Renal Physiology Flashcards
3 Major functions of the kidney
- Filtration: removal
- Production
- Regulation
Describe the 2 major waste products produced by body, cleared by kidneys
a. Ammonia NH3.
b. creatinine- made during muscle breakdown.
whats creatinine used to indicate and what may create false positive/negative values?
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
why and how (outline) does kidney regulate body fluids?
volume (post.pituitary), conc, distribution of body fluid - homeostasis
Renal glands (aldosterone release) and brain (ADH release)
whats normal amount water in body and how do kidneys control conc + vol?
- 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
tonicity of solutions and effect on RBC
isotonic: normal in RBC cytoplasm
hypertonic: RBC shrivel as water leaves
hypotonic: RBC swell as water comes in
water travels by osmosis
location and compositions (%) of fluid compartments in average 70kg male?
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
what is the functional barrier surrounding
a) plasma (also ECF)
b) ICF?
what do kidneys have access to?
a) capillary andothelium
b) cellular membrane
kidneys: control vol of all 3 compartments BUT only access to plasma
what pressures (+forces) regulate continuous exchange and mixing of body fluids?
hydrostatic and osmotic pressures
Starling’s forces: water and electrolytes freely cross, move by diffusion.
process of fluid moving out of: plasma
starlings forces mmHg
drive DIFFUSION
changes in HP=fluid movement
effect of different amounts of ions in plasma, interstitium, intracellular on fluid osmolality
no effect.
although ions in different amounts, fluid osmolality still approx. 285mOsm/Kg/H2O
why are plasma and interstitial fluid compartments of ECF similar?
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.
what 2 forced determine free and rapid movement of water between various fluid compartments?
hydrostatic pressure (heart pumping) osmotic pressure (exerted by plasma proteins - oncotic pressure)
effect of adding hypotonic NaCl IV infusion to ECF
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
effect of adding hypertonic NaCl IV infusion to ECF
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
name 3 things that get filtered through kidney
- metabolic waste: nitrogenous, excess ions. produced in body/excess from diet
- drugs
- toxins
4 things produced in kidney and roles?
- 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
what does the kidney regulate?
- body fluids
- Vol of extracellular fluid
- Osmolal of bf
- conc of electrolytes
- blood pH- acid-base balance
- BP
- RBC
how is ammonia made and cleared from kidneys?
made from protein catabolism.
toxic, water soluble.
convert to urea (aa breakdown) -> uric acid (nucleotide breakdown)
what do high serum creatinine levels suggest?
serum levels= test of kidney function. high = impairment/disease
Why does kidney need to regulate body fluids: osmolality?
- extreme variation=cells shrink/swell/burst
- damage cell struc and disrupt normal cell function
normal kidney/ body osmolality?
285mOsm/Kg water
what do changes in HP =
continuous fluid movement between plasma and IF and IF and cells.
process of fluid moving out of: ICF
osmotic pressure mosm/kgH2O
H2O free movement, not ions
OSMOSIS
changes in ionic content of IF =water movement
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.
what does plasma memb have that means fluids can easily cross?/permeate
plasma memb has h2o channels (aquaporins) = easily cross memb
Part 2: Glomerular filtration
basic kidney anatomy: what is the
a) inner layer called
b) outer layer called?
a) medulla
b) cortex
the kidney is covered by what?
transparent fibrous renal capsule
5 parts in the kidney
- 5-8 renal pyramids
- renal columns
- renal papilla
- renal pelvis: urine to ureter
- ureter: urine to bladder
where are the major blood vessels contained in the kidney?
renal columns
where empties into renal papilla?
all urine filled collecting ducts
what are nephrons?
functional units of kidneys-
hollow tubes. closed at proximal end and open at distal
role and length of nephron?
a) each is its own unit, produces miniscule amounts of urine
b) 3-4mm long
3 main regions of nephron?
- renal corpuscle
- tubule
- collecting tubule
a) what 2 structures are in the renal corpuscle?
bowmans capusles
glomerulus (capillaries)
b) 3 structures in the tubule
PCT
loop of henle
DCT
what regions of nephron found in the renal medulla?
