W18N The Renal System - PDF

**The Renal System 1-2** **Learning Objectives** - Understand and explain briefly the organs and function of the urinary system - Understand and explain in detail the anatomy of kidney including location, internal and external structure, the blood and nerve supply and also the fun...

**The Renal System 1-2** **Learning Objectives** - Understand and explain briefly the organs and function of the urinary system - Understand and explain in detail the anatomy of kidney including location, internal and external structure, the blood and nerve supply and also the function of the kidney - Understand and describe in detail the structure of the nephron and the organisation of its blood supply including its function - Understand and explain in detail the renal physiology including mechanism of urine formation, glomerular filtration, tubular reabsorption, tubular secretion and hormonal regulation and homeostasis **The Urinary System** - are paired, bean-shaped organs - Located along the back body wall below the **diaphragm** and adjacent to the **vertebral** **column** - Right kidney lower than the left because **liver** occupies larger area above the kidney on the right side **Structure of Kidney**  A diagram of the internal organs Description automatically generated **Blood and Nerve Supply** - Renal arteries deliver \~ ¼ (**1200** ml 25%) of cardiac output to the kidneys each minute - Arterial flow into and venous flow out of the kidneys follow **similar** paths - Only blood supply to medulla = **vasa recta** - Nerve supply is via sympathetic fibres from the renal **plexus**  **Functions of the Kidney** - Removal of toxins, metabolic wastes, and excess ions from the blood - Regulation of blood volume, chemical composition, and pH - **Gluconeogenesis** during prolonged fasting - Endocrine functions - Renin: regulation of blood pressure and kidney function - Erythropoietin: regulation of RBC production - Activation of **Vitamin D** a, The final common pathways of generation of 25 (OH)D and 1,25(OH) 2 D, the feedback loop, and the roles of skin, liver, and the kidney. Eighty percent of the vitamin D requirements of humans is generated through UVB rays after skin exposure to sunlight. b, Illustrate the physiologic role of PTH in the maintenance of serum calcium level. Key target organs for PTH; bone, kidney and intestine, and their feedback interactions with calcium are illustrated. c, Feedback hormonal control of calcium metabolism. Low serum ionized calcium enhances the secretion of PTH from parathyroid glands. Subsequently, PTH increases the synthesis of 1,25(OH) 2 D, stimulates calcium absorption from the intestine, and mobilizes calcium from the skeleton to maintain normocalcemia, and negatively regulates PTH synthesis and release. FGF-23-fibroblast growth factor-23; PTHparathyroid hormone; UVBultraviolet B **Nephron** - Structural and functional units that form urine - \~ 1 million per kidney - Each nephron consists - Renal corpuscle: an initial filtering component - Renal tubule: extends from the renal corpuscle - 80% → within cortex (cortical) / 20% → deep into medulla - Afferent arterioles found in cortex A diagram of the neuron Description automatically generated - **Cortical nephrons** make up about 80-85% of the 1 million microscopic nephrons - Their renal corpuscles are located in the outer portion of the cortex, with short loops of Henle that penetrate only a small way into the medulla - The ascending limbs of their loops of Henle consist of only a thick segment, **lacking** any thin portions - Nephrons with short loops receive their blood supply from **peritubular** **capillaries** that arise from efferent arterioles - The other 15-20% of the nephrons are **juxtamedullary** **nephrons** - Their renal corpuscles lie deep in the cortex, close to the medulla, and they have long loops of Henle that extend into the deepest region of the medulla - The ascending limbs of their loops of Henle consist of ***both*** thin and think segments - Nephrons with long loops receive their blood supply from the **vasa** **recta** that arise from peritubular capillaries before becoming peritubular venules A diagram of the body Description automatically generated - The distal convoluted ttubules of several nephrons empty into a single **collecting** **duct** - Collecting ducts unite and converge into several hundred large **papilary** **ducts** which drain into the minor calyces, major calyces, renal pelvis, and ureters  **Renal Corpuscle -- Clomerular (Bowman's) capsule and glomerulus** A diagram of the internal organs Description automatically generated  **Glomerular Filtration** A diagram of a structure Description automatically generated +-------------+-------------+-------------+-------------+-------------+ | SUBSTANCE | TOTAL | **FILTERED* | **REABSORBE | **SECRETED* | | | AMOUNT IN | * | D** | * | | | PLASMA | | (RETURNED | **SUBSTANCE | | | | (ENTERS | | ** | | | | GLOMERULAR | TO BLOOD) | | | | | CAPSULE) | | (TO BECOME | | | | | | URINE) | +=============+=============+=============+=============+=============+ | Water | 3 L | 180 L | 178-179 L | 1-2 L | | (passive) | | | | | +-------------+-------------+-------------+-------------+-------------+ | Protein | 200 g | 2 g | 1.9 g | 0.1 g | | (active) | | | | | +-------------+-------------+-------------+-------------+-------------+ | Glucose | 3 g | 162 g | 162 g | 0 g | | (active) | | | | | +-------------+-------------+-------------+-------------+-------------+ | Urea | 1 g | 40 g | 24 g | 30 g | | (passive) | | | | | | | | | (about 1/2) | (about 1/2) | +-------------+-------------+-------------+-------------+-------------+ | Greatinine | 0.03 g | 1.6 g | 0 g | 1.6 g | | | | | | | | | | | (all | (non-reabso | | | | | filtered) | rbed) | +-------------+-------------+-------------+-------------+-------------+  **Glomerular Filtration