1. PROSES PEMBENTUKAN URIN Rahmatina B. Herman Bagian Fisiologi Fakultas Kedokteran Universitas Andalas

2. Functions of Urinary System The urinary system performs a variety of functions aimed at maintaining homeostasis In concert with hormonal and neural inputs, the kidneys primarily responsible for maintaining the stability of ECF volume, electrolyte composition, and osmolarity (solute concentration) Excreting (eliminating) the end products (wastes) of bodily metabolism, such as urea, uric acid, creatinine; since these wastes are toxic, especially to brain Main route for eliminating potentially toxic metabolic wastes and foreign compounds from the body

3. Urine Formation The urinary system forms the urine and carries it to the outside that consists of: -The kidneys as the urine forming organs -The structures that carry urine from kidneys to the outside for eliminating from the body Three basic processes in urine formation: 1.Filtration by glomerolus 2.Reabsorption by tubules 3.Secretion by tubules

6. Filtration By Glomerolus Glomerular capillaries: impermiabel to protein Glomerular filtrates: - protein-free - concentration of materials that do not bind with protein as same as in plasma Filtration rate of glomerular capillary >> other capillaries, because of greater in: - hydrostatic pressure -glomerular filtration coefficient (K f ) product of permeability and effective filtration surface area of glomerular capillary

7. Layers of glomerular membrane: the pores between endothelium cells of glomerular capillary an acellular basement membrane filtration slits between foot processes of podocytes of inner layer of Bowman capsule 1 2 3 Capillary pore Efferent arteriole Afferent arteriole

8. …..Filtration By Glomerolus The factors governing filtration across glomerular capillaries (GC) are the same as all other capillaries For each nephron: -Glomerular filtration coefficient (K f ) -Mean hydrostatic pressure in GC (P GC ) -Mean hydrostatic pressure in Bowman’s capsule (P T ) -Colloid osmotic pressure of plasma in GC (π GC ) -Colloid osmotic pressure of filtrate (π T ) → protein free

9. P GC π GC PTPT P GC : Mean hydrostatic pressure in GC: 60 mmHg π GC : Colloid osmotic pressure of plasma in GC : 32 mmHg P T : Mean hydrostatic pressure in Bowman’s capsule : 18 mmHg Net filtration pressure: 60-32-18= 10 mmHg Glomerular capillary Bowman’s capsule Net Filtration Pressure

10. Is actual rate of filtration by glomerular capillaries Depends on: -Net filtration pressure -Filtration coefficient (K f ) In males: 125 mL/min (7.5 L/h or 180 L/d) in females: 115 mL/min (6.9 L/h or 160 L/d) Glomerular Filtration Rate (GFR) GFR = (K f ) x Net filtration pressure

11. Factors Affecting GFR Changes in renal blood flow Changes in glomerular capillary hydrostatic pressure -Changes in systemic blood pressure -Afferent or efferent arteriolar constriction Changes in hydrostatic pressure in Bowman’s capsule -Ureteral obstruction -Edema of kidney inside tight renal capsule Changes in concentration of plasma proteins -Dehydration, hypoproteinemia, etc (minor factors) Changes in K f -Changes in glomerular capillary permeability -Changes in effective filtration surface area

12. Filtration fraction: -Fraction of plasma flowing through glomeruli that is filtered into tubules -Ratio of GFR to renal plasma flow (RPF) -Normal: ± 0,20 it means: 20 % of plasma that enters glomeruli is filtered by glomerular capillaries -GFR varies less than RPF when there is fall in systemic blood pressure, GFR falls less than RPF, because of efferent arteriole constriction → filtration fraction rises GFR RPF …..Filtration

13. Filterability of solutes is determined by: - Size/ molecular weight (MW) -Electrical charge: Negative charge is more difficult than positive charge, because basement membran of glomerular capillary consists proteoglican with negative charge Filterability

14. Filterability of substances by GC decreases with increases MW SubstanceMWFilterability Water Sodium Glucose Inulin Myoglobin Albumin 18 23 180 5.500 17.000 69.000 1,0 0,75 0,005 ….. Filterability

15. Secretion and Reabsorption Once the glomerular filtrate is formed, then the tubular cells will: Increase the concentration of certain substances in the filtrate by secretion Reduce the concentration of certain substances in the filtrate by reabsorption Secretion or reabsorption rate depending on the needs of the body of the material

16. Basic Mechanism of Secretion and Reabsorption Active transport: -primary active transport -secondary active transport -active transport mechanism for protein reabsorption: pinocytosis (endocytosis) Passive transport: -through intercellular space -using carrier Osmosis: water

17. Transport Maximum (Tm) Limit of the rate at which the solute can be transported through active transport mechanism Due to transport carrier system becomes saturated as tubular load increases Passive transport does not demonstrate Tm, because the rate is determined by other factors: - Electrochemical gradient for diffusion - Permeability of the membrane for the substance - The time that the fluid containing the substance remains within the tubule This type of transport is referred to as gradient-time transport

