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Physiology of kidney and excretion I Romana Šlamberová, MD PhD Department of Normal, Pathological and Clinical Physiology Urinary system Organ system that produces, stores, and carries urine Includes two kidneys, two ureters, the urinary bladder, two sphincter muscles, and the urethra. Humans produce about 1.5 liters of urine over 24 hours This amount may vary according to the circumstances: fluid intake perspiration (sweating) and respiration Some medications interfere directly or indirectly with urine production, such as diuretics. Function of urinary system Excretion Keeping homeostasis Keeping acid-base balance Secretion (rennin, kallikrein, erytropoetin) Excreted products: Product of the metabolism Water Hormones Vitamins Toxic substances Composition of urine Substance urine (urine/plasma) 900-930 950 -- proteins (g/l) 70 0 -- glukose (mmol/l) 5,5 0 -- Na+ 130 152 1 Cl- 104 200 2 urea 5 325 65 Uric acid 0.23 2.9 12 Ca2+ 1.9 2.7 2 phosphates 2.9 48.4 16 creatinin 0.08 8.8 100 K+ 4.1 38.7 9 H2O (g/l) Plasma Kidneys Morphology It is paired organ (weight about 300 g) Compound from two parts cortex (isotonic urine) and medulla (hypertonic urine) Cortex: Glomerular apparatus Medulla: Divided: Outer and Inner Consists of about 1 million filtering units termed nephrons (basic structural and functional unit) The kidney plays a crucial role in regulating electrolytes in the human blood (e.g. Na+, K+, Ca2+). It clears urea, a nitrogenous waste product from the metabolism of amino acids. Nephron 1 A nephron (1-1.2 millions) is the basic structural and functional unit of the kidney. Function: regulate water balance and soluble substances filtering the blood and reabsorbing what is needed forming the final urine Each nephron is composed of an initial filtering component (the renal corpuscle) and a tubule specialized for reabsorption and excretion (the renal tubule). The renal corpuscle filters out large solutes from the blood, delivering water and small solutes to the renal tubule for modification. Nephron 2 Parts: Glomerular apparatus Proximal tubule Loop of Henle Distal tubule Types of nephrons: Cortical nephrons (glomerular apparatus belong the surface and Loop of Henle only to the outer part of the medulla) Intermedial nephrons (in the middle) Juxtamedullary nephrons (glomerular apparatus deep in cortex near the medulla and Loop of Henle is going deep to the inner part of the medulla) Nephron 3 Renal (Malphigian) corpuscle nephron's initial filtering component. Glomerulus capillary tuft with afferent arteriole and efferent arteriole Efferent arterioles of juxtamedullary nephrons (ie, the 15% of nephrons closest to the medulla) send straight capillary branches (vasa recta) that deliver isotonic blood to the renal medulla. The vasa recta = crucial role in the countercurrent exchange system Bowman's capsule - surrounds the glomerulus visceral (inner) layer parietal (outer) layer Glomerulus 2 The glomerulus has several characteristics the endothelial cells of the glomerulus contain numerous pores (fenestrae) glomerular endothelium sits on a very thick basement membrane On the surface of the cells are negatively charged glycosaminoglycans such as heparan sulfate. The negatively-charged basement membrane repels negativelycharged ions from the blood, helping to prevent their passage into Bowman's space. blood is carried out of the glomerulus by an efferent arteriole instead of a venule. Glomerular filter The filtration surface is 1.5 square meter Amount of the filtered solution 180-200 l. Final volume of urine is around (1.5 - 2 l per day) Glomerular filter: The rest (97 %) has to be reabsorbed in the tubules back to the body the capillary endothelium basal membrane epithelium of the Bowman’s capsule (PODOCYTES) Podocytes: special cells which have numerous of pseudopodia (pedicles) that interdigitate to form filtration slits along the capillary wall. Glomerular filtration barrier GLOMERULAR FILTRATION Depends on: Pressure gradient across the filtration slit (endothelium, basal membrane, epithelium = podocytes) Blood circulation throughout the kidneys Permeability of the filtration barrier Filtration surface The solution after filtration is very similar like plasma, but should be WITHOUT PROTEINS CLEARANCE The ability of kidneys to clear plasma from different products. GLOMERULAR FILTRATION RATE (GFR) measuring the excretion and plasma