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what are the four main organs of the urinary system?
kidney, ureter, bladder, urehtra
what are the three primary functions of the kidneys? give examples
1) synthetic function (erythropoietin, 1,25-dihydroxy vitamin D3, renin)
2) excretion (metabolic waste products and toxins)
3) regulation (water and electrolytes, acid-base balance, arterial blood pressure)
what is the functional unit of the kidney responsible for filtering the blood and producing the urine?
the nephron
two major parts of a nephron
renal corpuscle and renal tubule
what is the renal corpuscle?
the blood-filtering component of the nephron
what are the two main parts of the renal corpuscle?
the renal corpuscle comprises the glomerulus and the surrounding glomerular or Bowman capsule
what is the Bowman's capsule?
cup-shaped hollow structure; surrounds the glomerulus
what is the glomerulus?
a knot of capillaries wrapped by podocytes and enclosed within the Bowman's capsule
what is the function of the glomerulus?
- it is the main filtering unit of the kidney
- each glomerulus is located at the beginning of the nephron
where is the Bowman's space?
Inside the capsule, surrounds the glomeruli
what is meant by glomerular filtration?
a process in which water and some solutes in the blood plasma pass from capillaries of the glomerulus into the capsular space of the nephron
where does glomerular filtration take place?
at the renal corpuscle (more exactly, at the glomerulus)
a) what vessel is responsible for supplying blood to the glomerulus?
b) in which structure does the filtrated blood (filtrate) enter before flowing into the renal tubule lumen?
c) what is the function of the efferent arteriole?
the blood supply to the glomerulus is provided via the afferent arteriole
the blood then flows through the capillary network, where it gets filtered, and then leaves the glomerulus via the efferent arteriole
the ultra filtrate is collected in the Bowman space
what is net filtration pressure (NFP)?
the total pressure that promotes filtration (i.e., the movement of small solutes and water from the capillaries of the glomerulus toward the capsular space), 10mmHg
what 3 main pressures determine the NFP at the glomerulus?
1) glomerular hydrostatic pressure (GHP): is the blood pressure in the glomerular capillaries
2) glomerular colloid osmotic pressure (GCOP): mainly due to the presence of proteins (e.g., albumin) in blood plasma
3) capsular hydrostatic pressure (CHP): exerted by fluid already in the glomerular capsule
how do you calculate NFP?
GHP - (GCOP + CHP)
If GHP: 65 mmHg, GCOP: 20 mmHg, CHP: 15 mmHg, what is the value of NFP?
65 mmHg - (20 + 15 mmHg) = 30 mmHg
If the NFP is -10 mmHg, which process does it take place at the glomerulus: filtration or reabsorption?
when NFP is positive, there is net fluid filtration, and when it is negative, there is net fluid reabsorption
what are the three components of the filtration membrane?
1) fenestrated endothelium of the capillary
2) basement membrane of glomerulus
3) filtration slits between pedicles
what the podocytes in the kidneys?
specialized epithelial cells that cover the outer surface of glomerular capillaries
are podocytes and pedicles the same?
pedicles are the foot processes of the podocytes (cytoplasmic extensions)
what substances are found in the kidney filtrate?
Free amino acids, water, nitrogenous wastes, glucose, small ions
which substance should not be found in normal filtrate?
plasma proteins (e.g. albumin), blood cells
what are the main nitrogenous waste products of the body?
indicate their sources
urea and ammonia: from protein catabolism
uric acid: from nucleic acids catabolism
creatinine is a breakdown product of creatine
what is meant by glomerular filtration rate (GFR)
amount of filtrate formed per minute by the two kidneys combined
what is a normal GFR for males?
125 ml/min (180 L/day)
what is a normal GFR for females?