LoH, collecting ducts
what enters the nephron and what leaves?
fluid (filtrate) in and urine out
what structure(s) modify the fluid passing through the nephron?
lining of nephron
what does the glomerulus provide?
capillaries that provide blood for filtration- enters in the coiled networks of capilalries with large pores
what leaves the nephron? specifically
urine: toxic urea, nitrogenous waste products
name the first process of urine formation
glomerular filtration
what filters out of the capillaries into bowmans space?
plasma, low MW substances, electrolytes etc.
anything but blood cells and proteins
where is glomerulus structure found?
sits inside bowmans capsule- filtrate collecting bag.
fist in a balloon
what arrives at glomerulus and what leaves?
arriving: afferent arteriole
exiting: efferent arteriole
2 layers of BC and which one touches the glomerulus?
Parietal: outer wall
Visceral: inner wall, lines glom capillaries. !
where are podocytes found?
highly specialised epithelial cells of visceral layer of BC.
wrapped around glom capillaries.
role of podocytes?
along with the monolayers of fenestrated endothelium lining caps and glom basement in between,
form the filtration barrier
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
what helps plasma getting forced through pores in the fenestrated endothelial cells of the filtration barrier?
high hydrostatic pressure
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
what molecules can filter through the - charged basement memb into BC space?
+ charged molecules attracted to BM and uncharged mols.
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.
what does high hydrostatic pressure in capillaries ensure?
glom filtration.
plasma forced into nephron
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)
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)
why is net fluid outward = net fluid in, not favoured for nephron?
= no fluid accumulation inside, eqm.
- wont make urine. makes cap OP
where does the fluid filtered out of glomerulus go to?
high HP = fluid filtered out –> BC –> PCT
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
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
regarding water, elecs, glucose, waste products, how does glom filtrate composition compare to plasma?
identical
why is albumin (69,000Da) not filtered and kept out of filtrate?
filtration barrier cut off = 70,000Da.
Albumin also - charged= repelled by BM
what is difference in appearance of plasma and glom filtrate?
the blood cells
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
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
proteinuria: how do the proteins enter urine?
leak out form glomerulus into bowmans capsule due to disruption in filtration barrier for 3 reasons
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
consquences of excessive proteinuria? (3)
low level protein in plasma = oedema
* swolled around eyes, hands, feet
frothy/bubbly urine
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
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
how many times a day is the plasma in body filtered?
60 times a day
3L plasma but GFR is 180L/day
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
why ECF composition precisely regulated?
plasma reg precisely and often = urine often v important for removing unwanted substances
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)
Part 3: tubular function - PCT
what are the 4 basic renal processes that occur for filtration in nephron?
- glom filtration
- tubular reabsorption
- tubular secretion
- excretion
how is urine volume formed calculated?
approx how much is it a day?
Urine = Filtered - Reabsorbed + Secreted
1.5L urine a day
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
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
what drives filtration?
filtration is non selective
Starlings forces
HP forces plasma to BC.
everything gets through
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
what is reabsorption driven by?
active transport, diffusion, osmosis, starlings forces
Secretion is a 2nd chance to…?
actively eliminate unwanted substances from blood into urine.
only 19-20% filtered
What is secreted from blood to urine?
- nitrogenous waste( NH3, creatinine, urea, uric acid)
- inroganic ions if excess
- unwanted drugs
where are secreted substances moved from and to?
and what is the process driven by?
from peritubular caps into PCT lumen.
active transport
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
how is pct specialised for reabsorption?
PCT = approx 1/3 length of nephron and has increased SA due to brush border on tubular cells
PCT: whats reabsorbed?
- ions: 65%
- water: 65%
- glucose: ALL
- AAs: ALL
- vitamins: ALL
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
why is the same amount (65-67%) ions and water reabsorbed in the PCT?
same % as move together.
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
what does the clearance of drug depedn on? 5
- whether drug filtered/secreted/reabsorbed
- GFR
- structure of drug
- age
- disease
…
whys it important to know clearance rates of drugs?
determines dosage- correct to maintain plasma conc and = therapeutic effect
affect of renal function on clearance and plasma half life?
LOW renal func = LOW clearance and HIGH plasma half life
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.
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
what does PCT have a lot of for driving the reabsorption process?
mitochondia for energy
also brush border: increase absorptive capacity
why do DCT cells look like they have alarger lumen than PCT cells?
absence of brush border (which increases surface area) on DCT.
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
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
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
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.
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
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
- using the Na+K+ATPase, what is energy invested in ?
