renal system

Question 1

m

actions of renal system

Answer 1

1. reconditioning of blood
   
   • pH, H2O content/solute [x], [Na], [K] balance
   • regulate MAP
   • limit water excretion when dehydrated
2. get rid of waste
   
   • nitrogenous waste from protein breakdown
   • breakdown of products from drug or toxin
3. important for RBC synthesis: renal system receives a lot of bf → monitors PO2 in blood & secretes erythropoietin when arterial PO2

Question 2

bowman’s capsule

Answer 2

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

Question 3

proximal convoluted tubule (PCT)

Answer 3

• in cortex only
• receives filtrate from renal corpuscle
• unregulated reabsorption (majority of reabsorption (2/3))

Question 4

loop of henle

Answer 4

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

1. descending limb: unregulated reabsorption of water (towards medulla)
2. thin ascending limb: passive reabsorption of NaCl
3. thick ascending limb: active reabsorption of NaCl

Question 5

distal convoluted tubule (DCT)

Answer 5

• regulated reabsorption (also in collecting duct)
• Na, H2O (follows solutes), Cl (follows Na)
• regulated secretion of K

Question 6

bowman’s capsule epithelium

Answer 6

filtration barriers prevent proteins from crossing

• flat epithelium, normal apical membrane, squamous

Question 7

PCT epithelium

Answer 7

FX: reabsorption ∴ need lots of SA @ apical membrane
- lots of microvilli

Question 8

loop of henle epithelium

Answer 8

• shows lots of heterogeneity
• flat in descending portion
• cuboidal in thick ascending limb

Question 9

DCT epithelium

Answer 9

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

Question 10

renal fxs

Answer 10

1. filtration: produces filtrate → moves solutes from blood to lumen of nephron (renal corpuscle)
2. reabsorption: moves H2O/solutes from filtrate back into blood (PCT, descending limb of loop of henle, DCT, CD)
3. secretion: moves stuff from blood to lumen of nephron (DCT & CD)
4. excretion: remove urine from body

Question 11

filtration barriers

Answer 11

1. wall of capillaries ➞ fenestra are small enough to exclude cells (RBC, WBC, plasma proteins)
2. basal lamina surrounding capillaries = ⊖ charged layers of proteins repels majority of plasma proteins
3. 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

Question 12

mesangial cells

Answer 12

cells that lie w/in glomerulus

1. secrete extracellular matrix proteins that go into basal lamina
2. can also contract → change shape of glomerulus & alter overall SA
   
   • ↑ SA → ↑ filtration rate
   • ↓ SA → ↓ filtration rate

Question 13

primary pressure driving filtration across kidney

Answer 13

glomerular capillary hydrostatic pressure

Question 14

ultrafiltration pressure

Answer 14

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
• 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
• 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)

Question 15

filtration through the glomerulus

Answer 15

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

Question 16

what is a normal GFR?

Answer 16

125 mL of filtrate/min

• ≈ 20% of renal bf is converted into filtrate

Question 17

altering glomerular BP

Answer 17

afferent & efferent arterioles vasoconstrict/vasodilate (main controller = SNS)

1. vasoconstricting afferent arteriole ➞ ↓ bf into glomerulus ➞ ↓ RBF & ↓ GFR (stronger effects)
2. vasoconstricting efferent arteriole ➞ ↓ bf from leaving glomerulus ➞ ↑ GFR initially but ↓ GFR ultimately due to ↓ RBF

Question 18

factors influencing GFR

Answer 18

1. hydrostatic pressures of glomerulus & bowman’s space
2. oncotic/osmotic pressures of glomerulus & bowman’s space
3. reflection coefficient: how easily proteins cross bv
4. total SA → influenced by mesangial cells
   
   • contract → ↓ SA
   • relax → ↑ SA
5. hydraulic conductivity (Lp) (not significantly affected by mesangial cell contractions)

Question 19

glomerular autoregulation mechanisms

Answer 19

1. 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
2. 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

Question 20

where does renal autoregulation occur?

Answer 20

at afferent arterioles

Question 21

goal of renal autoregulation

Answer 21

• 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

Question 22

sympathetic stimulation of renal bf

Answer 22

• 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

Question 23

renal transport processes for H2O-soluble reabsorption

Answer 23

1. 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
2. channels
   
   • only for ions
   • ions interact w/ sides/wall of channels
   • tiny → only ions can manage to get through
   • requires [gradient]
   • no ATP
3. 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
4. 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

Question 24

Na reabsorption in PCT

Answer 24

• 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

Question 25

K reabsorption mechanisms in PCT

Answer 25

- majority of K - cannot put K channel in apical membrane → would diffuse into lumen down [K] 1. **paracellular via solvent drag**: water moves via osmosis 2. **paracellular via charge gradient**: ⊖ electrical charge in interstitium attracts K

Question 26

Cl reabsorption mechanisms in PCT

Answer 26

- 66-67% of filtered Cl 1. paracellular via attraction to Na (in early PCT) 2. transcellular via 1. HCO3-/Cl anion cotransporter in apical membrane in late PCT 2. Cl channel in basolateral membrane

Question 27

glucose reabsorption mechanisms in PCT

Answer 27

- 100% of filtered glucose 1. requires 2º active transport using sodium-dependent glucose transporters 1. SGLT-2: 1:1 Na:glucose → early in PCT 2. SGLT-1: 2 Na:1 glucose → late in PCT (lower concentration of glucose later on in PCT = harder to get across) 2. 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

Question 28

hyperglycemia:

Answer 28

- 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

Question 29

AA reabsorption mechanisms in PCT

Answer 29

- 100% of filtered AA - at both apical & basolateral membrane, uses: 1. 2º active transport 2. facilitated diffusion transporter that changes conformation

Question 30

small peptide reabsorption mechanisms in PCT

Answer 30

- get digested into single AA at apical membrane - then transported via AA mechanisms - albumin = exception → reabsorbed whole via pinocytosis

Question 31

function of the standing osmotic gradient

Answer 31

facilitates H2O reabsorption at: 1. descending limb of loop of henle - water permeable (impermeable to solutes) - aquaporins - not hormonally regulated 2. collecting duct - hormonally regulated

Question 32

Na reabsorption mechanisms in PCT

Answer 32

1. transcellular 2º active transport occurs in early PCT 2. paracellular via charge gradient towards end of PCT

Question 33

ascending limb of the loop of henle

Answer 33

1. creates standing osmotic gradient 2. 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**

Question 34

reabsorption in the distal convoluted tubule

Answer 34

hormonally regulated reabsorption of 1. water 2. 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)

Question 35

osmolarity in DCT

Answer 35

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

Question 36

kidney response to dehydration

Answer 36

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