PROSESPEMBENTUKAN URIN

Rahmatina B. HermanBagian Fisiologi

Fakultas Kedokteran Universitas Andalas

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

Urine FormationThe 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 glomerolus2. Reabsorption by tubules3. Secretion by tubules

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 rateof glomerular capillary >> other capillaries, because of greater in: - hydrostatic pressure - glomerular filtration coefficient (Kf)product of permeability and effective filtration surface area of glomerular capillary

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

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Capillary poreEfferent arterioleAfferent arteriole

…..Filtration By Glomerolus

The factors governing filtration across glomerular capillaries (GC) are the same as all other capillaries

For each nephron:- Glomerular filtration coefficient (Kf)- Mean hydrostatic pressure in GC (PGC) - Mean hydrostatic pressure in Bowman’s capsule (PT)- Colloid osmotic pressure of plasma in GC (πGC)- Colloid osmotic pressure of filtrate (πT) → protein free

PGC πGC

PT

PGC : Mean hydrostatic pressure in GC : 60 mmHgπGC : Colloid osmotic pressure of plasma in GC : 32 mmHg PT : 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

Is actual rate of filtration by glomerular capillariesDepends on:- Net filtration pressure- Filtration coefficient (Kf)

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 = (Kf) x Net filtration pressure

Factors Affecting GFRChanges in renal blood flowChanges in glomerular capillary hydrostatic pressure- Changes in systemic blood pressure- Afferent or efferent arteriolar constrictionChanges in hydrostatic pressure in Bowman’s capsule- Ureteral obstruction- Edema of kidney inside tight renal capsuleChanges in concentration of plasma proteins- Dehydration , hypoproteinemia, etc (minor factors)

Changes in Kf- Changes in glomerular capillary permeability- Changes in effective filtration surface area

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 RPFwhen there is fall in systemic blood pressure, GFR falls less than RPF, because of efferent arteriole constriction→ filtration fraction rises

GFRRPF

…..Filtration

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

Filterability of substances by GC decreaseswith increases MW

Substance MW FilterabilityWaterSodiumGlucoseInulin

MyoglobinAlbumin

18231805.50017.00069.000

1,01,01,01,00,750,005

….. Filterability

Secretion and Reabsorption

Once the glomerular filtrate is formed, then the tubular cells will:

Increase the concentration of certain substances in the filtrate by secretionReduce the concentration of certain substances in the filtrate by reabsorptionSecretion or reabsorption rate depending on the needs of the body of the material

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

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

Transport in Proximal Tubules

Proximal tubule epithelial cells are highly metabolic and have large numbers of mitochondria to support potent active transport processesProximal 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 transportEpithelial 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 processWater moves across membrane by osmosis

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

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 urineSo, PAH clearance can be used as index of renal plasma flow (RPF)

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

…..Transport in Loop of Henle

The descending thin segment:- Highly permeable to water- Moderately permeable to most solutes, including urea and sodiumThe ascending thin segment:- impermeable to water- reabsorption capacity is very lowThe 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

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

Transport in Late Distal Tubules and Cortical Collecting Tubule

The second half of distal tubule and the subsequent cortical collecting tubule have similar functional characteristicsAnatomically, composed of 2 distinct cell types:

> principal cells: reabsorb Na+ & water, and secrete K +

> intercalated cells: reabsorb K + & HCO3-, and

actively secrete H + → play a key role in acid-base regulationAlmost completely impermeable to ureaRate of Na+ reabsorption and K + secretion is controlled by aldosterone and their concentration in body fluidsPermeability to water is controlled by ADH (vasopressin) → important mechanism for controlling the degree of dilution or concentration of urine

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

Countercurrent Mechanism

Countercurrent mechanism produces hyperosmotic renal medullary interstitium concentrated urineCountercurrent 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

…..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

Tubule Characteristics – Urine Concentration

Segment of TubulesActiveNaCl

Transport

Permeability

H2O NaCl Urea

Thin descending limb 0 +++++ + +

Thin ascending limb 0 0 + +

Thick ascending limb +++++ 0 0 0

Distal tubule + + ADH 0 0

Cortical collecting tubule + + ADH 0 0

Inner medullary collecting tubule + + ADH 0 +++

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