Physiology: Nephron Function Flashcards
(92 cards)
1
Q
What is the primary function of the renal corpuscle?
A
Filtration of blood
2
Q
What is filtrated (5) from the blood in the renal corpuscle, and what percentage?
A
Glucose 100% Na+ 100% Cl- 100% K+ 100% H20 100%
3
Q
What is the pH of the filtrate in the renal corpuscle?
A
pH 7.4
4
Q
What does Starling’s Force do?
A
Governs the movement of water and solutes between plasma and interstitial fluid - using the capillary wall which is a semi-permeable membrane.
5
Q
What are the three components of Starling’s Force?
A
- Hydrostatic pressure (glomerular) - push out of blood
- Oncotic pressure - pull in to blood
- Hydrostatic pressure (capsular) - pull in to blood
6
Q
What is the equation for net filtration pressure?
A
GHP - OP - CHP = Net filtration pressure
60 - 32 - 18 = +10mmHg
7
Q
What is glomerular hydrostatic pressure?
A
Hydrostatic pressure is the force of water and solutes out of the blood in to interstitial fluid - due to the weight of fluid exerting on the membrane.
8
Q
What is oncotic pressure?
A
Oncotic pressure is the attraction of water and solutes back into the blood from the interstitial fluid - due to their attraction to plasma proteins which are not filtered.
9
Q
What is capsular hydrostatic pressure?
A
Capsular hydrostatic pressure resists flow across the membrane and so water and solutes are pulled towards the blood.
10
Q
The glomerulus - provide 3 points.
A
- A very leaky capillary tuft, much more leaky than other capillaries.
- Fenestrated endothelium.
- Glomerulus is located between two arteries (afferent and efferent) - no veins.
11
Q
What is standard glomerular filtration rate (GFR)?
A
125ml/min for both kidneys
12
Q
Why is it so important to ensure a constant GFR?
A
So that the kidney can tightly regulate ECF osmolality and pH.
13
Q
The primary regulation of GFR is achieved by…
A
Changes in glomerular hydrostatic pressure.
14
Q
Why do changes in systemic blood pressure not cause changes in GFR (healthy individuals)?
A
Autoregulation
15
Q
How does autoregulation work?
A
Involves feedback mechanisms that cause either - dilation or constriction of the afferent arteriole, or constriction of the efferent arteriole.
16
Q
What happens to glomerular filtration rate if afferent arterioles vasoconstrict?
A
Decreases blood flow > decreases glomerular hydrostatic pressure > decreases GFR
17
Q
What happens to glomerular filtration rate if afferent arterioles vasodilate?
A
Increases blood flow > increases glomerular hydrostatic pressure > increases GFR
18
Q
What happens to glomerular filtration rate if efferent arterioles vasoconstrict?
A
Increases glomerular hydrostatic pressure > increases GFR
19
Q
What are the 3 extrinsic mechanisms of renal auto-regulation (things outside the kidney)?
A
- Renin-angiotensin II
- Atrial natriuretic peptide (ANP) and BNP
- Sympathetic nervous system
20
Q
How does renin-angiotensin II contribute to renal auto-regulation?
A
Constriction of the efferent arteriole > increases glomerular hydrostatic pressure > increases GFR
21
Q
How does atrial natriuretic peptide contribute to renal auto-regulation?
A
Dilation of the afferent arteriole > increases glomerular hydrostatic pressure > increases GFR
22
Q
How does the sympathetic nervous system contribute to renal auto-regulation?
A
Constriction of afferent arteriole > decrease glomerular hydrostatic pressure > decrease GFR
(important in shock)
23
Q
What are the 2 intrinsic mechanisms of renal auto-regulation (things inside the kidney)?
A
- Myogenic
2. Tubuloglomerular feedback
24
Q
How does the myogenic mechanism contribute to renal auto-regulation?
A
Increased arterial pressure stretches the afferent arteriole inducing it to constrict > offsets pressure increase and keeps GFP stable.
25
How does the tubuloglomerular feedback mechanism contribute to renal auto-regulation?
Macula densa cells monitor NaCl levels in distal tubule, if high they signal to the afferent arteriole to constrict - decrease GFR.
26
In the tubuloglomerular feedback mechanism, what is NaCl used as a proxy for?
NaCl is a proxy for flow - if flow is high then a lot of Na is hitting the macula densa cells.
27
In relation tubuloglomerular feedback, explain what occurs when GFR is too high?
High GFR > more NaCl passes the macular densa cells > paracrine signals released > afferent arteriole constricts > decreased GFR
28
In relation to the renin-angiotensin II, explain what occurs when GFR is too low?
Low GFR > less NaCl passes the macular densa cells > paracrine signals released > JG cells release renin > angiotensin II produced >
1. constriction of efferent arteriole > increased GFR
2. aldosterone released > increased Na+ uptake from distal nephron > increased blood volume
29
Explain what happens when blood pressure drops.
