renal system

Question 1

nephrons

Answer 1

renal corpuscle made of:

• glomerulus = collection of capillaries hugged by bowman’s capsule that filters plasma into tubular component
• bowman’s capsule (glomerulus capsule) = cup shape around glomerulus formed from tubule

renal tubule made of:

• proximal tubule
• loop of henle
• distal tubule
• collecting duct

1. vascular component:
   
   • afferent arteriole (AA) brings blood to glomerulus
   • glomerulus
   • efferent arteriole (EA) carries blood from glomerulus (only place in body where arteriole comes from capillary)
   • peritubular capillaries from EA supply renal tissue & involved in exchanges w/ tubular lumen
2. tubular component:
   
   • bowman’s capsule collects globular filtrate
   • proximal tubule extends between Bowman’s capsule & loop of Henle where unregulated reabsorption & secretion occurs
   • loop of henle establishes osmotic gradient important in concentrating urine
   • distal tubule & collecting duct: regulated reabsorption of Na+ & H2O and secretion of K+ & H+

• 2 types:
  
  • juxtamedullary nephron found at border btwn cortex & medulla with a long loop of henle inside medulla & are specialized in concentration of urine
  • cortical nephron are the majority with a short loop of henle in medulla

Question 2

renal corpuscle

Answer 2

glomerulus = collection of capillaries inside bowman’s capillaries that filters plasma into tubular component

bowman’s capsule = cup shape around glomerulus formed from tubule

Question 3

renal tubule

Answer 3

• proximal tubule
• loop of henle
• distal tubule
• collecting duct

Question 4

vascular component of a nephron

Answer 4

• afferent arteriole (AA) brings blood to glomerulus
• glomerulus filters plasma into tubular component
  
  • glomerular capillaries = specialized for filtration
    
    • no ATP used so filtration depends on capillary pressure
• efferent arteriole (EA) carries blood from glomerulus
• peritubular capillaries from EA supply renal tissue & involved in exchanges w/ tubular lumen ➔ where reabsorbed solute is returned to blood

Question 5

tubular component of a nephron

Answer 5

• bowman’s capsule collects globular filtrate
• proximal tubule extends between Bowman’s capsule & loop of Henle where unregulated reabsorption & secretion occurs
• loop of henle establishes osmotic gradient important in concentrating urine
• distal tubule & collecting duct: regulated reabsorption of Na+ & H2O and K+ & H+ secretion

Question 6

types of nephrons

Answer 6

juxtamedullary nephron

• found at border btwn cortex & medulla
• long loop of henle inside medulla
• specialized in concentration of urine
• ~15 %

cortical nephron

• majority
• short loop of henle in medulla

Question 7

filtration through renal corpuscle

Answer 7

1. blood flows through AA into glomerulus & leaves through efferent arterioles
2. substances in blood < 8nm are filtered through pores & fenestrations btw/in glomerular capillary endothelial cells
   
   • mol too large to pass = RBC, plasma proteins, large anions, protein-bound minerals & hormones
3. then across basement membrane = acellular gelatinous layer that surrounds endothelial cells
4. then through filtration slits between podocytes in bowman’s capsule that line glomerulus & allow fluid to pass from capillaries to bowman’s capsule
5. transported to lumen of proximal tubule that exits bowman’s capsule

Question 8

juxtaglomerular apparatus

Answer 8

where the glomerulus meets the distal convoluted tubule

• ascending limb passes through fork btwn AA/EA
• distal convoluted tubule starts
• juxtaglomerular/JG cells = enlarged SM cells in AA with secretory vesicles containing renin
  
  • mechanoreceptors that sense BP around AA
  • renin = hormone part of renin-angiotensin system (RAS) that ↑ BP
• macula densa cells = chemoreceptors that respond to changes in NaCl of filtrate ➔ AP & osmotic balance
  
  • release endothelin as vasoconstrictor & bradykinin as vasodilator
• mesangial cells engulf macromolecules stuck in filtration

