The Urinary System Part 2

The Urinary System Part B

Tubular Reabsorption Our total plasma volume filters into the renal tubules about every 22 minutes (i.e 2750ml/125ml = 22min) Tubular Reabsorption is a transepithelial1 process Most tubule contents are returned to the blood by reabsorption. To reach back to blood , transported substances move through three barriers Luminal membrane of tubule cells Basolateral membrane of tubule cells Endothelium of peritubular capillaries

Tight junction between tubule cell, so movement between cells is limited. Only Ca2+, Mg2+, K+, and some Na+ are reabsorbed via paracellular pathways. i.e. (between cells)

Transcellular and paracellular routes of tubular reabsorption.

Movement from lumen to Peritubular capillaries through Transcellular route Paracellular route

The transcellular route consists of four steps: Transport across the luminal membrane, Diffusion through the cytosol, Transport across the basolateral membrane, Movement through the interstitial fluid and into the capillary.

Transcellular transport often involves the lateral intercellular spaces because ATP-dependent pumps located on the basolateral membrane pump ions into these spaces. Water and solutes following the paracellular route move through leaky tight junctions, particularly in the PCT.

Routes of Water and Solute Reabsorption

Tubular Reabsorption

Movement of substance across a memb. is by way of Ion channels Exchangers Cotransporters Pumps

Pumps and other units in the luminal membrane are different from those in the basolateral membrane. It is this different distribution that makes possible net movement of solutes across the epithelia.

Transport Proteins across Apical membrane of renal tubule cells

Tubular Reabsorption

Reabsorption may be through Active Transport (requiring ATP) (Transcellular) Primary Active Transport (Direct use of ATP) Secondary Active Transport( No direct Use of ATP) Co-Transport or Symport (Uni-directional) One along conc.gradient, other against in same direction eg Na+/Glucose Co-Tranporter

Counter Transport or Antiport (Opposite Directions) One along conc.gradient, other against in opposite directions eg Na+/H+ Antiporter

Passive process (No ATP required) Passive Diffusion (between cells) (Paracellular) Facilitated Diffusion (Through Cells) (Transcellular) Osmosis (Para, Trans both)

Sodium Reabsorption: Primary Active Transport

Single most abundant ions in filtrate 80 % energy used for active transport is for Na+ reabs. Sodium reabsorption is almost always by active transport and via transcellular pathway Two Basic Process Na+ enters the tubule cells at the luminal membrane Is actively transported out of the tubules by a Na+-K+ ATPase pump in interstitial fluid

From here, Na+ is swept along by the bulk flow of water into adjacent peritubular capillaries

Sodium Reabsorption: Primary Active Transport Its movement to peritubular capillaries due to: Low hydrostatic pressure High osmotic pressure of the blood

Active pumping of Na+ results in a strong electrochemical gradient It favors its passive entry at the luminal face via cotransport (symport or antiport) carriers or via facilitated diffusion through channels.

Sodium Reabsorption: Primary Active Transport

Passive entry of Na+ into cell is because The pump maintains the intracellular Na+ concentration at low levels, and (Cehmical Gradient) The K+ pumped into the tubule cells almost immediately diffuses out into the interstitial fluid via leakage channels, leaving the interior of the tubule cell with a net negative charge. (Electrical gradient)

Hence active Na+ reabsorption provides the energy and the means for reabsorbing most other solutes

Reabsorption by PCT Cells

“Downhill” Na+ entry at the luminal surface is usually coupled to the transport of another solute (a cotransport process referred to as secondary active transport). Active pumping of Na+ at the basolateral membrane creates concentration and osmotic gradients that drive reabsorption of Water by osmosis Anions and fat-soluble substances by diffusion, Organic nutrients and selected cations by secondary active transport (symport with Na+ at the luminal membrane).

Most organic nutrients reabsorbed in the PCT by facilitated diffusion.

Reabsorption by PCT Cells

Figure 25.12

Reabsorption of Water, Ions, and Nutrients

Obligatory water reabsorption Water moves by osmosis into the peritubular capillaries, by water channels called aquaporins. There are thirteen known types of aquaporins in mammals, and six of these are located in the kidney. Aquaporin-1 is localized in the proximal tubules Aquaporin-1 facilitates water transport @ a rate of approx. 3 billion H2O molecules/second Completely impermeable to charged species eg (Protons)

Reabsorption of Anions: Na+ ions establish an electrical gradient that favors passive reabsorption of anions (Cl– and HCO3– for example) to restore electrical neutrality in the filtrate and plasma.