↓ Blood pressure
↓ Hydro. pressure > myogenic> ↓ stretch of af. arterioles
↓GFR ↓
↓NaCl to md cells > tubuloglo> ↓ resist. of af. arterioles
↑Renin>↑Ang II (extrinsic pathway) ↓
↑Constric. of ef. arteriole > ↑ hydrostatic pressure
maintain stable GFR & tubular flow
30
What is the primary function of the proximal tubule?
Filtrate reabsorption
31
What is reabsorbed from the proximal tubule in to the blood, and what percentage?
Glucose and amino acids 100%
Bicarbonate 90%
Water 66%
Inorganic ions (Na+, Cl-, K+, Ca2+, PO43-) 66%
```
Glucose 0%
Na+ 33%
Cl- 33%
K+ 33%
H20 33%
```
32
What is the pH level of the filtrate in the proximal tubule, and why has it changed from that of which was in the glomerulus?
pH 6.7 (more acidic)
| Bicarbonate was removed from filtrate.
33
What are the major transport mechanisms in the proximal tubule?
Transcellular (x2) - across epithelial cells
| Paracellular - between cells (passive)
34
What two types of transcellular transport mechanisms exist?
1. Primary active transport, ATP drive
2. Secondary active transport, driven by another gradient.
A. Co-transport or symport
B. Counter-transport or antiport
35
How is the Na+ gradient formed in the proximal tubule cell?
Na+/K+ ATPase pumps (anti-porter) on the plasma surface of the proximal tubule cell drives active solute uptake - removal of Na+ in exchange for K+.
36
What transport mechanisms are located on the luminal surface of the proximal tubule cell?
Co-transporters - Na+ coupled glucose symporter, where Na+ is moving down the concentration gradient, and pulling glucose into the cell against its concentration gradient.
37
How does water movement occur within the proximal tubules?
Water follows the Na+ by paracellular osmosis via leaky tight junctions.
38
How is the osmolality of the lumen affected by these changes?
Not affected because water follows the NaCl and so the osmolality in the lumen remains constant.
39
Why is bicarbonate reabsorbed from the filtrate?
Bicarbonate is the key pH buffer in the body, so it needs to be reabsorbed.
40
Bicarbonate (HCO3-) cannot diffuse across the cell membrane so how is it reabsorbed?
Reabsorption is dependent on the presence of carbonic anhydrase (in brush border and cytoplasm).
41
Explain the process, 7 part, of bicarbonate reabsorption by the proximal tubule.
1. NHE (Na+/H+ exchanger) antiporter located on the luminal surface of the proximal tubule cell uptakes Na+ which drives H+ extrusion into lumen - lowering pH.
2. Together with the HCO3 (bicarbonate) the H+ in the lumen forms H2CO3 (carbonic acid).
3. In the presence of carbonic anhydrase the H2CO3 is converted to H2O and CO2.
4. CO2 is reabsorbed into the cytosol.
5. CO2 together with H2O and in the presence of carbonic anhydrase forms H2CO3
6. H2CO3 separates into H+ and HCO3
7. H+ cycles back out to lumen via NHE and HCO3 returns to plasma via basolateral membrane transporters.
42
What can proximal tubule dysfunction cause?
```
Proximal tubule (mediated) acidosis, due to loss of HCO3 in urine.
Insufficient bicarbonate returns to the body, body becomes more acidotic.
```
43
How does the proximal tubule generate new bicarbonate?
1. Proximal tubule cells metabolise glutamine to ammonium ion and bicarbonate.
2. The ammonium is secreted into the lumen by a Na+/NH4+ exchanger.
3. HCO3- is transported into the blood.
44
What is Fanconi syndrome?
Impaired ability of proximal tubule to reabsorb HCO3- and other solutes so it's all excreted in the urine - (genetic or acquired).
45
Where in the proximal tubule is chloride most concentrated and why?
Chloride is most concentrated in the late proximal tubule, this is because of prior reabsorption of water and solutes in the early tubule.
46
How does Cl- movement occur from the proximal tubule?
In response to the high concentration of Cl- in the lumen of the late proximal tubule -
1. Cl- moves down the concentration gradient into the ECF via leaky tight junctions paracellularly.
3. Thereby the lumen becomes electropositive which induces passive paracellular reabsorption of Na+.
47
Why is secretion in the proximal tubule of organic anions and organic cations important?
Important for the clearing of xenobiotic agents (synthetic chemicals) ingested from the diet, drugs, and environment.
48
What is solvent drag and when does it occur?
Some solutes are reabsorbed with water when water follows Na+ paracellulary - this is known as solvent drag.
This is important for the reabsorption of K+.
