The urinary system determines what stays in the body and what is lost.
Kidney.
Ureter.
Urinary bladder.
Urethra.
Divided into 2 main groups:
Kidneys: major excretory organs responsible for filtering blood and producing urine.
Urinary tract: moves urine out of the kidney to the outside of the body.
Ureter: carries urine from where it is formed in the kidneys to the urinary bladder.
Urinary bladder: temporary storage container for urine before it leaves the body.
Urethra: controls the expulsion of urine from the urinary bladder towards the outside of the body.
Regulation of fluid balance (water volume).
Maintenance of electrolyte balance.
Long-term acid-base balance.
Removal of metabolic wastes.
Maintenance of blood pressure.
Regulation of erythropoiesis.
Activation of Vitamin D.
Other metabolic functions
Homeostasis.
Regulation of fluid balance.
Angiotensin-II: affects fluid balance and peripheral resistance.
Like gluconeogenesis.
Filtrate: what is initially formed by the kidneys (made first), made by filtering the blood.
The components of the blood plasma proteins.
The filtrate is what you normally find in plasma without the protein.
Once formed, it is heavily modified by the kidneys until it becomes urine.
Urine: heavily modified filtrate, primarily composed of water with electrolytes and metabolic waste.
The substance that is lost by the blood.
Outside the peritoneal cavity.
Have a lot of layers to protect it from being outside the peritoneal cavity.
3 regions:
Renal cortex: outside and houses most of the BV within the kidneys and the filtration structures, where filtrate is formed.
Renal medulla: (renal pyramid) where filtrate is modified.
Renal pelvis: as filtrate is made and modified and exits the renal pyramids it moves to the renal pelvis and excretes the urine.
Made of smooth muscle.
2 main parts:
Renal corpuscle.
Renal tubule.
Filtering the blood and modification of filtrate until it becomes urine (millions).
Kidneys have extensive blood supply.
Hilum: where substances enter and exit from the kidney, blood flowing in and out of the hilum.
Blood flow around nephron: specialized blood flow called the portal system.
Pattern is repeated.
Blood comes from arteries and when it reaches the nephron it enters the afferent arteriole.
Goes to the capillary bed called the glomerulus.
Goes to the efferent arteriole.
Takes blood to the second capillaries.
Goes to the peritubular capillaries.
Flows out through the peritubular venules to the veins out of the body.
Capillary beds:
Glomerulus: located in the renal corpuscle and is responsible for filtration- the formation of the filtrate.
Peritubular: responsible for the exchange of substances between blood and filtrate.
Arteries \rightarrow Afferent \space arteriole \rightarrow Glomerulus \rightarrow Efferent \space arteriole \rightarrow Peritubular \space capillaries \rightarrow Peritubular \space venules \rightarrow Veins
Renal tubule: the rest of the yellow pathway after the corpuscle.
Renal corpuscle contains the glomerulus.
Made up of 2 parts:
Glomerulus capillaries: where filtrate is formed from blood being pushed out of the capillaries into the glomerular capsule, the fenestrations in the capillaries make them fairly permeable.
Glomerular capsule: made up of 2 layers
Outer parietal layer: provides a container for the structure.
Visceral layer: in contact with the capillaries and made up of podocytes that cover the surface of the capillaries.
Capsular space: in between the parietal and visceral and where the filtrate accumulates and can move into the lumen.
The podocytes: the legs make slits that are called filtration slits.
Once filtration is formed it moves into the renal tubule, just a hollow tube and its lumen is filled with filtrate and will be modified through processes where there is movement of substances between the filtrate (tubule) and the blood (capillaries).
Divided into 3 parts:
Proximal tubule: closest to the tubule, filtrate moves through the proximal to the nephron loop and the distal tubule.
Microvilli is the folds in the membrane facing the lumen, having these suggests that its important for exchanging substance between the filtrate and capillaries.
Divided into 2 parts:
Thin descending limb: filtrate descends down, lined with simple squamous epi.
Thick ascending limb: filtrate ascends up, lined with simple cuboidal epi but with no microvilli.
Both permeability for different substances.
Distal tubule: lined with simple cuboidal epi, some microvilli but not much.
