Renal Physiology II Flashcards

1
Q

*Understand Renal Clearance

A

Clearance of substance: the Volume of plasma from which the substance is completely cleared, by kidneys per unit time.

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2
Q

*Know the general principles of tubular reabsorption and secretion

A

A

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3
Q

*Understand the concept of transport maxima

A

A

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4
Q

*Understand the specific mechanisms of Solute transport in different nephron segments

A

A

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5
Q

*Understand how the nephron concentrates urine

A

A

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6
Q

What does principle of clearance emphasize? What is the formula for clearance??

A

Principle of Renal clearance: emphasizes Excretory function of kidneys. It considers only rate at which substance is excreted into urine
formula; Cx= UxV/Px: Cx= clearance of substance x
Ux= urine concentration of x; V= urine volume (mL/min)
Px= plasma concentration of x (mg/ml)\
clearance units: mL/min

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7
Q

What is another important factor in Renal system that clearance can be used to calculate? What is the formula and when will GFR equation only be true?

A
Renal clearance can be used to estimate GFR (glomerulus filtration rate)/ 
Formula: GFR= UwV/Pw. 
Equation only true if W is:
1. Freely filterable at the renal corpuscle
2. Not reabsorbed
3. Not secreted
4. Not synthesized by tubules
6. Not broken down by tubules
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8
Q

What substance fits the description of special properties needed to use clearance for GFR?

A

INULIN (polysaccharide)- fits the description and can be used to determine GFR. GFR= renal clearance of inulin.

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9
Q

Why is measuring GFR NOT convenient? What substance is frequently used instead? What are its properties and how does it affect GFR?

A

Measuring GFR by inulin is inconvenient because Inulin is NOT a naturally occurring substance
Clinic CREATINE is frequently used instead.
Clinic creatine is freely filterable (like inulin), and NOT reabsorbed, but a SMALL amount is SECRETED.
hence, Creatine is slightly HIGHER than GFR>

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10
Q

What is the normal value of plasma creatine? What happens to creatine levels when GFR decreases? What occurs when plasma creatine is raised (increased) ?

A

Normal Plasma Creatine= 10 mg/L.
If GFR Decreases 50%, Plasma creatine rises but stabilizes at 20 mg/L. Hence plasma creatine increases as GFR decreases?
large increase in creatine, can be small drop in GFR
When plasma creatine is raised, it indicates that RENAL function, especially GFR is IMPAIRED (less substance filtered)

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11
Q

What is the role of Para-aminohippurate (PAH)? what are its properties and what does it indicate? What is the equation for clearance of PAH? What is the RBF equation in terms of RPF (renal plasma flow)?

A

PAH- substance Filtered at Glomerulus and COMPLETELY SECRETED. NOT reabsorbed.
The clearance of PAH approximates Renal Plasma Flow.
10-15% of total renal plasma flow supplies non-filtering and non-secreting portions of kidney, such as (peripelvic fat) and this plasma cannot lose its PAH by secretion.
Clearance of PAH (CPAH)= UPAHV/PPAH= ERPF (effective renal plasma flow)
ERPF= 0.9RPF (90% of RPF)
RBF=RPF(1-hematocrit)

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12
Q

What are the 5 main types of transport mechanisms in nephron tubules ?

A
  1. Diffusion
  2. Facilitated Diffusion
  3. Primary active transport (requires energy; ATPASE)
  4. Secondary active transport (cotransport and countertransport)
  5. Bulk flow or Solvent drag
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13
Q

Define the term Diffusion?

A

Diffusion of uncharged solutes occur from area of HIGHER concentration to one of LOWER concentration. Diffusion of ions (Na+, K+) is affected by Electrical potential difference across cell membrane of renal tubule cells

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14
Q

What is facilitated diffusion? What proteins are involved?

A

Facilitated diffusion- depends on interaction of Solute with specific protein in the membrane that facilitates it movement across membrane.
The membrane proteins involved in facilitated transport are TRANSPORTERS

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15
Q

What is primary active transport? What is needed for this form of transport? How does active transport occur in renal tubule cells?

A

Primary Active Transport- movement of molecules through mechanism directly coupled to energy derived from metabolic processes (it consumes ATP)
Active transport of solutes- occurs against concentration gradient (from LOW [ ] to HIGH [ ]) Primary active transport in tubule cells use ATP-dependent transporters or through ENDOCYTOSIS.

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16
Q

Describe the process of endocytosis?

