Fluid and Electrolyte Balance in the Human Excretory System

Introduction to Excretion

Functions of the Excretory System

What is the Excretory System and what does it do?

• The excretory system regulates both the water content of the body and the ion concentration in body fluids

  • Essentially the kidney maintains the osmolarity of the body fluids = osmoregulation

  • Body fluids and water content include the watery components of the body including separate compartments such as the blood plasma (begins with this), the interstitial fluid, and cerebrospinal fluid.

• The kidney maintains the blood volume and interstitial fluid volume, thus it maintains blood pressure

  • Adequate blood volume is extremely important, if blood volume falls, then blood pressure can fall to zero. This prevents the heart from being able to pump blood through the body and you will die from low cardiac output

  • Interstitial fluid volume regulation is important to prevent edema (loss of blood volume when levels of fluid are too high), fluid accumulation in the lungs/heart, or dehydration (occurs when level of fluid are too low - Losing fluid in one compartment leads to compensation by pulling water from others.)

• The kidney eliminates nitrogenous wastes and other wastes

  • During metabolism we generate excess nitrogen in the from of ammonia NH₃, which needs to be excreted from the body because it is the most toxic in comparison to other nitrogenous compounds like urea and uric acid. In the body it is excreted in 4 different forms:

    • Ammonia*

      • The nitrogen in our body comes from the deamination of amino acids during protein catabolism

        • Aka protein in food gets broken down to amino acids which can be deaminated (or have the amino group removed) and then be metabolized to result in the accumulation of nitrogen.

        • Nitrogen is then removed in the form of ammonia (NH₃) a highly soluble gas and strong base that pulls four protons from water to create an ammonium ion (NH₄⁺)

      • Requires the most water to excrete

      • Requires the least energy to synthesize (make)

    • Urea*

      • humans have a relatively high concentration of urea in the blood

    • Uric Acid* (least toxic)

      • mostly insoluble, precipitates into white crystals

      • Requires the least amount of water to excrete

      • Requires the most energy to synthesize (make)

    • Creatinine

      • excreted in the urine

      • comes from the breakdown of creatine

    *= main human nitrogenous wastes

  • If an organism, such as fish, lives in freshwater, it is essentially living in distilled water. This means that their bodies are always accumulating water through osmosis and it is more difficult to get rid of excess water

    • This means a large amount of water is excreted through their kidneys and ammonia concentrations are always low, since they are continually excreting water to avoid lysis

  • If an organism lives in saltwater, it is hyperosmotic to the body fluids. This means that their bodies are always losing water through osmosis and it is easier to become dehydrated.

    • This means that these organism do not use or use less ammonia as their nitrogenous waste because it requires a lot of water to excrete (use uric acid)

  • Birds and other flying animals use a lot of energy to fly and cannot carry lots of water due to it’s weight, so nitrogen is converted to uric acid instead → the white stuff in bird poop

  • Humans mostly use urea as the form for excreting nitrogen from the body = a happy medium

• The excretory system also secretes hormones:

  • Erythropoietin (EPO)

    • Stimulates red bone marrow to produce RBCs

  • Renin (an enzyme)

    • Activates a set of hormones that regulate the salt content of body fluids

Overview of Excretion

The kidney is supplied by a big artery that carries blood at a high pressure, thus there is a high pressure, flow, and rate of blood throughout the kidney. This allows for increased fluid filtration

The kidney is comprised of units known as nephrons. Nephrons are a hollow tube made of a single layer of epithelial cells and consisting of a glomerulus and tubule. One end of the tubule is open and the other is closed

• The tubule that forms during embryonic development is closed, with one end expanding to form a bulb shape

• Sometime during embryonic development, the bulbous end is pushed in or invaginated

• At one point the invagination forms a double walled cup with a space in the middle

• Differentiation occurs and the inner wall of the cup are modified to support diffusion

• This is the bowman’s capsule, which has an inner layer comprised of podocytes

Inside the bowman’s capsule is the glomerulus which is a ball of capillaries that is supplied by an afferent arteriole. Once blood is filtered from the capillaries the it exits via the efferent arteriole and through the peritubular capillary

• Blood flowing through afferent arteriole is highly pressurized

• Blood flowing through efferent arteriole is at a lower pressure

  • Both the afferent and efferent arterioles, are arterioles because they contain smooth muscle