Multiple nephrons that are transporting into a single duct.
Located in the renal pyramids in the renal medulla and when filtrate reaches the end of the system and exits into the area that leads to the urinary pelvis its considered urine.
Histology like the distal tubule.
Divided into 2 parts:
Cortical collecting duct: located within the renal cortex.
Medullary collecting system: contains all the parts of the collecting system that are located in the renal medulla.
There is a part where the distal tubule comes into close proximity with the renal corpuscle and efferent/afferent arteriole.
Cells that make up the juxtaglomerular apparatus are going to generally help regulate the rate of filtrate formation and systemic BP.
Next to the glomerulus.
Macula densa (green): they are part of all of the wall of the distal tubule.
Chemoreceptors that are monitoring the concentrations of sodium and chloric ions (NaCl), salt in the filtrate.
Juxtaglomerular cells (JG cells), in purple, apart of the lining of the efferent arterioles.
Mechanoreceptors and going to monitor the BP within those arterioles.
Also produce an enzyme called renin: helps regulate BP.
Cortical nephrons
Located in the cortex.
Juxtamedullary nephrons
Located next to the medulla.
More abundant: make up about 80% of the nephrons in the kidneys.
Found almost entirely in the renal cortex (the renal corpuscle, proximal &distal tubules and majority of the nephron loop are all part of the renal cortex.
Tend to have shorter nephron loops that mostly stay in the cortex, if they do enter the medulla it's in small amounts.
Blood supply has peritubular capillaries that are wrapped around all the nephron loop allowing for exchange between the filtrate and the blood.
Much less common make up 20% in the kidneys.
Parts of the nephron located in the renal cortex and parts that are located in the renal medulla.
The corpuscle and the proximal/distal tubules are still located within the cortex.
Have long nephron loops that tend to be located in the renal medulla.
Blood supply: have peritubular capillaries but to the nephron loop is coming from the specialized type of capillary called vasa recta
Vasa recta: ladder like structure, important for regulation of urine concentration and volume.
3 main processes
Glomerular filtration: process of formation of filtrate in the first place.
Tubular reabsorption & Tubular secretion: process of modification of filtrate into urine.
Only occurs here.
Process where filtrate is formed from filtering the blood
Filtration membrane: within the renal corpuscles, layers that substances have to travel in order to leave blood and enter filtrate
3 layers:
Endothelial cells (line glomerular capillaries).
Basal lamina (associated w/ Endo cells).
Filtration slits and associated with podocytes.
As substances move into the capsular space they go through the 3 layers—-> endo cells (fenestrated)——> basal lamina (CT)——> filtration slits.
Endo cells (larger holes), basal lamina (smaller holes) some substances can get trapped. filtration slits (small holes), now apart of the filtrate, substances will get trapped and not able to pass all layers like RBCs, WBC, platelets are all stuck in the blood and not enter the filtrate, most proteins won't make it through the slits.
Water.
Ions.
Small dissolved solutes (e.g. glucose, amino acids, very small proteins).
Nitrogenous wastes (e.g. urea and ammonium ions, creatinine, uric acid).
come from metabolism.
The amount of filtrate formed by both kidneys in one minute.
Typical rate is 124 \space ml/min - the entire plasma is filtered about 60 times each day.
Very dependent on the net filtration in the glomerular capillaries.
Still consider COP and HP, but also consider another HP, because the glomerular capillaries fluid will build up in the glomerular capsule which means the filtrate being formed has a HP for it we consider the HP in the blood inside the capillaries.
Have to consider
Glomerular HP (GHP)-HP inside
Capsular HP (CHP)-HP in capsular space
Glomerular COP (GCOP)-HP inside
GHP-blood pushing on the walls of the capillaries, favors filtration (movement out of the blood into the filtrate in the capsular space, changes here will cause changes in the GFR
GCOP- pulling force, favors absorption of water (out of the filtrate into the blood)
CHP-filtrate in the capsular space is pushing on the walls of the capsule and the glomerulus capillaries, favor absorption (water out of filtrate into the capillaries)
Big favour filtration.
Occurs if the GFR is too low, if the kidneys aren't filtering blood as they need to.
