Slide Set 7: Urinary System Flashcards
What is the most important function of kidneys?
homeostatic regulation of:
- water
- ion content of the blood
= electrolyte balance.
The kidneys maintain normal blood concentrations of ions and water by balancing intake of those substances with their excretion in the urine, obeying the principle of ________
mass balance
Kidney function can be divided into 6 major categories:
- Regulation of extracellular fluid volume and blood pressure.
- Regulation of osmolarity.
- Maintenance of ion balance.
- Homeostatic regulation of pH
- Excretion of wastes.
- Production of hormones
How is regulation of extracellular fluid volume and blood pressure achieved?
When extracellular fluid volume decreases, blood pressure also decreases.
If ECF volume and blood pressure fall too low, the body cannot maintain adequate blood flow to the brain and other essential organs.
The kidneys work in an integrated fashion with the cardiovascular system to ensure that blood pressure and tissue perfusion remain within an acceptable range.
How is regulation of osmolarity achieved?
The body integrates kidney function with behavioural drives, such as thirst, to maintain blood osmolarity at a value close to 290 mOsM.
How is maintenance of ion balance achieved?
The kidneys keep concentrations of key ions within a normal range by balancing dietary intake with urinary loss.
Sodium (Na+) is the major ion involved in the regulation of extracellular fluid volume and osmolarity. Potassium (K + ) and calcium (Ca2 + ) concentrations are also closely regulated.
What is the major ion involved in the regulation of extracellular volume and osmolarity?
Sodium (Na+) is the major ion involved in the regulation of extracellular fluid volume and osmolarity.
How is homeostatic regulation of pH. achieved?
The pH of plasma is normally kept within a narrow range.
If extracellular fluid becomes too acidic, the kidneys remove H+ and conserve bicarbonate ions (HCO3-), which act as a buffer. Conversely, when extracellular fluid becomes too alkaline, the kidneys remove HCO3- and conserve H+. The kidneys play a significant role in pH homeostasis, but they do not correct pH disturbances as rapidly as the lungs do.
What happens if the ECF becomes too acidic?
the kidneys remove H+ and conserve bicarbonate ions (HCO3-), which act as a buffer.
What happens if the ECF becomes too alkaline?
the kidneys remove HCO3- and conserve H+.
Which one is faster in terms of ph correction: kidneys or lungs?
lungs
How is excretion of wastes achieved?
The kidneys remove metabolic waste products and foreign substances, such as drugs and environmental toxins.
Metabolic wastes include creatinine from muscle metabolism and the nitrogenous wastes urea and uric acid.
A metabolite of hemoglobin called urobilinogen gives urine its characteristic yellow color.
Hormones are another endogenous substance the kidneys clear from the blood. Examples of foreign substances that the kidneys actively remove include the articial sweetener saccharin and the anion benzoate, part of the preservative potassium benzoate, which you ingest each time you drink a diet soda drink.
What gives the yellow color to urine?
A metabolite of hemoglobin called urobilinogen gives urine its characteristic yellow color.
How is production of hormones achieved?
Although the kidneys are not endocrine glands, they play important roles in three endocrine pathways.
Kidney cells synthesize erythropoietin, the cytokine/hormone that regulates red blood cell synthesis.
They also release renin, an enzyme that regulates the production of hormones involved in sodium balance and blood pressure homeostasis.
Renal enzymes help convert vitamin D3 into a hormone that regulates Ca2+ balance.
Give examples of kidney enzymes
erythropoietin - RBC production
renin - sodium balance and blood pressure homeostasis
renal enzymes - convert vitamin D3 into a hormone that regulates Ca2+ balance.
Explain urine production and the route it takes for excretion
- water and solutes move from plasma into the hollow tubules (nephrons) that make up the bulk of the paired kidneys.
- modify the composition of the fluid as it passes through.
- The modified fluid leaves the kidney and passes into a hollow tube called a ureter. There are two ureters, one leading from each kidney to the urinary bladder.
- The bladder expands and fills with urine until, by reflex action, it contracts and expels urine through a single tube, the urethra.
What is micturition?
is the process by which urine is excreted - urination
A cross section through a kidney shows that the interior is arranged in two layers:
an outer cortex and inner medulla
The layers of kidneys are formed by the organized arrangement of microscopic tubules called _______.
nephrons
What is the functional unit of kidneys?
The nephron is the functional unit of the kidney
Each nephron has two components:
–Vascular component
–Tubular component
From nephrons the urine travels to the ______ which can be thought of as the start of the urinary plumbing, then to the ureter
calyx
Vascular elements of kidney and the order
afferent arteriole –> glomerulus –> efferent arteriole
- -> peritubular capillaries –> vasa recta (capillaries that dip into the medulla) –> renal capillaries –> venules
- -> small veins –> renal vein
What is the function of the renal portal system?