49
In relation to the proximal tubule - summarise the change in solutes, pH, and H20 - and how these changes occur.
Glucose 100% - 0% By Na+ transporter
Na+ 100% - 33% By Na+ transporter
Cl- 100% - 33% In response to conc. gradient (paracellularly)
K+ 100% - 33% By solvent drag (with water when water follows Na+ (paracellularly)
H20 100% - 33% Osmotic (Na+)
pH 7.4 - 6.7 HCO3 reabsorption
50
Name the 4 sections that make up the "Loop of Henle", in order?
1. Proximal straight tubule
2. Thin descending limb
3. Thin ascending limb
4. Thick ascending limb
51
What is the primary function of the Loop of Henle?
Water extraction - plays a central role in the production of urine that is more concentrated or more dilute than plasma.
52
What is the variation of urine concentration and volume?
1. Urine concentration can vary from 50 to 1200 mOsm/kg water.
2. Urine volume can vary from 0.5 to 20 litres per day.
53
What are the two theories on how the Loop of Henle works?
1. Countercurrent multiplication (most well defined)
| 2. Passive Hypothesis
54
Where does the countercurrent mechanism take place?
Outer medulla
55
Where does the passive hypotheses take place?
Inner medulla
56
What occurs in the proximal straight tubule?
NaCl is released from filtrate in to the interstitial space.
57
What occurs in the thick ascending limb, transporters/channels?
1. NKCC2 channels on luminal surface of cells remove Na+, K+, 2 x Cl- from the filtrate.
2. Na/K ATPase on basal membrane of cells transfers the Na+ from cells to ECF.
3. ROMK channels on luminal surface of cells recycle some of the K+.
4. Tight junctions are water-tight.
5. ECF becomes hypertonic ('single effect')
58
How does the thin descending limb respond to the ECF becoming hypertonic?
The thin descending limb releases H2O in to the ECF - thereby creating the countercurrent multiplication.
59
Where does the H2O go?
Vasa recta looped vessels around the Loop of Henle, which carry blood counter to the direction of the tubular fluid flow.
60
What is the key function of the vasa recta?
To preserve the salt gradient and take away the water that has been extracted.
61
In relation to the Loop of Henle - summarise the change in solutes, pH, and H20 - and how these changes occur.
Glucose 0% - 0%
Na+ 33% - 15% By NKCC2 and Na/K transporters
Cl- 33% - 22% By NKCC2 and Na/K transporters
K+ 33% - 8% By NKCC2 and Na/K transporters
H20 33% - 18% Countercurrent
pH 6.7 - ?
62
What is the primary function of the distal convoluted tubule?
Fine tuning of salt and pH levels.
63
How would you describe the tubular fluid leaving the TAL and entering the early distal convoluted tubule?
Dilute - and further dilution of the tubular fluid will occur by removing NaCl but not H2O.
64
Describe solute movement in the early distal convoluted tubule.
1. Na+/Cl transporters on the luminal surface of the tubule removes both Na and Cl from the filtrate.
2. Tight junctions are water-tight.
3. Na+/K+ ATPase pump on basal surface of tubule removes Na from cell into ECF.
65
What are TAL and early distal tubule referred to?
Diluting segment, as salt has been extracted.
66
Where does thiazide diuretics, widely used to treat hypertension and heart failure, target?
Block Na/Cl transporters (channels) so that Na is not taken up and high Na is excreted in urine. If Na is not taken up then H2O does not follow.
67
What is Gittleman Syndrome?
Mutation in the the Na/Cl transporter, resulting in Na+ and Cl- wasting, hyperaldosteronism, and resultant hypokalemic metabolic alkalosis. Patients are hypocalciuric and hypomagnesemic.
68
Name the two types of cells in the late distal convoluted tubule, connecting tubule, and collecting duct?
Principal cells and intercalated cells.
69
In relation to the late distal convoluted tubule, connecting tubule, and collecting duct - summarise the change in solutes, pH, and H20.
```
Glucose 0% - 0%
Na+ 15% - 5% - 1%
Cl- 22% - 16% - 6%
K+ 8% - 10% - 12%
H20 18% - 10% - 1%
pH ? - 6.0 - 4.5
```
70
What is the main function of the principal cells?
Na+ reabsorption - via the ENaC channel (electrogenic sodium channel).
71
How do the principal cells control Na+ and K+?
1. Reabsorption of Na+ (via ENac channels) makes lumen electronegative, drives K+ secretion from cell into lumen via ROMK channels.
2. More luminal Na+ present, the more K+ secreted.
72
Why is it important to understand the movement of Na+ and K+ in the principal cells?
The principal cells are the target for thiazide diuretics which cause the loss of K+ (hypokalemia) by delivering more Na+ to the late distal tubule - hypokalemia can cause ventricular arrhythmias.