Associated w/
Buildup of waste products in the blood
Homeostatic imbalance (no control on what's retained and what's lost)
Autoregulation
Hormonal Mechanisms
Neural Mechanisms
Should have a constant GFR to make filtrate located at a glomerulus
Hormone-based, affect not only GFR but systemic BP NS, may be affects from more than GFR like systemic BP
All 3 regulations work by changing the (GHP), is by changing the vessel diameter of the efferent/ afferent arterioles or both
Blood flows into the glomerulus (sink) through the afferent arteriole (faucet), out the efferent arteriole (drain)
Vasoconstrict the afferent (decreasing diameter)- turning down the faucet, allowing less blood to enter the glomerulus, less pressure put on the capillaries, brings the GHP down and GFR
Clogging the drain, less water leaving the blood in the glomerulus, more pressure and brings the GHP up and GFR
Turning up the faucet, more blood producing more pressure on the walls of the glomerulus bringing the HP up
Favoring filtration bringing up GHP and GFR
Unclogging the sink, allowing more blood to leave the glomerulus
Less blood putting pressure on the walls
Decreasing GHP and GFR and decreasing filtration rate
General goal is to maintain a constant GFR
Going to occur in response to change in BP
No regulation if systemic BP goes up more blood with higher pressure going into the glomerulus increasing pressure and increasing glomerular filtration rate, production of more filtrate
Stimulus is increase in BP and the autoregulation will decrease GFR to maintain it
To decrease GFR we need to decrease HP by first
Vasoconstricts the afferent arteriole
As bp goes up, allowing less blood to go in the capillaries bringing HP down and filtration down to normal
Vasodilation of the efferent arteriole
Can also do this to bring it back down
Goal is to maintain constant GFR
Stimulus is decreasing BP that decreases GFR
The myogenic mechanism Will vasodilate the afferent arteriole
More blood going into the glomerulus capillaries bringing up the HP which favors filtration bringing up to the normal level by increasing GFR
Goal is to maintain GFR
Anything that can increase GFR can lead to tubuloglomerular feedback
Stimulus is increase of GFR, means there is more filtrate being formed and flow,
This feedback regulation is stimulate by cells in the juxtaglomerular apparatus (JGA), more filtrate moving through the renal tubule, that increases the amount of Na+ and Cl- reaching JGA
The macula densa cells acting like chemoreceptors detecting changes in Na+ and Cl- levels sending signal to vasoconstrict the afferent arterioles decreasing GFR levels (turning down the sink)
Renin-angiotensin-aldosterone-system
Pathway that affects GFR directly and systemic BP broadly
Can be stimulated by
SNS
Low BP (systemic)
Macula densa (decrease in concentration of Na+ and Cl- in filtrate)
Sometimes a combination of all 3 things
Angiotensin-ll is activated by SNS,Low BP, Low Na+-Cl- and stimulates the JG cells and produce renin and release in the blood stream, kicks off activating angiotensinogen into angiotensin-l, ACE, converts it to angiotensi-ll
Angiotensin-ll causes vasoconstriction of the efferent arterial (clogging the drain), resulting in an increase of GFR and bringing it back into normal range (little change)
Efferent arteriole is more sensitive to angiotensin-ll than the afferent arteriole, if the levels get high of angiotensin-ll then you'll see vasoconstriction of the afferent arteriole
Angiotensin-ll is going to vasoconstrict blood vessels throughout the body, increasing peripheral resistance, increasing systemic BP
Angiotensin-ll promotes the absorption of Na+ and Cl- in the proximal tubule of the renal tubule, which increases the reabsorption of water (more water in the blood), increasing Blood volume and increasing systemic BP
Angiotensin-ll, stimulates production of more aldosterone(increasing reabsorption of Na+ & water) in the distal tubule increasing systemic BP
