Renal System

Question 1

Osmoconformer

Answer 1

Blood osmolarity will vary with the environment. Ex: Some fish and inverts.

Question 2

Osmoregulatory

Answer 2

The blood osmolarity is kept within a certain range. Mammals and most other verts. The ion concentration and water balance are strictly maintained around homeostatic setpoints.

Question 3

Saltwater Fish

Answer 3

Still osmoregulators. They are hypoosmotic to seawater, meaning that their osmolarity of the blood is lower than seawater, ranging from 300-400mOsm. 
		Teleost fish (rayfins): The water being lost and the ion uptake via gills from the water is an issue. Water is also lost from urine formation. So, these fish need to actively remove ions from the blood (excretion) and their urine output must be low to retain water but they have to drink a lot of seawater. Excess salts are excreted through gills via ionocytes (active transport). These cells have a lot of mitochondria to allow for the active transport that pushes ions against their gradient.
-The Na+K pump keeps Na+ low in cells, moving it to the ECF passively. Also used in secondary active transport to move Cl- into the cell to be excreted. Because Cl- = anion, it attracts Na+.
-These fish have to drink a lot of seawater but water tends to stay in the higher concentrated ingested sea water and not want to cross the intestinal lining.
-The movement of ions across the epithelium drives water absorption because water follows ions. Transporter cells help move ions from the lumen to the epithelium along with water.

Question 4

Freshwater Vertebrates

Answer 4

Hyperosmotic compared to surrounding water so they struggle to get ions. Also have ionocytes. Species have to excrete excess water (lots of urine) and actively absorb ions. Teleost fish absorb ions from ionocytes in the gills, less drinking of water.
-Freshwater verts also use voltage changes. H+ATPases (takes ENERGY) allow H+ from the ionocytes to go to the water, allowing for a higher negative charge within the cell, encouraging sodium to enter cell passively.

Question 5

Salt gland

Answer 5

Because birds and mammals don’t rely on water for gas exchange, they have impermeable skin to reduce water loss but some still do drink seawater. Extra salts are removed via the renal system (kidneys) and also salt glands. Counter current exchange occurs where salt moves from the blood into the lumen of the salt gland. The fluid in the lumen has a lower osmolarity, maintaining the ion gradient. So, salt can be secreted via the ECF and lost to the environment.

Question 6

Explain the functions of the kidneys. Differentiate between filtration and reabsorption in the nephron.

Answer 6

The mammalian renal system consists of the kidneys, ureters, urinary bladder, then urethra. The kidneys filter based on needs. Whatever remains in the filtrate becomes urine. The renal system functions to:

	- Regulate blood pressure / volume
	- Regulate osmolarity (amount of solute / volume)
	- Excrete toxins and excess substrates and formation of urine.

Question 7

Kidney regions

Answer 7

1. Renal cortex: Osmolarity of the interstitial fluid is about 300mosm, same as blood.
   
   2. Renal medulla: Osmolarity is 300mosm near cortex but increases to 1200mosm (hyperosmotic) towards the renal pelvis
   3. Renal pelvis: Filtrate in the nephrons drains into a cup like structure of the pelvis; further drains into ureter, leading to bladder.
      This variance in osmolarity helps with water absorption.

Question 8

Nephrons

Answer 8

are the structural / functional units that form the urine. There are more than 1million per kidney. Made of 2 parts: the renal corpuscle that produces the filtrate (made of bowman’s capsule and the glomerulus) and the renal tubule that balances to create the filtrate
-Nephrons are closely associated with capillaries, allowing for reabsorption and secretion of solutes and water.

Question 9

Filtration

Answer 9

Fluid moving from blood into the lumen of the nephron. Only in Bowman’s capsule.

Question 10

Reabsorption

Answer 10

Substances from the filtrate get reabsorbed into the blood. Proximal tubule, loop (ascend and descend), distal tubule, and collecting tubule.

Question 11

Secretion

Answer 11

Removing molecules from the blood and into filtrate (more selective)
180L of fluid is processed daily but only 1.5L of urine is formed. Occurs in proximal tubule, distal tubule, and collecting duct.

Question 12

Describe the main characteristics, locations, and functions of the following structures and cells of the renal system.