- to get Na+ out of filtrate and create Na+ electrochemical gradient
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
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
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
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
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
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
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.
what is reabsorbed into the peritubular capillary? (2) from diagrams
HCO3- and Na+.
recycled- (reabsorb bicarbonate H2CO3)
the equation for substances being filtered at PCT? (acid base transport)
CO2 + H2O ⇌ H2CO3 ⇌ HCO3− + H+
Slow Fast
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)
what process and route(s) does water reabsorption in the PCT occur by?
osmosis.
paracellular and transcellular (AQP1 aquaporin 1)
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.
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
how do the following travel from PCT tubule lumen into cell and peritubular capillary?
a) lipids
b) Cl-, K+, Ca2+….
a) transcellularly
b) paracellularly
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
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
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.
what 2 molecules weakly/not absorbed in PCT?
urea and Cl-: conc higher at end of PCT
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)
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
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
what is reabsorption of water by osmosis linked to? in context of PCT?
reabsorption of solutes.
obligatory H2O movement
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
what is the LoH (loop of henle) designed for?
looped region of nephron- has countercurrent flow inside it- going in opposite directions
what does the filtrate going around the LoH and changing concentrations as it moves down descending and up ascending limb, contain?
water and solutes
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!
the water absorbed in LoH is taken up by?
specialised blood vessels: vasa recta
where is filtrate osmolality highest in the nephron? what does this mean?
at bottom of LoH 1200mOsm/kg/water. = means water mustve come out
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
what does the cortico-medullary hyperosmotic interstitial gradient allow?
concentrated urine formation
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.
hat is the corticomedullary/ corticopapillary osmotic gradient?
outer renal cortex –> inner renal medulla:
interstitium of medulalry region becomes more concentrated (saltier)
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
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
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
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!!
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
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
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.
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
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
what is the filtrate in descending LoH surrounded by?
hyperosmotic medulla thanks to ascending LoH
what happens to filtrate when is equilibriates with interstitium? (descending LoH)
becomes hyperosmotic
difference in water reabsorption from PCT, at descending LoH?
not obligatory H2O reabsorption.
not directly linked with Na+ reabsorption as with at PCT
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
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
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
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
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.
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
role of the LoH/ countercurrent multiplier?
establish an osmotic gradient (300-1200mOsm) from renal cortex through to medulla
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.
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,..
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
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
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
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
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
Where does the passively reabsorbed urea accumulate?
passively reabsorbed from the inner medullary region of collecting duct, accumulates in medullary interstitium
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
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!
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
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
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
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
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
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
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
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
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
c) how does blood leave the kidney?
through the small venules and veins and finally: renal vein
what are the two capillary networks in the kidney?
first capillary network: glomerular caps
second capillary network: peritubular caps (branch to vasa recta)
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
what artery branches to form the afferent artery of glomerulus?
interlobular artery
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
what is blood pressure in glomerulus controlled by?
different diameters of EA and AA
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
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.
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.
a) external mechanism of tight regulation of GFR?
sympathetic and hormonal mechanisms
(cardiac physiology lecs)
BP maintained in response to nerves and hormones
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
3 major physiological body systems that activated and respond to drop in BP?
cardiovascular
renal
neuroendocrine: ADH released from pit. gland
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
how does renal system respond to drop in BP?
renin released from JGA (juxtaglomerular apparatus)
and
aldosterone from adrenal cortex
regardless of BP fluctuation, GFR and renal blood flow remain contant. at what values?
80-180mmHg
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
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
when is constriction of efferent arteriole most useful?
when BP drops.
= getting more blood to glom caps.
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.
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
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
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
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
how is perfusion of kidney different compared to perfusion of otehr organs?
done to retain filtration funcs instead of regulated to maintain organ nutrition
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
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
why are the vasa recta looped?
prevent high conc of solutes in medullary interstitium being washed away
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.
what does vasa recta remove?
reabsorbed water.
water entering VR from descending VR/ reabsorbed from descending LoH and CD.
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
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
How does furosemide essentially lower BP and swelling?
Helps body get rid of excess salt and water by increasing urine amount
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
Why would furosemide be given IV sometimes instead of orally?
Faster onset of action
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
How to check and monitor decrease of oedema in ankles?
Weigh patient regularly
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
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
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
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
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
Part 6: Urine conc and dilution
what is urine normally like compared with plasma?
urine normally HYPEROSMOTIC compared with plasma
400-1000mOsm/Kg H2O
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
where are decisions made to conc/dilute urine?
in last part of nephron- DCT and collecting ducts
what does urine look like with:
a) high osmolality
b) low osmolality?
a) darker, more conc with toxins = hyperosmotic
b) paler, more dilute
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!
