THE NEPRHON 

EDIT
Please note that there´s a mistake in the drawing. The place where the macula densa cells should be is in the Distal Tubule, not the Collecting Duct. Thanks

I did this a while ago but didn’t have the time to explain it… so i will do it now.
In a parallel universe, where The Magic School bus exists, and I’m the one that picks where can we have our next adventure, I’ll definitely choose the nephron (yes people, if you haven’t tell yet, I am this nerd)

It is, hands down, my favorite functional unit of the body. It’s just perfect!
And now I stop talking nonsense and start with the real deal. This is gonna take a while! (sorry, there’s no “Keep reading” option when reblogging)

-
Let’s start in the Renal Corpuscle (RC) 
The RC is the initial filter of the nephron, it has 2 structures:
Glomerulus: tuft of capillaries. Has 2 cells: endothelial cells & mesangial cells (responsible of the myogenic response that regulates RBF)
Bowman’s capsule: parietal layer (simple squamous ep), Bowman’s space, visceral layer (podocytes)
Also, the RC has 2 poles
Vascular pole: afferent & efferent arterioles communicate w/ the glomerulus. Remember that the majority of yuxtaglomerular cells are around the AFFERENT arteriole, and this smart cells secrete renin according to volume changes. Also, this cells have alpha1 & beta1 receptors, meaning that they respond to sympathetic activation to decrease (alpha) or increase (beta) renin secretion. See? they are fucking perfect. Both afferent & efferent arterioles are responsible for the regulation of filtration forces of the nephron. They are also influenced by the presence of ANP which promotes Natriuresis by increasing the GFR, how? Vasodilating the afferent and Vasoconstricting the efferent.
Urinary pole: the RC opens to the Proximal tubule

-
Let’s move on to the Proximal Tubule (PT)
Here, 2/3 of Na+, H2O, K+ & Cl- and 80-90% of HCO3- are reabsorbed.
All carbohydrates, proteins, aa, are reabsorbed via 2° active transport
Secretion of Cations & Anions happen here. I actually made a mnemonic that involves Michael Fassbender’s penis about this. You are welcome ;)
All the energy comes from two 3Na+/2K+ ATPase pumps (1° active transport). THIS is the most demanding process of the nephron!
When PTH levels in blood increase, this inhibit the reabsorption of HPO4- - 
Only 1/3 filtered remains

Secondary active transporters found here:
Cotransport or Symport:  Na+/Lactate, Na+/Glucose, 2Na+/HPO4
Countertransport or Antiport: Na+/H+. [Angiotensin II (AT II) stimulates Na+ and H+ exchange, to increase Na+ and H20 reabsorption, permitting contraction alkalosis (increase of blood pH when fluid w/o HCO3- is lost)]
Pathology
Renal Tubular Acidosis II (RTA II) or Proximal Renal Tubular Acidosis (pRTA): failure of the proximal tubular cells to reabsorb filtered HCO3-, leading to urinary HCO3- wasting and subsequent acidemia. (less severe than dRTA). Associated w/ Fanconi’s syndrome, [phosphaturia, glycosuria, aminoaciduria, uricosuria, tubular proteinuria & bone demineralization (osteomalacia or rickets) due to HPO4— wasting]
Pharmacology: (as in diuretics that act on this level)
Osmotic diuretics = MANNITOL:  inhibit H2O reabsorption throughout the tubule.
Carbonic Anhidrase (CA) inhibitors = ACETAZOLAMIDE, DORZOLAMIDE:inhibit CA in the PT, this decreases the amount of H+ formation inside the cell, H+ stop being available for the H+/Na+ antiport, hence, Na+ (and HCO3-) accumulate in the lumen, promoting diuresis.

CA= enzyme responsible of catalyzing the interconversion (reversible) of CO2 and H2O into H2CO3- and ultimately into H+ & HCO3-
-
Now onto the Loop of Henle
Up to this point, we only have 1/3 of the volume filtered into Bowman’s space & the fluid entering here is isotonic (300mOsm/L) since the reabsroption of e- was pretty much the same amount.
Let’s not forget that the long loops of Henle are in the renal medulla.
This part of the neprhon acts as a countercurrent multiplier to create a medullary interstitial osmolar gradient reaching its max at the tip of the loop. In order for this to work, the following characteristics are required:
Countercurrent flow: opposite directional flow = ascending & descending
Slow flow: to preserve the osmolar gradient of the intersticium, hence they have <PO2 and < metabolic rate. This is why the renal medulla is more succeptible to ischemia.
DESCENDING limb PERMEABLE to water but IMPERMEABLE to Na+: meaning, water leaves the loop and goes into the medullary intersticium and Na+ stays in the loop increasing its concentration. It can reach up to 1200mOsm/L, but this is the case of extreme dehydration. (Concentrating segment)
ASCENDING limb IMPERMEABLE to water but must REABSORB electrolytes:meaning, NaCl is being reabsorbed into the blood and water stays in the loop, diluting it. The osmolarity goes down to 100mOsml/L at the end of the loop. (Diluting segment)
Secondary active transporters found in Thick Ascending Loop:
Cotransport or Symport:  Na+/K+/2Cl- that allows Na+ to enter passively (with a little help of his friend the 3Na+/2K+ ATPase pump), also, it creates a positive potential in the lumen, and let Mg+ & Ca++ be reabsorbed.
Countertransport or Antiport:Na+/H+ exchange pump, that allows HCO3- to be reabsorbed.
Result: 25% of filtered e- and 15% of filtered water.