First to filter fluid out of the blood and into the lumen of the nephron at the glomerular capillaries, then to reabsorb fluid from the tubule back into the blood at the peritubular capillaries.
Tubular elements of kidneys and the order
Nephron –> Bowman’s capsule + glomerulus –>renal corpuscle –> proximal tubule –> loop of Henle –> descending limb –> ascending limb –> distal tubule –> collecting duct —> medulla —> cortex –> renal pelvis (urine) –> ureter
The nephron begins with a hollow, ball-like structure called __________ that surrounds the glomerulus
Bowman’s capsule
The combination of glomerulus and
Bowman’s capsule is called the___________.
renal corpuscle
The loop of Henle is divided into two:
descending limb
ascending limb
a hairpin-shaped segment that dips down toward the medulla and then back up
The loop of Henle
the final part of the ascending limb of the loop of Henle passes between the afferent and efferent arterioles. is region is known as the ______
juxtaglomerular apparatus
What is a key feature to kidney autoregulation?
The proximity of the ascending limb and the arterioles allows paracrine communication between the two structures, a key feature of kidney autoregulation.
What are the 3 basic processes that take place in kidneys?
Three basic processes take place in the nephron:
filtration
reabsorption
secretion
What is filtration in kidneys?
Filtration is the movement of fluid from blood into the lumen of the nephron.
Where does filtration take place in kidneys?
Filtration takes place only in the renal corpuscle, where the walls of glomerular capillaries and Bowman’s capsule are modi ed to allow bulk flow of fluid.
What happens to the “filtrate” once it is filtrated?
passes into the lumen of the nephron, it becomes part of the body’s external environment, just as substances in the lumen of the intestinal tract are part of the external environment. For this reason, anything that filters into the nephron is destined for excretion.
After filtrate leaves Bowman’s capsule, it is modified by reabsorption and secretion.
What is excretion?
removal in the urine, unless it is reabsorbed into the body.
What is reabsorption in kidneys?
is the process of moving substances in the filtrate from the lumen of the tubule back into the blood flowing through peritubular capillaries.
What is secretion in kidneys?
Secretion removes selected molecules from the blood and adds them to the filtrate in the tubule lumen. Although secretion and glomerular filtration both move substances from blood into the tubule, secretion is a more selective process that usually uses membrane proteins to move molecules across the tubule epithelium.
Both secretion and glomerular filtration move substances from the blood into the tubule but what is the major difference?
secretion is a more selective process that usually uses membrane proteins to move molecules across the tubule epithelium
Reabsorption occurs when ___________
proximal tubule cells transport solutes out of the lumen, and water follows by osmosis.
True/False
Filtrate leaving the proximal tubule has higher osmolarity than the filtrate that entered.
FALSE!!
Filtrate leaving the proximal tubule has the same osmolarity as filtrate that entered.
What is the primary function of the proximal tubule?
the primary function of the proximal tubule is the reabsorption of isosmotic fluid.
Where is the primary site for creating dilute urine?
Filtrate leaving the proximal tubule passes into the loop of Henle, the primary site for creating dilute urine.
What happens to the filtrate as it passes through the loop?
As filtrate passes through the loop, proportionately more solute is reabsorbed than water, and the filtrate becomes hyposmotic relative to the plasma.
When does the regulation of salt and water balance take place?
From the loop of Henle, filtrate passes into the distal tubule and the collecting duct. In these two segments, the fine regulation of salt and water balance takes place under the control of several hormones.
What determines the final composition of the filtrate?
Reabsorption and (to a lesser extent) secretion determine the final composition of the filtrate.
What do the final volume and osmolarity of urine depend on?
The final volume and osmolarity of urine depend on the body’s need to conserve or excrete water and solute.
The amount of any substance excreted in the urine reflects how that substance was handled during its passage through the nephron. What is the equation that proves that?
Amount filtered - amount reabsorbed + amount secreted = amount excreted
The percentage of total plasma volume that filters into the tubule is called the ___________.
filtration fraction
Where does filtration take place?
renal corpuscle, which consists of the glomerular capillaries surrounded by Bowman’s capsule.
Substances leaving the plasma must pass through three filtration barriers before entering the tubule lumen:
- the glomerular capillary endothelium,
- a basal lamina (basement membrane)
- the epithelium of Bowman’s capsule
What is the function of pores in the glomerular capillaries
to prevent blood cells from leaving the capillary.
The negatively charged proteins on the pore surfaces also help repel negatively charged plasma proteins.