Reabsorption of Water, Ions, and Nutrients

Phenomenon of Solute Following Solvents Filtrate becomes conc. as water leaves Passive absorption of lipid-Soluble Drugs, Cations, fatty acids and some urea.

Secondary Active Transport Luminal carrier moves Na+ down its concentration gradient as it transports another solute against its conc. gradient. Co-Transport (Symport) Same direction Counter Transport (Antiport) Opposite direction Glucose, Lactate, Amino acids, Vitamins, Cations are transported by secondary active transport

Reabsorption of Glucose Secondary Active Transport

Transport maximum

Transport maximum (Tm): Reflects the number of carriers in the renal tubules available Exists for nearly every substance that is actively reabsorbed Expressed in mg/min

When the carriers are saturated, excess of that substance is excreted eg Glucose Tm = 375mg /min in nephrons, excess will be excreted in urine causing Glucosuria resulting in osmotic diuresis.

Nonreabsorbed Substances

Substances are not reabsorbed if they: Lack carriers Are not lipid soluble Are too large to pass through membrane pores

Urea, creatinine, and uric acid are the most important nonreabsorbed substances

Absorptive Capabilities of Renal Tubules and Collecting Ducts

Proximal Convoluted tubule: PCT cells are most effective reabsorbers: All Glucose, Lactate, Amino acids 65 % Na+ and water 90 % HCO3-1 (Bicarbonate) 60 % Cl- & 55% K+ All of the uric Acid which is later secreted back

Absorptive Capabilities of Renal Tubules and Collecting Ducts

Loop of Henle reabsorbs: Decending Limb Ascending limb

Water

Osmosis

Na+, Cl- and K+

Secondary active transport via Na+, K+ and 2Clcotransport Na+/H+ Anitport Paracellular diff.

Ca2+, Mg2+ Passive paracellular diff

Loop of Henle Decending limb: Water can leave the descending limb (Aquaporin-1) but solutes can not.

Ascending limb: Water can not leave the ascending limb, aquaporins are less or absent in the tubule membrane, but solutes can.

Thin portion of the ascending limb, Na+ moves passively down the concentration gradient created by water reabsorption.

Thick portion of the ascending limb, Na+-K+-2Cl– symporter Na+-H+ antiporters, 50% of Na+ passes via the paracellular route.

A Na+-K+ ATPase operates at the basolateral membrane

Distal Convoluted Tubule and Collecting Duct 10% of NaCl and 25% of the water remain in the tubule. Some NaCl reabsorption in the DCT via Na+-Cl– symporters.

Most reabsorption depends on the body’s needs and is regulated by hormones 1) ADH for water, 2) Aldosterone for Na+, 3) PTH for Ca2+

No hormones, the DCT and collecting duct are almost impermeable to water. Water Reabsorption (ADH)1 Based on presence of ADH, by inserting aquaporins into the collecting duct luminal membranes.

Sodium Reabsorption: (Aldosterone Mediated)2 Decreased blood volume or blood pressure, Low extracellular Na+ concentration (hyponatremia), High extracellular K+ concentration (hyperkalemia) can cause the adrenal cortex to release aldosterone to the blood.

Distal Convoluted Tubule and Collecting Duct

Actions of Aldosterone Targets the principal cells of the collecting ducts and cells of the distal portion of the DCT Urging them to open or synthesize more luminal Na+ and K+ channels, and more basolateral Na+-K+ ATPases.

Facilitate water reabsorption: After Na+ is reabsorbed, water follows it back into the blood (if it can).

Reduces blood K+ concentrations as Na+ enters, K+ moves into the lumen.

In absence of aldosterone about 2% of filtered Na+ is lost daily.

Atrial Natriuretic Peptide Activity

Atrial natriuretic peptide (ANP) or atriopeptin released by cardiac atrial cells when blood volume or blood pressure is elevated ANP reduces blood Na+ which: Decreases blood volume Lowers blood pressure

ANP lowers blood Na+ by: Acting directly on medullary ducts to inhibit Na+ reabsorption Counteracting the stimulatory effect of angiotensin II on aldosterone secretion by the adrenal cortex, Indirectly stimulating an increase in GFR reducing water reabsorption

Na+ Entry into Tubule Cells

In the PCT: facilitated diffusion using symport and antiport carriers

In the ascending loop of Henle: facilitated diffusion via Na+-K+-2Cl− symport system

In the DCT: Na+-Cl– symporter

In collecting tubules: Diffusion through membrane pores

Tubular Secretion Reverse of reabsorption which was from tubule to peritubular capillaries, In tubular secretion substances move from peritubular capillaries or tubule cells into filtrate Tubular secretion is important for: Disposing of substances, which are tightly bound to plasma proteins. E.g. certain drugs and metabolites, Eliminating undesirable substances or end products that have been reabsorbed by passive processes (urea and uric acid). Ridding the body of excess K+. Virtually all K+ present in the filtrate is reabsorbed in the PCT and ascending loop of Henle, All K+ in urine is from aldosterone-driven active tubular secretion into the late DCT and collecting ducts.