Pharmacology: 
Loop Diuretics = ETHACRYNIC ACID, BUMETANIDE, PIRETANIDE, FUROSEMIDE, TORSEMIDE: they inhibit the Na+/K+/2Cl- pump, hence no K+ into the cell, no positive potential achieved, and  ↓ Mg+ & Ca++ reabsorption. All of these e- in the lumen, promote diuresis. (SE= hypokalemia, hypomagnesemia, hypocalcemia)

-
Next, the Distal Tubule (DT) & Collecting Duct (CD)
DT
The macula densa is present here lining the walls of the DT adjacent to the afferent arteriole at the vascular pole of the corpuscle from which the tubule arose.  It may function as a sensor for Na+ and/or Cl- concentration and gives the sensory input to the YG apparatus (correct the first drawing, those cells should not be around the collecting duct)

The early DT is different from the late DT.
The late DT is similar to the CD. Both are called distal nephron.
Early DT:
Is impermeable to water, meaning water does not leave the tubule. This portion of the nephron is the most hypotonic of all. The osmolarity can go down to 50mOsm/L
Here, NaCl is reabsorbed (Na+/Cl- symporter)
Ca++ enters the cell passively trhough Ca++ channels. This action is assisted indirectly by the PTH (remember: PTH acts via Gs, increases cAMP, which phosphorilates the Ca++ ch & opens it)
Ca++ goes into the blood via the Ca++ ATPase or the 3Na+/Ca++ antiporter.
Secondary active transporters:
Cotransport or Symport: Na+/Cl- (dependant of the 3Na+/2K+ ATPase pump)
Countertrasnport or Antiport: 3Na+/Ca++

Pharmacology
Thiazides = HYDROCHLOROTHIAZIDE, INDAPAMIDE, BENDROFLUMETHIAZIDE: Inhibit the Na+/Cl- symporter, hence Na+ and Cl- concentration build up in the lumen and promote diuresis. Also, little intracellular Na+ decreases Na+ & Ca++ exchange, so Ca++ builds up in blood (SE: hypercalcemia)

Distal nephron (Late DT + CD)
Composed of Principal cells and Intercalated cells
Principal cells:Na+ enters passively via channels, and acivetly pumped by 3Na+/2K+ ATPase in exchange for K+. This happens under the influence of aldosterone. The result: reabsorption of Na+, water, a little bit of Cl- and excretion of K+
Intercalated cells:2 types. One type secrete H+ to generate one HCO3- send to blood. The other type secretes HCO3- into the lumen. This way, the nephron get rid of fixed acids. 

33% H+ ions secreted into the lumen are buffered with Phosphate (H2PO4-) = titrable acid
66% H+ ions are buffered with Ammonium (NH4+) = nontitrable acid.
Pathology
Renal Tubular Acidosis Type I (RTA I) or Distal Renal Tubular Acidosis (dRTA): inability of the distal nephron to secrete and excrete fixed acid, hence, inability to form acid urine. This results in metabolic acidosis with alkaline urine
Pharmacology
K+ sparing diuretics =
SPIRONOLACTONE : Aldosterone Receptor blocker, gets rid of Na+, keeps K+, promotes diuresis.
AMILORIDE, TRIAMTERENE:Na+ channel blocker, this way, there’s no intracellular Na+ to exchange for K+, and K+ excretion decreases.

Collecting Duct
This is where the ADH have V2 receptors. When together, aquaporine water channels open and reabsorb water & urea. As it names say: Anti Diuretic Hormone, “you shall not pee”
Pathology: Nephrogenic Diabetes Insipidus, V2 receptors are fucked up, so it doesn’t matter how much ADH your Neurohpf produce, you are gonna pee like A LOT of hyposmolar urine
*THE END*

THE NEPRHON 

EDIT

Please note that there´s a mistake in the drawing. The place where the macula densa cells should be is in the Distal Tubule, not the Collecting Duct. Thanks

I did this a while ago but didn’t have the time to explain it… so i will do it now.

