Renal Physiology Flashcards
(456 cards)
1
Q
3 Major functions of the kidney
A
- Filtration: removal
- Production
- Regulation
2
Q
Describe the 2 major waste products produced by body, cleared by kidneys
A
a. Ammonia NH3.
b. creatinine- made during muscle breakdown.
3
Q
whats creatinine used to indicate and what may create false positive/negative values?
A
muscle mass= relatively same day to day- indicates kidney func.
high= malfucntion
levels altered by: eating too much meat/excessive exercice/lean muscle mass in elderly
4
Q
why and how (outline) does kidney regulate body fluids?
A
volume (post.pituitary), conc, distribution of body fluid - homeostasis
Renal glands (aldosterone release) and brain (ADH release)
5
Q
whats normal amount water in body and how do kidneys control conc + vol?
A
- 40-45L water in body dont want to go above/below: de/overhydration
- kidneys control urine vol thus conc
- excess water- removed in dilute conc vice versa
6
Q
tonicity of solutions and effect on RBC
A
isotonic: normal in RBC cytoplasm
hypertonic: RBC shrivel as water leaves
hypotonic: RBC swell as water comes in
water travels by osmosis
7
Q
location and compositions (%) of fluid compartments in average 70kg male?
A
total body water:45L 60% of body weight
extracellular fluid (ECF): 15L, 20%
- plasma: 3L, 20% of ECF
- Interstitial (IF): 12L, 80% of ECF
intracellular fluid (ICF):
-30L, 40% body weight
majority
8
Q
what is the functional barrier surrounding
a) plasma (also ECF)
b) ICF?
what do kidneys have access to?
A
a) capillary andothelium
b) cellular membrane
kidneys: control vol of all 3 compartments BUT only access to plasma
9
Q
what pressures (+forces) regulate continuous exchange and mixing of body fluids?
A
hydrostatic and osmotic pressures
Starling’s forces: water and electrolytes freely cross, move by diffusion.
10
Q
process of fluid moving out of: plasma
A
starlings forces mmHg
drive DIFFUSION
changes in HP=fluid movement
11
Q
effect of different amounts of ions in plasma, interstitium, intracellular on fluid osmolality
A
no effect.
although ions in different amounts, fluid osmolality still approx. 285mOsm/Kg/H2O
12
Q
why are plasma and interstitial fluid compartments of ECF similar?
A
separated by only capillary endothelium- freely permeable to small ions.
but difference in ECF and ICF: plasma more protein, K+ = main cation of ICF
Na+K+ATPase=maintains distribution differences across plasma memb.
13
Q
what 2 forced determine free and rapid movement of water between various fluid compartments?
A
hydrostatic pressure (heart pumping) osmotic pressure (exerted by plasma proteins - oncotic pressure)
14
Q
effect of adding hypotonic NaCl IV infusion to ECF
A
osmolality of ECF decreases = water moves into ICF by osmosis: low to high solute conc.
after osmotic eqm,ICF and ECF osmolalities equal but volumes increased
15
Q
effect of adding hypertonic NaCl IV infusion to ECF
A
osmolality of ECF increases = water moves out (low to high solute conc)- ICF –> ECF
after osmotic eqm,ICF and ECF osmolalities equal but ECF volume increased and ICF decreased
look at picture in lec notes last slide
16
Q
name 3 things that get filtered through kidney
A
- metabolic waste: nitrogenous, excess ions. produced in body/excess from diet
- drugs
- toxins
17
Q
4 things produced in kidney and roles?
A
- renin: BP
- erythropoietin: RBC maturation. hormone made if anemic
- prostaglandin: blood flow in the kidney. PGE2: vasodilation.
- Vit D (Calcitriol-active form): made by cholesterol, activated in kidney
18
Q
what does the kidney regulate?
A
- body fluids
- Vol of extracellular fluid
- Osmolal of bf
- conc of electrolytes
- blood pH- acid-base balance
- BP
- RBC
19
Q
how is ammonia made and cleared from kidneys?
A
made from protein catabolism.
toxic, water soluble.
convert to urea (aa breakdown) -> uric acid (nucleotide breakdown)
20
Q
what do high serum creatinine levels suggest?
A
serum levels= test of kidney function. high = impairment/disease
21
Q
Why does kidney need to regulate body fluids: osmolality?
A
- extreme variation=cells shrink/swell/burst
- damage cell struc and disrupt normal cell function
22
Q
normal kidney/ body osmolality?
A
285mOsm/Kg water
23
Q
what do changes in HP =
A
continuous fluid movement between plasma and IF and IF and cells.
24
Q
process of fluid moving out of: ICF
A
osmotic pressure mosm/kgH2O
H2O free movement, not ions
OSMOSIS
changes in ionic content of IF =water movement
25
what allows fluids in and out of cells?
no HP gradient across cell memb, only osmotic pressure diff between ICF and ECF = fluids in and out of cells.
26
what does plasma memb have that means fluids can easily cross?/permeate
plasma memb has h2o channels (aquaporins) = easily cross memb
27
Part 2: Glomerular filtration
basic kidney anatomy: what is the
a) inner layer called
b) outer layer called?
a) medulla
| b) cortex
28
the kidney is covered by what?
transparent fibrous renal capsule
29
5 parts in the kidney
- 5-8 renal pyramids
- renal columns
- renal papilla
- renal pelvis: urine to ureter
- ureter: urine to bladder
30
where are the major blood vessels contained in the kidney?
renal columns
31
where empties into renal papilla?
all urine filled collecting ducts
32
what are nephrons?
functional units of kidneys-
| hollow tubes. closed at proximal end and open at distal
33
role and length of nephron?
a) each is its own unit, produces miniscule amounts of urine
| b) 3-4mm long
34
3 main regions of nephron?
- renal corpuscle
- tubule
- collecting tubule
35
a) what 2 structures are in the renal corpuscle?
bowmans capusles
| glomerulus (capillaries)
36
b) 3 structures in the tubule
PCT
loop of henle
DCT
37
what regions of nephron found in the renal medulla?
LoH, collecting ducts
38
what enters the nephron and what leaves?
fluid (filtrate) in and urine out
39
what structure(s) modify the fluid passing through the nephron?
lining of nephron
40
what does the glomerulus provide?
capillaries that provide blood for filtration- enters in the coiled networks of capilalries with large pores
41
what leaves the nephron? specifically
urine: toxic urea, nitrogenous waste products
42
name the first process of urine formation
glomerular filtration
43
what filters out of the capillaries into bowmans space?
plasma, low MW substances, electrolytes etc.
anything but blood cells and proteins
44
where is glomerulus structure found?
sits inside bowmans capsule- filtrate collecting bag.
| fist in a balloon
45
what arrives at glomerulus and what leaves?
arriving: afferent arteriole
exiting: efferent arteriole
46
2 layers of BC and which one touches the glomerulus?
Parietal: outer wall
Visceral: inner wall, lines glom capillaries. !
47
where are podocytes found?
highly specialised epithelial cells of visceral layer of BC.
| wrapped around glom capillaries.
48
role of podocytes?
along with the monolayers of fenestrated endothelium lining caps and glom basement in between,
form the filtration barrier
49
what 3 layers of filtration barrier does plasma pass through to get from glom to BC?
fenestrated Endothelial cells: line glom caps that have large pores.
basement membrane: v thick fibrillar layer
podocytes:epithelial cells of BC visceral layer
50
what helps plasma getting forced through pores in the fenestrated endothelial cells of the filtration barrier?
high hydrostatic pressure
51
why does the basement memb of filtration barrier exclude proteins on size and negative charge?
the BM has negatively charged proteoglycans on it
- stops - passing through
52
what molecules can filter through the - charged basement memb into BC space?
+ charged molecules attracted to BM and uncharged mols.
53
why is blood pressure crucial for renal function?
need high pressure in glomeruli for filtration.
wide afferent arteriole and narrower efferent generates a high hydrostatic pressure in caps = favour net filtration.
54
what does high hydrostatic pressure in capillaries ensure?
glom filtration.
| plasma forced into nephron
55
Starlings forces in capillaries- what causes outward filtration? (fluid leaves)
HP (of blood in caps) > OP (of BC = 0)
AA wider and longer than EA no proteins filtered
towards arteriole end (left)
56
Starlings forces in capillaries- what causes inward filtration? (fluid enters)
OP (of caps) > HP (of filtrate in BC)
proteins in blood drawn fluid back fluid entering nephron, getting fuller with filtrate, pushed back to caps
towards venule end (right)
57
why is net fluid outward = net fluid in, not favoured for nephron?
= no fluid accumulation inside, eqm.
| - wont make urine. makes cap OP
58
where does the fluid filtered out of glomerulus go to?
high HP = fluid filtered out --> BC --> PCT
59
what would the starlings forces be for outward fluid movement?
glom HP: 50mmHg - out of glom
glom OP: 25mmHg - into
BC HP: 15mmHg - into
BC OP: 0mmHg -x
```
net filtration = 50-25-15-0 = 10mmHg
shoved out (HIGH HP) due to long efferent
```
60
why is glomerulus capillary HP 50mmHg (greater than normal cap: 35mmHg)?
due to narrow and long efferent
afferent arteriole, which delivers blood to the glomerulus, has little vascular resistance because it is short and wide
61
regarding water, elecs, glucose, waste products, how does glom filtrate composition compare to plasma?
identical
62
why is albumin (69,000Da) not filtered and kept out of filtrate?
filtration barrier cut off = 70,000Da.
| Albumin also - charged= repelled by BM
63
what is difference in appearance of plasma and glom filtrate?
the blood cells
64
3 main causes of proteinuria (protein in urine)
- diabetes mellitus: high plasma gluc-damage filter
- hypertension: high glom HP damage filter
- glomerulonephritis: inflamm damage from immunological attack
65
what is proteinuria and how detected?
proteinuria: protein in urine due to filtration barrier disrupted.
detected in urinalaysis- dipstick test.
green instead of yellow for proteins
66
proteinuria: how do the proteins enter urine?
leak out form glomerulus into bowmans capsule due to disruption in filtration barrier for 3 reasons
67
what condition may cause decreased plasma protein levels on fluid movement across capillaries and affect?
increased BP/ diabetes.
loss from plasma > gain to plasma instead of =.
imterstitial fluid vol increases= oedema
decrease in plasma proteins lowers plasma OP.