What is Glomerular filtration?
non discriminant, except blood cells and plasma proteins all constituents within the blood are filtered
What is basal lamina?
an acellular layer of extracellular matrix that separates the capillary endothelium from the epithelial lining of Bowman’s capsule
The basal lamina consists of negatively charged glycoproteins, collagen, and other proteins.
What are podocytes?
The portion of the capsule epithelium that surrounds each glomerular capillary consists of specialized cells called podocytes {podos, foot}. Podocytes have long cytoplasmic extensions called foot processes that extend from the main cell body.
What drives filtration across the walls of the glomerular capillaries?
The three pressures that influence glomerular filtration—-
- capillary blood pressure,
- capillary colloid osmotic pressure,
- capsule fluid pressure
What is hydrostatic pressure (PH)?
- The hydrostatic pressure (PH) of blood flowing through the glomerular capillaries forces fluid through the leaky endothelium.
- Capillary blood pressure averages 55 mm Hg and favors filtration into Bowman’s capsule.
- Although pressure declines along the length of the capillaries, it remains higher than the opposing pressures.
Consequently, filtration takes place along nearly the entire length of the glomerular capillaries.
What is colloid osmotic pressure (p)?
inside glomerular capillaries is higher than that of the fluid in Bowman’s capsule.
This pressure gradient is due to the presence of proteins in the plasma.
The osmotic pressure gradient averages 30 mm Hg and favours fluid movement back into the capillaries.
What is hydrostatic fluid pressure (Pfluid)?
Bowman’s capsule is an enclosed space (unlike the interstitial fluid), and so the presence of fluid in the capsule creates a hydrostatic fluid pressure (Pfluid) that opposes fluid movement into the capsule.
Fluid filtering out of the capillaries must displace the fluid already in the capsule lumen.
Hydrostatic fluid pressure in the capsule averages 15 mm Hg, opposing filtration.
What is the net driving force and is flitration achieved?
The net driving force is 10 mm Hg in the direction favouring filtration. Although this pressure may not seem very high, when combined with the very leaky nature of the fenestrated capillaries, it results in rapid fluid filtration into the tubules.
The volume of fluid that filters into Bowman’s capsule per unit time is the _______
glomerular filtration rate (GFR)
GFR is in inuenced by two factors:
the net filtration pressure just described and the filtration coefficient.
How is filtration pressure determined?
Filtration pressure is determined primarily by renal blood flow and blood pressure.
The filtration coefficient has two components:
the surface area of the glomerular capillaries available for filtration and the permeability of interface between the capillary and Bowman’s capsule.
True/False
if blood pressure increases, GFR increases, and if blood pressure falls, GFR decreases.
False
GFR is remarkably constant over a wide range of blood pressures.
How is GFR controlled?
GFR is controlled primarily by regulation of blood flow through the renal arterioles. If the overall resistance of the renal arterioles increases, renal blood flow decreases, and blood is diverted to other organs. The effect of increased resistance on GFR, however, depends on where the resistance change takes place.
If resistance increases in the ________, hydrostatic pressure decreases on the glomerular side of the constriction. This translates into a decrease in GFR.
afferent arteriole
If resistance increases in the _______, blood “dams up” in front of the constriction, and hydrostatic pressure in the glomerular capillaries increases (Fig. 19.8e). Increased glomerular pressure increases GFR.
efferent arteriole
Where does the absorption take place?
Most of this reabsorption takes place in the proximal tubule, with a smaller amount of reabsorption in the distal segments of the nephrons.
What is the main function of the distal nephron?
Regulated re- absorption in the distal nephron allows the kidneys to return ions and water to the plasma selectively—as needed to maintain homeostasis.
True/False
Once a substance filters into the lumen of Bowman’s capsule, it is no longer part of the body’s internal environment.
True
The lumen of the nephron is external environment, and anything in the filtrate is destined to leave the body in the urine unless there is a tubule mechanism for reclaiming it.
Reabsorption of water and solutes from the tubule lumen to the extracellular fluid depends on ______
active transport
How i concentration or electrochemical gradient created in the Bowman’s capsule for filtration?
The filtrate flowing out of Bowman’s capsule into the proximal tubule has the same solute concentrations as extracellular fluid. To move solute out of the lumen, the tubule cells must therefore use active transport to create concentration or electrochemical gradients
Water osmotically follows solutes as they are reabsorbed.
What does active transport of Na+ provide?
Active transport of Na+ from the tubule lumen to the extracellular fluid creates a transepithelial electrical gradient in which the lumen is more negative than the ECF.
Anions then follow the positively charged Na + out of the lumen.
What does removal of Na+ and anions from lumen to CF do?
