Lec 40-42 Intro to kidney, glomerulus, renal hemodynamics Flashcards
1
Q
What is normal extracellular Na? intracellular?
A
extracellular: 136-146 mEq/L
intracellular: 10 mEq/L
2
Q
What is normal extracellular K? intracellular?
A
extracellular: 3.5-5.5 mEq/L
intracellular: 145 mEq/L
3
Q
What is normal extracellular Cl? intracellular?
A
extracellular: 96-109 mEq/L
intracellular: 1-5 mEq/L
4
Q
What is normal extracellular Ca2+? intracellular?
A
extracellular: 4.5-5.5 mEq/L
intracellular: 10 mEq/L
5
Q
What is normal extracellular HCO3-? intracellular?
A
extracellular: 24-30 mMol/L
intracellular: 10 mEq/L
6
Q
What is normal extracellular pH? intracellular?
A
extracellular: 7.37-7.42
intracellular: 7.2
7
Q
What is normal extracellular osmolality? intracellular?
A
300 extracellular and intracellular
8
Q
What structures are contained in kidney cortex
A
- proximal convoluted tubule
- distale convoluted tubule
- glomeruli
9
Q
What structures are contained in renal medulla?
A
- thin limbs of henley
- some of the thick limbs
- vasa recta
- collecting ducts
10
Q
What is the papilla?
A
the tip of medulla where final urine drips out of nephron into calix
11
Q
Is the cortex or renal medulla more organized?
A
cortex is very disorganized
renal medulla is organized and has linear striations
12
Q
What is the renal corpuscle?
A
- interface between circulation and nephron
- made of end of nephron epithelial tube and glomerular capillary
- often just referred to as the glomerulus
13
Q
What is major function of glomerulus?
A
form primary urine -> filter plasma and put it into epithelial tube
14
Q
What is major function of proximal tubule and thick descending limb?
A
bulk reabsorption of filtered fluid
15
Q
What is major effect of thin loops of henle?
A
create potential that allows distal tubule and collecting duct to excrete either concentrated or dilute urine
16
Q
What is function of distal convoluted tubule and collecting duct?
A
- fine tune whats excreted vs kept
- acidify urine
17
Q
What are the two different types of nephrons? locations?
A
cortical nephron - glomerulus near surface of kidney
juxtamedullary nephron - glomerulus near cortico-medullary junction
18
Q
What is function of cortical nephron? what type of capillary?
A
- salt and water removing nephron
- this is what is used most of the time
- gives off peritubular capillary [PTC]
19
Q
What is peritubular capillary? where is it located in kidney?
A
- capillary associated with cortical nephrons
- stays exclusively in the cortex
- takes up fluid and salts from proximal and distal tubules and puts them back into circulation
20
Q
What is function of juxtamedullary nephron? what type of capillary
A
- has bigger/longer loop of henle
- salt and water conserving nephron
- allows urine to become very concentrated thus used more often when you are dehydrated
- gives off vasa recta
21
Q
What is vasa recta?
A
- long looping capillary associated with juxtamedullary nephrons
- important to loop of henle function
22
Q
What is normal CO per min?
A
6 L/min
23
Q
What is normal RBF per min?
A
1.2 L/min
24
Q
What is normal percentage RBF of CO?
A
20%
25
What is normal renal plasma flow [RPF]?
660 ml/min
26
What is normal glomerular filtration rate [GFR]?
125 ml/min
27
What is normal filtration fraction?
0.2
28
What is normal urine flow
1.0 ml/min or 1.5L/day
29
What are the 7 major roles of the kidney
- regulation volume and composition of extracellular fluid
- removal metabolic waste products
- acid-base balance
- blood pressure regulation [by regulation blood volume]
- removal of foreign substances
- endocrine function
- gluconeogenesis
30
What innervates the kidney?
- sympathetic nerves: terminate everywhere in tubular and vascular kidney
- sympathetic renal nerves from inner mesenteric plexus and celiac plexus -- travel along renal arteries
- sympathetic fibers from splanchnic that supply pain sensation to renal pelvis
- some parasympathetic vagal fibers
31
How many L filtered through glomerulus into bowmans space per day?
160 L/day
32
What are the 2 ways to get fluid in to nephron?
1. primary via glomerular capillary into bowmans space
| 2. secondary via secretion
33
What is secretion?
transepithelial transport
| - selectively taking ions out of capillary and transported in, very selective and regulated
34
What is reabsorption?
selective transport across epithelium into interstitum and then diffusion into capillary
35
Where are potocytes?
on the visceral inner part of epithelium
36
How is glomerular ultrafiltrate different from plasma?
identical except does not contain blood cells, plasma proteins, large macromolecules
37
How does Pgc [hydrostatic P in glomerular capillary] differ from system?