HP > OP: fluid moves out normal
here, glom damaged, protein leaks out into urine
68
consquences of excessive proteinuria? (3)
low level protein in plasma = oedema
* swolled around eyes, hands, feet
frothy/bubbly urine
69
whats GFR and what does it tell us?
fluid volume filtered from renal glom caps into BC during certain period of time.
overall index of renal function
70
normal GFR by both kidneys a min and a day?
125ml/min or 180L/day
must be maintained. will change if kidneys not working well
71
how many times a day is the plasma in body filtered?
60 times a day
| 3L plasma but GFR is 180L/day
72
what is urine and how much excreted a day?
non-reabsorbed filtrate that leaves kidneys/ minute
GFR x %(above) = 0.8%
0.8% x 125 = 1ml urine/ min or 1.5L urine/day
99% goes back into body
73
why ECF composition precisely regulated?
plasma reg precisely and often = urine often v important for removing unwanted substances
74
GFR depends on increased HP
consequence of:
a) GFR too high
b) GFR too low
a) needed substances not reabsorbed quickly, lostin urine. (goodies in urine)
b) everything reabsorbed inc waste (baddies in blood)
75
Part 3: tubular function - PCT
what are the 4 basic renal processes that occur for filtration in nephron?
1. glom filtration
2. tubular reabsorption
3. tubular secretion
4. excretion
76
how is urine volume formed calculated?
| approx how much is it a day?
Urine = Filtered - Reabsorbed + Secreted
1.5L urine a day
77
why is all the plasma not filtered?
How much plasma is filtered by the kidneys?
About 20% of the plasma volume passing through the glomerulus at any given time is filtered
would lead to sludgy cells leaving EA
78
Filtration, Reabsorption, Secretion (Urine).
what is the filtrate?
whats ultrafiltrate?
the plasma filtered from glomerulus into BC.
ultrafiltrate: whats left after cells, proteins, large mols filtered out of glomerulus. similar to plasma but no proteins
79
what drives filtration?
| filtration is non selective
Starlings forces
HP forces plasma to BC.
everything gets through
80
Filtration, Reabsorption, Secretion (Urine).
what is reabsorption and whats reabsorbed?
selective process.
solutes and water needed by body brough back in from PCT filtrate, into peri-tubular caps.
- organic nutrients (gluc, aas)
- inorganic ion if not excess
- water if not excess
81
what is reabsorption driven by?
active transport, diffusion, osmosis, starlings forces
82
Secretion is a 2nd chance to...?
actively eliminate unwanted substances from blood into urine.
only 19-20% filtered
83
What is secreted from blood to urine?
- nitrogenous waste( NH3, creatinine, urea, uric acid)
- inroganic ions if excess
- unwanted drugs
84
where are secreted substances moved from and to?
| and what is the process driven by?
from peritubular caps into PCT lumen.
active transport
85
what is the busiest part of the renal nephron and why?
PCT as most (2/3) reabsorption happens- lots of substances too valuable to risk losing by waiting later on.
all filtrate passing through and A LOT is reabsorbed
86
how is pct specialised for reabsorption?
PCT = approx 1/3 length of nephron and has increased SA due to brush border on tubular cells
87
PCT: whats reabsorbed?
- ions: 65%
- water: 65%
- glucose: ALL
- AAs: ALL
- vitamins: ALL
88
what 2 types of reabsorption processes can take place in PCT and how do they differ?
active reabsorption: uses ATP energy
| passive reabsorption: e.g. osmosis high-->low solute conc
89
why is the same amount (65-67%) ions and water reabsorbed in the PCT?
same % as move together.
90
difference between clearance and excretion of drug?
clearance: VOLUME OF BLOOD (vol) cleared of drug per unit of time.
excretion: AMOUNT OF DRUG (mg) excreted over period of time
91
what does the clearance of drug depedn on? 5
- whether drug filtered/secreted/reabsorbed
- GFR
- structure of drug
- age
- disease
...
92
whys it important to know clearance rates of drugs?
determines dosage- correct to maintain plasma conc and = therapeutic effect
93
affect of renal function on clearance and plasma half life?
LOW renal func = LOW clearance and HIGH plasma half life
94
whats meant by
a) high clearance
b) low clearance
a) rapid elimination from blood by kidneys
| b) inefficient excretion. only administer low levels tomaintain level in blood and prevent ADRs.
95
effect of low GFR from malfunctioning kidneys on clearance and dose of drug?
low GFR with age/disease etc = low clearance = may need to increase dose of drug
96
what does PCT have a lot of for driving the reabsorption process?
mitochondia for energy
| also brush border: increase absorptive capacity
97
why do DCT cells look like they have alarger lumen than PCT cells?
absence of brush border (which increases surface area) on DCT.
98
2 methods of reabsorption transport through PCT to the peritubular capillary?
1: transcellular (straight through)
- across apical memb
- through tubular cell cytosol
- across basolateral memb
- through interstitium to blood vessels
2: paracellular (between)
- through leaky 'tight' junctions
99
with transcellular reabsorption, why does the substance move into blood vessel passively by diffusion once in the interstitium?
when in interstitium, conc is higher than in peri-tubular caps
100
how are peritubular caps specialised for allowing reabsorption of substances back into them?
more porous than normal caps
have v low Blood pressure (as theyre second set of caps)
= good at allowing material to diffuse back into them
101
role of Na+K+ATPase pump?
pumps approx 100 Na+ ions per second
establish ionic gradient across tubular cell membrane.
Na+ pumped out of cell = intracellular Na+ lowered
= driving force for reabsorption of Na+ from filtrate to tubular cells, then out into blood.
102
what can the entry of Na+ through Na+K+ATPase also bring?
other solutes in too, which can be transported by 'secondary active transport' process with reabsorbed Na+ (symport).
grabs Na+ out of filtrate and likely to grab glucose too
103
why and how (literally) is Na+ reabsorbed?
non-selective
high Na+ conc = use ATP to move out, can take glucose with it :)
dont want to leave valuable nutrients till end to reabsorb.
movement of water by osmosis highest if NA+ absorbed
104
1. using the Na+K+ATPase, what is energy invested in ?
- to get Na+ out of filtrate and create Na+ electrochemical gradient
105
where are the 3Na+ molecules pumped out of by Na+K+ATPase in exchange for 2K+?
from the basal and basolateral side of tubular cell.
the high [Na+] conc in interstitium diffuses into blood
106
process by which sodium enters into proximal tubule cell from lumen and how moved in interstitium?
through Na channels, moving down its electrochem gradient.
by diffusion,
pumped into interstitium by Na+K+ATPase
107
what else happens when Na moves down its EC gradient (from tubule lumen into proximal tubule cell)?
glucose pulled into cells too using SGLT1 and SGLT2 co-transporter channels
108
where from and how does glucose diffuse out of proximal tubule cells?
out of the basolateral side of the cells using GLUT2 channel
Na pumped out by Na+K+ATPase
109
what channel is used to exchange NA+ for H+ in PT cell?
Na+/H+ anti-porter- Na+ exchanged for H+.
| Na+ pumped out by Na+K+ATPase
110
How is CO2 and H2O formed in the tubule lumen?
| what does the process require?
secreted H+ combines with filtered HCO3-. = CO2 and H2O.
requires carbonic anhydrase located on apical brush border of PCT tubulae cells
111
what happens to the CO2 produces from H+ and HCO3- using carbonic anhydrase in the tubule lumen?
where will it exit from after this?
CO2 diffuses into tubular cell and recombines with H2O --> HCO3-: exits cell from basolateral side and diffuses into blood.
112
what is reabsorbed into the peritubular capillary? (2) from diagrams
HCO3- and Na+.
| recycled- (reabsorb bicarbonate H2CO3)
113
the equation for substances being filtered at PCT? (acid base transport)
CO2 + H2O ⇌ H2CO3 ⇌ HCO3− + H+
| Slow Fast
114
why are carbonic anhydrase enzymes critical for HCO3− reabsorption and the creation of new HCO3−?
The carbonic anhydrase enzymes effectively bypass the slow reaction in the sequence CO2 + H2O ⇌ H2CO3 ⇌ HCO3− + H+
(first bit)
115
what process and route(s) does water reabsorption in the PCT occur by?
osmosis.
| paracellular and transcellular (AQP1 aquaporin 1)
116
why is water obliged to follow sodium into peritubular capillary?
- Na+ moves down EC grad due to ATPase
- many substances co-transported
- H2O reabsorbed by osmosis- many solutes (Na+) been reabsorbed and H2O obliged to follow as low Na+ conc inside.
117
what happens to conc of solutes left in filtrate and what is now moved?
conc of solutes left increases in filtrate. now move down chem gradient by diffusion.
filtrate conc > blood = gradient
118
how do the following travel from PCT tubule lumen into cell and peritubular capillary?
a) lipids
b) Cl-, K+, Ca2+....
a) transcellularly
| b) paracellularly
119
which 2 processes in 'Na+ reabsorption aids reabsorption of water and many other solutes' are active?
1: Na+ in and K+ out of peritubular cap into PCT via ATPase = PRIMARY ACTIVE
2. Na+ and something else cotransported into PCT= SECONDARY ACTIVE
120
which 2 processes in 'Na+ reabsorption aids reabsorption of water and many other solutes' are diffusion?
lipids and ions, urea... via trans/paracellular pathway:
| PASSIVE DIFFUSION
121
what process in 'Na+ reabsorption aids reabsorption of water and many other solutes' is driven by passive osmosis?
water following Na+, into peritubular cap from PCT lumen.
122
what 2 molecules weakly/not absorbed in PCT?
urea and Cl-: conc higher at end of PCT
123
what 6 molecules absorbed from PCT?