The removal of Na + and anions from lumen to ECF dilutes the luminal fluid and increases the concentration of the ECF, so water leaves the tubule by osmosis.
How are anions filtrated out to the lumen?
Anions follow the positively charged Na + out of the lumen.
What happens to the solute concentration if there is a loss of volume?
The loss of volume from the lumen increases the concentration of solutes (including K +, Ca2 +, and urea) left behind in the filtrate: the same amount of solute in a smaller volume equals higher solute concentration.
Once luminal solute concentrations are higher than solute concentrations in the extracellular fluid, the solutes diffuse out of the lumen if the epithelium of the tubule is permeable to them.
What happens once luminal solute concentrations are higher than solute concentrations in the extracellular fluid?
Once luminal solute concentrations are higher than solute concentrations in the extracellular fluid, the solutes diffuse out of the lumen if the epithelium of the tubule is permeable to them.
Reabsorption involves
epithelial transport and para-cellular transport.
epithelial transport
In epithelial transport (also called trans-cellular transport), substances cross the apical and basolateral membranes of the tubule epithelial cell to reach the interstitial fluid.
paracellular pathway
In the paracellular pathway, substances pass through the cell-cell junction between two adjacent cells. Which route a solute takes depends on the permeability of the epithelial junctions and on the electrochemical gradient for the solute.
For solutes that move by epithelial transport, their concentration or electrochemical gradients determine their transport mechanisms. Solutes moving down their gradient use _______ or ______ carriers to cross the cell membrane. Molecules that need to be pushed against their gradient are moved by either _____ or ______. Sodium is directly or indirectly involved in many instances of both passive and active transport.
open leak channels
facilitated diffusion
primary or indirect (usually secondary) active transport
What is the the primary driving force for most renal reabsorption?
The active reabsorption of Na+ is the primary driving force for most renal reabsorption.
Principles governing the tubular reabsorption of solutes
- Na+ is reabsorbed by active transport.
- Electrochemical gradient drives anion
reabsorption. - Water moves by osmosis, following solute reabsorption. Concentrations of other solutes increase as fluid volume in lumen decreases.
- Permeable solutes are reabsorbed by diffusion through membrane transporters or by the paracellular pathway.
Sodium reabsorption in the proximal tubule: active transport
- Na+ enters cell through various membrane proteins, moving down its electrochemical gradient.
- Na+ is pumped out the basolateral side of cell by the Na+-K+-ATPase.
Sodium-linked reabsorption: indirect (secondary) active transport
- Na+ moving down its electro-chemical gradient uses the SGLT protein to pull glucose into the cell against its concentration gradient.
- Glucose diffuses out the basolateral side of the cell using the GLUT protein.
- Na+ is pumped out by Na+-K+-ATPase.
Explain Passive Reabsorption: Urea
When water is reabsorbed, the concentration of urea in the lumen increases—the same amount of urea is contained in a smaller volume. Once a concentration gradient for urea exists, urea moves out of the lumen into the extracellular fluid by trans-port through the cells or by the paracellular pathway.
What causes urea concentration gradient to occur?
the active transport of Na+ and other solutes in the proximal tubule creates a urea concentration gradient by the following process.
How are nitrogenous waste product transported?
The nitrogenous waste product urea has no active transporters in the proximal tubule but can move across the epithelium by diffusion if there is a urea concentration gradient.
Where are filtered proteins reabsorbed?
Filtration of plasma at the glomerulus normally leaves most plasma proteins in the blood, but some smaller proteins and peptides can pass through the filtration barrier.
Most filtered proteins are reabsorbed in the proximal tubule, with the result that normally only trace amounts of protein appear in urine.
If the proteins are too large to be absorbed by carriers or through channels. How are they reabsorbed?
Small as they are, filtered proteins are too large to be reabsorbed by carriers or through channels. Instead they enter proximal tubule cells by receptor-mediated endocytosis at the apical membrane.
______ refers to the maximum rate of transport that occurs when all available carriers are occupied by (are saturated with) substrate.
Saturation = Transport maximum
Give an example of saturation in kidneys
Glucose reabsorption in the nephron is an excellent example of the consequences of saturation.
High glucose –> leakage in the urine
DIABETES
True/False
filtrate glucose concentration is always equal to the plasma glucose concentration.
True
The reabsorption we have just discussed refers to the movement of solutes and water from the tubule lumen to the interstitial fluid. How does that reabsorbed fluid then get into the capillary?
The answer is that the hydrostatic pressure that exists along the entire length of the peritubular capillaries is less than the colloid osmotic pressure, so the net pressure gradient favours reabsorption
What is secretion in kidneys?