- 10-12 mmHg higher
- need higher pressure for moving stuff out [filtering]
- pressure maintained throughout [rather than in system it decreases across]
38
How does the glomerular capillary shape unique?
- shaped like manacle so have capillaries in parallel rather than series
- means low total resistance, pressure maintained across capillary from afferent to efferent [may drop by 2-3 mmHg]
39
What is the juxtaglomerular appartatus? why is it important?
- distal tubule winds back to its own glomerulus and interacts with its own afferent arteriole
- allows feebdack mech for distal tubule to regulate GFR
- distal tubule macula densa cells control secretion of renin from afferent arteriole
40
Where are macula densa cells located?
- distal tubule
41
Where are juxtaglomerular cells located?
- afferent arteriole
| - synthesize, store, and secrete renin
42
What are fenestrations?
holes in endothelium
43
What is function of basement membrane in glomerulus?
acts as molecular sieve
44
What is between potocytes?
slit diaphragm --> blocks space between potoctyes, filtration occurs through slit pores
45
What are the barriers involved in glomerular filtration?
negatively charged protein forms cloud halo around membrane --> makes it harder to filter in negative charges
46
How do charge and size of molec affect filtration?
charge: + easier to filter than -
size: small filters easier than big
47
What is Kf?
- ultrafiltration coefficient
Kf proprtional to SA*K
SA = surface area
K = hydraulic conductivity
48
What is K? What are values?
hydraulic conductivity
K=0 --> doesn't move across at all
K=1 --> moves a lot
49
What is single nephron GFR? How can we simplify?
SN GFR = Net P in direction filtration - net Π in direction reasborption
SN GFR = Kf[(Pgc - Pbs) - (Πgc - Πbc)]
```
gc = glomerular capillary
bs = bowmans space
```
Since Πbs should = 0 [no proteins filter in] we can make the equation:
SN GFR = Kf(Pgc - Pbs - Πgc)
50
How does kidney stone change starling force? GFR?
- ion precipitates to nephron and forms crystal
- gets stuck in nephron or ureter
- increase in hydrostatic P at that point --> backs up so get increased Pbs --> decreased GFR
51
How does renal artery stenosis change starling force? GFR?
- form of hypertension
- some sort of blockade of renal artery, have obstruction of flow past that point
- downstream pressure low --> decreased Pgc --> decreased GFR
52
How does disruption of filtration barrier change starling force? GFR?
- can occur at big infection get hole in basement membrane
- increase K --> increase Kf --> increase GFR
- also now get increased Πbc since disruption barrier --> more increased GFR
53
What happens to P and Π across systemic capillary from arteriole to venule? filtration or reabsorption?
- hydrostatic: 35 --> 15, high resistance
- Π stays the same, little if any net fluid movement, constant 25
- filtration for first half
- reabsorption for second half
- two phases balance, 0 net filtration
54
What happens to P and Π across glomerular capillary from afferent to efferent? filtration or reabsorption?
- hydrostatic P 52 mmHg, relatively constant across [maybe drops 2-3 mmHg]
- low resistance
- Π increases toward hydrostatic P
- always in state of filtration [ no reabsorption]
55
Why does Π increase across glomerular capillary?
- plasma proteins trapped in capillary
| - lots of fluid being moved out so get higher concentration
56
What is filtration disequilbrium vs equilibrium?
filtration disequilibrium: Π can never reach hydrostatic P through length of capillary
filtration equilibrium: Π everntually = P and gets there faster than in disequilibrium
57
What is difference in Kf between glomerular and systemic capillaries?
Kf 100-200x higher in glomerular because:
- SA much greater in glomerular [in systemic its fixed, in kidney it can be regulated]
- K in glomerulus = 100x that of systemic --> water moves through barrier easier
58
What is equation for renal clearance of a substance x?
```
Cx = Ux * V. / Px
Cx =renal clearance
Ux = conc of x in urine
V. = volume of urine
Px = conc of x in plasma
```
59
What 4 things required for substance x for Cx [renal clearance] = GFR?
1. freely filterable
2. not reabsorbed or secreted at all
3. not metabolized or broken down
4. not synthesized in kidney
60
What is renal process equation?