Question 9

basic renal procceses

Answer 9

1. gomular filtration
2. tubular secretion
3. tubular absorption

amount extcreted = filtered + secreted - reabsorbed

Question 10

glomerular filtration

Answer 10

• pressure from large V of AA being squished into smaller arterioles forces plasma into bowman’s capsule
  
  • filtrate = plasma in bowman’s capsule
• will filter anything < 8nm
• only ~20% of plasma that enters is filtered
  
  • important to keep plasma proteins in plasma to maintain oncotic pressure (proteins in blood cause backwards pressure)
  • RBC or protein in urine (protinuria) = problem with filtration membrane (common for diabetes & hypertension)
• ↑ venous return
• majorty of of plasma reabsorbed ➔ prevents dehydration
• passive: hydrostatic force pushes fluids & solutes
• entire plasma volumes is filtered to kidneys ~65x/d
• more efficient than body capillaries b/c
  
  1. filtration membrane = ↑ SA & very permeable
  2. glomerular pressure is much higher
• forces involved:
  
  1. glomerular capillary BP (PGC) proportional to GFR ➔ favors filtration
  2. fluid pressure in bowman’s space (PBS) ➔ opposes filtration
  3. osmotic force from plasma proteins (πGC) ➔ opposes filtration

net glomerular filtration rate (GFR) = glomerular capillary BP − bowman’s space fluid pressure − plasma protein osmotic force

Question 11

oncotic pressure

Answer 11

backwards pressure created by plasma proteins

Question 12

GFR

Answer 12

glomerular filtration rate = V of filtrate/min

• affected by:
  
  1. V of SA
  2. membrane permeability
  3. net filtration pressure (NFP) (proportional to GFR)
• ↑ BP = ↑ NFP = ↑ GFR
• controlled by vascular changes (BP)
• regulated by
  
  • sympathetic control
    
    • baroreceptor reflex: arterial carotid sinus & aortic arch baroreceptors detect ↑ & ↓ in arterial BP & send signals to cardiovascular control center in brainstem that adjusts levels of sympathetic activity
    • ↑ CO & total peripheral resistance & ↓ GFR to maintain plasma V by constricting AA (conserving blood for FOF)
  • autoregulation
    
    • myogenic mechanism contracts in response to ↑ stretch & relaxes in response to ↓ stretch
    • tubuloglomerular feedback: macula densa cells in juxtaglomerular apparatus detect changes in fluid rate through [NaCl] & release hormones
      
      • endothelin = vasoconstrictor that ↓ GFR
      • bradykinin = vasodilator that ↑ GFR

Question 13

sympathetic regulation of GFR

Answer 13

• ↑ CO & total peripheral resistance ↓ GFR to maintain plasma V by constricting AA (conserving blood for FOF)
• baroreceptor reflex: arterial carotid sinus & aortic arch baroreceptors detect ↑ & ↓ in arterial BP ➔ CVCC in brainstem adjusts levels of symp

Question 14

regulation of GFR

Answer 14

sympathetic

• ↑ CO & total peripheral resistance & ↓ GFR to maintain plasma V by constricting AA (conserving blood for FOF)
• baroreceptor reflex: arterial carotid sinus & aortic arch baroreceptors detect ↑ & ↓ in arterial BP ➔ CVCC in brainstem adjusts levels of symp
• can override autoregulation

autoregulation changes caliber of AA to maintain constant blood flow into glomerular capillaries

• AA vasoconstriction ↓ blood flow = ↓ glomerular capillary BP = ↓ NFP = ↓ GFR
• AA vasodilation = ↑ glomerular capillary BP = ↑ NFR = ↑ GFR
• myogenic mechanism:
  
  • contracts in response to ↑ stretch
  • relaxes in response to ↓ stretch
• tubuloglomerular feedback in juxtaglomerular apparatus
  
  • macula densa cells detect changes in fluid rate through [NaCl] & release hormones
  • endothelin = vasoconstrictor
  • bradykinin = vasodilator

Question 15

control of GFR

Answer 15

vascular changes (BP)