A

Endocytosis- transport process where there is an invagination of a part of cell membrane until it pinches off and forms a vesicle in cytoplasm.

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17
Q

Compare and contrast secondary active transport and solvent drag

A

Secondary active transport in kidney cells, occur when the energy from downhill movement of solute provides energy for uphill movement of another solute
Solvent drag- when water is reabsorbed and solutes which have been dissolved in the water is reabsorbed with water.

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18
Q

What are the main routes of reabsorption?

A

Routes of reabsorption:
1. Transcellular - goes across the tubular cell;
susbtance must cross two membranes (must cross lumenal into cell, and then cross basolateral membrane into interstitial.
2. Paracellular- goes between the two cells
-go out of LUMEN between cells.

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19
Q

What must occur for substance to be reabsorbed transcellularly? What about transport?

A

For any substance to be reabsorbed transcellularly, ONE of its two movements have to be ACTIVE.
2 modes of transport must be DIFFERENT
ex: ubiquitous Na K+ ATPASE- form of PRIMARY Active transport:; transports sodium out of cell and potassium into the cell (3:2 ratio)
Na+ go into cell by facilitated diffusion and Na+ go Out of cell by primary active transport.

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20
Q

How does Glucose get transported in the cell? What about sodium?

A

Glucose goes OUT of cell through facilitated diffusion and glucose goes IN to the cell by SECONDARY active transport COUPLED with SODIUM (Na+).
Na+ out of cell by Na/K+ Atpase pump and sodium goes into cell by diffusion

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21
Q

Distinguish between how lipid soluble and poor-lipid soluble susbtances moves across cell?

A

Lipid soluble substances can transverse BOTH membrane (and cytosol) by Diffusion and Net Passive reabsorption occurs by transcellular route

  • transcellular movement for substances that are poorly lipid-soluble is active. Generalization is active net reabsorption of substance requires:
    1. that luminal and basolateral membranes are asymmetrical for substance (contain different channels/transporters)
    2. that energy be used for movement of substance either from lumen into cell or form cell into interstitial fluid.
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22
Q

What kind of transport is seen throughout entire nephron?

A

active transport mechanism: Na/K+ Atpase in basolateral membrane is present throughout nephron to keep sodium levels within cell LOW. This gives energy for sodium to be reabsorbed into cell.

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23
Q

What is transport maxima? How does it relate to kidneys?

A

many active reabsorptive systems in renal tubule have tm.
Tm- maximum amount that can be reabsorbed or secreted (moved in or out) is dependent on how saturated all transporters are.
if all transporters are saturated, the substance CANNOT be removed or reabsorbed by the kidneys anymore
Tm represent the maximum transport capacity of both kidneys. Also tm- sum of transport capacities of individual functional nephrons.

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24
Q

Describe the relationship between amount of substance filtered vs reabsorbed.

A

There is a LINEAR relationship between the amount of substance filtered and amount reabsorbed.
As Tm is approached, some nephrons reached their capacity and some of the substance appears in the urine.

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25
Q

What is renal threshold? How much glucose that is filtered is reabsorbed?

A

Renal threshold- the plasma concentration where the substance occurs in the urine. As more nephrons exceed their capacity the relationship between amount filtered and reabsorbed is not LINEAR (the Splay)
100% of glucose that is filtered is reabsorbed; hence renal clearance of glucose = 0. so Urinary concentration of glucose= 0

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26
Q

What happens when glucose is filtered? What about when there is too much glucose filtered? Is there glucose present in normal conditions of urine?

A

As glucose is filtered, it is reabsorbed (hence no glucose in urine0
When too much glucose is filtered, renal threshold is met and reabsorption PLATEAUS and glucose is EXCRETED (now glucose is seen in urea)
under normal circumstances, Glucose NEVER in urine because renal threshold is 200 mL (renal threshold is double normal limit of plasma glucose).

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27
Q

What happens to glucose for diabetic person that is controlled?

A

In diabetic person, glucose can be seen in urine which means glucose level is so HIGH, that kidneys cannot reabsorb any more (you can pee it out in urine). It causes no damage to kidneys.

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28
Q

What are the transport mechanisms used in secretion?

A

process begins with DIFFFUSION out of capillaries into interstitial fluid then crosses TIGHT junctions (paracellular) or across basolateral and luminal membranes (transcellular) into lumen.

29
Q

What occurs to PAH when it is totally secreted, Not filtered and excretions’?