Ux* V. = (Px * GFR) + TSx - TRx
| amount of substance in urine = amount filtered + amount secreted - amount reabsorbed
61
What is clearance of inulin?
120 ml/min
62
What is clearance of glucose?
0
63
What is clearance of protein?
0
64
What is clearance of Na?
0.8 ml/min
65
What is clearance of creatinine?
120 ml/min
66
What is clearance of PAH [para-aminohippurate]?
500 ml/min
67
What is significance of substance x Cx = C[creatinine]?
If Cx = C[cr] --> Cx = GFR
68
What is signficance of Cx < C creatinine for substance x?
There is net reabsorption
69
What is significance of Cx > C creatinine?
There is net secretion
70
What are the two substance whose clearance you can use to measure GFR? Endogenous or exogenous?
- creatinine: endogenous
| - inulin: exogenous
71
What happens to glucose filtered into kidney?
100% of it reabsorbed in proximal tubule
72
Is Na net reabsorbed or secreted?
reabsorbed
73
Is PAH net reabsorbed or secreted?
secreted
74
What is blood urea nitrogen [BUN]? How much is eliminated by kidney? Via filtration or secretion?
- breakdown product of creatine in muscle then released into circulation
- eliminated 100% by kidney
- --- 90% by filtration
- --- 10% by secretion
75
What type of relationship between plasma creatinine level and clearance?
inverse relationship
76
What are the problems of using plasma creatinine to measure GFR?
- varies across patients --> slim/less muscle patient will have lower plasma Cr
- changes with diet and exercise [steak and exercise will increase it]
- good way to do repeated measure to see changes but not good for one time spot checking
77
How do you check creatinine clearance?
- draw blood to get plasma creatinine
- check pee to calculate urinary conc
- calculate GFR
78
What are two ways creatinine used to measure GFR?
- plasma creatinine
| - creatinine clearance
79
What is eGFR?
- test for GFR that that works in you have declining function
- test doesn't really work if you have pretty normal function
80
What is equation for filtered load?
filtered load = GFR*plasma conc
81
What is the filtered load of Na
25K mEq
82
Is filtered load Na or Cl lower?
Cl lower because same GFR but much lower plasma conc
83
How is BUN used as clinical marker for GFR?
- measure BUN/creatinine ratio
| - BUN eliminated exclusively by kidney -- most filtered at glomerulus, low secretion
84
What is problem with using BUN as marker of GFR?
- urea is reabsorbed based on state of hydration
- if dehydrated --> reabsorb urea to use it as osmotic particle to reabsorb more water
- variability makes it difficult to use on its own
85
What is normal renal blood flow?
1.2 l/min
86
What is normal GFR?
125 mL/min
87
What are 3 measures of renal blood flow?
- electromagnetic flow probes
- imaging with contrast agents
- clearance of PAH
88
How are electromagnetic flow probes used to measure RBF?
- used in surgical procedures
| - can measure specific blood flow to specific organ
89
How are imaging techniques used to measure RBF?
- inject radio-opaque dye
| - watch rate at which moves through kidney
90
How is clearance of PAH used to measure RBF?
- 90-100% of PAH excreted via filtration and secretion
- used to measure renal plasma flow
- infuse into animal and collect blood and urine and measure clearance
- use clearance to estimate effective renal plasma flow and use that to get RBF
91
What is equation for effective renal plasma flow [RPF]?
Cpah = Upah * V. / Ppah
92
What is equation for RBF from RPF?
```
RBF = RPF/(1-hct)
hct = hematochrit
```
93
How does vascular regulation of GFR change RBF? what about nonvascular regulation?
vascular regulation changes RBF
| nonvascular regulation does not change RBF
94
What does increase tone [constricting] afferent arteriole do to RBF, GFR, FF?
- decrease RBF
- decrease GFR
- no change FF
95
What does increase tone [constricting] efferent arteriole do to RBF, GFR, FF?
- decrease RBF
- increase GFR
- increase FF
96
What does decrease tone [dilating] afferent arteriole do to RBF, GFR, FF?
- increase RBF
- increase GFR
- no change FF
97
What does decrease tone [dilating] efferent arteriole do to RBF, GFR, FF?
- increase RBF
- decrease GFR
- decrease FF
98
If GFR blood flow dependent?
not totally --> otherwise the dynamic relationship between the two parameters would be the exact same always
99
What is filtration fraction? What should you think of?
FF = GFR/RPF --> percentage of plasma that is filtered across capillary
think about proximal reabsorption automatically
100
What is significance of increased FF?