Answer 12

Blood goes from afferent arterole – glomerulus (capillary bed) – efferent arteriole – peritubular capillaries – vasa recta

Renal corpuscle : Part of nephron along with renal tubule. Produces filtrate. 2 parts	
				1. Glomerulus: capillary bed		
				2. Bowman’s capsule : Includes the parietal and visceral layers. The 				visceral layer wraps around the capillaries. 
Proximal Convoluted Tubule: In the renal cortex. Where the majority of secretion and reabsorption (of H2O, Na+, glucose) occurs. Has a brush border that acts as a filter?
Loop of Henle (Descending and Ascending)			
Distal tubule 
Collecting duct			
Juxtaglomerular apparatus	
Macula Densa cells
Granular cells			
Afferent arteriole		
Efferent arteriole   
Glomerulus				
Vasa Recta (Ascending and Descending)			
Ureter
Bladder				
Urethra

Question 13

Describe the composition of urine and changes to osmolarity.

Answer 13

• Urine is 95% water and 5% solutes including nitrogenous wastes from amino acid breakdown. It’s color is pale to deep yellow from urochrome (pigment from hemoglobin breakdown in RBCs).
• The osmolarity of urine varies from 50mosm-1200mosm depending on what how much solutes need to be excreted and how much the body needs to conserve water.
  - Average osmolarity = 500-800mosm.
  - Humans excrete 800-2000mL of urine per day depending on H2O conservation needs.

Question 14

Describe the pathway for filtrate flow through the nephron. Describes how volume changes as filtrate flows through the nephron. Describe the pathway for blood flow around the nephron.

Answer 14

1. Fluid from the blood flows into the lumen of the nephron in Bowman’s capsule.
2. Fluid then flows into the proximal tubule where substances are reabsorbed and secreted. High osmolarity
3. Next filtrate flows into the Loop of Henle where there is a lower volume of filtrate because it’s been absorbed by the proximal tubule.
4. End of Loop of Henle sees reabsorption back into blood and a much lower osmolarity. Less liquid is filtered here.
5. Filtrate flows from distal tubule into the collecting duct that is regulated by hormones. At the end of the collecting duct, 1.5L/day (low) goes through. The osmolarity is lower.
6. Filtrate goes to bladder and then external environment.

Question 15

Describe Describe the filtration barriers of the renal corpuscle. Describe and differentiate between how and what products each barrier excludes from the filtrate.

Answer 15

Filtration barriers are in the renal corpuscle to provide regulation. The pores in the capillary endothelium let most substances pass. RBCs are too big.
-The basement membrane also excludes most proteins, like a sieve.
-The tubule epithelium (outer layer) has filtration slits with podocytes that link together to form filtration slits.
The hydrostatic pressure in the glomerulus forces fluid and solutes out through filtration barriers, into Bowman’s capsule.

Question 16

Define glomerular filtration rate (GFR). Explain potential issues when GFR increases or decreases. Describe and compare and contrast the mechanisms for GFR regulation when systemic blood pressure increases and decreases. Be sure to include any important proteins and cells in your discussion. Apply this knowledge to hypothetical scenarios.

Answer 16

GFR = the volume of filtrate that forms per minute by both kidneys. Normal = 120-125 mL/min. Highly regulated. An issue with GFR changes indicates a change in hydrostatic pressure.

• Increased GFR: More filtrate flow through nephron can cause damage to cells and decrease reabsorption / secretion efficiency because the filtrate is moving too fast. Losing H2O / salt.
• Decreased GFR: Filtrate flow rate is too slow so secretion / reabsorption occurs too slowly. Pressure in glomerulus is too low and not producing sufficient filtrate.

Question 17

Mechanisms for GFR Regulation:

Answer 17

Myogenic (smooth muscle) feedback in the afferent arteriole:
-Increased BP / volume means that GFR is too high:
• Smooth muscle of the afferent arteriole stretches, stimulating vasoconstriction of the afferent arteriole, reducing blood flow through the afferent arteriole, slowing GFR
• The decreased BP stimulates vasodilation in the afferent arteriole, increasing blood flow.

Question 18

Tubuloglomerular feedback:

Answer 18

-Juxtaglomerular apparatus (JGA) is the area where the ascending loop of Henle contacts afferent / efferent arterioles. If GFR is too high, less Na is absorbed so increase in the NaCl in the proximal tubule. If GFR is too low, lower the NaCl in proximal tubule.
Two cell types:
• Macula Densa cells: on loop of Henle that are sensitive to NaCl levels.
• Granular cells: on afferent arteriole close to macula densa. Produce the enzyme renin.