Secretion is the transfer of molecules from extracellular fluid into the lumen of the nephron
The secretion of ______ ions by the ______ is important in the homeostatic regulation of those ions.
K+ and H+
distal nephron
organic anion trans- porter (OAT) family
is able to transport a wide variety of endogenous and exogenous anions, ranging from bile salts to benzoate used as a preservative in so drinks, salicylate from aspirin, and the artificial sweetener saccharine. Secretion of organic anions on the OAT is an example of tertiary active transport, where the use of energy from ATP is two steps removed from the OAT.
Organic Anion Secretion Steps
- Direct active transport. The Na+-K+-ATPase keeps intracellular [Na+] low.
- Secondary indirect active transport. The Na+-dicarboxylate cotransporter (NaDC) concentrates a dicarboxylate inside the cell using energy stored in the [Na+] gradient.
- Tertiary indirect active transport. The basolateral organic anion transporter (OAT) concentrates organic anions (OA–) inside the cell, using the energy stored in the dicarboxylate gradient.
- Organic anions enter the lumen by facilitated diffusion.
What is excretion in kidneys?
Urine output is the result of all the processes that take place in the kidney.
What does excretion equal to?
Excretion = filtration - reabsorption + secretion
The excretion rate of a substance depends on
(1) the filtration rate of the substance and
(2) whether the substance is reabsorbed, secreted, or both, as it passes through the tubule.
micturition
desire to pee
The internal sphincter is a continuation of the bladder wall and consists of
smooth muscle
The external sphincter is _________
a ring of skeletal muscle controlled by somatic motor neurons.
True/False
the kidneys cannot replenish lost water: all they can do is conserve it.
true
Removal of excess water in urine is known as _____
diuresis
Drugs that promote the excretion of urine are called _____
diuretics
What happens to the urine if the kidneys are conserving water?
becomes more concentrated
The kidneys control urine concentration by
varying the amounts of water and Na reabsorbed in the distal nephron (distal tubule and collecting duct).
To produce dilute urine, the kidney must _______
On the other hand, if urine is to become concentrated, the nephron must be able to ____________
reabsorb solute without allowing water to follow by osmosis. This means that the apical tubule cell membranes must not be permeable to water.
reabsorb water but leave solute in the tubule lumen.
water is reabsorbed only by osmosis through ______
water pores (aquaporins)
What is the mechanism of absorbing water?
the collecting duct cells and interstitial fluid surrounding them more concentrated than the fluid flowing into the tubule. Then, if the tubule cells have water pores, water can be absorbed from the lumen without first reabsorbing solute.
Osmolarity Changes Through the Nephron Step-by-Step
- Isosmotic fluid leaving the proximal tubule becomes progressively more concentrated
in the descending limb. - Removal of solute in the thick ascending limb creates hyposmotic fluid.
- Permeability to water and solutes is regulated by hormones.
- Urine osmolarity depends on reabsorption in the collecting duct.
What happens when the kidneys want to conserve water?
if the body needs to conserve water by reabsorbing it, the tubule epithelium in the distal nephron must become permeable to water. Under hormonal control, the cells insert water pores into their apical membranes. Once water can enter the epithelial cells, osmosis draws water out of the less- concentrated lumen and into the more concentrated interstitial fluid.
How do the distal tubule and collecting duct cells alter their permeability to water?
The process involves adding or removing water pores in the apical membrane under the direction of the posterior pituitary hormone vasopressin
vasopressin causes the body to retain water, it is also known as ________
antidiuretic hormone (ADH)
How does vasopressin act?
When vasopressin acts on target cells, the collecting duct epithelium becomes permeable to water, allowing water to move out of the lumen. The water moves by osmosis because solute concentration in the cells and interstitial fluid of the renal medulla is higher than that of fluid in the tubule.
What happens in absence of vasopressin?
In the absence of vasopressin, the collecting duct is impermeable to water. Although a concentration gradient is present across the epithelium, water remains in the tubule, producing dilute urine.
Water pores are aquaporins, a family of membrane channels with at least 10 different isoforms that occur in mammalian tissues. The kidney has multiple isoforms of aquaporins, including ________, the water channel regulated by vasopressin.
aquaporin-2 (AQP2)
AQP2 in a collecting duct cell may be found in two locations:
on the apical membrane facing the tubule lumen and in the membrane of cytoplasmic storage vesicles
How does vasopressin act in terms of AQP2?
When vasopressin arrives at the collecting duct, it binds to its V2 receptors on the basolateral side of the cell.
Binding activates a G-protein/cAMP second messenger system.
Subsequent phosphorylation of intracellular proteins causes the AQP2 vesicles to move to the apical membrane and fuse with it.
Exocytosis inserts the AQP2 water pores into the apical membrane.
