the urinary system part 2
TRANSCRIPT
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
1. Luminal membrane of tubule cells
2. Basolateral membrane of tubule cells
3. 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 throughTranscellular route
Paracellular route
The transcellular route consists of four steps: 1. Transport across the luminal membrane,
2. Diffusion through the cytosol,
3. Transport across the basolateral membrane,
4. 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 cellsTransport 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 directioneg Na+/Glucose Co-Tranporter
Counter Transport or Antiport (Opposite Directions)One along conc.gradient, other against in opposite directionseg Na+/H+ Antiporter
Passive process (No ATP required)Passive Diffusion (between cells) (Paracellular)Facilitated Diffusion (Through Cells) (Transcellular)Osmosis (Para, Trans both)
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 ProcessNa+ 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
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 reabsorptionWater 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/secondCompletely 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 SolventsFiltrate becomes conc. as water leaves
Passive absorption of lipid-Soluble Drugs, Cations, fatty acids and some urea.
Secondary Active TransportLuminal 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 TransportSecondary 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
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
Absorptive Capabilities of Renal Tubules and Collecting Ducts
Decending Limb
Ascending limb
Water
Na+, Cl- and K+
Ca2+, Mg2+
Osmosis
1. Secondary active transport via Na+,
K+ and 2Cl-
cotransport
2. Na+/H+ Anitport
3. Paracellular diff.
Passive paracellular diff
Loop of Henle reabsorbs:
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 Aldosterone1. 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.
2. Facilitate water reabsorption: After Na+ is reabsorbed, water follows it back into the blood (if it can).
3. 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 elevatedANP reduces blood Na+ which:
Decreases blood volumeLowers blood pressure
ANP lowers blood Na+ by:Acting directly on medullary ducts to inhibit Na+ reabsorptionCounteracting 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 filtrateTubular 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 risesBlood pH alkaline, Cl– is reabsorbed instead of HCO3
–
Regulation of Urine Concentration and Volume
OsmolalityThe 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
Urinary System: Late Filtrate ProcessingPLAYPLAY
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/PRC = 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 transparencyClear, 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
OdorFresh 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 gravityRanges 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