Angiotensin-ll stimulates thirst receptors, resulting in consumption of water, increase blood volume and systemic BP
ALL work by increasing the blood volume to increase the systemic blood pressure
Instead of causing small changes, ANP is going to change GFR dramatically
Produced by the heart if the BP is too high, the goal is to decrease blood pressure
ANP affects filtration in 2 ways:
Vasodilate the afferent arteriole, increasing GHP and filtration rate
Vasoconstriction of the efferent arteriole, blood backed up, increase in the HP and increase in filtration rate
If you put them together you are turning up the faucet and clogging the drain, which there more blood going into the glomerulus that can't leave increasing the GHP, increasing more filtrate produced a lot will be lost as urine dropping BV and SBP
Stimulation of the RAAS
Effect of the GFR depends on the level of stimulation, low or high level of SNS stimulation
Low levels will trigger the JG cells to produce more renin and kicking off the RAAS system which will increase GFR to maintain it
As well as increase systemic BP
Have a lot of angiotensin-ll being produced and that leads to vasoconstriction of the afferent and efferent arterioles, which will lead to high or low levels of GHP and GFR if both are happening at the same time the net effect on GFR will decrease because there’s less filtrate being produced which will help keep more fluid in the body
We would also suspect an increase in the systemic BP
Modify the filtrate until it becomes urine
Reabsorption is movement of substances out of the filtrate into the blood
Reabsorption is selective not everything is reabsorbed only things the body needs
Reabsorption happens everywhere may be passive or active
Secretion movement of substances out of blood into the filtrate, selective as well and occurs in fewer places not in the nephron loop always an active process
Processes for
Important to get rid of waste products, and filtrate from being lost
Homeostasis
Paracellular route: substances pass between cells, only seen in reabsorption because it's always a passive process
Transcellular route: Substances move through cells, have to cross cell membrane into the cell and out of the cell (2 times), happens in reabsorption and secretion is often an active process
Facilitated Diffusion
Active Transport (Primary or Secondary)
Symporters transports substances in the same direction
Antiporters transports substances in different directions
Transport proteins (membrane bound)
Passive process need ATP whether the ATP is used directly direct use of ATP to move a substance passed a membrane Indirect use of ATP, movement of the substance through the transport protein is dependent on a favorable concentration gradient created by another transport protein that did use ATP
Ex: transports multiple substances into the cell
EX: transports one substance into the cell and one out of the cell at the same time
Downside: only have a certain number of binding sites which can make transport proteins saturated-(limited space on how much they can transport)
Reabsorption in the proximal tubule is important because the proximal tubule is the site of the vast majority of reabsorption And going to help maintain homeostasis (fluid, electrolyte, acid-base)
Lots of microvilli to allow for lots of reabsorption Getting reabsorbed
Water- 65% of water throughout the renal tubule and collecting system is reabsorbed to maintain fluid homeostasis
Nutrients- almost 100% (only place they are reabsorbed)
Ions- Na+, K+, Cl- ect, to maintain electrolyte homeostasis
Bicarbonate ions (HCO3-)- primary help acid-base homeostasis.
Na^+ concentration gradients are necessary for the reabsorption of other substances in the proximal tubule.
The favorable concentration gradient is from a form of primary transport.
Angiotensin ll can stimulate Na^+ and water reabsorption in the proximal tubule by stimulating the Na/K+ pumps to pump more sodium out.