Regulation** 2016 Pearson Education, Inc. - ppt download - Two **hormones** contribute to regulation of GFR - **Angiotensin II** is a potent vasoconstrictor of both afferent and efferent arterioles (reduces GFR) - A sudden large increase in BP stretches the cardiac atria and releases **atrial natriuretic peptide (ANP)** - ANP causes the - Glomerulus to relax - Increasing the surface - Area for filtration  **Reabsorption Routes** A diagram of a cell Description automatically generated - **Routes of Reabsorption** a. **Paracellular Reabsorption**; water and solutes move between tubule cells b. **Transcellular Reabsorption**; water and solutes pass through a tubule cell - **Na⁺ Movement** - **Sodium-Potassium Pump** (Na⁺--K⁺ ATPase); Ejects Na⁺ from renal tubule cells at the basolateral membrane. - **Directionality**; The absence of Na⁺--K⁺ pumps in the apical membrane ensures one-way Na⁺ reabsorption. - **ATP** **Utilisation**; the pumps account for about 6% of the body's resting ATP consumption - **Tight** **Junctions**; maintain selective permeability and control solute movement  - **Mechanism** - Na⁺-Glucose Symporter: Transports two Na⁺ ions and one glucose molecule from tubular fluid into the cell - **Pathways**; a. **Apical** **Membrane** **Entry**: Na⁺ and glucose enter PCT cells via the symporter. b. **Basolateral** **Exit**: Glucose exits through facilitated diffusion into the interstitial fluid and then into peritubular capillaries - **Additional** **Symporters**; - Reabsorb other substances such as phosphate, sulfate, amino acids, and lactic acid similarly **Reabsorption in PCT** - **Na⁺ Reabsorption and H⁺ Secretion;** - Secondary Active Transport: Na⁺ enters PCT cells down its concentration gradient via Na⁺-H⁺ antiporters, while H⁺ is secreted into the tubular fluid - **Production of H⁺** - **Carbonic Anhydrase Reaction**: CO₂ and H₂O form carbonic acid (H₂CO₃), which dissociates into H⁺ and HCO₃⁻  - **Bicarbonate Reabsorption;** - **Facilitated Diffusion**: HCO3- exists the cell via transporters in the basolateral membrane, diffusing into the blood alongside Na⁺ - **Osmotic Gradient;** - Reabsorption of solutes induces osmosis of water into peritubular capillaries **- Passive reabsorption in second half of the PCT** - **Reabsorbed Solutes;** - Includes Cl⁻, K⁺, Ca²⁺, Mg²⁺, and urea - **Electrochemical Gradients;** - Drive passive reabsorption of these solutes via paracellular and transcellular routes - **Water Reabsorption** - Water follows solutes through osmosis, facilitated by aquaporin-1 in PCT cell membranes, enhancing water permeability **Reabsorption in thick ascending limb of loop of Henle** - **Na⁺-K⁺-2Cl⁻ Symporters Function**: - Located in the apical membrane of the thick ascending limb, they transport one Na⁺, one K⁺, and two Cl⁻ from tubular fluid into the cells - **Na⁺ Transport to Blood**: Na⁺ is actively pumped into the interstitial fluid at the base and sides of the cell, then diffuses into the vasa recta - **Cl⁻ Movement to Blood**: Cl⁻ exits through leakage channels in the basolateral membrane, reaching interstitial fluid and the vasa recta - **K⁺ Recycling**: Most K⁺ brought in by the symporters leaks back into tubular fluid via apical membrane channels, maintaining the system's efficiency - **Charge Imbalance Created**: K⁺ leakage into tubular fluid makes interstitial fluid and blood more negatively charged compared to the tubular fluid - **Cation Reabsorption via Paracellular Route**: This negativity attracts Na⁺, K⁺, Ca²⁺, and Mg²⁺, promoting their reabsorption into the blood through spaces between the cells **Reabsorption in distal convoluted tubule and in collecting duct** - **Reabsorption by the End of the Distal Convoluted Tubule**: - 90-95% of the filtered solutes and water are reabsorbed into the BS - **Cells in the Terminal Distal Convoluted Tubule and Collecting Duct**: Principal cells and intercalated cells are present - **Na⁺ Movement in Principal Cells**: - Na⁺ enters through Na⁺ leakage channels in the apical membrane - Na⁺ is actively transported out across the basolateral membrane by sodium-potassium pumps, keeping cytosolic Na⁺ concentration low - Na⁺ then passively diffuses into peritubular capillaries from surrounding interstitial spaces - **K⁺ Movement in Principal Cells**: - Sodium-potassium pumps continuously bring K⁺ into the cells, maintaining high intracellular K⁺ levels / K⁺ leaks out through channels in both apical and basolateral membranes - K⁺ diffuses down its concentration gradient into the tubular fluid, where its concentration is very low, making this the main source of K⁺ excreted in urine **Hormones and Homeostasis** - - **Five hormones** affect the extent of Na+, Cl-, Ca2+, and water reabsorption as well as K+ secretion by the renal tubules - These hormones, all of which are key to maintaining homeostasis of not only renal blood flow and B.P., but systemic blood flow and B.P., are: 1. Angiotensin II 2. Antidiuretic hormone (ADH) 3. Aldosterone 4. Atrial natriuretic peptide (ANP) 5. Parathyroid hormone (PTH)  A screenshot of a medical report Description automatically generated - **Antidiuretic hormone (ADH)** is released by the posterior pituitary in response to low blood flow in this part of the brain - **ADH** affects facultative water reabsorption by increasing the water permeability of principal cells in the last part of the distal convoluted tubule and throughout the collecting duct - In the absence of **ADH**, the apical membranes of principal cells are almost impermeable to water - Parathyroid hormone (PTH) is released by the parathyroid gland - Stimulates cells in early distal convoluted to reabsorb Ca2+ into the blood - Inhibits [HPO~4~^2−^]{.math.inline} (phosphate) reabsorption in proximal convoluted tubule thereby promoting phosphate excretion **Summary of filtration, reabsorption and secretion in nephron and collecting duct**