• The capillaries in the glomerulus are leaky, and leaking fluid that is then filtered through the slits between endothelial cells. The result of this filtration is water, ions, and small/medium organic molecules → this is called the filtrate

  • proteins DO NOT leak out

  • Has the same composition of plasma minus proteins

  • In capillaries in other areas of the body this filtrate becomes the interstitial fluid however in the nephron the filtrate passes through the bowman’s capsule and remains in the lumen of the tubule

• In the tubule the filtrate is forced out of the glomerulus into the bowman’s capsule by the difference between the blood (hydrostatic) pressure and the osmotic pressure: This is known as Filtration

  • The outward movement of water out of the capillary

• Filtrate moves along the tubule driven by the net pressure, which moves the filtrate until it reaches the end of the nephron

Along the length of the tubule, the epithelial cells will transport materials, taking in water ions and organic molecules that travel through the apical membrane (faces lumen) and out the basolateral membrane (faces away from lumen).

Materials can leak through the spaces between the epithelial cells, the can be:

• Taken out of the nephron lumen and into the surrounding interstitial fluid. Then the materials can diffuse into the leaky peritubular capillary: This is known as Reabsorption

  • The inward movement of water into the capillaries

    • This is because what is in the filtrate was initially in the blood plasma and it gets put back in the blood plasma

• Materials can be transported from the interstitial fluid to the nephron/tubule: This is known as Secretion

  • The movement of materials from the blood plasma into the tubule lumen

At the end of the tubule, urine comes out (is not modified after leaving the tubule)

So in short Excretion is:

• Filtration (amount put into tubule) - Reabsorption (amount moved from tubule to blood) + Secretion (amount moved from blood to tubule) = Excretion (amount peed out)

The Human Excretory System

• Humans have 2 kidneys composed of 2 different layers

  • Outer layer is the renal cortex

  • Inner layer is the renal medulla

  • The kidneys have a renal pelvis, or a series of tubes/funnels that collect urine from the nephron

• We have two kidneys in the abdomen that process blood and make urine; if you cut a kidney in half, you’ll see repeated pointy units called renal pyramids. Within these renal pyramids are nephrons. 

  • Nephrons are densely packed together within the renal pyramids

  • Nephrons means the same thing as kidney tubule

  • Nephrons are not short and straight, like in the simplified diagram before, they are long, bendy, and convoluted. These tubules filter out the plasma minus the proteins and modify the tubular fluid to form urine, which is then excreted.

• The ureter is a big tube that propel urine to the bladder, which leads to the urethra

The Nephron

There are two types of nephrons:

• Cortical Nephron: Resides in the renal cortex and has a short loop of henle (80% of nephrons)

• Juxtamedullary Nephron: Extends down into the renal medulla and has a long loop of henle (20% of nephrons)

The nephron consists of the glomerulus (w/ glomerular capillaries → highest pressure capillaries in the body) that is supplied by the afferent arteriole, which delivers blood to the glomerular capillaries at a high pressure and flow rate. The afferent arteriole is a smaller vessel that stems form the big renal artery

• There is 25x more blood flow through the kidney than the average of other organs

• It gets a lot of blood because the kidney continually adjusts the fluid, ion, and molecular composition of the plasma → 60 time the plasma volume/day

How does the process work?

Fluid is filtered out of the bowman’s capsule and pushed along the tubule buy the net filtration pressure. The fluid then reaches the curlicued proximal tubule (near bowman’s capsule) and down a long straight branch into the medulla that then comes up again. This is the Loop of Henle composed of the descending and ascending limbs. Once fluid passes the loop of henle it arrives at the distal tubule and then empties into a straight section of the tubule collecting duct (multiple nephrons can feed into one duct) where the fluid is further modified and comes out as urine. Urine is conveyed to the bladder via the ureters

The peritubular capillaries parallel the flow of fluid traversing through the nephron and are supplied by the efferent arteriole.

• The peritubular capillaries take blood from the efferent arterioles and take it to venules, larger veins, then the renal vein, which leads to the vena cava and right atrium. The blood through the peritubular capillaries can flow all the way down the loop or a short distance down the loop. 