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
what does solute and water conc in man vary depending on?
diet
external factors
climate
…
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
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
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
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
whats the major factor that = conc/dilute urine?
ADH- tells CD when to draw water out
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
how does water move out of CD? (gradient)
from LOW to HIGH solute conc
where does the water reabsorbed from CD go to?
nearby peritubular capillary/ vasa recta etc.
affect of drinking lots of water on ADH production?
little ADH produced as dont reabsorb a lot
what does ADH precisely control?
plasma OSMOLALITY not volume
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
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
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
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
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).
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
where and when is ADH secreted?
secreted into blood from pituitary gland in response to hypovalaemia and plasma hyperosmolality
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
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
how are CDs acting in absence of ADH?
CDs not permeable to water even with the gradient, if no ADH
what type of urine produced in presence of ADH?
released when dehydrated.
small volume of conc urine as maximum watre reabsorbed
what does production of ADH depend on?
how hydrated.
very = little ADH
dehydrated = some ADH
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
ADH makes the CD permeable to water and what else?
urea.
- helps salt pull out more water
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
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
why is filtrate always ISOTONIC at end of PCT?
285mOsm.
similar water and solute reabs. into peritubular caps
why is filtrate always HYPERTONIC at end of desc LoH?
up to 1200mOsm
lots of water reabs into vasa recta.
no solute reabs
why is filtrate always HYPOTONIC at end of asc LoH?
90mOsm
lots of solute into interstitium and some into vasa recta
no water reabs
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.
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
2 possible causes of central diabetes insipidus?
No ADH:
- not produced by pit gland
- OR kidneys dont respond to it
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
how does desmopressin compare to ADH and work?
more powerful than endogenous ADH.
stops kidneys producing urine
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
what 5 factors work together hand in hand to control urine conc?
LoH: creates hyperosm... grad urea recycling vasa recta CDs ADH
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)
Part 7: Osmoregulation
what 3 things does kidney control regarding body fluids?
- correct osm (285mOsm)
- vol of fluid in body
too much = increase plasma = increase BP :(
linked.
- correct pH
A variation of how many mOsm/KgH2O triggers sensors in the body to return osmolality back to normal?
± 3mOsm/KgH2O
How do changes in plasma/ECF osmolality affect cell volume?
can increase or decrease it, due to movement of water created between compartments
Which organ’s interstitial fluid compartment has varying osmolality?
kidney, due to LoH ascending limb throwing out salt into interstitium
The 4 stages of body fluid osmolality regulation?
1) stimulus
2) receptor (sensor)
3) control centre
4) effector
What is the stimulus that triggers ADH release?
a change in osmolality e.g. eating salty meal or sweating
What receptors detect a change in osmolality?
osmoreceptors in the hypothalamus, communicate with control centre (pituitary gland)
What is the control centre’s action in response to osmoreceptors’ signal?
ADH is triggered to be released from the posterior pituitary gland
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
Where is the pituitary gland located?
by the eye socket
Where is ADH made?
in the hypothalamus
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
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
affect of the following on urine production:
a) diuretic (drugs)
b) ADH hormone
a) increase urine production
b) decrease
affect of eating salt on urine volume?
-> salty conc blood -> ADH makes you urinate less. reabsorb fluids etc
also stimulate thirst-> dilute body fluid
What other receptors are located close to the osmoreceptors?
thirst receptors (lateral pre-optic area)
Where is ADH stored?
posterior pituitary
Why is ADH said to be unstable in circulation?
it has a half-life of 10 minutes
ADH is released into the blood when plasma osmolality increases or decreases?
ADH is released when plasma osmolality increases
ADH release is inhibited when plasma osmolality increases or decreases?
ADH release is inhibited when plasma osmolality decreases
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
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
How does ADH release affect urine concentration?
increases it, increasing its osmolality
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
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
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
ADH release can be completely suppressed with only a XXmOsm/Kg water drop?
5mOsm/Kg water
for every 1mOsm/Kg increase in plasma osmolarity, hm will [ADH] increase?
by 0.38pg/ml
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
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
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
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
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.
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
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
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
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
What is necessary on the collecting ducts in order for water to be reabsorbed under the effect of ADH?