Situation A: The Macula Densa cells respond to the increased NaCl in proximal tubule because of the high GFR. A high GFR increases the flow rate — more NaCl stays in the filtrate and is detected by the Macula Densa cells in the loop of Henle.
–So the MD cells on the tubule secrete paracrine that stimulates afferent arteriole to constrict, lowering GFR. So, lowers blood flow into glomerulus, lowers HP.

Situation B: The MD cells respond to decreased NaCl (slow / low GFR) by stimulating granular cells to secrete renin. Renin is an enzyme that leads to the production of angiotensin II, which is the main hormone that functions to constrict blood vessels. The EFFERENT arteriole constricts, increasing GFR, therefore increasing NaCl in the proximal tubule.
Angiotensinogen is the inactive form, gets activated by renin to form angiotensin I then II.

Question 19

Describe reabsorption of Na+ and water in the proximal tubule.

Answer 19

Where majority of secretion / reabsorption occurs. NO OSMOLARITY CHANGES
Na+ enters the apical membrane of proximal tubule via facilitated diffusion using Na+ channels. This also helps glucose reabsorption (SGLTs).
-As the solute concentration of the filtrate (tubular fluid) decreases, water goes into the cell via osmosis (aquaporins). Isosmotic reabsorption: The osmolarity from the beginning of the proximal tubule doesn’t change, but the volume does (it reduces)
-Na+/K+ ATPase removes Na+ from the cells to keep the concentration low. Put in ESF
***So, although the solute concentration is decreasing, because of the osmosis causing water to flow into the cell too, the osmolarity from the beginning to end of proximal tubule doesn’t really change.

Question 20

Define renal threshold. Describe the relationships between transport maximum, renal threshold, filtration of a substance, and presence of substance in urine. Apply this knowledge to hypothetical scenarios.

Answer 20

Renal threshold: The plasma concentration of the solute at which it appears in urine. This is met when the transport rate is met.
- Above the threshold, there aren’t enough transporters. Where we would see more glucose excreted
Transport max: the rate at which all transporters for the specific substance are saturated.

Question 21

Describe the transport / movement of water and solutes in the loop of Henle. Differentiate between the ascending and descending segments of the loop of Henle.

Answer 21

Descending LOH: Osmosis occurs and the interstitial fluid becomes more concentrated deep in the medulla, drawing water out of the filtrate. Osmolarity goes 300-600-1200, loss of H2O.
Ascending LOH: Solutes are being actively pumped out of the filtrate. No osmosis occurs. Osmolarity from 1200-400-200-100 because loss of ions, not gain of H2O.

Question 22

Describe the countercurrent multiplier mechanism of the loop of Henle. Include changes to osmolarity and permeability in all segments of the loop of Henle and the vasa recta. Describe the importance of this mechanism to maintaining osmolarity of the medulla and water reabsorption from the nephron.

Answer 22

LOH and vasa recta flow in opposite directions.
The vasa recta picks up ions (hyperosmotic) but then picks up H2O to become hypoosmotic.
-Solutes enter the vasa recta (capillary network) via passive transport. The blood becomes hyperosmotic (more solutes) compared to the interstitial fluid. The ascending portion of the VR gets the removed water leaving LOH and descending VR.
-Blood is more hyperosmotic as it goes down the vasa recta so it picks up H2O to become hypoosmotic.
-This is done to keep the osmolarity of the medullary fluid near the renal pelvis higher (inner medulla), to help with water absorption from the nephron.
—————————————————————————————————————–
-Animals in a more dry environment need more water reabsorption from the LOH so kangaroo rats have longer loops.
-Animals with more access to freshwater have shorter LOH, cutting down on the water being reabsorbed.
-Humans are in the middle with both types of loops.

Question 23

Differentiate between the following hormones / enzymes. For each, explain where and how the hormone is produced, stimuli that cause its release, the hormone’s actions, and how this information applies to water, Na+, osmolarity, blood volume, and blood pressure regulation. Apply this knowledge to hypothetical situations.