In a parallel universe, where The Magic School bus exists, and I’m the one that picks where can we have our next adventure, I’ll definitely choose the nephron (yes people, if you haven’t tell yet, I am this nerd)

It is, hands down, my favorite functional unit of the body. It’s just perfect!

And now I stop talking nonsense and start with the real deal. This is gonna take a while! (sorry, there’s no “Keep reading” option when reblogging)

-

Let’s start in the Renal Corpuscle (RC) 

The RC is the initial filter of the nephron, it has 2 structures:

  1. Glomerulus: tuft of capillaries. Has 2 cells: endothelial cells & mesangial cells (responsible of the myogenic response that regulates RBF)
  2. Bowman’s capsule: parietal layer (simple squamous ep), Bowman’s space, visceral layer (podocytes)

Also, the RC has 2 poles

  1. Vascular pole: afferent & efferent arterioles communicate w/ the glomerulus. Remember that the majority of yuxtaglomerular cells are around the AFFERENT arteriole, and this smart cells secrete renin according to volume changes. Also, this cells have alpha1 & beta1 receptors, meaning that they respond to sympathetic activation to decrease (alpha) or increase (beta) renin secretion. See? they are fucking perfect. Both afferent & efferent arterioles are responsible for the regulation of filtration forces of the nephron. They are also influenced by the presence of ANP which promotes Natriuresis by increasing the GFR, how? Vasodilating the afferent and Vasoconstricting the efferent.
  2. Urinary pole: the RC opens to the Proximal tubule
-

Let’s move on to the Proximal Tubule (PT)

  • Here, 2/3 of Na+, H2O, K+ & Cl- and 80-90% of HCO3- are reabsorbed.
  • All carbohydrates, proteins, aa, are reabsorbed via 2° active transport
  • Secretion of Cations & Anions happen here. I actually made a mnemonic that involves Michael Fassbender’s penis about this. You are welcome ;)
  • All the energy comes from two 3Na+/2K+ ATPase pumps (1° active transport). THIS is the most demanding process of the nephron!
  • When PTH levels in blood increase, this inhibit the reabsorption of HPO4- - 
  • Only 1/3 filtered remains

image

Secondary active transporters found here:

  • Cotransport or Symport:  Na+/Lactate, Na+/Glucose, 2Na+/HPO4
  • Countertransport or Antiport: Na+/H+. [Angiotensin II (AT II) stimulates Na+ and H+ exchange, to increase Na+ and H20 reabsorption, permitting contraction alkalosis (increase of blood pH when fluid w/o HCO3- is lost)]

Pathology

  • Renal Tubular Acidosis II (RTA II) or Proximal Renal Tubular Acidosis (pRTA): failure of the proximal tubular cells to reabsorb filtered HCO3-, leading to urinary HCO3- wasting and subsequent acidemia. (less severe than dRTA). Associated w/ Fanconi’s syndrome, [phosphaturiaglycosuria, aminoaciduria, uricosuria, tubular proteinuria & bone demineralization (osteomalacia or rickets) due to HPO4— wasting]

Pharmacology: (as in diuretics that act on this level)

  • Osmotic diuretics = MANNITOL:  inhibit H2O reabsorption throughout the tubule.
  • Carbonic Anhidrase (CA) inhibitors = ACETAZOLAMIDE, DORZOLAMIDE:inhibit CA in the PT, this decreases the amount of H+ formation inside the cell, H+ stop being available for the H+/Na+ antiport, hence, Na+ (and HCO3-) accumulate in the lumen, promoting diuresis.

image

CA= enzyme responsible of catalyzing the interconversion (reversible) of CO2 and H2O into H2CO3- and ultimately into H+ & HCO3-

-

Now onto the Loop of Henle

Up to this point, we only have 1/3 of the volume filtered into Bowman’s space & the fluid entering here is isotonic (300mOsm/L) since the reabsroption of e- was pretty much the same amount.

Let’s not forget that the long loops of Henle are in the renal medulla.