- water
-Na+
-K+
-H3O-
same conc at end of PCT
```
strongly:
-glucose
-amino acids
none at end of PCT
(done at start)
```
124
how is there same osmolality at beginning and end of PCT if volume decreases?
35 things in 1L = approx same as 12 things in 350mL
change in volume AND concs
125
how does filtrate remain isotonic with plasma by end of PCT despite going through glom filtration etc?
squash through sieve analogy:
filtrate not diluted or reabsorbed = same conc and osmolality.
non-selective filtration
126
what is reabsorption of water by osmosis linked to? in context of PCT?
reabsorption of solutes.
| obligatory H2O movement
127
Part 4: tubular function - LoH
What is the role of the 'straight nephron' inland animals adapted from aquatic, and why is it needed?
glom: filters plasma
PCT: reabsorbs good things and water -65%
ensure max water absorption as water reabsorbed from plasma not sufficient
128
what is the LoH (loop of henle) designed for?
looped region of nephron- has countercurrent flow inside it- going in opposite directions
129
what does the filtrate going around the LoH and changing concentrations as it moves down descending and up ascending limb, contain?
water and solutes
130
role of LoH (regarding other structures of nephron too)?
creates a hyperosmotic medullary inetrstitium to ensure maximum water rebasorbed form LoH, but primarily from DCT and collecting ducts!
131
the water absorbed in LoH is taken up by?
specialised blood vessels: vasa recta
132
where is filtrate osmolality highest in the nephron? what does this mean?
at bottom of LoH 1200mOsm/kg/water. = means water mustve come out
133
at which site of nephron is the filtrate:
a) hypotonic with plasma
b) hypertonic with plasma
a) top of and after LoH, just before DCT. 90mOsm
| b) bottom of collecting tubule- urine. 400-1000mOsm
134
what does the cortico-medullary hyperosmotic interstitial gradient allow?
concentrated urine formation
135
the cortico-medullary hyperosmotic interstitial gradient makes XXX have a very high solute osmolality
fluid of the medullary interstitium surrounding LoH AND also surrounding collecting ducts.
136
hat is the corticomedullary/ corticopapillary osmotic gradient?
outer renal cortex --> inner renal medulla:
| interstitium of medulalry region becomes more concentrated (saltier)
137
whats the role of the thick ascending limb of the LoH?
| affect of this?
actively extrudes solutes into surrounding interstitium
- will increase interstitial osmolality but
- decrease that of filtrate
= hypo-osmotic
138
how is the tonicity of fluid entering and leaving LoH changed?
isotonic fluid from PCT enters
hypotonic fluid leaves to DCT
- Na+ and Cl- leave at LoH ascending limb
139
what does the removal of Na and Cl from filtrate in LoH require?
lots of energy so lots of Na+K+ATPase found on tubular cells here
140
why does water not follow the Na leaving in ascending limb/diluting segment of LoH?
as this part of LoH is impermeable to H2O and only permeable to solutes.
H2O stays in filtrate!
osmolality changes!!
141
what affect does the action of ascending limb of LoH have on the medullary interstitium surrounding it?
throws out solutes: Na and Cl = making it hyperosmotic
142
what drugs act on the thick ascending limb of LoH? how?
Loop diuretics: diuretics that act on the Na-K-Cl cotransporter along the thick ascending limb of LoH of the kidney.
- block channel, diuretics increase urine as make kidneys pass out more fluid
143
what does the Na-K-Cl cotransporter along the thick ascending limb of the loop of Henle do?
- when all 3 are present, picks up Na, 2Cl and K follow, on apical side.
- then Na+K+ATPase transports Na and 2Cl- out of LoH, in exchange for K+
water cannot enter at transporter OR actual LoH.
144
what do drugs acting on thick ascending limb of LoH treat? give an example drug.
loop diuretics e.g. Furosemide (suphonamide derivative)
Treat hypertension and edema often due to congestive heart failure/ CKD
145
what is the role of the thin descending LoH (concentrating segment)?
extrudes water.
| H2O passively reabsorbed by osmosis. enters medullary interstitium and picked up by vasa recta
146
what is the filtrate in descending LoH surrounded by?
hyperosmotic medulla thanks to ascending LoH
147
what happens to filtrate when is equilibriates with interstitium? (descending LoH)
becomes hyperosmotic
148
difference in water reabsorption from PCT, at descending LoH?
not obligatory H2O reabsorption.
| not directly linked with Na+ reabsorption as with at PCT
149
what is the concentrating segment/ descending LoH behaviour towards solutes and water and meaning?
impermeable to solute
permeable to water
solute stays in filtrate and water thrown out using aquaporins! = salty gradient and v conc filtrate at bottom of LoH
150
what is the consequence of extrusion of Na+ / Cl- from ascending limb and H2O reabsorption from descending limb of Loh?
creates ! increasing vertical ! hyperosmotic gradient in medullary interstitium.
Thus, LoH, DCT, collecting ducts are bathed in very concentrated interstitium.
=water can be reabsorbed by osmosis from descending LoH BUT will have same effect on DCT and collecting ducts
151
why is a vertical corticomedullary gradient creates in LoH i.e. what is the menaing?
outer cortex = less hyperosmotic (closer to plasma osmolality)
inner medulla = more
152
what happens at LoH after Na and water pumped out?
equilibriate = reason for the gradient- differing concs down the LoH!
until 200mOsm difference because cells get tired
153
why is the interstitial fluid made only 200mOsm/Kg H2O more concentrated than the fluid in the ascending LoH at each level?
energy needed to pump Na+ and Cl- out and uses Na+K+ATPases.
| millions on each basolateral side BUT have their limits.
154
what is the countercurrent multiplication mechanism? (reason for concentration values)
although ascending limb can generate gradient of only 200mOsm/L at each horizontal level, this effect is multiplied into a large vertical gradient because of the countercurrent flow within the loop.
hence LoH= countercurrent multiplier
155
role of the LoH/ countercurrent multiplier?
establish an osmotic gradient (300-1200mOsm) from renal cortex through to medulla
156
how can urine be made more concentrated from cortex to medulla?
because H2O can be removed from collecting ducts by osmosis
extruded Na+/Cl- accumulate in interstitium aroudnd LoH and collecting ducts = both can use gradient to reabsorb water and cocn urine.
157
describe the postive feedback cycle that uses flow of fluid to multiply power of salt pumps
- water leaves descending limb
- filtrate conc here increases (as does osmolality)
- more solute available for pumping out of ascending limb
- increased interstitial fluid osmolality
salt pumped out, increase osm of IF, water leaves, increase osm of filtrate,..
158
difference in filtrate osmolality between ascending and descending limbs of LoH/ countercurrent multiplier?
Descending:
INcreases to 1200mOsm/KgH2O at base of LoH: hypERosmotic
Ascending:
DEcreases to 90-100mOsm/KgH2O before start of DCT: hypOsmotic
159
difference in permeability to water/ Na and Cl
| between ascending and descending limbs of LoH/ countercurrent multiplier?
Descending:
H2O: freely permeable
Na+ and Cl-: impermeable
Ascending:
H2O: impermeable
Na+ and Cl-: permeable
160
what is the permeability in ascending LoH mediated by?
impermeable to water but Na+ and Cl-: permeable -
| mediated by Na+/K+/2Cl- apical carrier - inhib by loop diuretics e.g. Furosemide
161
what do the specialised blood vessels: vasa recta do?
descending limb :
carry away the water passing out of filtrate from descending limb into hyperosmotic medullary interstitial fluid
ascending limb:
carry some of solute away that passes out of filtrate to make the hyperosmotic medullary interstitial fluid
162
Role of urea?
extrusion (very osmotically active) also increases the medullary osmotic gradient- makes it stronger/more hyperosmotic
contributes approx half the osmotic gradient and Na, Cl the rest
163
Where does the passively reabsorbed urea accumulate?
passively reabsorbed from the inner medullary region of collecting duct, accumulates in medullary interstitium
164
affect of water reabsorption from collecting duct filtrate on urea conc?
urea conc increases, so can move out of these urea-permeable areas of nephron by diffusion
165
3 points of urea recycling
- some reabsorbed from terminal CDs and accumulates in surrounding interstitium
- most urea lost in urine
- urea secreted into LoH and recycled - dont job, not needed. thrown out
loop-can have gradient!
166
what does the presence of ADH mean for water reabsorption?
| specific region?
generation of vertical cortico-medullary gradient = more water reabsorbed by osmosis mainly from CDs when ADH present.
especially from inner medullary region
167
normally late DCT and collecting ducts not permeable to water, but what may change this?
ADH presence: aquaporins are inserted and tubules become water permeable.
= allows for small vol conc urine to be produced
168
how do loop diuretics work?
increase urine frlow by acting on thick ascending LoH.
- block Na K 2Cl ion channels in ascending LoH
- no reabsorption/ Na/Cl extrusion into med interstitium
- no corticomedullary gradient formed
- no hypertonic interstitium around loh, dct, cds
- more urine made, less in body = DIURETIC
169
how do loop diuretics decrease blood pressure?
| why used for hypertension treatment
decreased Na+ reabsorption at asc. LoH = more Na+ excreted
blood volume decrease
blood pressure decrease
170
summary:
| effect of increasing interstitial osmotic gradient with Na, Cl, urea from isotonic --> hypertonic parts of kidney?
= more and more water reabsorbed by osmosis as filtrate goes down LoH, CDs
= concentrate urine
conservation of water
171
Part 5: Renal blood supply
```
renal autoregulation (mechanisms later)
myogenic control of GFR
vasa recta importance in maintaining corticom.....
