Kuliah 1. Proses Pembentukan Urin(Print Hal 8,13,25)

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    PROSESPEMBENTUKAN URIN

    Rahmatina B. HermanBagian Fisiologi

    Fakultas Kedokteran Universitas Andalas

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    Urine Formation

    The urinary system forms the urine and carriesit to the outside that consists of:

    - The kidneys as the urine forming organs

    - The structures that carry urine from kidneysto the outside for eliminating from the body

    Three basic processes in urine formation:

    1. Filtrationby glomerolus

    2. Reabsorptionby tubules

    3. Secretionby tubules

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    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 ofgreater in:

    - hydrostatic pressure- glomerular filtration coefficient (Kf)

    product of permeabilityand effective filtration surface

    area of glomerular capillary

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    ..Filtration By Glomerolus

    The factors governing filtration acrossglomerular 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 Bowmans capsule (PT)- Colloid osmotic pressure of plasma in GC (GC)

    - Colloid osmotic pressure of filtrate (T) protein

    free

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    PGC GC

    PT

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

    PT : Mean hydrostatic pressure in Bowmans capsule : 18 mmHg

    Net filtration pressure: 60-32-18= 10 mmHg

    Glomerular capillary

    Bowmans capsule

    Net Filtration Pressure

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    Is actual rate of filtration by glomerularcapillaries

    Depends 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

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    Factors Affecting GFR

    Changes in renal blood flowChanges in glomerular capillary hydrostatic pressure

    - Changes in systemic blood pressure- Afferent or efferent arteriolar constriction

    Changes in hydrostatic pressure in Bowmans capsule- Ureteral obstruction- Edema of kidney inside tight renal capsule

    Changes in concentration of plasma proteins- Dehydration , hypoproteinemia, etc (minor factors)

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

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    Filtration fraction:- Fraction of plasma flowing through glomeruli that

    is filtered into tubules

    - Ratio of GFR to renal plasma flow (RPF)

    - Normal: 0,20it means: 20 % of plasma that enters glomeruli isfiltered by glomerular capillaries

    - GFR varies less than RPFwhen there is fall in systemic blood pressure, GFR fallsless than RPF, because of efferent arteriole constriction

    filtration fraction rises

    GFRRPF

    ..Filtration

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    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

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    Filterability of substances by GC decreaseswith increases MW

    Substance MW Filterability

    Water

    Sodium

    Glucose

    InulinMyoglobin

    Albumin

    18

    23

    180

    5.50017.000

    69.000

    1,0

    1,0

    1,0

    1,00,75

    0,005

    ..Filterability

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    Secretion and Reabsorption

    Once the glomerular filtrate is formed, then thetubular 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

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    Basic Mechanism of Secretion and Reabsorption

    Active transport:- primary active transport

    - secondary active transport

    - active transport mechanism for proteinreabsorption: pinocytosis (endocytosis)

    Passive transport:

    - through intercellular space

    - using carrier

    Osmosis: water

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    Transport Maximum (Tm)

    Limit of the rate at which the solute can betransported 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

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    Transport in Proximal Tubules

    Proximal tubule epithelial cells are highly metabolicand have large numbers of mitochondriato supportpotent active transport processes

    Proximal tubule epithelial cells have extensive brush

    border on the luminal side and also extensivelabyrinth of intercellular and basal channelsextensive surface area for rapid transport

    Epithelial brush border is loaded with protein carrier

    molecules and a large number of sodium ionssecondary active transport (co-/ counter transport)

    So, it is the most active reabsorption process

    Water moves across membrane by osmosis

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    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 chlorideconcentration 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

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    Secretion in Proximal Tubule

    Proximal tubule is important site for secretionof many substances that must be rapidlyremoved 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 plasmaflowing through kidneys and excrete it into urine

    So, PAH clearance can be used as index of renalplasma flow (RPF)

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    Transport in Loop of Henle

    Loop of Henle consists of 3 functionally distinctsegments:

    - 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 activityThe thick segmenthas thick epithelial cells that have

    high metabolic activity and are capable of active

    reabsorption of sodium, chloride, and potassium

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    ..Transport in Loop of Henle

    The descending thin segment:- Highlypermeable 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

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    Transport in Distal Tubules

    The very first portion of distal tubule forms part ofjuxtaglomerular complex that provides feedback

    control of GFR and blood flow in the same nephron

    The next early part of distal tubule is highly convolutedand 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

    T i L Di l T b l

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    Transport in Late Distal Tubulesand Cortical Collecting Tubule

    The second half of distal tubule and the subsequent corticalcollecting tubule have similar functional characteristics

    Anatomically, composed of 2 distinct cell types:

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

    > intercalated cells: reabsorb K+& HCO3-, and activelysecrete H+ play a key role in acid-base regulation

    Almost completely impermeable to urea

    Rate of Na+ reabsorption and K+ secretion is controlled by

    aldosteroneand 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

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    Transport in Medullary Collecting Duct

    Play an extremely important role in determining thefinal 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

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    Tubule CharacteristicsUrine Concentration

    Segment of Tubules

    Active

    NaCl

    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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