Controlling blood pH. Acidic pH, the renal tubule cells actively secrete more H+ into the filtrate and retain more HCO3–– (a base). blood pH rises Blood pH alkaline, Cl– is reabsorbed instead of HCO3–

Regulation of Urine Concentration and Volume

Osmolality The number of solute particles dissolved in 1L of water Reflects the solution’s ability to cause osmosis

Body fluids are measured in milliosmols (mOsm) The kidneys keep the solute load of body fluids constant at about 300 mOsm This is accomplished by the countercurrent mechanism

Countercurrent Mechanism

Interaction between the flow of filtrate through the loop of Henle (countercurrent multiplier) and the flow of blood through the vasa recta blood vessels (countercurrent exchanger) The solute concentration in the loop of Henle ranges from 300 mOsm to 1200 mOsm Dissipation of the medullary osmotic gradient is prevented because the blood in the vasa recta equilibrates with the interstitial fluid

Osmotic Gradient in the Renal Medulla

Figure 25.13

Loop of Henle: Countercurrent Multiplier

The descending loop of Henle: Is relatively impermeable to solutes Is permeable to water

The ascending loop of Henle: Is permeable to solutes Is impermeable to water

Collecting ducts in the deep medullary regions are permeable to urea

Loop of Henle: Countercurrent Exchanger

The vasa recta is a countercurrent exchanger that: Maintains the osmotic gradient Delivers blood to the cells in the area

Urinary System: Early Filtrate Processing

Loop of Henle: Countercurrent Mechanism

Figure 25.14

Formation of Dilute Urine

Filtrate is diluted in the ascending loop of Henle Dilute urine is created by allowing this filtrate to continue into the renal pelvis This will happen as long as antidiuretic hormone (ADH) is not being secreted Collecting ducts remain impermeable to water; no further water reabsorption occurs Sodium and selected ions can be removed by active and passive mechanisms Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Formation of Concentrated Urine

Antidiuretic hormone (ADH) inhibits diuresis This equalizes the osmolality of the filtrate and the interstitial fluid In the presence of ADH, 99% of the water in filtrate is reabsorbed ADH-dependent water reabsorption is called facultative water reabsorption ADH is the signal to produce concentrated urine The kidneys’ ability to respond depends upon the high medullary osmotic gradient PLAY

Urinary System: Late Filtrate Processing

Formation of Dilute and Concentrated Urine

Figure 25.15a, b

Diuretics

Chemicals that enhance the urinary output include: Any substance not reabsorbed Substances that exceed the ability of the renal tubules to reabsorb it Substances that inhibit Na+ reabsorption

Osmotic diuretics include: High glucose levels – carries water out with the glucose Alcohol – inhibits the release of ADH Caffeine and most diuretic drugs – inhibit sodium ion reabsorption Lasix and Diuril – inhibit Na+-associated symporters

Renal Clearance

The volume of plasma that is cleared of a particular substance in a given time Renal clearance tests are used to: Determine the GFR Detect glomerular damage Follow the progress of diagnosed renal disease

RC = UV/P RC = renal clearance rate U = concentration (mg/ml) of the substance in urine V = flow rate of urine formation (ml/min) P = concentration of the same substance in plasma

Physical Characteristics of Urine

Color and transparency Clear, pale to deep yellow (due to urochrome) Concentrated urine has a deeper yellow color Drugs, vitamin supplements, and diet can change the color of urine Cloudy urine may indicate infection of the urinary tract

Odor Fresh urine is slightly aromatic Standing urine develops an ammonia odor Some drugs and vegetables (asparagus) alter the usual odor

Physical Characteristics of Urine

pH Slightly acidic (pH 6) with a range of 4.5 to 8.0 Diet can alter pH

Specific gravity Ranges from 1.001 to 1.035 Is dependent on solute concentration

Chemical Composition of Urine

Urine is 95% water and 5% solutes Nitrogenous wastes include urea, uric acid, and creatinine Other normal solutes include: Sodium, potassium, phosphate, and sulfate ions Calcium, magnesium, and bicarbonate ions

Abnormally high concentrations of any urinary constituents may indicate pathology