A

PAH is totally secreted (NOT reabsorbed)
substance is being filtered so filtered load goes up. whatever is not filtered is SECRETED. Excretion (sum of secretion plus filtered load) will be higher than sum.
When secretion stops, whatever is being filtered is excreted?

30
Q

How are most substances transported?

A

most substances are transported BI-DIRECTIONALLY
some part of substance will be reabsorbed and some will be secreted (Net process)
bidirectional transport can also occur if the tubular segment contains opposing pathways.
Reabsorption and/or secretion mentioned here are NET Processes.

31
Q

What happens with reabsorptive processes and where do they occur?

A

Active reabsorptive processes tend to establish a concentration LOWER in lumen than in Interstitial fluid and this concentration difference favors PASSIVE Paracellular secretion. We are dealing with Pump-leak system where active transport creates a diffusion gradient that opposes own action by favoring back-diffusion.
This process occurs in the PROXIMAL TUBULE.

32
Q

What are the important characteristics of Proximal tubule?

A

Proximal Tubule:

  1. Luminal membrane has microvilli which increases surface area available for reabsorption.
  2. Tight junction is relatively leaky. Leakiness allows some reabsorption to occur passively down osmotic gradient through junction
  3. Na+-K+ ATPase pump in basolateral membrane has greater activity than in most nephron segments.
33
Q

Describe how much of the substances are filtered and reabsorbed? What occurs if GFR is low?

A

Water- filters 180 L/day (GFR) and 99.2% of filtered water is reabsorbed.
If GFR is low, less water will be filtered and less will be will be reabsorbed (even if 99% of filter load is reabsorbed). Water will go to different part of your bodies.
Na) have 99.4% of filtered sodium is reabsorbed (similar to water)
Glucose- 100% of glucose is reabsorbed
Urea- 50% will be reabsorbed

34
Q

What substance is urine composed of in high levels?

A

Urine has HIGH levels of SODIUM

35
Q

What is the role of ubiquitous Na+ K+ ATPASE pump? Where is it located? Why is it important?

A

In Proximal Tubule: Ubiquitin Na/K Atpase pumps out Na+ out and K+ in.
It is the driving force that helps reabsorb Sodium.

36
Q

What substance is the reabsorption of organic solutes coupled to?

A

In proximal tubule, the reabsorption of all inorganic solutes (Glucose, phosphate, lactate, Amino acid, citrate) is Coupled to Sodium.
Hence if driving force to reabsorb sodium is high, it helps reabsorption of all organic solutes.

37
Q

What is the role of the sodium/hydrogen exchanger? How does this affect Hydrogen secretion?

A

Sodium/Hydrogen exchanger- takes sodium in, and pumps Hydrogen out.
The Hydrogen ion secretion (out of cell, into lumen) is coupled to Na+ reabsorption.

38
Q

Define what occurs during Isosmotic Reabsorption

A

Isosmotic reabsorption- in proximal tubule, sodium and water reabsorption occur to the same degree.
As sodium is reabsorbed (to interstitial fluid, increase their concentration of music)water is being reabsorbed at the same time

39
Q

What part of the urinary system is strictly isoosmotic?

A

PROXIMAL tubule- only tubule that is strictly isosmotic

40
Q

What is the driving force of moving solutes from interstitial to peritubular capillaries?

A

Driving force: STARLING’s FORCES.
hydrostatic pressure of peritubular capillary
oncotic pressure of peritubular capillary
interstitial fluid hydrostatic pressure
oncotic pressure of interstitial fluid
interstital fluid forces cancel each other out.

41
Q

What are the two major components of reabsorption into peritubular capillaries? What happens when oncotic peritubular pressure is increased?

A

Peritubular oncotic pressure and peritubular capillary Hydrostatic pressure
When peri oncotic pressure is INCREASED, it drives the solutes in the fluid into peritubular capillary.

42
Q

How is bicarbonate reabsorbed and filtered? What are substances formed during this process? What enzyme is used?

A

Bicarbonate is reabsorbed, filtered and released in lumen.
Na/H exchanger will secrete Hydrogen ion
H ion can react with bicarbonate (HCo3) to form carbonic acid (H2Co3)
carbonic acid- SHORT-lived substance
Carbonic acid can be acted on by Carbonic anhydrase to dissociate into CO2 and water.

43
Q

What enzyme does reabsorption of Bicarbonate (HCO3) depend on? What bicarbonate’s reabsorption coupled to?
What would happen to reabsorption of bicarbonate with carbonic anhydrase inhibitor?

