Early Filtrate ProcessingEarly Filtrate Processing

Gambaran seluler dari Gambaran seluler dari tubulus renalistubulus renalis

Tubulus proximal: simple cuboidal cells Tubulus proximal: simple cuboidal cells (brush border cells ok terdapat microvilli)(brush border cells ok terdapat microvilli)

Thin loop of henle: simple squamous cell, Thin loop of henle: simple squamous cell, highly permeable to water not to solutehighly permeable to water not to solute

Thick ascending loop of henle & early Thick ascending loop of henle & early distal tubule: cuboidal cells, highly distal tubule: cuboidal cells, highly permeable to solutes, particularly NaCl permeable to solutes, particularly NaCl but not to waterbut not to water

Late distal tubule and cortical collecting Late distal tubule and cortical collecting duct: cuboidal cells has two distinct duct: cuboidal cells has two distinct function: function:

1. principal cells; permeability to water and 1. principal cells; permeability to water and solutes are regulated by hormones and,solutes are regulated by hormones and,

2. intercalated cells; secretion of hydrogen 2. intercalated cells; secretion of hydrogen ion for acid/base balancingion for acid/base balancing

Medullary collecting duct; principal cells; Medullary collecting duct; principal cells; hormonally regulated permeability to water hormonally regulated permeability to water and ureaand urea

Tubular ReabsorptionTubular Reabsorption

By passive diffusionBy passive diffusion By primary active transport: SodiumBy primary active transport: Sodium By secondary active transport: By secondary active transport:

Sugars and Amino AcidsSugars and Amino Acids Endositosis ; small proteins and Endositosis ; small proteins and

peptide hormonespeptide hormones

Reabsorption PathwaysReabsorption Pathways

There are two reabsorption There are two reabsorption pathways:pathways:

1. the transcellular pathway (>>)1. the transcellular pathway (>>)

2. the paracellular pathway2. the paracellular pathway

Reabsorpsi FiltratReabsorpsi Filtrat

Trancellular pathway : Through Trancellular pathway : Through luminal and basolateral membranes of luminal and basolateral membranes of the tubular cells into the interstitial the tubular cells into the interstitial space and then into the peritubular space and then into the peritubular capillaries. capillaries.

Paracellular pathway : through the Paracellular pathway : through the tight junctions into the lateral tight junctions into the lateral intercellular space. intercellular space.

Water and certain ions use both Water and certain ions use both pathways, especially in the proximal pathways, especially in the proximal convoluted tubule. convoluted tubule.

Diffusion of WaterDiffusion of Water

Water diffuses from the lumen Water diffuses from the lumen through the tight junctions into the through the tight junctions into the interstitial space:interstitial space:

1. Water will move from its higher 1. Water will move from its higher concentration in the tubule through concentration in the tubule through the tight junctions to its lower the tight junctions to its lower concentration in the interstitium. concentration in the interstitium.

2. Water will also move through the 2. Water will also move through the plasma membranes of the cells that plasma membranes of the cells that are permeable to water are permeable to water

Sodium ReabsorptionSodium Reabsorption

Keluar dari sel ke Keluar dari sel ke interstiitalinterstiital

Lumen

Plasma

Cells

PUMP: Na/K ATPase

Sodium

Potassium

Chloride

Water

Tubular SecretionTubular Secretion

Protons (acid/base balance)Protons (acid/base balance) PotassiumPotassium Organic ionsOrganic ions Zat-zat lain yg tidak normal ada Zat-zat lain yg tidak normal ada

dalam darah spt obat-obatan dan dalam darah spt obat-obatan dan bahan-bahan toksikbahan-bahan toksik

Transport Maximum (Tm)Transport Maximum (Tm)

For most actively reabsorbed solutes, the For most actively reabsorbed solutes, the amount reabsorbed in the PCT is limited amount reabsorbed in the PCT is limited only by the number of available transport only by the number of available transport carriers for that specific substance.carriers for that specific substance.

This limit is called the transport maximum, This limit is called the transport maximum, or Tm. or Tm. If the volume of a specific solute in the If the volume of a specific solute in the filtrate exceeds the transport maximum, filtrate exceeds the transport maximum, the excess solute continues to pass the excess solute continues to pass unreabsorbed through the tubules and is unreabsorbed through the tubules and is excreted in the urine.excreted in the urine.

Reabsorption: Receptors can LimitReabsorption: Receptors can Limit

Figure 19-15: Glucose handling by the nephron

The final processing of filtrate in the The final processing of filtrate in the late distal convoluted tubule and late distal convoluted tubule and collecting ducts comes under direct collecting ducts comes under direct physiological control in response to physiological control in response to changing physiological conditions changing physiological conditions and hormone levels. and hormone levels.

Membrane permeabilities and Membrane permeabilities and cellular activities are altered in cellular activities are altered in response to the body's need to response to the body's need to retain or excrete specific retain or excrete specific substances.substances.