Answer 23

Vasopressin: INCREASED H2O ABSORPTION. Peptide hormone that can’t cross cell membrane. Increases the permeability of the collecting duct cell membrane to water. This allows for water from the collecting duct to move into the ISF and then back into blood capillaries. The hypothalamus receives signals regarding water needs. Detects osmolarity, blood volume, and blood pressure and releases anti-diuretic hormone accordingly.
• If osmoreceptors detect a high osmolarity in the blood, it stimulates ADH release.
• A decreased blood volume (decreased atrial stretch) stimulates the release of ADH.
• Decreased BP stimulates the release of ADH
-These 3 signals signa. to hypothalamus to synthesize more vasopressin to reabsorb water More vasopressin = more aquaporins = more water reabsorbed

Question 24

Aldosterone

Answer 24

INCREASED NA+ ABSORPTION. Steroid hormone that can cross the cell membrane. Increases Na+ reabsorption from the collecting duct. Increases the activity of the Na+/K+ pump and causes transcription of mRNA so new pumps / channels can be created
• Increases Na+ channels so that it can move down it’s gradient from the filtrate into the cell. The Na+/K+ pump moves Na+ out and puts it into the blood (reabsorption)
• K+ is usually higher in the cells so Aldosterone lets more K+ leave the cell and enter the filtrate, the opposite of Na+.
Hyperkalemia induces aldosterone release by directly acting on the adrenal cortex (where Ald. is made) so excess K+ can be excreted.
-Low blood pressure in the afferent arteriole initiates Renin-angiotensin pathway:
Angiotensinogen activated by renin to ANG I then ANG II (a vasoconstrictor that stimulates the adrenal gland to release aldosterone.)
ACE (angiotensin converting enzyme) is something taken for hypertension (high BP) which inhibits ANG I conversion to ANG II so vasoconstriction doesn’t occur.

Question 25

Angiotensin II

Answer 25

Is the main vasoconstricter. Constricts EFFERENT arteriole, increasing glomerular filtration rate. Increases blood pressure in multiple ways:
• Vasoconstricts arterioles
• Cardiovascular control center in the medulla oblongata
• The hypothalamus to increase vasopressin and thirst, increasing volume to maintain OSM
• The adrenal cortex to increase aldosterone, increasing Na+ reabsorb, maintaining OSM
• Proximal tubule (most Na+ and H2O reabsorb location) by increasing Na+ reabsorption

Question 26

Describe water and sodium reabsorption from the collecting duct and changes to urine output (volume and concentration). Apply this knowledge to hypothetical situations.

Answer 26

The amount of reabsorption varies based on homeostatic needs.

? If blood osmolarity was high, what would happen to aldosterone and ADH secretion? How would this correct high blood osmolarity.

• Aldosterone would decrease to lower reabsorption so excess Na+ can be excreted and not be put into the blood.
• Increase vasopressin (ADH) to increase the absorption of water.

? Urine sample is 50mosm. Were levels of aldosterone and ADH high or low?

• Levels of ADH (vasopressin) were low, less reabsorption of water and more excretion of water.
• Aldosterone levels were also low, causing less reabsorption of Na+ from the collecting duct.

? High aldosterone and ADH levels. What type of urine and what homeostatic imbalance?

• Lots of water reabsorption from high vasopressin levels. Dehydrated homeostatic imbalance.
• High aldosterone levels would cause a high concentration of K+ in the urine and more Na+ being absorbed into the blood.

Question 27

Define and differentiate between metabolic / respiratory acidosis and alkalosis. Explain pH regulation by the kidneys. Differentiate between mechanisms in the proximal tubule and collecting duct.

Answer 27

The pH of the body is usually 7.4, slightly basic. Changes to the pH can denature proteins, affecting membrane channels / transporters, enzymes, and the nervous system. Increasing acids (H+) comes from food and metabolic products.

Acid-Base Balance: The concentration of H+ is regulated by 3 mechanisms:
1. Chemical buffer systems: The rapid, first line of defense

Carbonic acid intermediate
Plasma buffers: CO2 from metabolic processes leads to production of HCO3-. When the buffers aren’t enough to regulate pH, we need to be able to regulate excess H+ and make more buffers.
2. Brain stem respiratory centers: Acts in 1-3 minutes to change breathing rate, changing CO2 levels.
3. Renal mechanisms: Most potent but takes hrs / days to affect pH. Excretes excess H+

Question 28

RENAL COMPENSATION

Answer 28

Acidosis: (Happens in proximal tubule). H+ is secreted into the tubule lumen by active transport and binds with the filtered buffers. Traps H! NH3+H+  NH4+
HPO4-+H+  H2PO4-
So H+ is trapped and can’t go back into cell. Can be excreted into urine.
Cells actively secrete buffer. Carbonic anhydrase is enzyme that converts CO2 and H2O into H+s and Bicarbonates! So, the cells are actively producing H+s but cancelled out by the extra buffer being made.