  • Some of the blood coming from the first arteriole goes a looooooooongggg way before it gets to the first venule

• The long straight capillaries of this network are known as the vasa recata (these parallel the loop of henle)

• These receive water, irons, and organic molecules removed from the tubule (reabsorption) and supply waster products from the blood to the tubule (secretion). These are highly selective processes

Fluid Exchange Across Capillaries

Fluid gets driven out of capillaries by high blood pressure at the beginning of a vessel. This movement of fluid out of the capillaries is opposed by the inward movement of fluid caused by osmotic pressure (from the plasma proteins remaining in the blood). Thus there is a net movement out at upstream.

When BP falls at the end of a capillary, the outward movement of fluid decreases and the osmotic pressure remains the same, thus there is a net movement in at downstream

***In the kidney a back pressure is created by the net movement of fluid out of the capillary, as that fluid must displace the interstitial fluid within the bowman’s capsule. This back pressure is what moves the fluid in the nephron (kidney tubule)

• The pressure in bowman’s capsule is not zero, its higher

As blood travels through the peritubular capillaries, BP will decreases. BP starts high in the glomerular capillaries and at the vasa recta BP is much much lower, and thus there is a shift towards net reabsorption (AKA movement of materials from nephron to capillaries). At the distal tubule BP is low and there is reabsorption, but it is not as high as at the vasa recta

Glomerular Filtration

• The bowman’s capsule has an inner, visceral layer composed of podocytes

  • These podocytes form filtration slits, are motile, and respond to stimuli and hormones

  • These slits can widen or narrow to adjust rate of filtration

  • The fluid coming out of the bowman’s capsule and glomerulus complex has the SAME COMPOSITION OF BLOOD PLASMA EXCEPT IT DOES NOT HAVE THE PLASMA PROTEINS and then travels down the rest of the nephron

  • Net Filtration Pressure = Capillary Blood P - Osmotic P - Hydrostatic P in Lumen of Bowman’s Capsule

Tubular Transport

How does transportation and modification of fluid occur in the Nephron?

Proximal Tubule

• For epithelia that line a hollow organ, one side (the apical membrane that faces the lumen) performs different functions than the other (the basolateral membrane that faces the interstitial fluid → these cells are polarized

  • The cells adhere to one another with intercellular and tight junctions that form a belt around the cell

    • These tight junction limit the diffusion of materials in between cells, sealing off the extracellular space

  • The cells are in control of of what moves across epithelium

  • These cells facilitate the reabsorption of materias from the lumen to the blood and the secretion of materials from the interstitial fluid to the lumen

• Materials in the interstitial fluid will diffuse into or out of the peritubular capillary down a concentration gradient.

• Epithelial cells have pumps, ion channels, and transporters.

  • ATPases

    1. sodium-potassium pump (orange circle)

       • In the basolateral membrane

       • This drives everything in the cell as it pumps out 3 Na+ ions for ever 2 K+ ions in using 1 ATP molecule. This pump uses a lot of glucose/O2

       • Active transport of Na out of cells, makes intracellular sodium levels low (inside cell). This makes the inside of the cell negative and causes and inward sodium electrochemical gradient, which allows sodium ions to flow back into the cell through a passive sodium selective channel (yellow circle to the right - in apical membrane).

         • Sodium ions are being reabsorbed into the blood

       • Potassium ion channels in the aplical membrane pump K out of the cell, as the build up of it inside the cell creates an outward electrochemical gradient

         • This allows for secretion of K into the tubule fluid and excretion of it in the urine

    2. Sodium dependent, secondary active transporters (yellow circle in the middle)

       • In apical membrane

       • Do not directly use ATP, but use energy stored in the inward sodium electrochemical gradient to transport molecules (glucose, amino acids, chloride) against their concentration/electrochem gradients into the cell

    3. Facilitated diffusion, passive transporters (blue circle)

       • In basolateral membrane

       • Transport the same substances as secondary active transporters, but do so down a concentration gradient

       • Diffuse out of the cell into the interstitial fluid and then into the peritubular capillary,

         • These substances are reabsorbed into the blood)

  • An osmotic gradient is created by the reabsorption of solute into the blood. This causes water to diffuse from the nephron to the blood, via osmosis through 2 paths. This drives the reabsorption of water in the blood

    • Some water diffuses through the tight junctions

    • Travel though aquaporin channels

• An osmotic gradient is created by the reabsorption of all the solute into the blood. This causes water to diffuse via osmosis through 2 paths. This drives the reabsorption of water in the blood

  • Diabeties mellitus occurs when the glucose levels in the plasma are too high which show up in the urine.

