Early Filtrate Processing

In the early tubular segment of the nephron reabsorb solutes and water of the filtrate back into the blood to restore its volume and composition. They also remove some solutes from the blood and secrete them into the filtrate to fine tune the bloods composition

Gambaran seluler dari tubulus renalis

Tubulus proximal: simple cuboidal cells (brush border cells ok terdapat microvilli) Thin loop of henle: simple squamous cell, highly permeable to water not to solute Thick ascending loop of henle & early distal tubule: cuboidal cells, highly permeable to solutes, particularly NaCl but not to water

Late distal tubule and cortical collecting duct: cuboidal cells has two distinct function: 1. principal cells; permeability to water and solutes are regulated by hormones and, 2. intercalated cells; secretion of hydrogen ion for acid/base balancing Medullary collecting duct; principal cells; hormonally regulated permeability to water and urea

Tubular Reabsorption
By passive diffusion By primary active transport: Sodium By secondary active transport: Sugars and Amino Acids Endositosis ; small proteins and peptide hormones

Reabsorption Pathways

There are two reabsorption pathways:

1. the transcellular pathway (>>)

2. the paracellular pathway

To be reabsorbed into the blood, substances in the filtrate must cross the barrier formed by the tubular cells.

Reabsorpsi Filtrat

Trancellular pathway : Through luminal and basolateral membranes of the tubular cells into the interstitial space and then into the peritubular capillaries. Paracellular pathway : through the tight junctions into the lateral intercellular space. Water and certain ions use both pathways, especially in the proximal convoluted tubule.

Diffusion of Water
Water diffuses from the lumen through the tight junctions into the interstitial space: 1. Water will move from its higher concentration in the tubule through the tight junctions to its lower concentration in the interstitium. 2. Water will also move through the plasma membranes of the cells that are permeable to water Air dapat berdifusi di seluruh bagian tubulus kecuali di thick segment of the ascending limb loop of Henle

Sodium Reabsorption
Dapat mengalami reabsorpsi di seluruh tubulus kecuali thin segmeny of the limb Loop of Henle
PUMP: Na/K ATPase Lumen Sodium

Cells
Potassium Plasma Chloride Water

Keluar dari sel ke interstiital

Tubular Secretion
Protons (acid/base balance) Potassium Organic ions Zat-zat lain yg tidak normal ada dalam darah spt obat-obatan dan bahan-bahan toksik

Transport Maximum (Tm)

For most actively reabsorbed solutes, the amount reabsorbed in the PCT is limited only by the number of available transport carriers for that specific substance. This limit is called the transport maximum, or Tm. If the volume of a specific solute in the filtrate exceeds the transport maximum, the excess solute continues to pass unreabsorbed through the tubules and is excreted in the urine.

Reabsorption: Receptors can Limit

Figure 19-15: Glucose handling by the nephron

Renal threshold of the plasma- past this point the kidney cannot reabsorb any longer and substance will be secreted (ie: too much glucose). Minimal 225 mg/min glucose Tm pada beberapa nefron Renal treshold; ambang maks konsentrasi zat dalam darah yg tidak dijumpai dalam urin

The final processing of filtrate in the late distal convoluted tubule and collecting ducts comes under direct physiological control in response to changing physiological conditions and hormone levels. Membrane permeabilities and cellular activities are altered in response to the body's need to retain or excrete specific substances.

Distal Tubule & Collecting Duct

The Late Distal Tubule & CCT are composed of principal cells & intercalated cells Intercalated cells secrete hydrogen ions into filtrate Principals cells perform hormonally regulated water & sodium reabsorption & potassium secretion

Role of Aldosteron
Principal cells are more permeable to sodium ions and water in the presence of Aldosterone & ADH Low level of Aldosterone result in little basolateral sodium/potassium ATPase ion pump activity & few luminal sodium & potassium channel

Aldosteron increases the number of basolateral Na/K pump and luminal Na & K channels Since there are no basolateral K channel, K ion are secreted into the instead of returning to the interstitium Without an increase in water permeability, the interstitial osmolarity increases

Role of ADH

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

80% of the blood goes back, only 20% of the volume is filtered. Of this 20%, only 19% will be reabsorbed. -total volume that is filtered is only about 180L/day, and 1% of this will excreted.

Reabsorption in Proximal Tubule

Glucose and Amino Acids 67% of Filtered Sodium Other Electrolytes 65% of Filtered Water 50% of Filtered Urea All Filtered Potassium

Juxtaglomerular apparatus
As the thick ascending loop of henle transition into early distal tubule, the tubule runs adjacent to the afferent and efferent arteriole. Where these structure are contact they form the monitoring structure called the juxtaglomerular apparatus (JGA), which is composed macula densa and JG cells

Figure 19-9: The juxtaglomerular apparatus

TUBULOGLOMERULAR FEEDBACK & GLOMERULOTUBULAR BALANCE

Signals from the renal tubule in each nephron feedback to affect filtration in its glomerulus. As the rate of flow through the ascending limb of the loop of Henle and first part of the distal tubule increases, glomerular filtration in the same nephron decreases, and, conversely, a decrease in flow increases the GFR This process, which is called tubuloglomerular feedback, tends to maintain the constancy of the load delivered to the distal tubule. The sensor for this response is the macula densa.

The amount of fluid entering the distal tubule at the end of the thick ascending limb of the loop of Henle depends on the amount of Na+ and Cl in it. The Na+ and Cl enter the macula densa cells via the NaK2Cl cotransporter in their apical membranes. The increased Na+ causes increased Na, K ATPase activity and the resultant increased ATP hydrolysis causes more adenosine to be formed.

Presumably, adenosine is secreted from the basal membrane of the cells. It acts via adenosine A1 receptors on the macula densa cells to increase their release of Ca2+ to the vascular smooth muscle in the afferent arterioles. This causes afferent vasoconstriction and a resultant decrease in GFR. Presumably, a similar mechanism generates a signal that decreases renin secretion by the adjacent juxtaglomerular cells in the afferent arteriole but this remains unsettled

Conversely, an increase in GFR causes an increase in the reabsorption of solutes, and consequently of water, primarily in the proximal tubule, so that in general the percentage of the solute reabsorbed is held constant. This process is called glomerulotubular balance, and it is particularly prominent for Na+.

The change in Na+ reabsorption occurs within seconds after a change in filtration, so it seems unlikely that an extrarenal humoral factor is involved. One factor is the oncotic pressure in the peritubular capillaries. When the GFR is high, there is a relatively large increase in the oncotic pressure of the plasma leaving the glomeruli via the efferent arterioles and hence in their capillary branches. This increases the reabsorption of Na+ from the tubule. However, other as yet unidentified intrarenal mechanisms are also involved.

Sympathetic control In extreme stress or blood loss, sympathetic stimulation overrides the autoregulation

Increased sympathetic discharge cause intense constriction of renal blood vessel Blood is shunted to other vital organs GFR reduction causes minimal fluid loss from blood

Reduction filtration can not go indefinitely, a waste product build up & metabolic imbalances increase in blood IV fluid increases blood volume restores blood pressure to resting levels reduced sympathetic stimulation allows for normal arteriole diameter GFR & filtrate flow is normalized

Sympathetic Regulation of GFR

Insert fig. 17.11