Now the cell is permeable to water.
What stimuli control vasopressin secretion? There are three:
plasma osmolarity, blood volume, and blood pressure
Osmolarity is monitored by _________, stretch-sensitive neurons that increase their firing rate as osmolarity increases.
osmoreceptors
True/False
Decreases in blood pressure and blood volume are less powerful stimuli for vasopressin release.
true
Countercurrent Exchange Systems
require arterial and venous blood vessels that pass very close to each other, with their fluid ow moving in opposite directions (the name countercurrent reflects the fact that the two flows run counter to each other). This anatomical arrangement allows the passive transfer of heat or molecules from one vessel to the other.
Countercurrent Exchange Systems in kidneys
because the kidney forms a closed system, the solutes are not lost to the environment. Instead, the solutes concentrate in the interstitium. This process is aided by active transport of solutes out of the ascending limb of the loop of Henle, which makes the ECF osmolarity even greater. A countercurrent exchange system in which exchange is enhanced by active transport of solutes is called a countercurrent multiplier.
True/False
blood flow in the vasa recta moves in the same direction from filtrate flow in the loops of Henle
false
blood flow in the vasa recta moves in the opposite direction from filtrate flow in the loops of Henle
Describe the fluid movement in loop the Henle
Isosmotic filtrate from the proximal tubule first flows into the descending limb of the loop of Henle. The descending limb is permeable to water but does not transport ions. As the loop dips into the medulla, water moves by osmosis from the descending limb into the progressively more concentrated interstitial fluid, leaving solutes behind in the tubule lumen.
The filtrate becomes progressively more concentrated as it moves deeper into the medulla.
What happens when the fluid enters the ascending limb of loop de Henle?
When the fluid flow reverses direction and enters the ascending limb of the loop, the properties of the tubule epithelium change. The tubule epithelium in this segment of the nephron. is impermeable to water while actively transporting N+, K+ and Cl- out of the tubule into the interstitial fluid. The loss of solute from the lumen causes the filtrate osmolarity to decrease steadily.
What is the net result of the countercurrent multiplier in the kidney?
The net result of the countercurrent multiplier in the kidney is to produce hyperosmotic interstitial fluid in the medulla and hyposmotic filtrate leaving the loop of Henle.
What is the function of the NKCC symporter?
The NKCC symporter uses the energy stored in the Na+ concentration gradient to transport Na+, K+, and 2 Cl- from the lumen into the epithelial cells of the ascending limb. The Na+K+ATPase removes Na from the cells on the basolateral side of the epithelium, while K+ and Cl leave the cells together on a cotransport protein or through open channels.
What happens to the osmolarity when we ingest NaCl?
The addition of NaCl to the body raises osmolarity.
What are the signals triggered by the increased osmolarity in the body?
vasopressin secretion and thirst. Vasopressin release causes the kidneys to conserve water (by reabsorbing water from the filtrate) and concentrate the urine. First prompts us to drink water or other fluids.
The reabsorption of Na+ in the distal tubules and collecting ducts of kidney is regulated by the steroid hormone called
ALDOSTERONE
the more aldosterone, the more Na reabsorption.
Where is aldosterone synthesized?
adrenal cortex
What is the primary action site of aldosterone?
The primary site of aldosterone action is the last third
of the distal tubule and the portion of the collecting duct that runs through the kidney cortex (the cortical collecting duct).
What is the primary target of aldosterone?
The primary target of aldosterone is principal cells, or P cells. Principal cells are arranged much like other polarized transporting epithelial cells, with Na -K -ATPase pumps
What are the channels called on the apical surface of the primary cells?
ENaC, for epithelial Na+ channel
ROMK, for renal outer medulla K+ channel
Step by Step aldosterone action on P cells
- Aldosterone combines with a cytoplasmic receptor.
- Hormone-receptor complex initiates transcription in the nucleus.
- Translation and 2 protein synthesis makes new protein
channels and pumps. - Aldosterone-induced proteins modulate existing channels and pumps.
- Result is increased Na+ reabsorption and K+ secretion.
True/False
Na+ and water reabsorption are regulated together in the distal nephron
FALSE
Na+ and water reabsorption are separately regulated in the distal nephron
True/False
Aldosterone is increased activity of the Na -K -ATPase, aldosterone also causes K+ secretion
True
Why are Na+ and water reabsorption separately regulated?
Na+ and water reabsorption are separately regulated in the distal nephron. Water does not automatically follow Na reabsorption: vasopressin must be present to make the distal-nephron epithelium permeable to water. In contrast, Na reabsorption in the proximal tubule is automatically followed by water reabsorption because the proximal tubule epithelium is always freely permeable to water.