• constrict AA = ↓ blood flowing through glomerular capillary = ↓ pressure = ↓ GFR
• dilate EA = more blood can flow easily out = ↓ glomerular capillary pressure = ↓ GFR
• constrict EA = less blood can exit ➔ backflow ↑ glomerular capillary pressure = ↑ GFR
• dilate AA = more blood enters & must squeeze into smaller glomerular capillary = ↑ GCP = ↑ GFR

Question 16

tubular secretion

Answer 16

• from peritubular capillaries to tubular lumen
• important for:
  
  1. disposing of drugs & drug metabolites
  2. eliminating undesired substances/end products that have been reabsorbed by passive processes (urea & uric acid)
  3. removing excess K
  4. controlling blood pH

Question 17

K secretion & absorption

Answer 17

K reabsorption:

• active reabsorption in in proximal tubule
• constant & unregulated
• ~all filtered K is reabsorbed
  
  • [K] between proximal & distal tubule: ≈ 0

K secretion:

• active secretion is regulated in distal & collecting tubules
  
  • ~all K in urine was secreted
  • ↓ [K] ➔ ↓ secretion in distal portion of nephron
  • ↑ [K] ➔ ↑ secretion in distal portion of nephron
• basolateral pump simultaneously transports Na into lateral space & K into tubular cell then K passively diffuses into tubular lumen
• aldosterone triggered by:
  
  • ↑ [K] in plasma ➔ activates adrenal cortex to secrete aldosterone ➔ cortical collecting ducts ↑ rate of K secretion & Na & H2O reabsorption ➔ ↑ K excretion in urine ∴ less K in plasma
  • renin-angiotensin pathway
• maintaining proper ECF levels of K = extremely important: ↑ [K] ➔ depolarization & ↓ [K] ➔ hyperpolarization
• could lead to over or under excitability of neurons & muscle cells

Question 18

tubular reabsorption general

Answer 18

• filtrate moves from tubular lumen back into peritubular capillaries
• 80% reabsorbed so no dehydration
• active Na reabsorption responsible for passive reabsorption of Cl, H2O, & urea
• begins once filtrate enters tubular lumen (of nephron)
• tubular endothelial cells:
  
  • luminal (apical) & basolateral membranes
  • tight junctions btwn cells
  • interstitial fluid in lateral spaces
• most materials besides water have to pass through cells to enter blood
• transcellular transport requires substances cross 5 barriers
  
  1. luminal membrane of tubular cell
  2. cytosol of tubular cell
  3. basolateral membrane of tubular cell
  4. intersitial fluid
  5. capillary wall

Question 19

active transport for reabsorption

Answer 19

in Na/K pump in basolateral membrane of intertubular lumen

Na = 99.5% reabsorbed through

• proximal tubule (main): role = reabsorbing glucose, AA, H2O, Cl & urea
• loop of henle: role = varying concentrations & volumes produced by kidneys
• distal & collecting tubule: absorption influenced by hormones ➔ important in regulation of ECF volume

Question 20

Na transport during reabsorption

Answer 20

• extracellular [Na] < intracellular: Na diffuses into tubular cell
• intracellular [Na] < interstitial: Na/K ATPase required to transport into interstitial fluid
• interstitial [Na] > peritubular capillary: Na diffuses into blood

Question 21

reabsorption in proximal tubule

Answer 21

• Na important for reabsorbing glucose, AA, H2O, Cl-, & urea
• glucose & AA are reabsorbed against [gradient] from lumen in proximal tubule into tubule cells via Na cotransporter
• Na/K ATPase generates electrochemical gradient that powers the transport of glucose & AA via secondary active transport
  
  • G-coupled protein receptor that activates adenylate cyclase which activates cAMP which activates protein kinase A which phosphorylates proteins for aquaporins in the tubular & basolateral membranes
  • responsible for passive reabsorption of Cl, H2O, & urea
  • Cl- pass between tubular cells
• aquaporins in proximal tubule always open

Question 22

reabsorption in loop of henle

Answer 22

• Na invoved in producing urine of varying concentrations & volumes
• water passively reabsorbed via osmosis
• key to ECF tonicity control ➔ kidneys can excrete urine at diff concentrations