Distal Tubule & Collecting Distal Tubule & Collecting DuctDuct

The Late Distal Tubule & CCT are The Late Distal Tubule & CCT are composed of principal cells & composed of principal cells & intercalated cellsintercalated cells

Intercalated cells secrete hydrogen Intercalated cells secrete hydrogen ions into filtrateions into filtrate

Principals cells perform hormonally Principals cells perform hormonally regulated water & sodium regulated water & sodium reabsorption & potassium secretionreabsorption & potassium secretion

Role of AldosteronRole of Aldosteron

Principal cells are more permeable to Principal cells are more permeable to sodium ions and water in the sodium ions and water in the presence of Aldosterone & ADHpresence of Aldosterone & ADH

Low level of Aldosterone result in Low level of Aldosterone result in little basolateral sodium/potassium little basolateral sodium/potassium ATPase ion pump activity & few ATPase ion pump activity & few luminal sodium & potassium channelluminal sodium & potassium channel

Aldosteron increases the number Aldosteron increases the number of basolateral Na/K pump and of basolateral Na/K pump and luminal Na & K channelsluminal Na & K channels

Since there are no basolateral K Since there are no basolateral K channel, K ion are secreted into channel, K ion are secreted into the instead of returning to the the instead of returning to the interstitiuminterstitium

Without an increase in water Without an increase in water permeability, the interstitial permeability, the interstitial osmolarity increasesosmolarity increases

Role of ADHRole of ADH

Principals cells are more permeable Principals cells are more permeable to water on the presence of ADHto water on the presence of ADH

Reabsorption in Proximal Reabsorption in Proximal TubuleTubule

Glucose and Amino AcidsGlucose and Amino Acids 67% of Filtered Sodium67% of Filtered Sodium Other ElectrolytesOther Electrolytes 65% of Filtered Water65% of Filtered Water 50% of Filtered Urea50% of Filtered Urea All Filtered PotassiumAll Filtered Potassium

Juxtaglomerular apparatusJuxtaglomerular apparatus

As the thick ascending loop of henle As the thick ascending loop of henle transition into early distal tubule, the transition into early distal tubule, the tubule runs adjacent to the afferent and tubule runs adjacent to the afferent and efferent arteriole.efferent arteriole.

Where these structure are contact they Where these structure are contact they form the monitoring structure called the form the monitoring structure called the juxtaglomerular apparatus (JGA), which juxtaglomerular apparatus (JGA), which is composed macula densa and JG cellsis composed macula densa and JG cells

Figure 19-9: The juxtaglomerular apparatus

Glomerulotubular Glomerulotubular BalanceBalance

is the intrinsic ability of the tubules is the intrinsic ability of the tubules to increase their reabsorption rate in to increase their reabsorption rate in response to increased tubular load response to increased tubular load (increased tubular inflow).(increased tubular inflow).

occurs in other tubular segments, occurs in other tubular segments, especially the loop of Henle.especially the loop of Henle.

TUBULOGLOMERULAR TUBULOGLOMERULAR FEEDBACKFEEDBACK

a feedback mechanism that links a feedback mechanism that links changes in sodium chloride changes in sodium chloride concentration at the macula densa with concentration at the macula densa with the control of renal arteriolar resistance.the control of renal arteriolar resistance.

helps ensure a relatively constant helps ensure a relatively constant delivery of sodium chloride to the distal delivery of sodium chloride to the distal tubule and helps preventspurious tubule and helps preventspurious fluctuations in renal excretion that would fluctuations in renal excretion that would otherwise occur.otherwise occur.

The tubuloglomerular feedback The tubuloglomerular feedback mechanism has two components that mechanism has two components that act together to control GFR:act together to control GFR:

(1) an afferent arteriolar feedback (1) an afferent arteriolar feedback mechanism and mechanism and

(2) an efferent arteriolar feedback (2) an efferent arteriolar feedback mechanism.mechanism.

depend on the depend on the juxtaglomerular juxtaglomerular complexcomplex

Sympathetic controlSympathetic control

In extreme stress or blood loss, In extreme stress or blood loss, sympathetic stimulation overrides the sympathetic stimulation overrides the

autoregulationautoregulation

Increased sympathetic discharge Increased sympathetic discharge cause intense constriction of renal cause intense constriction of renal blood vesselblood vessel

Blood is shunted to other vital organsBlood is shunted to other vital organs GFR reduction causes minimal fluid GFR reduction causes minimal fluid

loss from bloodloss from blood

Reduction filtration can not go Reduction filtration can not go indefinitely, a waste product build up & indefinitely, a waste product build up & metabolic imbalances increase in blood metabolic imbalances increase in blood

IV fluid increases blood volume IV fluid increases blood volume restores blood pressure to resting levels restores blood pressure to resting levels reduced sympathetic stimulation reduced sympathetic stimulation allows for normal arteriole diameter allows for normal arteriole diameter GFR & filtrate flow is normalizedGFR & filtrate flow is normalized

Sympathetic Regulation of GFRSympathetic Regulation of GFR

Insert fig. 17.11