```
whats the main thing kidneys need in order to regulate pH, fluid volume, BP, osmolal, electrolytes.....
need a rich blood supply
172
how much of the cardiac output is supplied to the kidneys and via what?
renal arteries supply approx 20% - 1.1L blood/ min
| A LOT
173
a) how does blood enter the kidney?
through renal artery - branches to smaller ones, some divide more into afferent arterioles, supply glomerullar capillaries. = where ultrafiltration happens
174
b) what happens after ultrafiltration and blood coming to glomerular capillaries?
blood flows to efferent arterioles - supply second capillary network: peritubular capillaries and subset: vasa recta.
involved in reabsorption
175
c) how does blood leave the kidney?
through the small venules and veins and finally: renal vein
176
what are the two capillary networks in the kidney?
first capillary network: glomerular caps
| second capillary network: peritubular caps (branch to vasa recta)
177
levels of blood supply travel to kidney
```
renal artery and arteries (interlobular artery)
afferent arteriole
glomerulus
efferent arteriole
(arcuate artery)
```
peritubular caps vasa recta (reabsorption)
venules
renal vein
178
what artery branches to form the afferent artery of glomerulus?
interlobular artery
179
why is the efferent artery smaller in diamerter than afferent?
efferent leaving G: smaller than A arriving.
| maintain hydrostatic pressure (HP) in glomerular caps = allows plasma to be filtered into bowmans space
180
what is blood pressure in glomerulus controlled by?
different diameters of EA and AA
181
from what are the peritubular capillaries formed and what do they surround?
EA gives rise to them and they surround the renal tubules.
| towards medulla, they become vasa recta, then renal venous system
182
role of the peritubular capillaries? (2)
branch off efferent arterioles and give nutrients to epithelial and interstitial cells there
also supply blood for reabsorption and secretion in PCTs.
183
role of vasa recta?
long hairin shaped blood vessels, run alongside loh
provide nutrients and O2 to cells here
mainly: countercurrent exchangers!- contribute to urine conc by CDs.
184
a) external mechanism of tight regulation of GFR?
sympathetic and hormonal mechanisms
(cardiac physiology lecs)
BP maintained in response to nerves and hormones
185
b) intrinsic mechanism of tight regulation of GFR?
autoregulation- help itself by changing diameter of AA and EA = blood vessels consrict, pressure increases= alter GFR
MYOGENIC CONTROL
and
TUBULOGLOMERULAR FEEDBACK later lec
186
3 major physiological body systems that activated and respond to drop in BP?
cardiovascular
renal
neuroendocrine: ADH released from pit. gland
187
how does cardiovasc system respond to drop in BP?
aorta and carotid arteries. --> detected by baroceptors = activates sympathetic nervous system (ANS) constricts the blood vessels
188
how does renal system respond to drop in BP?
renin released from JGA (juxtaglomerular apparatus)
and
aldosterone from adrenal cortex
189
regardless of BP fluctuation, GFR and renal blood flow remain contant. at what values?
80-180mmHg
190
myogenic mechanism:
| what changes in EA and AA diameters are ideal when BP increased?
constrict afferent, dilate efferent: less blood enters glom caps
or
dilate both: blood leaves glom caps quicker
= net cap HP and glom filt DECREASED
191
myogenic mechanism:
| what changes in EA and AA diameters are ideal when BP decreased?
dilate afferent/ constrict efferent. or both:
more blood enters glom caps
or
blood stays in glom caps lonegr
= net cap HP and glom filt INCREASED
192
when is constriction of efferent arteriole most useful?
when BP drops.
| = getting more blood to glom caps.
193
what is the role of prostaglandins produced by kidney?
released locally, counteract with Angiotensin II etc.
blood flow within kidney
modulate renal microvascular response to drop in BP.
194
how do prostaglandins cause vasodilation?
PGs protect renal hemodynamics against excessive vasoconstrictors: Ang II.
essentially minimise/ offset any potent vasoconstriction.
dont want everything to construct: would decrease kidney function
195
what drugs interfere with PG synthesis and what would this lead to?
NSAIDs.
= renal func deterioration and renal blood flow insufficiency in patients with vasoconstrictor stimuli to kidney.
e.g. those losing blood/ with low BP
196
what occurs in volume depleted states? (NSAIDs and renal failure) (2)
Ang II released = renal efferent vasoconstriction to maintain GFR
or
PG release to offset potent vasconstriction- NSAIDs TARGET. detect hypoxic kidney
this one is cancelled by NSAIDs
197
how do NSAIDs = renal failure?
target PGs- then not released to offset potent vasoconstriction in volume depleted states.
unopposed vascoconstriction --> poor renal perfusion --> acute renal failure
198
how is perfusion of kidney different compared to perfusion of otehr organs?
done to retain filtration funcs instead of regulated to maintain organ nutrition
199
paracrine factors: NO and PGs are released locally by kidneys. which is AA more sensitive to?
role of PGs?
vasodilator effects of NO.
PGs modulate effects of vasoconstrictors (AngII) and protect against potent vasoconstriction,
renal symp nerves also innervate AA and EA = vasconstriction
200
what do vasa recta specifically allow- blood flow in what?
| what are they permeable to?
coutercurrent loops. blood flows SLOWLY in opposite directions to filtrate in LoH.
freely permeable to water and solutes
201
why are the vasa recta looped?
prevent high conc of solutes in medullary interstitium being washed away
202
2 things vasa recta provide/allow?
provide oxygenated blood to renal medullary region, carry away metabolic toxins (same as normal cpas)
preserve corticomedull osmotic gradient - doesnt wash away, prevents rapid salt removal from medullary interst.
203
what does vasa recta remove?
reabsorbed water.
| water entering VR from descending VR/ reabsorbed from descending LoH and CD.
204
3 causes of oedema in ankles
Diet: salty foods
LVF heart failure: can’t pump blood and remove fluid
Less plasma protein: reduced OP caused by kidney failure- glom filtration
205
Effect of furosemide on kidney
Loop diuretics block NaClK transporter in asc LoH.
Na absorption and plasma volume reduced
Fluid put back into circulation to be excreted and BP decreased
206
How does furosemide essentially lower BP and swelling?
Helps body get rid of excess salt and water by increasing urine amount
207
How does furosemide reach its site of action?
Orally admin
Absorbed in GI tract
Binds to plasma proteins- albumin, made harder to get to site, limiting glom filt and enters LoH to exert effect
Actively secrete into PCT
208
Why would furosemide be given IV sometimes instead of orally?
Faster onset of action
209
What problems may furosemide cause?
Loop diuretic:
Electrolyte imbalance: metabolic alkalosis due to hypokalaemia loss of K, nausea
Dehydration: headaches, dizziness fatigue postural hypotension
Want to avoid risk of fall
210
How to check and monitor decrease of oedema in ankles?
Weigh patient regularly
211
Drug class of Spironolactone and effect on kidneys?
Aldosterone antagonist
Block aldosterone production, Na rea sorted by kidneys so more water excreted
Can lower BP and fluid around heart
212
Affect of using aldosterone antagonist e.g. spironolactone with ACEi/ARB
When used with ACEi/ARB may cause high K in blood/ decline in kidney function
Sodium and water secreted
K sparing!!! K retained
213
Drug class of bendroflumethiazide and affect on kidneys
Thiazide: DCR
reduce Na absorption, and plasma volume and BP.
Increase urine flow promote diuresis
Reduce hypertension 
K lost too through collecting duct
214
Why must BP be controlled with using thiazide? I.e how are kidneys affected by BP?
=maybe damaged arteries and won’t filter blood well at nephrons
Hypertension is asymptomatic:
- Damage filter and lumen: direct kidney damage
- HF
- damage to brain stroke
- eyes
215
What to monitor with diuretic and how often?
Blood:
-pressure
-K+ and Na+
Every 3 months then 6 months onwards etc
Impaired glucose tolerance- not suitable for diuretic and already have that
216
Part 6: Urine conc and dilution
what is urine normally like compared with plasma?
urine normally HYPEROSMOTIC compared with plasma
| 400-1000mOsm/Kg H2O
217
concentrated urine is produced by reabsorbing water from:? (4)
PCT: obligatory Na+ reabsorption
LoH (descending): needs medullary gradient
DCT: needs medullary gradient and ADH
CDs: needs medullary gradient and ADH
218
where are decisions made to conc/dilute urine?
in last part of nephron- DCT and collecting ducts
219
what does urine look like with:
a) high osmolality
b) low osmolality?
a) darker, more conc with toxins = hyperosmotic
| b) paler, more dilute
220
roughly what % of the 180L/day filtered water from glomerulus is reabsorbed in:
a) PCT
b) DCT
c) LoH
d) CD
a) 70%
b) 10%
c) 5%
d) 15% - 23L/day that VARIES!
221
what would be the consequence if collecting duct failed?
would produce 23L urine a day as no decisions made to reabsorb any of it.
= 1L urine an hour! approx
222
what does solute and water conc in man vary depending on?
diet
external factors
climate
...
223
affect on urine of
- low water intake
- excess water intake
- need to conserve water, product little, conc urine
pungent smell as urea toxins etc removed with little water
- need to excrete water, produce more, dilute urine
224
what happens to body fluid osmolality when you drink too much? and therefore to urine?
increased water intake absorbed in blood
bf = hypo-osmolar:
<285mOsm/Kg H2O.
in healthy person: when BF become hypo-osmolar, so does urine.
= produce lots of dilute
225
what happens to body fluid osmolality when you drink little? and therefore to urine?
bf = hyper-osmolar:
>285mOsm/Kg H2O.
insufficient water= kidneys pass out less water.
in healthy person: when BF become hypo-osmolar, so does urine.
= produce lots of dilute
226
what does ADH do?
regulated water reabsorption from the collecting ducts (the fine tuners)
therefore segment can fine tune electrolyte and water concs in urine thus plasma
227
whats the major factor that = conc/dilute urine?
ADH- tells CD when to draw water out
228
what does the LoH create to then help with fine tuning of urine?
corticomedull. hyperosmotic interstitial gradient.
very salty cortex --> medulla.
water moves out CD to blood vessel as result of salty grad outside.
ONLY if ADH tells it to draw water out
229
how does water move out of CD? (gradient)
from LOW to HIGH solute conc
230
where does the water reabsorbed from CD go to?
nearby peritubular capillary/ vasa recta etc.