V2 (vasopressin) receptors
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.
where are aquaporins always present?
on basolateral surface to allow water into these cells for survival
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
What is diabetes insipidus caused by?
hyposecretion of/ insensitivity to the effects of, antidiuretic hormone (ADH), also known as arginine vasopressin (AVP)s
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
What are the symptoms of diabetes insipidus?
- polyuria
- polydipsia (excessive thirst)
- nocturia
- urinary incontinence may occur
What will the plasma and urine osmolality be in patients with diabetes insipidus?
raised: >295 mOsmol/kg, despite having dilute urine <700 mOsmol/kg
what does osmoregulation actually do (and not do)?
controls plasma Na+ conc by changing water volume
NOT controlling actual bodys water content.
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
How do osmoregulation and volume link?
osmoregulation disturbs volume, so you need a volume regulator
affect of adding salt to fluid volume?
does not change water volume but changes osmolality = increased fluid volume
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
Renal handling of Na+ sets plasma volume or plasma osmolality?
Plasma volume is set by renal handling of Na+
linked with ADH
ADH action on H2O reabsorption sets plasma volume or plasma osmolality?
ADH action on H2O reabsorption sets plasma osmolality
linked with Na+
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)
What does the body directly control the volume of? (terms of effective circ volume)
the intravascular fluid -> influences vol of the other compartments
body cant measure total body water volume in all cmptms easily , but can monitor what instead?
blood perfusing tissues/ ECV effective circ volume
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
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
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)
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
What are the baroreceptors within the afferent arterioles called? (they are modified from the smooth muscle)
juxtaglomerular cells (or granular cells)
juxtaglomerular cells (or granular cells) act as baroreceptors but also the same cells do what?
release renin enzyme when blood volume/ pressure drops
4 things that may induce renin secretion?
through BP/ blood volume drop
haemorrhage
sweating
diarrhoea
What other receptors are found in the nephron that help regulate blood volume?
chemoreceptors (osmoreceptors)in the DCT
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)
In actuality, how far are the DCT and the glomerulus?
very close, hence the name of the juxtaglomerular cells
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
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
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
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
what is the RAAS system? role
hormone based system.
increase effective circulating volume.
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 :)
how does renin production change if BP too high?
decreased renin produced
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
pressure receptors on PCT release renin when..?
blood volume decreased. as baro. not stretched out as much.
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.
What does renin need to do to have an action?
cleave angiotensinogen –> angiotensin I
What is angiotensin I further cleaved into and what by?
angiotensin II by ACE (angiotensin-converting enzyme)
Where is angiotensin I converted to angiotensin II?
Pulmonary and renal endothelial cells
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
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
What is the aldosterone action of angiotensin II?
Aldosterone secretion stimulated from adrenal cortex = increases Na+ absorption from DCT/CD’s
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).
What is the ADH action of angiotensin II?
ADH release stimulated from posterior pituitary – aquaporin insertion in CDs = H2O reabsorption
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.
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
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
RAAS system: effect of vasoconstriction on arterioles?
inc TPR = inc BP as:
BP = CO x TPR
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
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)
ACE enzyme reaction happens where?
pulmonary blood- lungs!
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+
how does ADH inc water reabs?
it causes aquaporins to move to CD plasma membrane = increases water reabsorption
physiological response of renin?
does not have direct response.
its substrate = circulating protein: angiotensinogen = produced by liver
2 important sites for conversion of AngI and AngII?
pulmonary and renal endothelial cells
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
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)
4 drug classes that inhibit RAAS system? Clinically inhibit
Renin inhibitors: Aliskiren
ACEi: ramipril
AngII rec antagonists/blockers (ARB): Candesartan
Aldosterone rec antagonists: Spironolactone
how may Aliskiren be prescribed?
a renin inhibitor.
used alone/ combine with other anti-hypertensives
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
When are Ang II receptor blockers (ARBs) used?
to treat hypertension and heart failure when ACE inhibitors are not tolerated
How do aldosterone antagonists work?
by blocking aldosterone receptor sites and promoting renal excretion of Na and H2O.
= prevents Na+ absorb.
diuretic.
What are aldosterone antagonists used to treat?
hypertension as well as oedema associated with cirrhosis, congestive heart failure etc.
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
What stores and secretes atrial natriuretic peptide? ANP
cardiac myocytes
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.