A

CARBONIC ANYHDRASE
reabsorption of bicarbonate is INDIRECTLY COUPLED to REABSORTION of SODIUM
if Carbonic anhydrase inhibitor: reabsorption of bicarbonate would DECREASE

44
Q

What would happen to reabsorption of Na if you have carbonic anhydrase inhibitor? What would occur to reabsorption of water in proximal tubule?

A

The reabsorption of Na would decrease (since reabsorption of bicarbonate is coupled to reabsorption of Na)
in proximal tubule, Reabsorption of water would DECREASE: since reabsorption of water follows that of sodium.
if Na reabsorption goes down, then reabsorption of water would also go down.

45
Q

What would occur in solution if bicarbonate was in blood? What would happen to blood pH with carbonic anhydrase inhibitor? What would happen to Urinary pH

A

Bicarbonate in blood would make the solution BASIC
Reabsorbing Na helps to make blood Basic.
blood pH would DECREASE (substance more acidic) if
there was carbonic anhydrase inhibitor.
with carbonic anhydrase inhibitor: Urinary pH would INCREASE as (bicarbonate stays in lumen and is excreted)

46
Q

How is chlorine reabsorbed? What is the mechanism?

A

Chloride can be reabsorbed PARACELULLARLY (between cells).
One mechanism for chloride reabsorption: as all solutes (glucose, amino acids HCO3-)are reabsorbed, the concentration of Chloride in proximal tubule becomes HIGHER, and then it goes down its Concentration gradient between the cells.

47
Q

What is the relationship between water and sodium in the proximal tubule?

A

reabsorption of water follows sodium?

48
Q

Describe the relationship between formate and chloride How does Na+ relate?

A

Reabsorption of Chloride is COUPLED to Formate (HF)
formate and Cl- are counterexchanged
Na+ reabsorption indirectly coupled to formate (as Na+ reabsorbed, H+ is secreted to form formate)
HF drives chloride reabsoprtion

49
Q

What is the filtration fraction? Why is it important?

A

Filtration fraction= GFR/Renal Blood Flow
When filtration fraction goes up, your peritubular capillary oncotic pressure has gone UP
renal plasma flow has DECREASED, and ability to concentrate proteins is HIGH, so oncotic pressure increased, hence greater driving force for reabsorption of solutes

50
Q

What happens to GFR when there is constriction? How does renal blood flow change, and what happens to filtration fraction

A

increase constriction, GFR DECREASES after period time (GFR goes up, then goes down), Renal blood flow will go DOWN MORE, so filtration fraction INCREASES

51
Q

what happens to filtration fraction when Angiotensin II or sympathetic nervous system works on afferent/efferent arterioles?

A

Filtration fraction ALWAYS goes up (INCREASES)
increase resistance, decrease renal blood flow
GFR will decrease a little, so oncotic pressure in peritubular capillaries, will increase (proteins not filtered), Hydrostatic pressure goes Down, because of constriction, greater force that drives reabsorption of salt and water.

52
Q

What happens when you constrict the afferent arteriole vs efferent arteriole?

A

Constrict afferent arteriole- Decrease GFR and decrease RPF (renal blood flow)
Constrict Efferent arteriole- decrease RPF , Increase GFR and Increase Filtration fraction

53
Q

What is the main function of Thick Ascending loop of Henle?

A

Thick Ascending loop of Henle- impermeable to water
Na/K+ ATPase pump drives Na+ out of cell on basolateral membrane
Na+/K+ 2 CL- co-transporter and K+ channel secretion keeping Lumen net POSITIVE (Drives cation reabsorption into paracellular fluid)
Key components here:
Na/K+ 2 Cl- co transporter and paracellular reabsorption of cations.

54
Q

What kind of osmolarity is seen proximal tubule?

A

ISOOSMOLARTIY

55
Q

What components are present in Early Distal tubule?

A

Early Distal Tubule:

Na+/Cl- electroneutral Co-transporter that is driven by Na+ /K ATPASE pump

56
Q

What are components of principle cells in Late Distal Tubule ? What kind of process is this? What drives this process?

A

Late Distal Tubule- Na+/K+ ATPase pump and Na+ channels
This is is a form of PASSIVE DIFFUSION (ATP not required)
Low concentration of sodium in the cell drives passive diffusion (due to Na+/K+ Atpase pump)
Driving force for K+ secretion in cell is the high K+ in cell
secretion of K+ out of cell into Lumen through K+ channel

57
Q

What are two main cells of the Late Distal Tubule and collecting duct? Which cell is more abundant?