231
affect of drinking lots of water on ADH production?
little ADH produced as dont reabsorb a lot
232
what does ADH precisely control?
plasma OSMOLALITY not volume
233
steps to dilute urine production from over hydration? (3)
- low osmolality of ECF in plasma
- less ADH release- no water reabs from DCT and CD
- lots of dilute urine made. low as 100mOsm/Kg water
234
steps to conc urine production from dehydration? (4)
- high osmolality of ECF
- more ADH release- aquaporin insertion to facilitate water reabs from DCT and CD
- less, conc urine made. high as 1200mOsm/Kg water
235
whats the real problem as a results of decreased ECF osmolality from overhydration?
hyponatremia! low Na
- affect heart AP, nerve stimulation
normally: plasma has higher Na than in blood
236
affect of drinking TOO MUCH water?
water intoxication
affects electrolyte balance in blood.
Na+ dilution/hyponatraemia occurs in ECF. = water enters cells by osmosis (low -> high solute conc) ECF->ICF
237
who is particularly at risk of water intoxication (too much water)?
athletes- sweat a lot and when dehydrated person drinks lot of water without accompanying electrolytes (energy drinks).
238
adverse effects of water intoxication?
| how is it fixed?
irregular heart beat
brain and nerve damage
need saline drip= solution to replenish salts and electrolytes in body
239
where and when is ADH secreted?
secreted into blood from pituitary gland in response to hypovalaemia and plasma hyperosmolality
240
what does amount of water absorbed in presence of ADH depend on?
interstitial hyperosmolality gradient made by LoH
thus urine becomes conc in medullary CD as it equilibriates with surrounding interstitium
241
what 2 factors work together to allow CD to reabsorb water?
interstitial hyperosmolality: nice and salty (estab by LoH)
&&
ADH
= help CD pull out water from lumen by osmosis
242
how are CDs acting in absence of ADH?
CDs not permeable to water even with the gradient, if no ADH
243
what type of urine produced in presence of ADH?
released when dehydrated.
| small volume of conc urine as maximum watre reabsorbed
244
what does production of ADH depend on?
how hydrated.
very = little ADH
dehydrated = some ADH
245
when dehydrated, urine gets v concentrated and interstitium osmolality can go up to?
up to 1200mOsm/kg water. max due to LoH
| -> pull out lot of water! = conc urine
246
ADH makes the CD permeable to water and what else?
urea.
| - helps salt pull out more water
247
to produce dilute urine, at the end of these regions filtrate is...
a) PCT
b) desc LoH
c) asc LoH
d) DCT and CD
FIXED:
a) isotonic
b) hypertonic
c) hypotonic
varied
d) hypotonic- 65-70mOsm
248
to produce conc urine, at the end of these regions filtrate is...
a) PCT
b) desc LoH
c) asc LoH
d) DCT and CD
FIXED:
a) isotonic
b) hypertonic
c) hypotonic
varied
d) hypertonic- up to 1200mOsm
249
why is filtrate always ISOTONIC at end of PCT?
285mOsm.
| similar water and solute reabs. into peritubular caps
250
why is filtrate always HYPERTONIC at end of desc LoH?
up to 1200mOsm
lots of water reabs into vasa recta.
no solute reabs
251
why is filtrate always HYPOTONIC at end of asc LoH?
90mOsm
lots of solute into interstitium and some into vasa recta
no water reabs
252
what disease state is caused by no ADH production?
whats a consequence/symptom?
nothing reabsorbed
Central diapetes insipidus.
| v HIGH urine vol = 25L a day. = frequent urination as bladder capacity only 400mls.
253
affect of extreme ADH: maximal on urine osmolality (and whats this same as) and urine volume?
urine osm: 1200mOsm
same as interstitial osm of deepest part of medulla/close to papilla
urine vol: 300-400ml/day
v little
254
2 possible causes of central diabetes insipidus?
No ADH:
- not produced by pit gland
- OR kidneys dont respond to it
255
what drug is a synthetic version of ADH and why is it prescribed?
Descmopressin
when simply drinking water not enough for pateints with central diabetes insipidus.
also used in nocturnal enuresis and bed wetting in kids
256
how does desmopressin compare to ADH and work?
more powerful than endogenous ADH.
| stops kidneys producing urine
257
affect of too much desmopressin OR drinking too much fluid with it and symptoms of this?
= water retention.
```
headaches
dizzy
bloated
HYPONATRAEMIA- seizures
too much water in body
```
258
what 5 factors work together hand in hand to control urine conc?
```
LoH: creates hyperosm... grad
urea recycling
vasa recta
CDs
ADH
```
259
what 3 structures/ factors involved in the two counter currents created and maintained for increasing urine conc?
LoH (CC multipliers)
Urea recycling = makes gradient stronger
maintained by vasa recta (CC exchangers)
260
Part 7: Osmoregulation
what 3 things does kidney control regarding body fluids?
1. correct osm (285mOsm)
2. vol of fluid in body
too much = increase plasma = increase BP :(
linked.
3. correct pH
261
A variation of how many mOsm/KgH2O triggers sensors in the body to return osmolality back to normal?
± 3mOsm/KgH2O
262
How do changes in plasma/ECF osmolality affect cell volume?
can increase or decrease it, due to movement of water created between compartments
263
Which organ's interstitial fluid compartment has varying osmolality?
kidney, due to LoH ascending limb throwing out salt into interstitium
264
The 4 stages of body fluid osmolality regulation?
1) stimulus
2) receptor (sensor)
3) control centre
4) effector
265
What is the stimulus that triggers ADH release?
a change in osmolality e.g. eating salty meal or sweating
266
What receptors detect a change in osmolality?
osmoreceptors in the hypothalamus, communicate with control centre (pituitary gland)
267
What is the control centre's action in response to osmoreceptors' signal?
ADH is triggered to be released from the posterior pituitary gland
268
What is the effector response to ADH?
Change in the H2O permeability of Renal DCT and COLLECTING DUCTS:
- ADH -> insertion of aquaporins into CD wall
269
Where is the pituitary gland located?
by the eye socket
270
Where is ADH made?
in the hypothalamus
271
ADH regulates which of the following?
A) H2O retention or loss
B) solute amount
A) H2O retention or loss
| it only affects the reabsorption of water at the CD, but doesn't directly change the salt content
272
role of hypothalmic osmoreceptors and how sensitive are they?
detect small changes is plasma osmolal. and regulate release of ADH (vasopressin) - modulates water retention/loss.
NO effect on solutes
273
affect of the following on urine production:
a) diuretic (drugs)
b) ADH hormone
a) increase urine production
| b) decrease
274
affect of eating salt on urine volume?
-> salty conc blood -> ADH makes you urinate less. reabsorb fluids etc
also stimulate thirst-> dilute body fluid
275
What other receptors are located close to the osmoreceptors?
thirst receptors (lateral pre-optic area)
276
Where is ADH stored?
posterior pituitary
277
Why is ADH said to be unstable in circulation?
it has a half-life of 10 minutes
278
ADH is released into the blood when plasma osmolality increases or decreases?
ADH is released when plasma osmolality increases
279
ADH release is inhibited when plasma osmolality increases or decreases?
ADH release is inhibited when plasma osmolality decreases
280
What is the main effect of ADH?
Causes kidneys to conserve H2O by stimulating passive H2O reabsorption from CDs
- normally these areas are not H2O permeable
281
ADH leads to the insertion of what in collecting ducts? What is the effect on the collecting ducts' permeability to H2O?
ADH =insertion of aquaporins in CDs = increases their permeability to H2O thus = H2O reabsorption
282
How does ADH release affect urine concentration?
increases it, increasing its osmolality
283
Apart from a rise in plasma osmolality, what else triggers ADH release?
- change in plasma volume
- E.g. if you cut arm, lose blood and volume is decreasing
- Fluid and salt are being lost at the same time - osmolality isn't changing but fluid volume change is massive
284
affect of too little solute in plasma (low plasma osmol) on water and ADH?
too little solute in plasma
plasma too dilute
low plasma osmolal.
need to lose water to concentrate it
LESS ADH
dilute urine
285
affect of too much solute in plasma (high plasma osmol) on water and ADH?
too much solute in plasma
plasma too conc
increased plasma osmolal
need water to dilute it (conserve water)
MORE ADH
conc urine
286
ADH release can be completely suppressed with only a XXmOsm/Kg water drop?
5mOsm/Kg water
287
for every 1mOsm/Kg increase in plasma osmolarity, hm will [ADH] increase?
by 0.38pg/ml
288
How does the osmolality of urine change as you continue to insert aquaporins?
- At top - assume 300mOSm interstitium, water leaves, aquaporins inserted until urine reaches 300 too-If dehydrated, more aquaporins inserted further down duct
- As outside is 400, water leaves until it's 400
- going down, osmolality will increase so more aquaporins will be required to be inserted
- Urine will match interstitium's osmolality up to which aquaporins were inserted
289
Why does ADH also make the collecting ducts permeable to urea?
increases osmotic gradient of the already salty medullary interstitium, so more water can be pulled out by osmosis
290
summary of effect of increased plasma osmolality. (6)
Plasma osmolality increased....
- osmoreceptors in hypothalamus detect
- more ADH released from pituitary gland
- CDs become more permeable to H2O
- increased water reabsorption by osmosis into blood
- decreased volume of conc urine produced
- H2O in blood reduces plasma osmolality
291
summary of effect of decreased plasma osmolality. (6)
osmoreceptors in hypothalamus detect
- less ADH released from pituitary gland
- less ADH travels in blood to kidneys
- CDs less/ not permeable to H2O now
- decreased water reabsorption by osmosis into blood
- increased volume of dilute urine produced
- H2O in blood increases plasma osmolality
292
following release from pituitary, how does ADH travel? and where to?
in bloodstream to the V2 receptors on basolateral memb of cells lining the CDs.
