renal system Flashcards
1
Q
m
actions of renal system
A
-
reconditioning of blood
- pH, H2O content/solute [x], [Na], [K] balance
- regulate MAP
- limit water excretion when dehydrated
-
get rid of waste
- nitrogenous waste from protein breakdown
- breakdown of products from drug or toxin
- important for RBC synthesis: renal system receives a lot of bf → monitors PO2 in blood & secretes erythropoietin when arterial PO2
2
Q
bowman’s capsule
A
location of filtrate formation: liquid w/ same solute/ion composition as blood plasma except proteins
- filtration (not exchange)
- visceral layer = right up against bv (epithelial cells)
- parietal layer = not against bv
- bowman’s space in between visceral & parietal layers
3
Q
proximal convoluted tubule (PCT)
A
- in cortex only
- receives filtrate from renal corpuscle
- unregulated reabsorption (majority of reabsorption (2/3))
4
Q
loop of henle
A
establishes standing osmotic gradient → allows us to reabsorb water
- dissolved [solute] varies w/ depth in medulla
- osmolarity increases towards papilla (300 → 1200 mOsm)
- allows us to use osmosis to pull water out in DCT & CD
- allows us to concentrate urine
- descending limb: unregulated reabsorption of water (towards medulla)
- thin ascending limb: passive reabsorption of NaCl
- thick ascending limb: active reabsorption of NaCl
5
Q
distal convoluted tubule (DCT)
A
- regulated reabsorption (also in collecting duct)
- Na, H2O (follows solutes), Cl (follows Na)
- regulated secretion of K
6
Q
bowman’s capsule epithelium
A
filtration barriers prevent proteins from crossing
- flat epithelium, normal apical membrane, squamous
7
Q
PCT epithelium
A
FX: reabsorption ∴ need lots of SA @ apical membrane
- lots of microvilli
8
Q
loop of henle epithelium
A
- shows lots of heterogeneity
- flat in descending portion
- cuboidal in thick ascending limb
9
Q
DCT epithelium
A
fx: reabsorption &/or secretion
- not as much microvilli
- less filtrate volume than PCT
-
principal cells
- mediate Na reabsorption in response to aldosterone
- mediate K secretion stimulated by aldosterone
- ADH mediates H2O reabsorption (ADH = vasopressin)
- also the cells of the collecting duct
10
Q
renal fxs
A
- filtration: produces filtrate → moves solutes from blood to lumen of nephron (renal corpuscle)
- reabsorption: moves H2O/solutes from filtrate back into blood (PCT, descending limb of loop of henle, DCT, CD)
- secretion: moves stuff from blood to lumen of nephron (DCT & CD)
- excretion: remove urine from body
11
Q
filtration barriers
A
- wall of capillaries ➞ fenestra are small enough to exclude cells (RBC, WBC, plasma proteins)
- basal lamina surrounding capillaries = ⊖ charged layers of proteins repels majority of plasma proteins
- podocytes in visceral layer of bowman’s capsule have foot processes that interdigitate & join via proteins in filtration slits that act as barrier for tiny ⊖ charged proteins
12
Q
mesangial cells
A
cells that lie w/in glomerulus
- secrete extracellular matrix proteins that go into basal lamina
- can also contract → change shape of glomerulus & alter overall SA
- ↑ SA → ↑ filtration rate
- ↓ SA → ↓ filtration rate
13
Q
primary pressure driving filtration across kidney
A
glomerular capillary hydrostatic pressure
14
Q
ultrafiltration pressure
A
force driving fluid out of glomerulus
- ~ 10-15 mmHg
- never ⊖
- PUF = Kf x [(PGC — PBS) — σ(πGC — πBS)
- Kf = SA x Lp
- Lp = hydraulic conductivity = how easy fluid flows through the membrane in response to pressure → influenced by size of pores/fenestra
- σ = reflection coefficient: how easily proteins cross over the bv
- 1 = nothing crosses over
- 0 = crosses easily
- Kf = SA x Lp
- depends on hydrostatic pressures (PGC — PBS)
- PGC = stronger
- favors filtration: pulls water across from blood to bowman’s space
- on avg ≈ 50-55 mmHg (higher than systemic circulation)
- influenced mainly by afferent arteriole
- PBS = pressure due to fluids (filtrate) inside of bowman’s space
- opposes filtration
- filtrate constantly made but immediately drains into PCT
- ~ 15 mmHg
- PGC = stronger
- depends on oncotic/osmotic pressures (𝛑GC — 𝛑BS)
- 𝜋BS ≈ 0 → no proteins in normal filtrate
- favors filtration: pulls water across from blood to bowman’s space
- 𝜋GC due to blood proteins: albumin, fibrinogen, globulins
- opposes filtration
- ~ 25 mmHg (same as systemic circulation)
- 𝜋BS ≈ 0 → no proteins in normal filtrate
15
Q
filtration through the glomerulus
A
glomerulus filters across first 1/3-1/2 of the way through, then balance between forces s.t. there is no net filtration
- as we filter across glomerulus: PGC ↓ & 𝜋GC ↑ so balance out so no additional exchange
16
Q
what is a normal GFR?