Big Picture (Tubular Transport)

• The Loop of Henle has 3 total parts

  • Descending limbs moves fluid down

    • Only facilitates reabsorption water passively

  • Ascending limb moves fluid up and can be broken down into upper and lower parts.

    • the epithelial cells are permeable to salt, but not to water. The bottom of the ascending limb has thin epithelial cells which transport salt passively to blood and the top part of the ascending limb has thick epithelial cells which transport salt actively to blood using Na/K pumps

• Although similar, there is a difference between the process of the distal tubule and the proximal tubule

  • The mechanisms of secretion/reabsorption in the proximal tubule are unregulated (constitutive) due to occuring at a high rate

  • In the distal tubule, the fluid coming through is not very salty (because of the ascending limb’s reabsorption). Along the distal tubule, the solute concentration is adjusted by passive water reabsorption and active salt and bicarbonate reabsorption, along with active potassium and proton secretion. All of these processes are very regulated via hormones. This low-salt and high-water content fluid then dumps into the collecting duct

• In the collecting duct, the high water content/low solute fluid travels downwards and towards the salty medulla. There are two situations to know

  1. You are dehydrated and want to reabsorb water: Active transport is thus needed to take out more salt from this fluid. Furthermore, water and urea are reabsorbed. This happens because the medulla is very salty, which pulls water out of the tubular fluid. 

  2. You drank too much water and want to get rid of it: the collecting duct becomes impermeable to water, limiting reabsorption and promoting the dumping of water to prevent body fluids from becoming hypoosmotic

***Note: The medulla of the kidney contains high concentrations of salt and urea, with the highest concentrations being in the inner medulla, then the outer medulla is a little lower. The kidney does this so it can adjust its final extraction of water from the tubular fluid. 

• As the descending limb gives up water and enters the high-urea/salt-concentration regions of the medulla, there is a large drive of water to be reabsorbed into the vasa recta capillaries

• As water is reabsorbed down the length of the proximal tubule and descending loop of henle, the tubular fluid becomes saltier and saltier, but the salt cant leave until the ascending limb, wherein salt is reabsorbed. Reabsorption of salt is passive at first due to the high concentration of salt in the tubular fluid and then active due to the higher concentration.

• The thick ascending limb’s epithelial cells are thick, producing lots of ATP to fuel the sodium potassium pump, pumping salt out of the tubular fluid and into the vasa recta capillaries. 

• By the time the tubular fluid reaches the distal tubule, most of the salt is removed. 

• This mechanism is what makes the medulla so salty/hyperosmotic. The passive secretion of salt in the thin ascending limb/inner medulla and the active transport of salt out in the thick ascending limb/outer medulla creates the salty/hyperosmotic medulla. 

• The collecting duct traverses the salty medulla, and if the walls of the collecting duct are permeable, then water will flow out (be reabsorbed) in order to dilute the salty medulla. The vasa recta picks up this water and returns the water to the blood volume. THIS HAPPENS WHEN YOU ARE DEHYDRATED/TRYING TO CONSERVE WATER BY MINIMIZING FLUID LOSS. 

  • IF YOU DRINK TOO MUCH WATER: the body wants to prevent your body fluid from becoming hypoosmotic. It then adjusts its water permeability of the collecting duct, making it impermeable to water, preventing the reabsorption of water and making the urine watery. 

• In short, the permeability of the collecting duct is adjustable, and controlled by a hormone. 

  • When the hormone is present– the collecting duct is permeable to water

  • When the hormone is absent– the collecting duct is impermeable to water

• The salt that the blood gains on the way down (descending limb), it loses on the way up (ascending limb). The water that the blood loses on the way down (descending limb), it gains on the way up (ascending limb)

  • This is known as countercurrent exchange: the exchange between 2 limbs of a vessel that are flowing in opposite directions

Regulation of Kidney Function by ADH

• The kidney is regulated by Antidiuretic Hormone (ADH), which is also known as Arginine Vasopressin (AVP)

  • Diuresis refers to the production of urine, so antidiuretics = prevention of urine production

  • Has arginine in a key location

• The picture above is an illustration of a negative feedback loop that regulates the kidney function by monitoring plasma osmolarity

• An increase in plasma osmolarity (stemming from too much salt or lack of water in the blood → eating salty meals or dehydration) causes osmoreceptors in the hypothalamus to fire more nerve impulses. These impulses activate the pituitary gland to release ADH.