105 ml/min (150 L/day)
what happens if the GFR is too low?
fluid flows sluggishly through the renal tubules, they reabsorb wastes that should be eliminated in the urine
what happens if the GFR is too high?
fluid flows through the renal tubules too rapidly for them to reabsorb water and solutes -> dehydration and electrolyte depletion
what is the difference between intrinsic vs. extrinsic regulation of GFR?
intrinsic: within the kidney (local responses)
extrinsic: outside (systematic responses, indirectly affect the GFR)
what is the main goal of the intrinsic control of the GFR?
directly regulate GFR maintain nearly constant the GFR & protect the glomerulus from changes in BP that could damage them
what is the main goal of the extrinsic control of the GFR?
- to control and maintain systematic BP
- they are activated for example when there is a vast decrease in BP (that can compromise life) to restore the BP
- they will indirectly affect the GFR
what are the two intrinsic auto regulation mechanisms for maintaining the GFR?
the myogenic response and tubuloglomerular feedback
what do the two intrinsic auto regulation mechanisms for maintaining the GFR have in common?
both modify the diameter of the afferent arteriole in response to moderate changes in BP
how do changes in the afferent arteriole's diameter affect the GFR?
If the afferent arteriole diameter increases (due to smooth muscle relaxation), more blood will enter the glomerulus and can be filtered. As a result, the GFR will increase.The opposite will happen when its diameter decreases (vasoconstriction) since less blood will arrive at the glomerulus
how does the myogenic response regulate the glomerular filtration rate?
It is based on the tendency of smooth muscle to contract when stretched
considering the myogenic mechanism, how does the afferent arteriole react to increased or decreased blood pressure?
When the blood pressure (BP) increases, the hydrostatic pressure against the walls of the afferent arteriole will also increase, resulting in the activation of stretch receptors located at the walls of the arteriole. This activation will result in contraction of the smooth muscle (vasoconstriction) and a decrease in the GFR.In case of low BP, the afferent arteriole smooth muscle relaxes (Vd) allowing blood to flow easily into the glomerulus, which increases the GFR
what are the three components of the juxtaglomerular apparatus, and where are they located?
1. Macula densa (lining the wall of the loop/distal convoluted tubule).
2.Mesangial cells (inside the glomerulus and in between the capillaries).
3.Granular cells (they are modified smooth muscle cells wrapped around the afferent arteriole)
how does the juxtaglomerular apparatus regulate the GFR?
1. Macula densa cells sense tubule flow: [NaCl]. When GFR ↑: these cells secrete ATP.
2. Mesangial cells metabolize ATP to adenosine.
3. Granular cells constrict the afferent arteriole in response to adenosine
where is angiotensinogen produced?
in the liver
is angiotensinogen active or inactive?
inactive
what does ACE stand for?
angiotensin-converting enzyme
where is ACE produced?
Primarily in the vascular endothelium of the lungs and kidneys
what is renin?
An enzyme that converts angiotensinogen into angiotensin-I
where is renin produced?
in the juxtaglomerular cells
when renin is released: when is a high blood pressure (BP) or low BP?
When systemic blood pressure decreases, causing a decrease in the GFR
What enzyme converts angiotensinogen into angiotensin I?
renin
What enzyme converts angiotensin I to angiotensin II?
ACE
what affect does angiotensin-II have on the afferent arterioles diameter? and in systemic blood vessels?
decrease their diameter (vasoconstriction)
does angiotensin-II promote the reabsorption or the excretion of NA+ in the urine? how?
Promotes the reabsorption of sodium ions from the urine by: (1) Stimulating the Na+/H+ antiport in the PCT, (2) Promoting aldosterone release from the adrenal gland.
what is the order in which fluid flows through the kidney? (from the glomerulus to the papillary duct)
0- Glomerular corpuscle
1-Proximal convoluted tubule
2-Loop of Henle (or Nephron Loop)
3- Distal convoluted tubule.
4-Collecting duct
5- Papillary duct
what strucutres converge to form the major calyx?
2 or 3 minor calyces
what is the path of the urine through the urinary system?