This part of the neprhon acts as a countercurrent multiplier to create a medullary interstitial osmolar gradient reaching its max at the tip of the loop. In order for this to work, the following characteristics are required:

  • Countercurrent flow: opposite directional flow = ascending & descending
  • Slow flow: to preserve the osmolar gradient of the intersticium, hence they have <PO2 and < metabolic rate. This is why the renal medulla is more succeptible to ischemia.
  • DESCENDING limb PERMEABLE to water but IMPERMEABLE to Na+: meaning, water leaves the loop and goes into the medullary intersticium and Na+ stays in the loop increasing its concentration. It can reach up to 1200mOsm/L, but this is the case of extreme dehydration. (Concentrating segment)
  • ASCENDING limb IMPERMEABLE to water but must REABSORB electrolytes:meaning, NaCl is being reabsorbed into the blood and water stays in the loop, diluting it. The osmolarity goes down to 100mOsml/L at the end of the loop. (Diluting segment)

Secondary active transporters found in Thick Ascending Loop:

  • Cotransport or Symport:  Na+/K+/2Cl- that allows Na+ to enter passively (with a little help of his friend the 3Na+/2K+ ATPase pump), also, it creates a positive potential in the lumen, and let Mg+ & Ca++ be reabsorbed.
  • Countertransport or Antiport:Na+/H+ exchange pump, that allows HCO3- to be reabsorbed.

Result: 25% of filtered e- and 15% of filtered water.

image

Pharmacology: 

  • Loop Diuretics = ETHACRYNIC ACID, BUMETANIDE, PIRETANIDE, FUROSEMIDE, TORSEMIDE: they inhibit the Na+/K+/2Cl- pump, hence no K+ into the cell, no positive potential achieved, and  ↓ Mg+ & Ca++ reabsorption. All of these e- in the lumen, promote diuresis. (SE= hypokalemia, hypomagnesemia, hypocalcemia)

image

-

Next, the Distal Tubule (DT) & Collecting Duct (CD)

DT

  • The macula densa is present here lining the walls of the DT adjacent to the afferent arteriole at the vascular pole of the corpuscle from which the tubule arose.  It may function as a sensor for Na+ and/or Cl- concentration and gives the sensory input to the YG apparatus (correct the first drawing, those cells should not be around the collecting duct)

The early DT is different from the late DT.

The late DT is similar to the CD. Both are called distal nephron.

Early DT:

  • Is impermeable to water, meaning water does not leave the tubule. This portion of the nephron is the most hypotonic of all. The osmolarity can go down to 50mOsm/L
  • Here, NaCl is reabsorbed (Na+/Cl- symporter)
  • Ca++ enters the cell passively trhough Ca++ channels. This action is assisted indirectly by the PTH (remember: PTH acts via Gs, increases cAMP, which phosphorilates the Ca++ ch & opens it)
  • Ca++ goes into the blood via the Ca++ ATPase or the 3Na+/Ca++ antiporter.

Secondary active transporters:

  • Cotransport or Symport: Na+/Cl- (dependant of the 3Na+/2K+ ATPase pump)
  • Countertrasnport or Antiport: 3Na+/Ca++

Pharmacology

  • Thiazides = HYDROCHLOROTHIAZIDE, INDAPAMIDE, BENDROFLUMETHIAZIDE: Inhibit the Na+/Cl- symporter, hence Na+ and Cl- concentration build up in the lumen and promote diuresis. Also, little intracellular Na+ decreases Na+ & Ca++ exchange, so Ca++ builds up in blood (SE: hypercalcemia)

image

Distal nephron (Late DT + CD)

Composed of Principal cells and Intercalated cells

  • Principal cells:Na+ enters passively via channels, and acivetly pumped by 3Na+/2K+ ATPase in exchange for K+. This happens under the influence of aldosterone. The result: reabsorption of Na+, water, a little bit of Cl- and excretion of K+
  • Intercalated cells:2 types. One type secrete H+ to generate one HCO3- send to blood. The other type secretes HCO3- into the lumen. This way, the nephron get rid of fixed acids. 

image

  • 33% H+ ions secreted into the lumen are buffered with Phosphate (H2PO4-) = titrable acid
  • 66% H+ ions are buffered with Ammonium (NH4+) = nontitrable acid.

Pathology

  • Renal Tubular Acidosis Type I (RTA I) or Distal Renal Tubular Acidosis (dRTA): inability of the distal nephron to secrete and excrete fixed acid, hence, inability to form acid urine. This results in metabolic acidosis with alkaline urine

Pharmacology

  • K+ sparing diuretics =
  • SPIRONOLACTONE : Aldosterone Receptor blocker, gets rid of Na+, keeps K+, promotes diuresis.
  • AMILORIDE, TRIAMTERENE:Na+ channel blocker, this way, there’s no intracellular Na+ to exchange for K+, and K+ excretion decreases.

image

Collecting Duct

  • This is where the ADH have V2 receptors. When together, aquaporine water channels open and reabsorb water & urea. As it names say: Anti Diuretic Hormone, “you shall not pee”
  • Pathology: Nephrogenic Diabetes Insipidus, V2 receptors are fucked up, so it doesn’t matter how much ADH your Neurohpf produce, you are gonna pee like A LOT of hyposmolar urine

*THE END*

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