Kidney's Role in Urine Production

Kidney's Role in Urine Production

• Kidneys create an environment that allows the reabsorption of water and solutes to produce either highly concentrated, low volume urine (when dehydrated) or dilute, large volume urine (when over-hydrated)

Osmotic Pressure

• Renal ultrafiltrate has an osmotic pressure of approximately 300 mOsm/L, coming from 140 mmol NaCl (280 mOsm/L) and other solutes

Nephron Function

• Glomerular filtration is the first step of nephron function
• Sodium bicarbonate, glucose, amino acids, and water are reabsorbed after glomerular filtration
• The fluid is hyposmotic in the distal tubule
• Osmolarity is adjusted in the cortex
• Remaining filtrate becomes urine

Proximal Convoluted Tubule Reabsorption

• Main components of blood are reabsorbed, and all blood constituents are reabsorbed minus cells and protein
• Osmolarity is approximately 300 mOsm/L
• Approximately 70% of the filtrate is reabsorbed when GFR is normal
• Volume reabsorbed typically does not vary in this location
• Plays no regulatory role and returns most of the filtrate to the blood

Loop of Henle Reabsorption

• Approximately 20% of the filtrate is reabsorbed
• Volume reabsorbed is typically constant
• Reabsorption is a part of the countercurrent mechanism

Distal Tubule and Collecting Duct

• Approximately 10% of the filtrate enters
• Variable reabsorption of salt and water takes place
• In low water intake, water reabsorption is high
• In high water intake, water reabsorption is low or nonexistent

Sodium and Water Regulation

• Aldosterone controls sodium reabsorption
• Anti-diuretic hormone (ADH/vasopressin) regulates water reabsorption
• Normal water intake leads to ~12 ml entering the collecting duct, with ~11 ml reabsorbed, resulting in a normal urinary output of ~1 ml/min

Water Intake and Urinary Output

• High water intake leads to no water reabsorption and a urinary output up to ~12 ml/min
• Low water intake leads to maximal water reabsorption and a urinary output down to ~0.5 ml/min

Water Reabsorption Variations in the Collecting Duct

• Variations in water reabsorption can occur and urinary output can vary from 0.5 to 12 ml/min depending on conditions and hydration

Sensing Osmolarity

• High plasma osmolarity stimulates osmoreceptors in the anterior hypothalamus

CD Water Reabsorption Requirements

• The presence of anti-diuretic hormone (ADH) makes the collecting duct permeable to water otherwise the collecting duct is impermeable to water
• ADH inserts aquaporins
• Hypertonic interstitium generates the osmotic gradient to reabsorb water

Hypertonic Interstitium

• Hypertonic interstitium refers to the osmolarity of the interstitium being greater than that of the interstitium in other tissues, which is 300 mOsm/L

Loop of Henle Function

• Loop of Henle generates and maintains a hypertonic interstitium using a countercurrent multiplier

Countercurrent Mechanism

• Countercurrent establishes a concentration gradient in the medulla
• Countercurrent occurs when fluid moves in opposite directions in the loop of Henle

Key Adaptations

• Desert kangaroo rats have longer loops of Henle when compared to beavers and humans

Loop Characteristics for Countercurrent Multiplier Operation

• Descending limb allows filtrate to flow down and ascending limb allows filtrate to flow up
• Descending limb is permeable to water
• Ascending limb is impermeable to water and has salt pumps that deposit salt into the interstitium

Salt Pumps

• Salt pumps in the walls of the ascending limb generate and maintain a difference in salt concentration of about 200 mosmol/L between the filtrate in the ascending limb and the surrounding interstitium

Countercurrent Exchange System

• Anatomical arrangement has vessels in opposite directions to flow in the adjacent vessel

Countercurrent Multiplier

• Anatomical arrangement of the loop of Henle concentrates solute in the renal medulla

Regions of the Loop of Henle:

• Thin-walled descending limb is highly permeable to water, not solutes; water flows out via osmosis
• Thin-walled, lower ascending limb is permeable to Na+ and Cl-, moderately permeable to urea, impermeable to water
• Thick-walled, upper ascending limb actively pumps Na+ & Cl- out of the filtrate

Steps in Creating Concentrated Urine

• Active salt pump in the ascending limb transports sodium chloride until the surrounding interstitium is more concentrated than the tubular fluid by 200 mosom/L
• Water moves passively out of the descending limb until the osmolarities become equal
• Advance the entire column of fluid around the loop of Henle
• Ascending limb again transports salt out while water passively diffuses from the descending limb until a 200 mosom/l difference is re-established between ascending limb and interstitium at each level
• Continue this process and the fluid in the descending limb becomes increasingly hypertonic until it reaches a maximum of 1,200 mosm/l at the bottom of the loop
• Concentration of tubular fluid in ascending limb decreases as salt is pumped out
• Equilibrium is achieved in interstitial fluid in the medulla
• Countercurrent flow multiplies the gradient

Collecting Ducts

• Collecting ducts course from the cortex to the medulla and are surrounded by the interstitium

Vertical Gradient

• Vertical osmotic gradient enables water movement by osmosis down the concentration gradient to produce highly concentrated low volume urine

Key Permeabilities

• Vasopressin leads to distal and collecting tubules becoming permeable to water

Water Conservation Requirements

• Water conservation requires presence of ADH and a vertical osmotic gradient

The Salt Pump

• Carrier protein NKCC2 transports 1Na+, 1K+ and 2Cl-
• Inhibited by loop diuretics such as furosemide and bumetanide leads to reduced hypertonic interstitium
• Reduced ability to reabsorb by osmosis, and salt and water excretion is increased

Urea Facts

• Urea is a small organic molecule made up of amide groups
• Urea is produced in the liver and excreted in the urine and plasma concentrations should be 2.5-6.0 mmol/L

Urea Handling

• Ascending LOH and DT highly impermeable so tubular [urea] increases concentration
• ADH increases urea permeability by promoting UT-A1 and UT-A3 urea transporters

Urea Recycling

• Urea exits collecting duct due to ADH increasing urea permeability
• Urea enters loop of Henle and helps concentrate the surrounding intersitium of the inner medullary region of kidney
• After entering the loop of Henle, urea is recycled via UT-Bs
• The recycling allows a high amount of urea to build up in the medulla

Urea's Role

• Many nephron segments have urea which results in a buildup in the tubule
• ADH increases the urea permeability in the inner medullary collecting duct, allowing the urea to diffuse passively out of the IMCD into the medullary fluids
• Some of the urea then diffuses and recycles into the thin ascending limb of the loop of Henle
• Urea, as a result of recycling, accounts for 50% of the osmotic pressure of the medullary fluids in a maximally concentrating human kidney
• Without ADH, urea is not recycled and more excretion occurs

Hypertonic Interstitium and the Vasa Recta capillaries

• Vasa recta capillaries are hairpin shaped and blood flows countercurrent, allowing salt and water to be carried away

Salt and Water Removal

• The loop configuration of the vasa recta to continuously removes salt and water from the interstitium without increasing osmolality or volume in the medullary interstitium.