What controls physiological aldosterone secretion from the adrenal cortex?
There are two primary stimuli: increased extracellular K+ concentration and decreased blood pressure (Fig. 20.9a). Elevated K+ concentrations act directly on the ad- renal cortex in a re ex that protects the body from hyperkalemia. Decreased blood pressure initiates a complex pathway that results in release of a hormone, angiotensin II, that stimulates aldosterone secretion in most situations.
Two additional factors modulate aldosterone release in
pressure, but retention of Na increases osmolarity, which stimulates thirst. Fluid intake when the person drinks more water increases ECF volume (see Fig. 20.8). When blood volume in- creases, blood pressure also increases.
pathological states: an increase in ECF osmolarity acts directly dehydration, and an abnormally large (10–20 mEq>L) decrease
What is the Renin-Angiotensin Pathway (RAS)?
the renin-angiotensin system (RAS), a complex, multistep pathway for maintaining blood pressure.
How does Renin-Angiotensin Pathway (RAS) work?
The RAS pathway begins when juxtaglomerular granular cells in the afferent arterioles of a nephron secrete an enzyme called renin. Renin converts an inactive plasma protein, angiotensinogen, into angiotensin I (ANG I). When ANG I in the blood encounters an enzyme called angiotensin-converting enzyme (ACE), ANG I is converted into ANG II.
When ANG II in the blood
reaches the adrenal gland, it causes synthesis and release of aldosterone. Finally, at the distal nephron, aldosterone initiates the intracellular reactions that cause the tubule to reabsorb Na+
What are the stimuli that begin the RAS pathway?
They are all related either directly or indirectly to low blood pressure
- The granular cells are directly sensitive to blood pressure. They respond to low blood pressure in renal arterioles by secreting renin.
- Sympathetic neurons, activated by the cardiovascular control center when blood pressure decreases, terminate on the granular cells and stimulate renin secretion.
- Paracrine feedback—from the macula densa in the distal tubule to the granular cells—stimulates renin release. When fluid flow through the distal tubule is relatively high, the macula densa cells release paracrines, which inhibit renin release. When fluid flow in the distal tubule decreases, macula densa cells signal the granular cells to secrete renin.
Does Na+ reabsorption rise blood pressure?
Sodium reabsorption does not directly raise low blood pressure, but retention of Na increases osmolarity, which stimulates thirst. Fluid intake when the person drinks more water increases ECF volume. When blood volume increases, blood pressure also increases.
What are the other 5 pathways that ANG II increases the blood pressure?
1 ANG II increases vasopressin secretion.
ANG II receptors in the hypothalamus initiate this reflex. Fluid retention in the kidney under the influence of vasopressin helps conserve blood volume, thereby maintaining blood pressure.
2 ANG II stimulates thirst.
Fluid ingestion is a behavioral response that expands blood volume and raises blood pressure.
3 ANG II is one of the most potent vasoconstrictors known in humans.
Vasoconstriction causes blood pressure to in- crease without a change in blood volume.
4 Activation of ANG II receptors in the cardiovascular control center increases sympathetic output to the heart and blood vessels.
Sympathetic stimulation increases cardiac out-input and vasoconstriction, both of which increase blood pressure.
5 ANG II increases proximal tubule Na+ reabsorption. ANG II stimulates an apical transporter, the Na -H exchanger (NHE). Sodium reabsorption in the proximal tubule is followed by water reabsorption, so the net effect is reabsorption of isosmotic fluid, conserving volume.
What is Atrial natriuretic peptide and how does it work?
is a peptide hormone produced in specialized myocardial cells primarily in the atria of the heart. ANP is synthesized
ANP is released when increased blood volume
causes increased atrial stretch. At the systemic level, ANP enhances Na and water excretion to decrease blood volume. ANP acts at multiple sites. In the kidney it increases GFR by dilating the afferent arterioles, and it directly decreases Na reabsorption in the collecting duct.
What happens if K+ intake exceeds?
Under normal conditions, mass balance matches K+ excretion to K+ ingestion. If intake exceeds excretion and plasma K+ goes up, aldosterone is released into the blood through the direct effect of hyperkalemia on the adrenal cortex. Aldosterone acting on distal-nephron P cells keeps the cells’ apical ion channels open longer and speeds up the Na+-K+-ATPase pump, enhancing renal excretion of K+.
Explain < increased volume, increased osmolarity > situation
A state of increased volume and increased osmolarity might occur if you ate salty food and drank liquids at the same time, such as popcorn and a soft drink at the movies. The net result could be ingestion of hypertonic saline that increases ECF volume and osmolarity. The appropriate homeostatic response is excretion of hypertonic urine. For homeostasis to be maintained, the osmolarity and volume of the urinary output must match the salt and water input from the popcorn and soft drink.