18. Transport in Proximal Tubules Proximal tubule epithelial cells are highly metabolic and have large numbers of mitochondria to support potent active transport processes Proximal tubule epithelial cells have extensive brush border on the luminal side and also extensive labyrinth of intercellular and basal channels  extensive surface area for rapid transport Epithelial brush border is loaded with protein carrier molecules and a large number of sodium ions  secondary active transport (co-/ counter transport) So, it is the most active reabsorption process Water moves across membrane by osmosis

19. Reabsorption in Proximal Tubule In the first half of proximal tubule: -sodium is reabsorbed by co-transport along with glucose, amino acids, and other solutes -leaving behind solution that has higher chloride concentration flow to the second half of proximal tubule In the second half of proximal tubule: -sodium is reabsorbed mainly with chloride ions -little glucose and amino acids remain to be reabsorbed

20. Secretion in Proximal Tubule Proximal tubule is important site for secretion of many substances that must be rapidly removed from body, such as: -organic acids and bases -end product of metabolism -many potentially harmful drugs or toxin -para-aminohippuric acid (PAH) Normal person can clear ± 90 % of PAH from plasma flowing through kidneys and excrete it into urine So, PAH clearance can be used as index of renal plasma flow (RPF)

21. Transport in Loop of Henle Loop of Henle consists of 3 functionally distinct segments: -the descending thin segment -the ascending thin segment -the thick ascending segment The thin segments have thin epithelial membranes with no brush borders, few mitochondria, and minimal levels of metabolic activity The thick segment has thick epithelial cells that have high metabolic activity and are capable of active reabsorption of sodium, chloride, and potassium

22. …..Transport in Loop of Henle The descending thin segment: -Highly permeable to water -Moderately permeable to most solutes, including urea and sodium The ascending thin segment: -impermeable to water -reabsorption capacity is very low The thick ascending segment -impermeable to water -highly metabolic → active reabsorption of Na, Cl, K (25%) - has Na-H counter transport mechanism ↓ tubular fluid becomes very dilute

23. Transport in Distal Tubules The very first portion of distal tubule forms part of juxtaglomerular complex that provides feedback control of GFR and blood flow in the same nephron The next early part of distal tubule is highly convoluted and has many of the same reabsorptive characteristics of the thick segment of ascending limb of loop of Henle: -avidly reabsorbs most of ions including Na, Cl, K -virtually impermeable to water and urea  Also dilutes the tubular fluid

24. Transport in Late Distal Tubules and Cortical Collecting Tubule The second half of distal tubule and the subsequent cortical collecting tubule have similar functional characteristics Anatomically, composed of 2 distinct cell types: > principal cells: reabsorb Na + & water, and secrete K + >intercalated cells: reabsorb K + & HCO 3 -, and actively secrete H + → play a key role in acid-base regulation Almost completely impermeable to urea Rate of Na + reabsorption and K + secretion is controlled by aldosterone and their concentration in body fluids Permeability to water is controlled by ADH (vasopressin) → important mechanism for controlling the degree of dilution or concentration of urine

25. Transport in Medullary Collecting Duct Play an extremely important role in determining the final urine output of water and solutes Epithelial cells are nearly cuboidal with smooth surfaces and relatively few mitochondria Permeability to water is controlled by ADH Permeable to urea → reabsorbed into medullary interstitium → raise osmolality → concentrated urine Capable of secreting H + → also play key role in acid- base regulation

26. Countercurrent Mechanism Countercurrent mechanism produces hyperosmotic renal medullary interstitium  concentrated urine Countercurrent mechanism depends on special anatomical arrangement of the loops of Henle and vasa recta (specialized peritubular capillaries of renal medulla) Basic requirements for forming a concentrated urine: -High level of ADH  increases permeability of distal tubules and collecting ducts to water  avidly reabsorb water -High osmolarity of renal medullary interstitial fluid  osmotic gradient necessary for water reabsorption to occur in the presence of high levels of ADH

27. …..Countercurrent Mechanism Major factors that contribute to build up of solute concentration into renal medulla: 1. Active transport of Na + and co-transport of K +, Cl - and other ions out of thick limb into medullary interstitium 2. Active transport of ions from collecting ducts into medullary interstitium 3.Passive diffusion of large amounts of urea from inner medullary collecting ducts into medullary interstitium 4.Diffusion of only small amounts of water from medullary tubules into medullary interstitium, far less then reabsorption of solutes into medullary interstitium

28. Tubule Characteristics – Urine Concentration Segment of Tubules Active NaCl Transport Permeability H2OH2ONaClUrea Thin descending limb0+++++++ Thin ascending limb00++ Thick ascending limb+++++000 Distal tubule++ ADH00 Cortical collecting tubule++ ADH00 Inner medullary collecting tubule++ ADH0+++