Glucose is going to move through a symporter (Na+/glucose symporter) and taking advantage of the favorable concentration gradient
In order for the symporter to work the Na^+ concentration gradient has to be maintained by the Na+/K+ pump on the basolateral membrane that is using ATP and moving Na+ to the ISF
Once glucose gets into the cell it travels to the basolateral membrane and travels out of the cell through facilitated diffusion once its in the ISF and can easily get into the blood and the reabsorption is complete
This mechanism is responsible for the reabsorption of nutrients
Both of the HCO3^- reactions are occurring first in the filtrate and in reverse inside the tubule cells to allow HCO3^- to enter the cells
Involves a Na+/H+ antiporter- is dependent of that using ATP to pump Na^+ out of the cells to make that concentration gradient
Analogy: H+ is a bounty hunter and gets sent out by the cell into the filtrate and finds the bounty H2CO3^- (bicarbonate ion) picks it up (binds) and brings it back into the cell, once in the cell H+ drops off the bounty and go out in the filtrate to find another one and H2CO3^- goes into jail (the blood) Facilitted diffusion Maintains acid base homeostasis
Water reabsorption divided into 2 parts
Obligatory: in the proximal tubule, and aquaporins are present in the membranes of the tubule cells water is obliged to follow reabsorbed solutes, if there's an osmotic gradient water will follow
Facultative: occurs when the presence of absence of aquaporins in the tubule cells membrane is depending on hormones based on the needs of the body and under tight control due to the presence or absence of various hormones
The difference is based on the aquaporins: transport proteins that allow water to move in or out of a cell is the osmotic gradient is there Depending on the movement of solutes due to osmosis as they move they create a favorable osmotic gradient for water to move, high to low gradients Solutes move water follows Fluid + electrolyte homeostasis
Nitrogenous waste products:
Uric acid, NH_4, creatinine, urea
Drugs (e.g. penicillin, morphine)
If they didn't make it to the filtration will be secreted why we have to readminister drugs
As filtrate is formed it goes to the proximal tubule to the nephron loop
Thin descending limb
Reabsorption of water only, obligatory so aquaporins are always present
Thick ascending limb
Reabsorption so Cl- and Na+ ions via secondary active transport
Have implications of concentrated or dilated urine no secretion just absorption
By the time it makes it to the distal and collecting system a lot of reabsorption has occurred, 85% of water, nearly 100% nutrients 90% of ions, so its fine-tuning to meet the needs of the body to maintain homeostasis
Main things reabsorbed is water and ions (Na+, H2CO3^-) secretion of k^+ and H^+ ions, by hormones involved in regulating the amounts of what's reabsorbed and secreted all water reabsorption is considered facultative reabsorption (based on the needs to the body and dependent on hormones) aquaporins have to be present
3 hormones that affect the amount of reabsorption and secretion
Aldosterone: effect of increasing the reabsorption of Na^+ ions and water, it does this by increasing the number of Na+/K+ pumps on the basolateral membrane but also increases secretion of K^+
ADH: helps increase the reabsorption of water by causing the aquaporins to be inserted into the cell membranes, facultative reabsorption is depended on ADH, aldosterone can only reabsorb water if ADH is present
ANP: it will decrease the reabsorption of Na^+ ions and water, also inhibits aldosterone and ADH
These determine what gets reabsorbed based on the needs of the body
2 ways kidneys can manipulate the pH of the blood
Reabsorption of bicarbonate ions
More bicarbonate ions in the blood and then they can combine with H+ to make carbonic acid decreasing H+ in the blood and increasing the pH
Secretion of H^+ ions
Taking free H^+ out of the blood and sending it to the filtrate, increase pH in the blood by decreasing free H^+ ions if the pH the blood is too low (acidosis), the kidneys are going to increase the secretion of bicarbonate and H^+ ions to bring the pH back up by decreasing free H^+ in the blood
If the pH in the blood is too high (alkalosis), the kidneys would decrease the secretion of bicarbonates and H^+ ions to maintain a higher concentration of H^+ ions bring the pH back down
This will affect the pH of the filtrate and if you have less secretion of an ion there will be more in the filtrate and urine
Caused by an issue with insulin so there's high blood glucose levels, when it gets to the kidneys it will be filtrate
If there are high levels of glucose, there will be high levels in the filtrate and then will have to cross the membrane through the Na/glucose symporter, this causes the protein to saturate so some will be left and will be in the urine Too much glucose in the urine
Dependent on the water needs of the body at any given time, (urine concentration and volume will change)
Dependent on facultative water reabsorption (ADH)
Facultative reabsorption is happening in the distal tubule and collecting system (based on the water in here)
Body is well hydrated, produced diluted urine, low solute concentration it's fine to lose water, very little facultative water reabsorption reabsorption of salt instead of water, low solute high water concentrations, water stays in filtrate until it becomes urine
The body is dehydrated there is a high solute concentration, reflected in the blood and filtrate, high solutes low water concentration
You don't want to lose water in the urine so produces a very concentration urine, Lots of facultative water reabsorbed.