Glomerulus→
Proximal Convoluted Tubule (PCT) →
Nephron loop →
Distal Convoluted Tubule (DCT) →
Collecting Duct (CD) →
Papillary Duct →
Minor calyx →
Major calyx →
Renal pelvis →
Ureter →
Urinary Bladder →
Urethra
in which part of the nephron does glomerular filtration occur?
at the glomerulus
what is the overall purpose of tubular reabsorption?
to recover substances filtrated the glomerulus (back to the blood)
what part of the nephron usually reabsorbs the most water and sodium?
proximal convulted tubule (PCT)
where are glucose and amino acids mostly reabsorbed?
PCT
what is meant by tubular secretion?
It is the transfer of materials from peritubular capillaries (blood) to the renal tubular lumen* (tubular fluid); it is the opposite process of reabsorption. [Lumen: The inside space of a tubular structure, such as an artery or intestine].
why is tubular secretion necessary during urine formation?
It helps to get rid of molecules not filtered at the glomerulus due to large size.It is a major mechanism for the elimination of most administered drugs and their metabolites. It helps to maintain the ionic, acid-base and other bodily fluid balances (secretion of K+, H+,NH4+, creatinine, and urea)
what is the difference between paracellular and transcellular transport routes across tubule cells?
The prefix "para-" came from Greek and means "next to" and "side by side".
"Prefix "trans-" means "across, through" (the cell)
what structures must the substances inside the renal tubular lumen cross to be reabsorbed by the peritubular capillaries?
Apical membrane of the tubular epithelial cells → cytosol → basolateral membrane of the tubular epithelial cells → interstitial fluid → endothelial cell of the capillary
what does Tm stand for?
Transport Maximum - The maximum rate of reabsorption
when is the Tm reached?
when the transporters that move solutes out of the tubular lumen to be reabsorbed are saturated
what factors limit the amount of solute the renal tubule can reabsorb and, thus the Tm?
The number of transport proteins available for that solute. Transport saturation occurs when all the protein transporters are being used for the transport of the molecule.
what pump generates a strong concentration gradient for sodium reabsorption in the renal tubule?
Na+/K+ pump = Renal Na-K-ATPase
where is it located? (apical or basolateral membrane)
basolateral membrane
what is the direction of ion movement in a sodium-potassium pump?
It moves sodium and potassium ions against large concentration gradients. It moves potassium ions into the tubule cell where potassium levels are high, and pumps sodium ions out of the cell and into the interstitial fluid.
how are organic solutes such as glucose and amino acids, as well as phosphate, reabsorbed at the PCT?
Via specific symporters that transport Na+ with another solute. Because their reabsorption is powered by the sodium electrochemical gradient (generated by the Na-K ATPase), their transport is considered to occur through secondary active transport. Once inside the tubular epithelial cells, these organic solutes or phosphate cross the basolateral membrane via specific membrane transporters
how is Na+ reabsorbed at the PCT?
1. Transcellular transport through the luminal (apical) membrane via a variety of symporters (that transport Na+ with other solutes, such as glucose).
2. Transcellular transport by Na-H Antiporters (=exchangers) which link secretion of hydrogen with reabsorption of sodium.
3. Paracellular route across tubular epithelial cell tight junctions (together with chloride ions)- In late PCT
how is the concentration gradient needed to move Na+ from the tubular lumen to the cell generated?
By the Na-K ATPase, which is continuously pumping Na+ outside of the cell, decreasing [Na+] inside the cell.
where is the Na+/H+ antiporter (=Na+/H+ exchanger 3) located?
apical membrane of epithelial cells at the PCT
what is the direction of ion movement in the Na+/H+ antiporter?
it secretes H+ from the cells in exchange for luminal Na+ entry, therefore contributing to Na+ reabsorption and body acid-base balance
which hormone upregulates its expression and/or activity?
angiotensin II
most water is reabsorbed in the PCT by obligatory reabsorption. what does it mean?
Water must "follow" sodium and other ions/molecules to maintain osmotic balance (=electrolytes, non-electrolytes & water balance)
what does SGLT stand for?
Sodium-glucose cotransporters (SGLTs)
in which renal tubule can you find SGLT?
