptors) diovascular centre in medulla Hormone: RAAS -epinephrine released via sympathetic nerves Sympathetic nervous oconstriction of afferent arteriole system irects blood to other parts of the body can also activate RAAS to restore BP and fluid balance EXTRINSIC CONTROLS: that originating outside of the kidney H2 O Affects GFR, however, primary function is to maintain systemic blood pressure The NEURAL AND HORMONAL controls function to meet the whole body’s needs, not just those of the kidneys. The kidneys are innervated by the sympathetic neurons of the ANS Hormones: Atrial natriuretic peptide These extrinsic mechanisms can (ANP) Activated by increased blood volume override renal autoregulation and Hormone produced in the heart, decrease the glomerular filtration Secreted when your plasma volume increases rate when necessary (volume receptors in atrial wall) w to measure GFR: Creatinine clearance Creatinine is a waste product of creatine Urine collected over a 24-hour period metabolism produced in muscle when creatine Blood samples take. is metabolised to generate energy Used to calculate how much creatinine your kidneys filter over the 24-hour Creatinine not reabsorbed or secreted, but is window filtered through the kidneys Its rate of excretion from your bloodstream is directly related to how efficiently your kidneys are filtering By measuring the amount of creatinine in a sample of your blood, and combining this with other information age, ethnicity, gender, height and weight, estimate glomerular (GFR), Indicator how well the kidneys are working Learning outcomes Describe the structure and functions of the renal system Describe the process of filtration across the glomerulus Understand Glomerular filtration rate Describe the mechanisms that regulate GFR intrinsic and extrinsic Any questions?