level of a substance that freely filtered through the glomeruli neither secreted nor reabsorbed by the tubules such as INULIN (polymer of fructose) GFR = U x V/P U = concentration of inulin in urine V = volume of the urine P = concentration of inulin in plasma Normal GFR is around 125 ml/min (7.5 l/h) Juxtaglomerular apparatus 1 The juxtaglomerular cells - synthesize, store, and secrete the enzyme renin Specialized smooth muscle cells in the wall of the afferent arteriole that are in contact with distal tubule. Have mechano-receptors for blood pressure The macula densa specialized cells lining the distal convoluted tubule (lies next to the juxtaglomerular apparatus) Cells of macula densa are taller and have more prominent nuclei than surrounding cells. Sensitive to the concentration of sodium ions in the fluid. Juxtaglomerular apparatus 2 Proximal tubule Morphology: 15 mm long and 55 µm in diameter Function: Reabsorption of the largest volume of solution filtered in glomerular apparatus. epithelium cells have a striate brush border (projections) enlarge the surface for the reabsorption 75 - 80 % water Na+, Cl-, HCO3-, K+, Ca2+, Mg2+, HPO42Glucose Results in ISOOSMOTIC SOLUTION Fluid in the filtrate entering the proximal convoluted tubule is reabsorbed into the vasa recta, including approximately 2/3 of the filtered salt and water and all filtered organic solutes (primarily glucose and amino acids). Lining of tubules Trojan: Fyziologie Glucose transport Loop of Henle A U-shaped tube descending limb (thin part) ascending limb (thin and thick part) Begins in the cortex and extends into the medulla and then returns to the cortex. Its primary role is to concentrate the salt in the intersticium. Loop of Henle - Descending limb Permeable to water and salt hypertonic intersticium - water flows freely out of the descending limb by osmosis Longer descending limbs allow more time for water to flow out of the filtrate Longer limbs make the filtrate more hypertonic than shorter limbs. Results in HYPERTONIC SOLUTION Water and ion transport Loop of Henle - Ascending limb Impermeable to water, permeable for salts. Actively pumps sodium out of the filtrate, generating the hypertonic intersticium Important for counter-current exchange Results in HYPOTONIC SOLUTION Counter-current exchange Water and ion transport Distal tubule 1 Morphology: Reabsorption: direct part. Convolute part – Juxtaglomerular apparatus (the part of distal tubule near the glomerular apparatus) = special cells = MACULA DENSA (thin cells very tight next to each other) Large nucleus, secretion of RENIN Water Na+ Results in ISOOSMOTIC SOLUTION After traveling the length of the distal convoluted tubule, only 3% of water remains, and the remaining salt content is negligible. 97.9% of the water in the glomerular filtrate enters the convoluted tubules and collecting ducts by osmosis. Distal tubule 2 The distal convoluted tubule = similar to the proximal convoluted tubule in structure and function. regulated by the endocrine system Cells lining the tubule have numerous mitochondria, enabling active transport to take place by the energy supplied by ATP. parathyroid hormone = reabsorbs more Ca2+ and excretes more phosphates aldosterone = more Na+ is reabsorbed and more K+ excreted Atrial natriuretic peptide = excretes more Na+ In addition, the tubule also secretes hydrogen and ammonium to regulate pH. Collecting duct 1 Collects about 10 distal tubules Continues as medullary pyramides (about 2700 nephrons). begin in the renal cortex and extend deep into the medulla. Final adjustment (hypertonic intersticium) – loosing water Results in HYPERTONIC SOLUTION Collecting duct 2 The collecting duct is normally impermeable to water becomes permeable under the actions of antidiuretic hormone (ADH). As much as 3/4 of the water from urine can be reabsorbed as it leaves the collecting duct by osmosis The levels of ADH determine whether urine will be concentrated or dilute. Dehydration results in an increase in ADH, while water sufficiency results in low ADH allowing for diluted urine. Collecting duct 3 Lower portions of the collecting duct are also permeable to urea - helps to maintain its high ion concentration. Urine leaves the collecting duct through: the renal papilla the renal calyces the renal pelvis The ureter the collecting duct is not part of nephron – different development the collecting duct from endoderm the nephron is from mesoderm