PCT, 100% glucose is reabsorbed here
what is the function of SGLT?
responsible for the tubular reabsorption of filtered glucose from the kidney into the bloodstream.
which segment of the nephron loop is permeable to water?
descending limb
which segment of the nephron loop is impermeable to water?
ascending limb
which segment of the nephron loop is permeable to solutes?
ascending limb
which segment of the nephron loop is impermeable to solutes?
descending limb
why is the ascending limb of the nephron loop considered "the diluting segment of the nephron"?
The reabsorption of large amounts of sodium in the ascending limb (from the tubular lumen to the interstitial fluid) in the absence of water (the ascending limb is impermeable to water) results in a significant dilution of the tubular fluid (= a lot of water and low concentration of solutes within the lumen of the tubule)
In which kidney tubule segment are the Na +-K +-2Cl- symporters (NKCC2) found?
At the ascending limb of the nephron loop (on the luminal or apical membrane of the epithelial cells).
what is the direction of ions movement in the Na +/K +/ 2Cl symporter?
All three ions are transported in the same direction: from the lumen to inside the cell. Reabsorption of Na+ is powered by a basolateral Na-K ATPase - it generates low Na+ concentrations within the tubular epithelial cells
in the thick ascending loop of henle, how many potassium and chloride ions are transported together with sodium ions through co-transport?
2 chloride ions (2 negative charges), 1 potassium ion + 1 sodium ion (2 positive charges)
which region(s) of the nephron does the term "distal tubule" refer to?
The term distal tubule has been used by anatomists to denote the region of the nephron that extends downstream from the macula densa to the confluence of another tubule (i.e., the collecting system). It includes two nephron segments, the distal convoluted tubule (DCT) and the connecting tubule (CNT)
what does NCC stand for?
NaCl cotransporter
where is the NCC located?
Distal convoluted tubule (DCT), subsegments 1 (early DCT) and 2 (late DCT). Apical membrane tubule epithelial cells.
what is the function of the NCC? (indicate the direction of ion's movement)
it transports Na+ and Cl- from the lumen to the cell
what are the main functions of the late DCT and cortical CD?
1. Electrolytes (such as sodium & potassium) homeostasis by fine‐tuning the amount of electrolytes that are excreted in the urine. The principal cells play an important role in this process- regulated by aldosterone.
2-pH homeostasis & acid-base regulation by controlling the amount of H+ excreted in urine- important role for type A intercalated cells
what ENaCs stand for?
epithelial sodium channels
where are the ENaCs channels located?
in the late distal convoluted tubule (DCT 2) and cortical collecting duct (CD)
what regions of the nephron are collectively termed the "aldosterone-sensitive distal nephron"?
late distal convoluted tubule (DCT 2), connecting tubule (CNT), cortical collecting duct (CCD)
what are the main functions of the medullary CD?
1-In this segment, urea is reabsorbed from the lumen to the interstitial fluid. Urea contributes to generate a hyperosmotic medulla.
2-It plays a crucial role in urine concentration by reabsorbing more or less water depending on the hydratation state of the individual- controlled by the ADH hormone.
what hormone controls water reabsorption and, therefore, urine concentration in the CD?
ADH (antidiuretic hormone, also known as vasopressin)
which two factors allow the kidney to produce concentrate (hypertonic) urine?
1-ADH acting on the late DCT and medullary CD to increase water permeability (without ADH these segments are impermeable to water).
2-A medullary osmotic gradient in the interstitial fluid of the renal medulla that drives the reabsorption of water by osmosis.
to produce concentrated urine, do you need to reabsorb more or less water?
reabsorb more water (i.e., the urine will contain less amount of water so the solutes will be concentrated)
where can you find more concentrated interstitial fluid, deep in the medulla or in the cortex?
deep in the medulla
which three mechanisms help with creating and/or maintaining the medullary osmotic gradient?
1-A countercurrent multiplier system in the nephron loops of juxtamedullary nephrons.
2-The recycling of urea- it passively diffuses into the interstitial fluid of the medulla from the CD. This urea will be taken back into the tubular fluid at the nephron loop.
3-A countercurrent exchanger in the vasa recta.
where does the countercurrent multiplier occur?
nephron loops of juxtamedullary nephrons