73
ENaC is the target of what medications?
Potassium-sparing diuretics eg amiloride (others act via inhibition of aldosterone).
74
What is Liddle's Syndrome?
A mutation that causes an increase in ENaC channels, too much NaCl is reabsorbed, leading to increased ECF volume and hypertension.
75
What does aldosterone do in the principal cells?
Aldosterone stimulates Na+ reabsorption and K+ secretion by gene expression changes - within hours channels (ENaC & Na/K ATPase) are up-regulated and within days more ENaC and Na/K ATPase are inserted on membranes.
76
What is the main function of the intercalated cells?
Acid and base balance and K+ absorption
77
What transporters/channels are responsible for the functions of the intercalated cells?
1. H+ ATPase and H+/K+ ATPase are located on the apical surface of the cell - thereby secreting H+.
2. Some H+ in lumen is used to reabsorb HCO3.
3. Some H+ can be freely secreted generating new HCO3 in the ECF.
78
In relation to the collecting duct - summarise the change in solutes, pH, and H20.
```
Glucose 0% - 0%
Na+ 5% - 1%
Cl- 16% - 6%
K+ 10% - 12%
H20 10% - 1%
pH 6.0 - 4.5
```
79
Why is it important to secrete H+ and reabsorb HCO3-?
1. Normal body fluid pH is 7.4 (outside of this cellular function is disturbed).
2. pH is related to the H+ concentration - high H+ = low pH, low H+ = high pH.
3. Body fluid pH is determined by the CO2/HCO3 - buffer system.
80
What is the pH equation?
CO2 + H2O < > H2CO3 (carbonic acid) < > HCO3 + H+
81
How are each of the components of the pH equation created or eliminated?
1. CO2 - from metabolism, eliminated by the lungs
2. HCO3 - from kidneys
3. H+ - from diet (metabolism), eliminated by kidney
82
In relation to diffusion trapping of ammonium in the collecting duct - why does excess H+ (after all HCO3 has been reabsorbed) combine with NH3 -?
Because pH 4.5 is the max urine (H+) attainable, this is not enough to excrete all dietary H+ therefore there is a need to take-up the H+ in another way (NH3 + H+ = NH4 ammonium.
83
How is the remaining H+ excreted in the urine?
Ammonia (NH3) freely diffuses from the cells of the collecting duct in to the lumen - but NH4- charge is trapped in the urine and excreted (voiding H+).
84
In the collecting duct (cortical), what is water movement dependent on?
Anti-diuretic hormone (AHD) - aka Arginine Vasopressin (AVP)
85
In the collecting duct (cortical), how does water movement occur?
1. ADH causes aquaporin water channels to be inserted into the apical membrane.
2. Water gets reabsorbed rather than excrete in the urine (tubule fluid can be 300 mOsm).
3. Response to ADH is rapid, once ADH hormone is present the aquaporins are placed.
86
What occurs in the absence of AHD?
Water remains in the tubule lumen (remains at 50 mOsm).
87
How does high ADH and low ADH affect water reabsorption and urine?
High ADH > high water reabsorption into blood > high urine concentration
Low ADH > low water reabsorption into blood > low urine concentration
88
Simplified model of "passive hypothesis"
High ADH in the collecting duct promotes the release of H2O from the tubule.
Step 1. Urea becomes very high in the cortical collecting when ADH is present due to H2O reabsorption.
Step 2. ADH increases urea and H2O permeability of inner medulla collecting duct.
Step 3. Urea deposited in interstitium, H2O causes NaCl to drop
Step 4. NaCl moves out of tip and ascending limb down its concentration gradient.
So when there's high ADH you get a deposition of urea and NaCl.
Collecting duct is permeable to urea.
89
How does the Loop of Henle function in the outer medulla?
NaCl gradient formed by countercurrent multiplication - extracting H2O in response to NaCl gradient.
Short-loop countercurrents involving NaCl.
90
How does the Loop of Henle function in the inner medulla?
NaCl and urea gradient formed by 'Passive' mechanism, which is dependent on high ADH levels.
Long-loop "passive hypothesis" involving NaCl and urea (urea as a result of H2O from urea).
91
What is the role of the vasa recta in relation to the counter-current exchange?
Helps preserve osmotic gradient and carries water away.
92
What is the relationship between urea and low ADH, 5 points?
1. The inner medullar collect duct is permeable to urea even when ADH is low.
2. When ADH is low water is not reabsorbed in the distal nephron and cortical collecting duct so urea does not increase.
3. If urea of the interstitium > urea of collecting duct then urea will diffuse into the collected from and be excreted "wash out".
4. As long as ADH is low the urea of the inner medulla will be low.
5. When ADH becomes high, urea is deposited again, so urea comes and goes from the interstitium.