A

Late Distal Tubule:
1. Principle cells
2. Alpha-Intercalated cell
more principle cells than alpha intercalating cells in Collecting duct

58
Q

What are the components of alpha-intercalated cell in Late Distal Tubule?

A

Alpha intercalated cell of Late Distal Tubule:
-Na/K ATPase pump
-H+ ATPase pump- pumps H+ out of cell into lumen
another H+ ion ATPASE pump that pumps H+ out and K+ into cell

59
Q

What occurs in a bicarbonate secreting cell?

A

bicarbonate secreting cell - where bicarbonate and chloride are being exchanged which is dependent on Carbonic anhydrase (to form bicarbonate)
Bicarbonate is going out of cell and chloride is moving into cell.
Also, H+ is leaving the cell and moving out

60
Q

Where does most reabsorption of ions occur?

A

most reabsorption of ions occurs in PROXIMAL TUBULE
over 65% Na+ reabsorbed in proximal tubule
-over 65% water reabsorbed in proximal tubule
proximal tubule- so many solutes are reabsorbed and coupled with reabsorption of sodium.
Reabsorption of sodium is ISOSMOTIC in proximal tubule
water FOLLOWS sodium

61
Q

How is Urine concentrated?

A

Urine concentrated:
Thin descending limb- permeable to water, impermeable to Solute
The proximal tubule is isoosmotic, so fluid leaves this tubule, it will be same osmolarity as blood (300 ml)
Process:
1) reabsorption of Na+ and other salts from the Thick ascending limb- increase in interstitial fluid osmolarity.
2) Movement of water to equilibrate with the higher concentration of solute (osmotic concentration of interstitial fluid)
3. More fluid comes in (300 milliosmoles)
step 1 occurs again: more solute reabsorbed, then more water absorbed to equilibrate, then steps occur again until reach gradient going down

62
Q

How do you get higher osmolarity?

A

Higher osmolarity as you go deep into medullary interstitial area.

63
Q

what happens to osmolarity in peritubular capillary when solutes are reabsorbed?

A

As solutes are reabsorbed, they go to adjacent vasa recta (peritubular capillary)
Peritubular capillary- osmolarity increases, which is a driving force for water to come out and go into ascending limb of vasa recta.
how to keep osmolarity high at medullary interstitial.

64
Q

What occurs when there is high medullary interstital?

A

high medullary interstitial, there is a DRIVING Force for water to be reabsorbed in the collecting duct. Water will be driven from the lumen of collecting duct into high medullary interstitial; high osmolarity in medullary interstitial.
Water follows its OWN gradient here

65
Q

What happens if you destroy the hypersomotic medullary interstitial?

A

Destroy hyperosmotic medullary interstitial:

you will not be able to move water out of kidney nephron and you will pee out a dilute urine.

66
Q

What is the role of counter-current exchange?

A

Counter current exchange: accounts for 50% of the force that helps concentrate urine
The other 50% that helps concentrate urine is UREA.

67
Q

Describe the characteristics of Urea? What happens with reabsorbed urea? What is Urea’s major function?

A

Urea- freely filterable, 50% of Urea gets reabsorbed and 50% gets peed out.
Reabsorbed urea: adds to osmotic pressure, which adds to osmolarity to medullary interstitial.
Urea ADDS to osmolarity of medullary interstitial which helps water get reabsorbed into collecting duct.

68
Q

What are the different concentration component for various parts of urinary system?

A

proximal tubule- SAME amount of Sodium and water
Descending thin limb: Water is reabsorbed (no sodium)
Ascending thin limb: 25% Na+ reabsorbed
Thick Limb of Loop of Henle- Sodium reabsorbed to about 25% of filtered load (NO water)
-Distal convoluted tubule- Mostly sodium (5% Na+ reabsorbed)
Collecting duct: about 5% Na+ reabsorbed through principle cells and water is reabsorbed through high medullary interstitial osmolarity (driving force for water)

69
Q

What would happen if you if you inhibited Na+K+ 2 Cl- Co-transporter in thick ascending limb?

A

inhibitor of Na+/K+ 2-Cl- co-transporter:
You will pee a DILUTE urine (less water is reabsorbed) and you will Urinate MORE
drug that can be used (Lasix, pherosomide)