- filter larger percent of delivered plasma
- higher conc of protein in GC since removing more plasma --> higher Πgc --> higher Πptc [in peritubular capillary] --> increased proximal reabsorption
- increase FF = get increase proximal reabsorption
101
What are effects on aff/eff of sympathetic nerves? on RBF? on GFR [Pgc]?
- constrict afferent and efferent
- decrease RBF
- at moderate physiologic response no change in GFR
102
What are effects on aff/eff of angiotensin II? on RBF? on GFR [Pgc]?
- constrict afferent and efferent but efferent a little more
- decrease RBF
- no change or small decrease
- you would expect increase GFR cause constricts efferent more than afferent
- BUT also acts on mesangial cells to lower Kf
103
What are effects on aff/eff of ANP? on RBF? on GFR [Pgc]?
- afferent dilation, efferent constriction
- no change RBF [because balance]
- increase GFR
104
What are effects on aff/eff of histamine? on RBF? on GFR [Pgc]?
- afferent and efferent dilation
- increases RBF a lot
- also effects mesangial cells --> decrease Kf indirectly by local activation antiogensin II
- same GFR, may get slightly higher Pgc
105
What are effects on aff/eff of EDRF/NO? on RBF? on GFR [Pgc]?
- constituively released and sets baseline tone of vessels
- dilates afferent only
- no change to RBF [not clear why]
- increase GFR
106
What are effects on aff/eff of Endothelin? on RBF? on GFR [Pgc]?
- just mediator in pathological circumstance
- constrict afferent and efferent
- decrease RBF
- decrease GFR
107
What are effects on aff/eff of ADH? on RBF? on GFR [Pgc]?
- just mediator in pathological
- no vascular effect in kidney
- no change in afferent/efferent tone or in RBF
- may decrease, super high conc can decrease Kf, Pbs
108
What are effects on aff/eff of thromboxane A2? on RBF? on GFR [Pgc]?
- just mediator in pathological
- constricts afferent only
- decrease BFR
- decrease GFR
109
What are effects on aff/eff of PGE2/PGI2? on RBF? on GFR [Pgc]?
- just mediator in pathological
- vasodilation [mostly afferent]
- increase RBF
- increase GFR
110
What are the two effects of angiotensin II that balance each other to get net no change GFR?
- constricts efferent more than afferent --> would cause increase GFR
- constricts mesangial cells --> lowers Kf --> would cause decrease GFR
111
Two ways of regulating GFR by non-vascular mech?
contract
- mesangial cells [decrease SA]
- potocytes [decrease K or SA]
112
What is role of mesangial cells in regulation GFR?
- mesangial cells are scaffold bind basement membrane to capillaries
- contract ("purse strings") to decrease surface area --> decrease Kf --> decrease GFR
113
What happens to Kf and GFR when relax mesangial cells?
- increase Kg
| - increase GFR
114
What is role of potocytes in regulation GFR?
- potocytes wrap around capillary
- contract in one direction --> decrease SA and thus Kf
- contract in other direction --> change nature of slit diaphragm, decrease K and thus Kf
115
What is autoregulatory range of GFR/RBF?
80-150 mmHg MAP
116
What happens in autoregulatory range?
- GFR and RBF are constant
| - as BP increases, we vasoconstrict renal vasculature to maintain BP and GFR
117
At high BP what happens to GFR/RBF/afferent?
- have high BP would cause high GFR and high RBF
- so you constrict afferent to lower GFR and lower RBF so you can maintain constant GFR and RBF even in spike of high BP
- GFR only responds over long term
118
What are the 3 mech of autoregulation?
- renal nerves [not v. important]
- myogenic mech
- tubuloglomerular feedback [TGF]
119
What is myogenic mech of autoregulation?
- increase in BP causes stretch in vascular smooth muscle --> get increase in contractile force that brings you back down to smaller diameter [constriction] so you don't get the increase in blood flow you would expect get from higher BP --> keeps blood flow and GFR constant
- opposite: if BP gets lower and thus less stretch --> get relaxation of vascular smooth muscle so get dilation --> don't get the decrease in blood flow you would have expected --> keep blood flow and GFR constant
120
What is the tubuloglomerular feedback mechanism?
1. GFR increases
2. flow through nephron tubule increases
3. flow past macula densa in distal convoluted tubule increases, macula densa detects it via NaCl conc
4. paracrine signal from macula densa cells to afferent arteriole
5. afferent arteriole constricts
6. resistance in afferent increases
7. Pgc decreases
8. GFR decreaes