293
Describe the steps that lead to the insertion of aquaporins in collecting ducts (4)
1) ADH release from pituitary
2) ADH binds to V2 receptors on basolateral membrane of the cells lining CD
3) raises cAMP levels -> intracellular vesicles containing AQP2 (aquaporins) fuse with apical membrane
4) H2O reabsorbed from CDs by osmosis, gradient bought about by high solute conc in he surrounding medulla, into the vasa recta
294
result of ADH binding to V2 receptors on basolat memb of cells lining CD?
cAMP levels raised = intracellular vesicles containing AQP" fuse with apical memb
295
What is the maximum concentration of urine that can be reached and why?
1400 mOsm/kg H2O - highest osmolality of interstitium at base of collecting duct
296
What is the shape of the cells lining the collecting ducts that aquaporins are inserted into, and on what 2 sides?
- columnar
| - luminal / apical surface
297
What is necessary on the collecting ducts in order for water to be reabsorbed under the effect of ADH?
V2 (vasopressin) receptors
298
why is no water reabsorbed from regions when no ADH released?
no ADH = no aquaporins in luminal/apical surface of columnar cells lining CDs = no water reabsorbed here.
299
where are aquaporins always present?
on basolateral surface to allow water into these cells for survival
300
Why is drinking sea water bad?
- Sea water osmolality 2000mOsm/KgH2O
- Urine osmolal can reach 1400mOsm/Kg H2O
- To clear 1Kg (1L) of sea water will require : 2000mosm/1400mOsm= 1.4L of water to clear
- therefore result in dehydration - more body water removed than amount drank
301
What is diabetes insipidus caused by?
hyposecretion of/ insensitivity to the effects of, antidiuretic hormone (ADH), also known as arginine vasopressin (AVP)s
302
What are the 2 types of diabetes insipidus?
- Cranial DI: less ADH;cant concentrate urine- polyuria and polydipsia
- Nephrogenic DI: cant concentrate urine. resistance to ADH in the kidney.
both= produce lot of dilute urine
303
What are the symptoms of diabetes insipidus?
- polyuria
- polydipsia (excessive thirst)
- nocturia
- urinary incontinence may occur
304
What will the plasma and urine osmolality be in patients with diabetes insipidus?
raised: >295 mOsmol/kg, despite having dilute urine <700 mOsmol/kg
305
what does osmoregulation actually do (and not do)?
controls plasma Na+ conc by changing water volume
| NOT controlling actual bodys water content.
306
Part 8: regulation of body fluid volume
After ingesting NaCl, what happens to the: a) osmolality,
b) thirst,
c) ADH concentration,
d) collecting duct permeability to H2O and e) H2O retention?
all increase:
osmolality- salt only goes in ECF compartment but this draws H2O out of ICF and increases osmolality in ICF compartments
thirst and ADH increase, collecting duct permeability to H2O increase
=H2O retention
all restore the osmolality to 285mOsm /KgH2O
307
How do osmoregulation and volume link?
osmoregulation disturbs volume, so you need a volume regulator
308
affect of adding salt to fluid volume?
does not change water volume but changes osmolality = increased fluid volume
309
How are [Na+] and H2O volume in body connected?
| and what does this therefore mean for volume regulation?
water follows Na due to the gradient Na generates
therefore ECF volume can be regulated by body Na+ content
↑ Na+ = osmolal = ADH = water ↑
↑ ECF Na+ = ↑ ECF vol
↓ Na+ = osmolal = ADH = water ↓
↓ ECF Na+ = ↓ ECF vol
310
Renal handling of Na+ sets plasma volume or plasma osmolality?
Plasma volume is set by renal handling of Na+
linked with ADH
311
ADH action on H2O reabsorption sets plasma volume or plasma osmolality?
ADH action on H2O reabsorption sets plasma osmolality
linked with Na+
312
What is effective circulating volume (ECV)?
| and normal value?
part of ECF that is in the arterial system (normally about 700 mL in a 70 kg man) and is effectively perfusing tissues.
(blood volume to kidneys)
313
What does the body directly control the volume of? (terms of effective circ volume)
the intravascular fluid -> influences vol of the other compartments
314
body cant measure total body water volume in all cmptms easily , but can monitor what instead?
blood perfusing tissues/ ECV effective circ volume
315
Why is 'effective circulating volume' used rather than 'total blood volume' in physiology?
‘effective’ vol of blood perfusing organs/tissues can change even w no changes in blood vol
- kidney ‘sees’ the ECV + decides if low/ high
- e.g. in heart failure, lot of blood may remain in ventricles instead of perfusing organs but total blood volume > that perfusing organs = dec ECV
316
how does ECV affect organs/ systems in
a) heart failure
b) liver cirrhosis
a) ↓ cardiac output
b) ↑ splanchnic vasodilatation- less diffusing, blood vessels smaller in liver- harder to push out. liver dilates- more blood held there
317
What detects the changes in pressure of the effective circulating volume?
```
baroreceptors
detect pressure (stretch) perfusing through them rather than volume
```
overstretch (overhydrated)
not enough stretch (dehydrated)
318
What are the 2 types of baroreceptors? (that detect changes in ECV)
- Systemic arterial baroreceptors
in aortic arch and carotid sinus - cardiovascular physiology
- Renal glomerular *afferent arterioles*: hence can detect changes in body H2O volume by getting kidneys to scrutinise blood volume going through
319
What are the baroreceptors within the afferent arterioles called? (they are modified from the smooth muscle)
juxtaglomerular cells (or granular cells)
320
juxtaglomerular cells (or granular cells) act as baroreceptors but also the same cells do what?
release renin enzyme when blood volume/ pressure drops
321
4 things that may induce renin secretion?
through BP/ blood volume drop
haemorrhage
sweating
diarrhoea
322
What other receptors are found in the nephron that help regulate blood volume?
chemoreceptors (osmoreceptors)in the DCT
323
What are chemoreceptors called in the DCT? (they are modified from the tubular cells as it reaches the glomerulus)
macula densa cells - modified tubular cells (can also cause renin release from juxtaglomerular cells when Na+ is low)
324
In actuality, how far are the DCT and the glomerulus?
very close, hence the name of the juxtaglomerular cells
325
What is the juxtaglomerular apparatus made of?
chemoreceptor macula densa cells of the DCT and
the baroreceptor and renin releasing juxtaglomerular cells of the afferent arteriole just before it enters the glomerulus
326
what does the JGA do?
maintain BP and act as a quality control mechanism to ensure proper GFR + efficient Na+ reabsorption
detects vol change and pressure (baroreceptors) in blood vessels
327
How is renin release triggered by low fluid volume/BP (juxtaglomerular cell version)?
- AA have less blood volume to them
- JGA cells detect lack of stretch in arteriole
release renin into bloodstream
328
How is renin release triggered by low fluid volume/BP (macula densa version)?
- Filtrate flows slowly through PCT =more time to reabsorb lots of Na+
- By the time filtrate hits macula densa in DCT, not enough fluid in filtrate due to more Na absorbed (macula densa detect low Na content)
More renin released by JGA cells
329
what is the RAAS system? role
hormone based system.
| increase effective circulating volume.
330
what 2 things does RAAS system regulate?
BP:
-cardiovasc and symp. NS regulate BP. renal system can also help
fluid volume:
- Na+ content through renal reabs and excretion can change fluid volume
both work together :)
331
how does renin production change if BP too high?
decreased renin produced
332
how does renin production change if BP too low?
BP/ vol decreased.
filtrate through PCT flows slower = more time to reabsorb lots of Na+.
= less Na+ appears in DCT, sensed by macula densa cells.
paracrine signals sent by these to nearby JG cells = MORE renin released.
baroreceptors detect as not stretched out as much with low BP
333
pressure receptors on PCT release renin when..?
blood volume decreased. as baro. not stretched out as much.
334
What is necessary for renin to have a physiologic function?
angiotensinogen, produced by the liver
| = a globulin released in bloostream and acted upon by renin.
335
What does renin need to do to have an action?
cleave angiotensinogen --> angiotensin I
336
What is angiotensin I further cleaved into and what by?
angiotensin II by ACE (angiotensin-converting enzyme)
337
Where is angiotensin I converted to angiotensin II?
Pulmonary and renal endothelial cells
338
Summarise how renin results in production of angiotensin II
- renin cleaves angiotensinogen into ang I
| - ang I cleaved by ACE in renal/pulmonary endothelial cells into ang II
339
role of angiotensin II (Ang II), the final product formed in process of angiotensinogen->angI->angII. ?
what 5 things does it affect?
exerts affects to bring blood volume back up!.
affects:
- vasoconstriction
- EA constriction
- ADH
- Aldosterone
- Thirst
340
What is the aldosterone action of angiotensin II?
Aldosterone secretion stimulated from adrenal cortex = increases Na+ absorption from DCT/CD’s
341
how does AngII stimulate aldosterone to stimulate Na+ reabsorption?
Na+/Cl- reabsorption enhanced in DCT and CDs (principle cells) and hence obligatory H2O reabsorption from the PCT (increases Na+/H+ exchange).
342
What is the ADH action of angiotensin II?
ADH release stimulated from posterior pituitary – aquaporin insertion in CDs = H2O reabsorption
343
What is the vasoconstriction action of angiotensin II?
- Vasoconstriction of arterioles/venules in the body = raise BP and
- renal efferent arteriole to increase GFR through inc glom HP = ensures kidneys still filter depsite drop in BP.
344
What is the thirst action of angiotensin II?
thirst centres in hypothal stimulated
| encourage increased fluid volume as drop in water volume (from dry mouth too) will increase fluid osmolality
345
RAAS system: myogenic control affect on GFR?
| what is this an indicator of?
myogenic control on EA contriction... narrower. = inc pressure = inc GFR.
check kidney still working through GFR
346
RAAS system: effect of vasoconstriction on arterioles?
inc TPR = inc BP as:
| BP = CO x TPR
347
RAAS system: effect of vasoconstriction on venules?
increased:
- venous return (blood back to heart)
- EDV
- stroke volume
- BP as:
CO = SV x HR
and BP = CO x TPR
348
What is the action of aldosterone? from stim by RAAS system
reduces NaCl excretion by stimulating = Na+ reabsorption/uptake by thick ascending LoH, CD, DCT (apical cell membrane)
349
ACE enzyme reaction happens where?
pulmonary blood- lungs!