Question 29

Reabsorbing HCO3-

Answer 29

back into the cell (must bind with H+ to reabsorb): H+ is secreted into filtrate, Na+ is reabsorbed. H+ binds with HCO3- to make H2O and CO2, which diffuses back into the cell. Proximal tubule cells convert CO2 and H2O into H+ and bicarb (which gets secreted back into blood. H+ secreted back into filtrate with help of sodium transporters.

Question 30

The intercalated cells in the distal tubule (then collecting duct) have 2 types:

Answer 30

Type A Intercalated Cells- Acidosis. H+ is secreted into the filtrate using H+ATPase and H+/K+ATPase transporters. H+ put into filtrate ACTIVELY.
-Often linked with hyperkalemia. The pumps put K+ into the cell from the urine so leak channels allow it to leak back into blood. Hyperkalemia can occur!
-Also see production of bicarbonate in cell and its secretion into the ISF. Along with this we see Cl- coming into the cell.
Type B Intercalated Cells- Alkalosis. H+ gets reabsorbed into the cell and then ISF by H+ATPase and H+K+ATPase transporters. Done to lower pH.
-Bicarbonate gets excreted into urine via Bicarb/Cl- channels.
-Hypokalemia can occur. K+ is being put into cell so H+ can be transported into blood and then K+ leak channels push it into the filtrate to be excreted.

Question 31

Metabolic Acidosis: H+

Answer 31

input from metabolism and diet is more than excretion. Can also happen when bicarbonate is lost through diarrhea.
↑CO2 + H2O ← H2CO3 ← ↑H+ + ↓HCO3-
– Rising H+ leads to reactions with HCO3- leads to more CO2 production.
Respiratory compensation= Increased ventilation removing extra CO2 from blood
– Renal compensation= Excreting H+, reabsorbing bicarbonate

Question 32

Metabolic Alkalosis

Answer 32

Increased pH because of excess vomiting or excess eating of bicarbonate.
Less H+ slows the rxn with HCO3 so less CO2.
↓ CO2 + ↓ H2O → H2CO3 → ↓ H+ + ↑ HCO3-
–Respiratory compensation= hypoventilation to retain CO2. HCO3 keeps rising so hypoventilation stops once plasma O2 reaches 60mmHg via Medulla Oblongata.
–Renal compensation= HCO3 excreted, H+ reabsorbed via Type B intercalated cells!

Question 33

Respiratory Acidosis

Answer 33

Hypoventilation increases plasma CO2 because of drugs, alcohol, asthma, COPD. Increased CO2 causes more of the reaction with water, creating extra H+! Even though HCO3 is increasing, it can’t compensate for pH rise.
-Renal compensation: Excrete H+ excess, reabsorb HCO3 (like metabolic acidosis)

Question 34

Respiratory Alkalosis

Answer 34

Hyperventilation causes low plasma CO2 because of anxiety / stress. Low CO2 causes a low H+ concentration.

• bag breathing raises plasma CO2
• Renal compensation= excrete HCO3- and reabsorb H+

Question 35

Describe the structure and function of insect Malpighian tubules.

Answer 35

The malphigian tubes arise from the midgut and hindgut. Each tubule has a single layer of epithelial cells.

1. K+ secretion into the distal tubule draws Cl- in and H2O which are metabolic wastes).
2. Metabolic wastes are transported into the tubule in the midgut.
3. In the rectum, ions and water become reabsorbed.

Question 36

Principal Cells

Answer 36

are in the majority of malphigian tubules. Have lots of mitochondria because lots of active transporters (of K+) using H+, creating more [H+], powering H+/K+ transporters via secondary active transport. Makes sure that K+ doesn’t reach EQ
-Lots of villi for increased surface area.

Question 37

Stellate cells

Answer 37

have water follow K+ (and Cl-) via osmosis