In areas where obligatory water reabsorption occurs there's a predictable pattern filtrate is formed at the renal corpuscle —>enter into the proximal tubule (osmolarity volume doesn't change due to H2O & Solutes are being reabsorbed)—-> nephron loop, thin decedent limb (reabsorption water only, high solute concentration more solutes)—> thick descending limb (reabsorption of solutes only, fewer solutes same amount of water), this brings the osmolarity concentration back down—-> determines down the line if it's forming concentration urine
Osmolarity=solute concentration
Not doing much facultative reabsorption of water
Well hydrated (measuring solute concentration at the hypothalamus) low solute concentration ADH is low (just have to turn off ADH to make dilute urine)
Dilute urine is made
Dehydrated Higher solute Concentration more ADH Produced (aquaporins present) Also need Favorable osmotic gradient
Lots of facultative reabsorption Medullary osmotic gradient Concentrated urine!
Low concentration in ISF, high concentration in ISF this gradient is being formed by the juxtamedullary nephrons
Setting up the gradient (moving solutes in the ISF), adds solutes to the gradient, Maintaining the gradient
Dependent of each other absorbing H20 or solutes since there's a high solute concentration at the loop it provides a higher gradient for more reabsorption
Setting up the osmotic gradient based off the different types of reabsorption in the thick/thin descending limb which determines what's going on in the ISF allowing this gradient to be set up important for the JMN that is located in the renal medulla
Adding additional solutes to the concentration gradient to make it stronger, removed from the body but small amount of urea is reabsorbed to go back into the filtrate and repeats
Based off the different blood supply that's the nephron loops of the JMN (vasa recta, allows for the tubule cells to receive the O2 and nutrients without losing the solutes in the osmotic gradient) helping maintaining the gradient
If ADH is present when entering and favorable osmotic gradient there is facultative reabsorption occurs, moving out of filtrate and into the blood the filtrate becomes more concentration as it loses more water, we need the ISF to maintain high as well to maintain the gradient once at the bottom and lost a lot of water you produce concentrated urine
Formation of kidney stones they are crystals of salts and can be lodged in the distal tubule, collecting system of urinary tract high concentration of solutes it's more likely they will create kidney stones dehydration diets high in proteins, salts, meat
Made up of:
water, solutes, metabolic waste
Color: yellow, urochrome (bilirubin)
Normal clear Low concentration ->pale urine high concentration ->dark urine
if translucent: cloudy, infections, unneeded proteins
PH: Slightly acidic (6): reflection Of Kidney's maintaining blood pH
Normal less Concentrated -Closer to 1, diluted (ex: 1.002), more concentrated further away to 1 (ex. 1.04) higher Specific gravity more concentrated urine
Made up of 3 parts:
ureters
urinary bladder (storage for urine)
urethra (connects to the outside of the body)
Responsible for conveying urine from the kidneys to the bladder travels to the urine the mucosa layer (made up of transitional epithelial) muscularis layer (made up of smooth muscle, helps propel urine from kidneys to the urinary bladder Adevntitia (connective tissue)
3 layers
transitional layer
detrusor muscle (smooth muscle)
outer connective tissue
the base the thickening of the detrusor muscle forms a sphincter (valve) called the internal urethral sphincter controls the urine out of the urinary bladder
Located more anteriorly in the female due to the uterus the length of the urethra differs
Urethra helps carry and expel the urine, internal urinary sphincter controls the flow of urine into the urethra external urethra sphincter is made up of skeletal muscle and passes through the levator ani muscle causes a second sphincter and helps allow urine to exit the urethra to the outside of the body and located part way the urethra closer to the rectum caused increased risk of UTIS
Opening further away from the rectum external urethral sphincter controls urinary flow (skeletal muscle by the levator ani muscle male urethra also carries semen and it broken up into regions
prostatic urethra (closest to bladder)
membranous urethra (part surrounded by ani muscle)
Spongy urethra (penile urethra, to exit to outside).
2 components:
Involuntary reflex
Voluntary step: allowing urination to happen Smooth Muscle (Involuntary) Skeletal Muscle (Voluntary) Internal: parasympathetic, stimulus is bladder getting full and stretch receptors send signal to spinal cord tells it to relax (involuntary) sometime will result in urination if you don't have control of voluntary External: signal also travels to the brain stem and cerebral cortex creates voluntary response and allow for relaxation of external sphincters and urine is expelled out if you don't allow urination the reflex will come again later, if the bladder is too full you lose voluntary control.