350
what is renin released from JGS in response to ? (2)
- afferent baroreceptors detecting low fluid volume/BP and
| - paracrine signals from macula densa cells detecting low Na+
351
how does ADH inc water reabs?
it causes aquaporins to move to CD plasma membrane = increases water reabsorption
352
physiological response of renin?
does not have direct response.
| its substrate = circulating protein: angiotensinogen = produced by liver
353
2 important sites for conversion of AngI and AngII?
pulmonary and renal endothelial cells
354
summary of the 5 key actions of AngII to increase ECV?
aldosterone secretion stim from adrenal cortex = inc Na+ abs from DCT/CDs
Na+/Cl- reabs enhanced so oblig water reabs from PCT (inc Na+/H+ exchange)
ADH release stim from post pit.- aquaporin insertion in CDs = inc water reabs
Vasoconstriction of arterioles/venules in body = raise BP and renal efferent arteriole to increase GFR.
thirst stimulated
355
What is inhibiting RAAS useful in treating?
```
hypertension,
congestive HF,
LV dysfunction,
pulmonary and systemic oedema,
diabetic nephropathy,
liver cirrhosis,
migraines
```
as this system works to increase fluid volume (and hence, BP)
356
4 drug classes that inhibit RAAS system? Clinically inhibit
Renin inhibitors: Aliskiren
ACEi: ramipril
AngII rec antagonists/blockers (ARB): Candesartan
Aldosterone rec antagonists: Spironolactone
357
how may Aliskiren be prescribed?
a renin inhibitor.
| used alone/ combine with other anti-hypertensives
358
What are ACE inhibitors used to treat?
used alone or combination with other anti-hypertensives to treat
hypertension, congestive heart failure, acute MI, cardiac failure, diabetic nephropathy
359
When are Ang II receptor blockers (ARBs) used?
to treat hypertension and heart failure when ACE inhibitors are not tolerated
360
How do aldosterone antagonists work?
by blocking aldosterone receptor sites and promoting renal excretion of Na and H2O.
= prevents Na+ absorb.
diuretic.
361
What are aldosterone antagonists used to treat?
hypertension as well as oedema associated with cirrhosis, congestive heart failure etc.
362
What is the role of atrial natriuretic peptide (ANP)?
| what happens when blood volume increases?
atrial = heart, Na = sodium, riuretic = urine
- acts to put Na in urine
- when blood volume increases, the atria of the heart are stretched - they release ANP
363
What stores and secretes atrial natriuretic peptide? ANP
cardiac myocytes
364
ANP. 2 ways the renal system excretes Na+ in urine and thus restores volume?
switch off RAAS system
heart releasing ANP. when blood vol inc, heart atria stretched - ANP released.
365
ANP and lack of renin = ?
removes excess Na+ from body
all work to dec blood volume
366
how are the following interlinked and maintained?
a) osmolality
b) volume
a) maint. at expense of volume changes -> ADH
b) main. by altering Na+ content -> RAAS system (mulitple pathways).
both communicate and linked
changes affect both
367
what 2 things regulate
a) Na+?
b) water?
a) volume changes & RAAS and ANP
| b) osmolality changes & ADH
368
summary of factors that maintain water balance
green table in lc 8 revisit
369
Part 9: Regulation of body fluid pH
What is the normal body pH?
and what is this dictated by?
7.35-7.45
The concentration of H+ ion dictates body pH
370
role of buffer
too few H+: could go into alkalosis and death
release H+ into fluid/blood
too many H+: could go into acidosis and death
need to mop up H+
restore pH to 7.34
371
What happens if the body pH goes outside the range of 7.35-7.45?
```
proteins denatured,
enzyme function lost,
nerves hypersensitive,
muscle spasms,
heart rate changes etc.
```
372
What type of processes cause pH changes?
daily metabolic - produce and consume substantial volumes of free H+ ions/acids that are efficiently removed from body
373
What 6 examples of H+ ion sources?
- Ingested protein metabolism
- Cell metabolism - produce CO2, can disturb acid-base balance if not breathed out !
- Food: processed, sodas, sweetened drinks, meats, citrus fruits, yoghurt, sauerkraut...
- Meds - aspirin, warfarin, indomethacin
- Metabolic intermediate by-products e.g. exercise produces lactic acid
- Disease processes - e.g. diabetes may cause improper breakdown of fats and generation of keto-acids
374
why must ingested protein metabolism be kept in check?
source of H+ ions and produces amino acids
375
What buffer systems exist in the intracellular fluid compartments?
- phosphates (HPO42-)
- amino acids
- both accept H+ relatively quickly
376
What buffer system exists in the interstitial fluid compartments? ICF
hint: very powerful buffer!
the carbonic acid/bicarbonate buffer system
H2CO3/HCO3-
377
What buffer systems exist in the blood? (3)
- haemoglobin
- plasma proteins
- carbonic acid/bicarbonate buffer system
Hb also accepts H+ relativey quickly
378
What 2 organs use the carbonic acid/bicarbonate buffer system to restore pH?
the kidneys and the lungs
great ECF buffer
379
Carbonic acid/bicarbonate buffer system equation
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3–
380
What end of the carbonic acid/bicarbonate buffer system equation can be altered by the lungs?
left - it alters depth and rate of ventilation to alter arterial PCO2
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3–
381
What end of the carbonic acid/bicarbonate buffer system equation can be altered by the kidneys?
right - it causes either tubular excretion or reabsorption of H+ and HCO3-
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3–
382
What are the 3 defence mechanisms in the body buffering against pH changes in decreasing speed?
- 1st defence: Chemical buffering – seconds (< 1sec)
- 2nd defence: Respiratory – minutes
- 3rd defence: Renal – days (5-7)
383
why are multiple organs involved in regulating body fluid pH?
if one organ unable to do job e.g. kidney damage/ lungs etc, others can compensate
384
How do we check if the pH, PCO2 and HCO3- levels in a patient are normal?
using arterial blood gas samples obtained from radial artery
385
What is the normal values from an arterial blood gas sample for:
a) pH
b) PCO2
c) HCO3-
a) 7.4
b) 40mmHg (35-45)
c) 24mmol/L (22-26)
386
what 2 things must be kept constant for pH to remain unaltered
CO2 and HCO3- levels
387
What do the kidneys do to HCO₃⁻ and H⁺ when the pH is too low?
- reabsorb HCO₃⁻
- excrete H⁺
- generate HCO₃⁻
acidic want kidneys to excrete it into urine
all HCO₃⁻ reabsorbed abck into blood stream
388
What do the kidneys do to HCO₃⁻ and H⁺ when the pH is too high?
- excrete HCO₃⁻
| alkaline: bic. into urine
389
Why is there a limit to how much free H⁺ can be excreted in the urine? (hint: what does H⁺ do to the urine?)
H⁺ increases the acidity (decreases the pH) of urine; if it becomes too acidic it will become painful to excrete and damage the bladder and urethra
390
How else can H⁺ be excreted in the urine to prevent it from changing the pH of the urine?
- buffered with phosphate (HPO₄²⁻) to form H₂PO₄⁻ (titratable acid)
- buffered with ammonia (NH₃ - produced by PCT cells) to form NH₄⁺ released into urine
(but wont change urine pH)
acidic urine will hurt urethra etc.
391
Why is there a limit how much H⁺ that can be excreted as H₂PO₄⁻?
75% of HPO₄⁻ is reabsorbed as our body needs it to mineralise bones and teeth and act as a buffer within cells
392
reminder from lec 3:
| How is HCO₃⁻ reabsorbed by the kidneys?
in tubule lumen
secreted H+ combines w filtered HCO₃⁻ = h2o and co2.
requires carbonic anhydrase on apical brush border of PCT tubular cells.
back into proximal tubule cell
co2 difffuses into cell, recombines w h20 = hco3- = exits cell from basolateral side and diffuses back into blood.
393
Until what pH can H⁺ be excreted in the urine freely and unbound?
until the urine pH reaches 4.4
after this, acidosis dealt with by kidneys in 2 ways...
394
....acidosis dealt with by kidneys in 2 ways which are?
removes some excess H+ via:
H2PO4- or NH4+
bind to remove acidity.
generate extra bicarbonate
395
renal phosphate buffer system
What is generated by the renal tubules when HPO₄⁻/ NH₃ buffers H⁺ before being excreted in the urine?
new HCO₃⁻
the system can be used as an intracellular buffer
396
renal ammonia buffer system
How is ammonia produced in the PCT cells of the kidney?
glutamine (added/ alr in) into the PCT cells is converted to ammonia which accepts a base H+ to become ammonium
again new HCO3- gen by renal tubules
397
Why is 99% of HCO₃⁻ reabsorbed back into the body?
if lost, it would result in acidosis as nothing could buffer H⁺ from metabolic processes
398
ammonia buffers and excretes how much of excess H+ in urine and contributes to how much of new HCO3-?
50/50
399
Under what circumstance is HCO₃⁻ excreted in the urine?
when the plasma is too basic, to allow H⁺ to build up and decrease the pH
400
what can acid base imbalances arise due to?
respiratory dysfunction: change in PCO2
or
metabolic dysfunction: change in [HCO3-]
therefore change in [H+]/pH are reflected by changes in [HCO3-]:[co2]
pH = [HCO3-]/PCO2
401
definition of repiratory acidosis
Low pH < 7.35
| High pCO2 >45mmHg
402
causes of respiratory acidosis
hypoventilation (CO2 retained. not ventiliating alveoli)
holding CO2 in body- most common AB disorder
lung problems: emphysema/obstruction/oedema
trauma to resp centre
dysfunction of resp muscles
403
how does repiratory acidosis affect carbonic acid equation?
more to RIGHT as (MORE CO2) and MORE HCO3- and H+
CO2 accumulation in blood stream increases H+/HCO3-
404
renal compensatory mechanisms of repiratory acidosis
peripheral chemoreceptors sense pH change, try to change ventilation rate. BUT lungs unresponsibe as this is where problem is
therefore kidneys try and remove excess H+ in acidic urine and conserve HCO3-
INCREASED:
- renal secretion and excretion of H+
- renal reabs of HCO3-
- renal generation of HCO3-
405
whats a davenport diagram? (resp acidosis)
representation (simple) of pH/ HCO3- and PCO2 (isobars)
shows the 4 types off AB disturbances and renal/resp compensations that happen to restore pH.