A
125 mL of filtrate/min
- ≈ 20% of renal bf is converted into filtrate
17
Q
altering glomerular BP
A
afferent & efferent arterioles vasoconstrict/vasodilate (main controller = SNS)
- vasoconstricting afferent arteriole ➞ ↓ bf into glomerulus ➞ ↓ RBF & ↓ GFR (stronger effects)
- vasoconstricting efferent arteriole ➞ ↓ bf from leaving glomerulus ➞ ↑ GFR initially but ↓ GFR ultimately due to ↓ RBF
18
Q
factors influencing GFR
A
- hydrostatic pressures of glomerulus & bowman’s space
- oncotic/osmotic pressures of glomerulus & bowman’s space
- reflection coefficient: how easily proteins cross bv
- total SA → influenced by mesangial cells
- contract → ↓ SA
- relax → ↑ SA
- hydraulic conductivity (Lp) (not significantly affected by mesangial cell contractions)
19
Q
glomerular autoregulation mechanisms
A
-
myogenic mechanism: VSM automatically contracts or relaxes as afferent arteriolar BP changes
- ↑ afferent arteriole BP → SMC contract
- ↓ afferent arteriole BP → SMC relax
- not mediated by SNS
- local response
-
tubuloglomerular feedback
-
signal factor comes from juxtaglomerular apparatus (JGA)
- adenosine, ATP, or thromboxane released by JGA in response to ↑ PGC & ↑ GFR (↑ in filtrate flow in DCT)
- signal factor binds to SMC on afferent arteriole → vasoconstriction → ↓ GFR
-
signal factor comes from juxtaglomerular apparatus (JGA)
20
Q
where does renal autoregulation occur?
A
at afferent arterioles
21
Q
goal of renal autoregulation
A
- keeps PGC constant → keeps GFR constant
- body sees small changes in MAP → autoregulation ensures bf into glomerulus is constant
- ↑ MAP → vasoconstrict afferent arteriole
- not to regulate MAP/BP
22
Q
sympathetic stimulation of renal bf
A
- sympathetic activity overrides autoregulatory response
- ↓ MAP detected by high-pressure baroreceptors → ↓ PSNS & ↑ SNS
- ↑ SNS causes afferent arteriole to vasoconstrict → ↓ GFR
- ↑ SNS activity to kidney causes ↓ renal bf (RBF)
- ↑ SNS to efferent arteriole ↑ PGC, ↓ RBF, initial rise in GFR then ↓
- SNS input ↓ bf in but vasoconstricting efferent arteriole keeps P in glomerulus high enough to maintain filtration for a little
23
Q
renal transport processes for H2O-soluble reabsorption
A
- facilitated diffusion/membrane transporter-mediated diffusion
- uses transporter in PM
- changes conformation
- can be at either apical or basolateral membrane
- requires [gradient]
- no ATP used
- channels
- only for ions
- ions interact w/ sides/wall of channels
- tiny → only ions can manage to get through
- requires [gradient]
- no ATP
- active mechanisms
- ATP is used directly or indirectly
- Na/K ATPase helps establish Na [gradients] → keeps Na inside cell very low
- secondary active transport: allows us to move items using Na gradient
- indirectly uses ATP
- other items co-transport
- primary active transport directly uses ATP
- ex: Na/K ATPase
- gradient does not matter
- endocytosis
- ATP dependent
- moves very big items
- wrapped by membrane & enveloped
- if it involves a transport protein, we only have a set # of transporters → if overwhelmed w/ substrate transporters are overwhelmed ∴ cannot be reabsorbed → excreted in urine = exceeded transport maximum
24
Q
Na reabsorption in PCT
A
- 66-67% of filtered Na is reabsorbed
- unregulated
- Na/K ATPase in basolateral membrane establishes low intracellular [gradient]
- energy of Na flowing into cell down [gradient] used to drive secondary active transport of other solutes
25
Q
K reabsorption mechanisms in PCT
A
- majority of K
- cannot put K channel in apical membrane → would diffuse into lumen down [K]
- paracellular via solvent drag: water moves via osmosis