• Alcohol blocks the secretion of ADH, which can result in increased urine output and subsequent dehydration, compounding the effects of hyperosmolarity.

• The release of ADH has 3 effects

  1. Affects collecting duct epithelial target cells

     • Presence of ADH causes presence of aquaporins on the apical membrane (in comparison to only the basolateral membrane). This makes both membranes permeable to water, thus stimulating the osmotic reabsorption of water. This reabsorption counteracts the initial osmolarity increase

  2. ADH activates the hypothalamus cells that control thirst

     • These cells will signal thirst to the body, causing you to drink more water. When more water is drank, osmolarity is reduced down to the normal point

  3. ADH stimulates the contraction of smooth muscle around arterioles

     • ADH causes arteriolar vasoconstriction all through the body, which raises blood pressure - which is where the name vasopressin comes from.

     • If plasma molarity is high, then all the watery components of the body lack water including plasma. This also means that blood volume is low, so the filling of the heart during diastole is low. Cardiac output will be low and so will blood pressure

Regulation of Kidney Function by RAA

• RAA = Renin Angiotensin Aldosterone

  • Renin → enzyme that activates the hormones below

  • Angiotensin → hormone

  • Aldosterone → hormone

• In the location where the afferent arteriole supplies blood to the nephron, there is a loop of the distal tubule that passes very close to that arteriole (Juxatglomerular apparatus = JGA)

  • Arterioles have smooth muscle on the outside and epithelial cells on the inside

  • The smooth muscle at the JGA are modified to sense the flow of NaCl (from the filtrate which comes from the blood) through the distal tubule

  • Low blood pressure or blood volume results in less filtrate and less NaCl flow. This causes the cells to secrete Renin enzyme which will enter the blood and activate the hormone percursor angiotensinogen. Angiotensinogen will become Angiotensin II eventually

  • Angiotensin II has two effects

    1. Affect on outer layer of the adrenal gland

       • The adrenal gland is on the outer layer of the kidney and has an outer part (adrenal cortex) and inner part. The adrenal cortex itself has 3 layer, the outer one of it contains cells with receptors for angiotensin II.

       • When receptors bind to angiotensin II, aldosterone is secreted.

         • Aldosterone is a lipophilic (not soluble in water) hormone that is synthesized from cholesterol

         • Is made on demand and released immediately

       • Aldosterone increases sodium and water reabsorption in the distal tubules. This attracts the reabsorption of chloride

       • This reabsorption increases the blood plasma, volume, and pressure. This means more filling during ventricle diastole. And this counteracts the initial decrease in blood pressure/volume

    2. Stimulates the vasoconstriction of arterioles

       1. This raises blood pressure directly without affecting blood volume, this counteracts he initial decrease in blood pressure/volume

Regulation of Kidney Function by ANH⁺ and Urodilatin

• Is an antagonistic control system

• ANH⁺ = Atrial Natriuretic Hormone

  • A hormone secreted by the atria of the heart, stimulates the excretion of sodium in the urine → this lowers blood pressure

• When there is an increase in blood pressure and blood volume, the atria of the heart fill more with blood.

  • This overfilling of the atria, causes them to overstretch and secrete ANH⁺ in proportion to the amount of stretching

• The release of ANH⁺ has 3 effects

  1. Inhibits the release of renin from the juxtaglomerular apparatus (JGA)

     • remember renin’s release is the first step in RAA regulation of the kidney → so ANH⁺ inhibits the RAA system

  2. Inhibits the synthesis/release of aldosterone in the adrenal cortex

     • This will lower BP and BV

  3. Inhibits NaCl reabsorption (aldosterone’s effect) and ADH-stimulated water reabsorption

     • lowers BP and BV

• Urodilation is released by the cells in the distal tubule, which respond to increased BP or BV by secreting this peptide hormone. → only has effects on the collecting duct and has the same affect as ANH⁺