Explain < increased volume, no change in osmolarity > situation
Moving one cell to the left in the top row, we see that if the proportion of salt and water in ingested food is equivalent to an isotonic NaCl solution, volume increases but osmolarity does not change. The appropriate response is excretion of isotonic urine whose volume equals that of the ingested fluid.
Explain < increased volume, decreased osmolarity > situation
This situation would occur if you drank pure water without ingesting any solute. The goal here would be to excrete very dilute urine to maximize water loss while conserving salts. However, because our kidneys cannot excrete pure water, there is always some loss of solute in the urine. In this situation, urinary output cannot exactly match input, and so compensation is imperfect.
Explain < no change in volume, increased osmolarity > situation
This disturbance (middle row, right cell) might occur if you ate salted popcorn without drinking anything. The ingestion of salt without water increases ECF osmolarity and causes some water to shift from cells to the ECF. The homeostatic response is intense thirst, which prompts ingestion of water to dilute the added solute. The kidneys help by creating highly concentrated urine of minimal volume, conserving water while removing excess NaCl.
Explain < no change in volume, decreased osmolarity > situation
This scenario might occur when a person who is dehydrated replaces lost fluid with pure water, like the golfer described earlier. The decreased volume resulting from the dehydration is corrected, but the replacement fluid has no solutes to replace those lost. Consequently, a new imbalance is created. This situation led to the development of electrolyte-containing sports beverages. If people working out in hot weather replace lost sweat with pure water, they may restore volume but run the risk of diluting plasma K+ and +Na concentrations to dangerously low levels
Explain < decreased in volume, increased osmolarity > situation
Dehydration is a common cause of this disturbance. Dehydration has multiple causes. During prolonged heavy exercise, water loss from the lungs can double while sweat loss may increase from 0.1 liter to as much as 5 liters! Because the fluid secreted by sweat glands is hyposmotic, the fluid left behind in the body becomes hyperosmotic.
In both sweating and diarrhea, if too much fluid is lost from the circulatory system, blood volume decreases to the point that the heart can no longer pump blood effectively to the brain. In addition, cell shrinkage caused by increased osmolarity disrupts cell function.
Explain < decreased in volume, no change in osmolarity > situation
This situation occurs with hemorrhage. Blood loss represents the loss of isosmotic fluid from the extracellular compartment, similar to scooping a cup of seawater out of a large bucketful. If a blood transfusion is not immediately available, the best replacement solution is one that is isosmotic and remains in the ECF, such as isotonic NaCl.
Explain < decreased in volume, decreased osmolarity > situation
This situation might also result from incomplete compensation of dehydration, but it is uncommon.
What happens in severe dehydration?
In severe dehydration, compensatory mechanisms are aimed at restoring normal blood pressure, ECF volume, and os- molarity by
(1) conserving fluid to prevent additional loss,
(2) triggering cardiovascular reflexes to increase blood pressure, and
(3) stimulating thirst so that normal fluid volume and os- molarity can be restored.
Tubuloglomerular Feedback
Step-by-Step
- GFR increases.
- Flow through tubule increases
- Na flow past macula densa increases
- Paracrine factor adenosine from macula densa to afferent arteriole
- Afferent arteriole constricts
- Resistance in afferent arteriole increases.
- Hydrostatic pressure in glomerulus decreases
- GFR decreases.
What part of the nephron forms the juxtaglomerular apparatus?
Where the ascending limb of henle joins the distal tubule
What happens to GFR when the afferent arteriole dilates?
It increases
The plasma is most similar in chemical composition to the fluid in the _______.
Bowman’s capsule
“Secretion” in a nephron always refers to transport of
a solute into the nephron lumen
What happens when there is low blood pressure?
Initiates the renin-angiotensin-aldosterone system (RAAS)
Causes of renal failure
–Infectious organisms –Toxic agents –Inappropriate immune responses –Obstruction of urine flow –An insufficient renal blood supply
After drinking a large volume of water, compensation is primarily achieved by a decrease in the level of the hormone ______.
vasopressin
Aldosterone secretion will be _____ by an increase in plasma [K+].
increased
An 83–year–old woman with severe orthostatic hypotension is given Florinef, a potent aldosterone agonist. In addition to following her blood pressure, what parameter should also be monitored?
Serum potassium
The hormone that most directly influences Na+ balance in the body is
aldosterone
Eating salty dry food without drinking will cause (before any response) a(n) ________ in body fluid osmolarity and ________ in the volume of the body fluids.
increase; no change
The vasa recta are the
peritubular capillaries associated with the loop of Henle