- paracellular via charge gradient: ⊖ electrical charge in interstitium attracts K
26
Q
Cl reabsorption mechanisms in PCT
A
- 66-67% of filtered Cl
- paracellular via attraction to Na (in early PCT)
- transcellular via
- HCO3-/Cl anion cotransporter in apical membrane in late PCT
- Cl channel in basolateral membrane
27
Q
glucose reabsorption mechanisms in PCT
A
- 100% of filtered glucose
- requires 2º active transport using sodium-dependent glucose transporters
- SGLT-2: 1:1 Na:glucose → early in PCT
- SGLT-1: 2 Na:1 glucose → late in PCT (lower concentration of glucose later on in PCT = harder to get across)
- using facilitated diffusion: GLUT transporters
- blood removes glucose from ECF which maintains [gradient]
- no energy required
- inslulin-independent
- GLUT-2 → early in PCT
- GLUT-1 → late in PCT
28
Q
hyperglycemia:
A
- resting glucose >200 mg/dL (type I DM)
- reabsorption of glucose is not complete (cannot remove all glucose from filtrate) transporters have hit transport maximum
- glucose stays in filtrate ∴ water is retained in filtrate → PU/PD
29
Q
AA reabsorption mechanisms in PCT
A
- 100% of filtered AA
- at both apical & basolateral membrane, uses:
- 2º active transport
- facilitated diffusion transporter that changes conformation
30
Q
small peptide reabsorption mechanisms in PCT
A
- get digested into single AA at apical membrane
- then transported via AA mechanisms
- albumin = exception → reabsorbed whole via pinocytosis
31
Q
function of the standing osmotic gradient
A
facilitates H2O reabsorption at:
- descending limb of loop of henle
- water permeable (impermeable to solutes)
- aquaporins
- not hormonally regulated
- collecting duct
- hormonally regulated
32
Q
Na reabsorption mechanisms in PCT
A
- transcellular 2º active transport occurs in early PCT
- paracellular via charge gradient towards end of PCT
33
Q
ascending limb of the loop of henle
A
- creates standing osmotic gradient
- filtrate becomes more hypotonic (watery)
- osmolarity in the interstitium of the inner medulla:
- 600 out of 1200 mOsm due to urea
- 300 due to NaCl (300 mOsm Na+ + 300 mOsm Cl- = 600 mOsm)
- osmolarity in the thin ascending limb:
- 600 mOsm NaCl (600 Na + 600 Cl)
- creates a NaCl [gradient]
- in thin ascending limb: Na & Cl flow out passively from loop to interstitium
- in thick ascending limb: Na (+Cl) are actively transported using Na/K ATPase at basolateral membrane
34
Q
reabsorption in the distal convoluted tubule
A
hormonally regulated reabsorption of
- water
- Na (+ Cl + water)
- sweat → dehydration → ↑ osmolarity → reabsorb water only (need to correct osmolarity)
- hemorrhage → blood volume loss → reabsorb water + NaCl (no change in osmolarity so no need to correct it)
35
Q
osmolarity in DCT
A
H2O reabsorption causes filtrate to rise to 300 mOsm
- filtrate at beginning of DCT (coming out of loop of henle) = 100-180 mOsm (majority = Na, some Cl, K)
- in cortex = 300 mOsm
- ∴ pulling water across from filtrate to cortex
- filtrate osmolarity increases as it flows through DCT & CD → allows us to concentrate urine & prevent water loss/dehydration
36
Q
kidney response to dehydration
A
blood plasma osmolarity ↑ due to water loss
- detected by osmoreceptors in hypothalamus
- releases ADH (vasopressin) from posterior pituitary
- also associated w/ thirst drive
- acts on principal cells in DCT & CD
- inserts AQP-2 in apical membrane of principal cells → recruits vesicles holding AQP-2 in membrane fuse w/ apical membrane
- AQP-1 & AQP-3 always present & open in basolateral membrane → not under hormonal regulation
- P w/ hypertension tx w/ diuretics → prevents additional insertion of AQP-2 channels → excrete more water