ANP and lack of renin = ?
removes excess Na+ from body
all work to dec blood volume
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
what 2 things regulate
a) Na+?
b) water?
a) volume changes & RAAS and ANP
b) osmolality changes & ADH
summary of factors that maintain water balance
green table in lc 8 revisit
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
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
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.
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
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
why must ingested protein metabolism be kept in check?
source of H+ ions and produces amino acids
What buffer systems exist in the intracellular fluid compartments?
- phosphates (HPO42-)
- amino acids
- both accept H+ relatively quickly
What buffer system exists in the interstitial fluid compartments? ICF
hint: very powerful buffer!
the carbonic acid/bicarbonate buffer system
H2CO3/HCO3-
What buffer systems exist in the blood? (3)
- haemoglobin
- plasma proteins
- carbonic acid/bicarbonate buffer system
Hb also accepts H+ relativey quickly
What 2 organs use the carbonic acid/bicarbonate buffer system to restore pH?
the kidneys and the lungs
great ECF buffer
Carbonic acid/bicarbonate buffer system equation
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3–
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–
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–
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)
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
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
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)
what 2 things must be kept constant for pH to remain unaltered
CO2 and HCO3- levels
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
What do the kidneys do to HCO₃⁻ and H⁺ when the pH is too high?
- excrete HCO₃⁻
alkaline: bic. into urine
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
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.
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
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.
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…
….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
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
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
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
ammonia buffers and excretes how much of excess H+ in urine and contributes to how much of new HCO3-?
50/50
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
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
definition of repiratory acidosis
Low pH < 7.35
High pCO2 >45mmHg
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
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-
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-
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.
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 )
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 )
definition of respiratory alkalosis
high pH > 7.45
low pCO2 <35mmHg
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
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-
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)
whats metabolic alkalosis
high pH > 7.45
high HCO3- > 24mEq/L
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)
what drug class (excessive use of) may lead to metabolic alkalosis?
alkaline drugs- antacids
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
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+
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)
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
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
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
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
what are the 3 layer sof the glomerular filtration barrier?
endothelial cells- fenestrates lining of glomerulii
basement membrane
podocytes- cover whole glomeruli
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)
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
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
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!
plasma levels of erythropoetin usually low but when may it increase?
in hypoxic stress/ anaemia
up to 1000 fold inc!
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
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+
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
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+.
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
which is not included in the system for formulation of conc/dilute urine?
CDs Medullary interstitium LoH PCT Vasa Recta
PCT.
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
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
what are the 3 major solutes contributing to plasma osmolality of 285mOsm/Kg
Na+ 140mOsm/Kg
Cl- 115mOsm/Kg
HCO3- 25mOsm/Kg
= 280mOsm/Kg
5 steps in the journey of Na+/Cl- through the counter-current exchanger
Na+/Cl-…
- leaves thin and thick asc Loh
- accumulates in medullary interstitium
- absorbed by desc vasa recta
- flows into asc vasa recta
- returned to medullary interstitium
in renal tubule, what hormone regulates:
a) water volume
b) sodium reabsorption
a) ADH
b) aldosterone
whats the principal regulator of plasma osmolality?
Plasma [Na+] ADH aldosterone AngII volume of water
ADH
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
4 factors to tell if patient had diabetes indipidus?
extreme thirst
decrease in ADH
large volume urine
urine with very low osmolality
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
whats the function of macula densa cells?
monitor NaCl conc in filtrate
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
where is thr key hormone in reg water reabs secreted from?
post pit gland
there are osmoreceptors in hypothalamus
T/F?
true
how is body volume regulated?
changing body sodium content and maintaining normal osmolality
what provides info about body volume?
stretch receptors
what provides info about osmolality?
rec in hypothalamus (osmoreceptors)
whats the main influence of body volume?
renal sodium exretion
normally in urine what is most of H+ tied up wiht?
ammonia
how to decide if metabolic/resp alka/acidoss is COMPENSATED?
pH is normal
regardless of low/high Co2/HCO3-
what does the vasa recta preserve?
Countercurrent Exchange in the Vasa Recta Preserves Hyperosmolarity (Salty gradient) in renal medullary interstitium
Why is there lots of bicarbonate in blood? What’s it’s role
Na, Cl, Bicarbonate
Acts as buffer
What’s acidosis?
H+ sitting in blood, not being breathed out
Hyperventilate to help
Breathe out acid
Inc resp rate
What ion is most abundant inside cell and outside cell?
Na extracellular
K intracellular
Salty banana