406
renal compensatory mechanisms of repiratory acidosis 3 steps to increase blood pH?
excrete H+ into urine
retain HCO3-
generate HCO3-
blood pH increased
(think of pH = [HCO3-]/pCO2 )
407
renal compensatory mechanisms of respiratory ALKALosis 2 steps to increase blood pH?
retain H+
excrete HCO3- into urine
blood pH decreased
(think of pH = [HCO3-]/pCO2 )
408
definition of respiratory alkalosis
high pH > 7.45
| low pCO2 <35mmHg
409
causes of respiratory alkalosis
hyperventilation
removing co2 from body too quickly
anxiety, fear, pain- hysterical overbreathing not just panting
lungs: pneumonia
aspirin OD/toxicity; too much caffeine
over ventilation on mechanical respirator
410
how does repiratory alkalosis affect carbonic acid equation?
more to LEFT as LESS CO2 and (LESS HCO3- and H+)
CO2 loss from blood stream decreases H+/HCO3-
411
renal compensatory mechanisms of repiratory alkalosis
peripheral chemoreceptors sense pH change, try to change ventilation rate. BUT lungs unresponsibe as this is where problem is
therefore kidneys RETAIN H+ and EXCRETE HCO3-
INCREASED:
- renal excretion of HCO3- (dont reabsorb/ generate)
- renal reabs of H+ (dont excrete)
412
whats metabolic alkalosis
high pH > 7.45
| high HCO3- > 24mEq/L
413
5 things that may lead to metabolic alkalosis?
- severe vomiting= acid loss (common)
- gastric suction
- diuretics -> renal dysfunction
- excesisve intake of alkaline drugs - antacids
- excessive intake of fruits (fad-diets ricch in fruits)
414
what drug class (excessive use of) may lead to metabolic alkalosis?
alkaline drugs- antacids
415
what direction would the carbonic eqn shift in metabolic alkalosis?
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3–
RIGHT
loss of H+ (or gain of HCO3-) = increased HCO3-
hold onto CO2
416
compensatory mechanisms in metabolic alkalosis?
| i.e. which system has major role?
peripheral chemoreceptors sense change in pH
lungs hypOventilate to retain CO2 (and thus H+)
- pulmonary compensation for metabolic alkalosis
= will raise HCO3- even more!
kidneys remove excess HCO3- in urine, conserve H+
417
compensatory mechanisms FOR change in HCO3- and H+ in metabolic alkalosis?
INCREASED:
renal excretion of HCO3- (dont reabsorb/generate it)
renal reabsorption of H+ (dont excrete it)
418
Metabolic alkalosis increases blood pH. how does pulmonary and renal system respond/compensate for this change?
renal:
- retain H+
- excrete HCO3- in urine
- blood pH decreased
pulmonary
- hypoventilate
- blood pH decreased
419
Summary:
How is Acidosis responded/compensated for by: pulmonary and renal systems
i.e. what happens to the H+? (3)
H2CO3 -> H+ + HCO3-
Problem = Addition of H+/loss of HCO3-
H+:
- more turned into H2CO3 --> goes to lungs and leaves as CO2 (inc resp rate to remove and lower PCO2
- more absorbed by other buffers in body
- more excreted in acidic urine --> HCO3- reabsorbed and generated
420
Summary:
How is Alkalosis responded/compensated for by: pulmonary and renal systems
i.e. what happens to the H+? (3)
H2CO3 -> H+ + HCO3-
Problem = Addition of HCO3-/loss of H+
H+:
- Resp rate decreased to retain thus increase PCO2 = inc H2CO3
(lungs hold onto CO2)
- more donated by other buffers in body
- more reabsorbed from kidneys--> HCO3- secreted in alkaline urine
421
Part 10: Revision session
Why is the glomerular filtration barrier effective? (4)
- tiny pores in endothelial layer only let plasma through (no big MW mols)
- BM thicker than normal
- BM = negative so large proteins repelled
- podocytes = 3rd barrier to plasma components
422
what are the 3 layer sof the glomerular filtration barrier?
endothelial cells- fenestrates lining of glomerulii
basement membrane
podocytes- cover whole glomeruli
423
which force favours filtration:
a) glom cap HP
b) capsular HP
c) glom cap osmotic P
d) capsular osmotic P
= a) glom cap HP
reason= Bowmans Capsule not interstitium surrounds glomerulus = should not be any proteins in filtrate (oncotic pressure)
424
net filtration pressure favours XXX fluid movement?
| reason and what is the net filtratiion pressure?
net filtration pressure favours OUTWARD fluid movement
Starlings forces:
OUT
glom HP: 50mmHg
IN
glom OncoticP: 25mmHg
BC's HP: 15mmHg
BC's OncoticP: 0mmHg
net = 50-25-15-0=10mmHg
425
Meant arterial pressure (MABP) increases from 90mmHg to 110mmHg.
what could happen to prevent an increase in pressure in glom caps?
constriction of AA.
= less blood into glom caps. could occur when BP increased to decrease it
426
which out of the following hormones does NOT influence kidney function?
ADH
erythropoeitin
ANP (atrial natriuretic peptide)
aldosterone
erythropoetin
- produced and secreted by kidney when hypoxic to increase RBC production - hence acts on RBC progenitors and precursors in bone marrow!
427
plasma levels of erythropoetin usually low but when may it increase?
in hypoxic stress/ anaemia
| up to 1000 fold inc!
428
how does ANP (atrial natriuretic peptide) act on kidney?
| and when is it released
produced by heart myocytes
released in response to atrial stretch due to high blood volume
acts on kidney to decrease Na+ reabsorption
429
where does most of the 99% of glom filtrate produced each day, get reabsorbed and what ion reabsorption is it linked to?
PCT... linked ot reabsorption of Na+
430
what do Na+K+ pumps in basal membrane do to Na+? i.e. whats their effect
move Na+ out of tubule cell, keeping intracellular Na+ conc low.
Na+ is filtered so filtrate conc is high
431
how does Na+ get through apical membrane of tubule cell?
| then what happens regarding organic nutrients?
diffuses through co-transporters in apical membrane of tubule cell
then organic nutrients reabsorbed across apical surface by secondary active transport with Na+.
432
what does reabsorption of Na+ create? what does this lead to?
(4)
osmotic gradient => h2o reabsorption
conc of solutes left behind in tubule lumen increases
lipid soluble subs diffuse through apical and basal mem bilayers
remaining solutes (K+,Ca2+...) diffuse betweent ubule cells
433
which is not included in the system for formulation of conc/dilute urine?
```
CDs
Medullary interstitium
LoH
PCT
Vasa Recta
```
PCT.
434
what parts of nephron are:
a) concentrating
b) diluting
c) least permeable to water
a) desc LoH
b) ascending LoH
c) ascending LoH- throwing out Na+. now ater
435
which solutes = main contributors to high osmolality of interstitial fluid in renal medulla?
Na+
Cl-
Urea
salts and urea help strengthen cortico-medullary interstitium. urea secreted back into desc LoH
436
what are the 3 major solutes contributing to plasma osmolality of 285mOsm/Kg
Na+ 140mOsm/Kg
Cl- 115mOsm/Kg
HCO3- 25mOsm/Kg
= 280mOsm/Kg
437
5 steps in the journey of Na+/Cl- through the counter-current exchanger
Na+/Cl-...
1. leaves thin and thick asc Loh
2. accumulates in medullary interstitium
3. absorbed by desc vasa recta
4. flows into asc vasa recta
5. returned to medullary interstitium
438
in renal tubule, what hormone regulates:
a) water volume
b) sodium reabsorption
a) ADH
| b) aldosterone
439
whats the principal regulator of plasma osmolality?
```
Plasma [Na+]
ADH
aldosterone
AngII
volume of water
```
ADH
440
in sosmeone with excess water consumed, you would expect to see:
X ADH, Y dilute urine, Z urea permeability
less ADH, more dilute urine, less urea permeability
441
4 factors to tell if patient had diabetes indipidus?
extreme thirst
decrease in ADH
large volume urine
urine with very low osmolality
442
which RENAL substance works with CVS to raise BP:
```
ADH
aldosterone
renin
ANP
ACE
?
```
renin.
| ACE can be found in renal endothelial cells and pulmonary endothelium but renin is purely form kidney
443
whats the function of macula densa cells?
monitor NaCl conc in filtrate
444
what happens to blood osmolality and volume when severly dehysrated?
blood osmolal: increase = stim osmorec in hypothal
blood volume: decrease = decrease BP= more renin released and Ang II made
= thirst
445
where is thr key hormone in reg water reabs secreted from?
post pit gland
446
there are osmoreceptors in hypothalamus
| T/F?
true
447
how is body volume regulated?
changing body sodium content and maintaining normal osmolality
448
what provides info about body volume?
stretch receptors
449
what provides info about osmolality?
rec in hypothalamus (osmoreceptors)
450
whats the main influence of body volume?
renal sodium exretion
451
normally in urine what is most of H+ tied up wiht?
ammonia
452
how to decide if metabolic/resp alka/acidoss is COMPENSATED?
pH is normal
| regardless of low/high Co2/HCO3-
453
what does the vasa recta preserve?
Countercurrent Exchange in the Vasa Recta Preserves Hyperosmolarity (Salty gradient) in renal medullary interstitium
454
Why is there lots of bicarbonate in blood? What’s it’s role
Na, Cl, Bicarbonate
Acts as buffer
455
What’s acidosis?
H+ sitting in blood, not being breathed out
Hyperventilate to help
Breathe out acid
Inc resp rate
456
What ion is most abundant inside cell and outside cell?
Na extracellular
K intracellular
Salty banana