Question 23

reabsorption in distal tubules

Answer 23

• subject to hormonal control
• Na important in the regulation of ECF volume
• ~20% water reabsorbed
• vasopressin regulates aquaporins
• aldosterone ↑ Na reabsorption by inserting Na channels in luminal membrane & Na/K ATPases carriers in basolateral membranes
• atrial natriuretic peptide (ANP) inhibits Na reabsorption

Question 24

Na reabsorption

Answer 24

• Na is most cation in tubular lumen filtrate
• via active transport
• 67% in proximal tubule
• 25% in loop of henle
• 8% in distal tubule ➔ regulates balance
• proximal tubule & loop of henle: always absorbed (body [Na] does not matter)
• in distal & collecting tubules: under hormonal control
  
  • aldosterone stimulates Na reabsorption
  • atrial natriuretic peptide (ANP) inhibits Na reabsorption

Question 25

renin-angiotensin-aldosterone system

Answer 25

1. ↑ Na reabsorption (Cl follows passively)
2. conserve H2O
3. ↑ thirst & fluid consumption
4. ↑ arteriolar vasoconstriction

• net result: ↑ ECV & BP
• angiotensinogen = synthesized in liver & present in plasma
• renin = released into plasma from JG cells in kidneys ➔ activates/converts angiotensinogen ➔ angiotensin I
• angiotensin-converting enzyme (ACE) in lungs converts angiotensin I ➔ angiotensin II
• angiotensin II stimulates
  
  • vasopressin
  • thirst
  • arteriolar vasoconstriction
  • adrenal cortex to release aldosterone
  • ↑ resistance
  • kidney holds on to more water ➔ ↑ SV
• aldosterone increases Na reabsorption in distal & collecting tubules by inserting Na channels in luminal membranes & Na/K ATPase carriers in basolateral membranes

Question 26

hypertension

Answer 26

↑ BP

• sometimes due to abnormal ↑ in renin-angiotensin-aldosterone activity
  
  • tx: diuretics &/or ACE inhibitors
• inactivity

Question 27

atrial natriuretic peptide (ANP)

Answer 27

• hormone that ↑ Na urine output
• specialized cardiac atrial cells produce & store ANP
• released when cells are mechanically stretched from↑ ECF volume
  
  • ↑ ECF = ↑ SV
• inhibits Na reabsorption in distal & collecting tubules
• inhibits
  
  • renin secretion by kidneys
  • aldosterone secretion from adrenal cortex
  • SM of AA ➔ leads to dilation of AA & ↑ GFR
  • SNS ➔ ↓ CO & total peripheral resistance
• net effect: ↓ in ECF volume & BP

Question 28

countercurrent exchange

Answer 28

• maintenance of osmolarity
• fluids in adjacent tubiles flow in opposite directions which ↑ exchange by ↑ SA
• involved in urine concentration
• powered by differences in permeability in the different parts of the loop of henle
  1. produces: hypotonic urine that can be excreted if body’s ECF has too much water
  2. establishes vertical osmotic gradient that collecting ducts can use to concentrate urine w/in body if not enough water

Question 29

ECF tonicity during urine concentration

Answer 29

• H2O > solute = hypotonic (ECF osmolarity < normal)
• H2O < solute = hypertonic (ECF osmolarity > normal)
• vertical osmotic gradient in interstitial fluid of medulla balances ECF osmolarity
  
  • osmolarity in cortex stays constant
  • gradient ↑ inward through medulla
  • junction between inner medulla & renal pelvis = highest osmolarity
  • juxtamedullary nephrons = specialized in concentrating urine
  • any osmolarity > 300 is in medullary

Question 30

filtrate osmolarity throughout the loop of henle

Answer 30

• filtrate = isotonic as it approaches loop of henle
• unregulated osmotic reabsorption of filtered H2O happens immediately after filtrate formation in proximal tubule (secondary to active Na reabsorption)
• descending limb
  
  • highly permeable to water
  • does not secrete Na
  • water leaves ➔ ↑ osmolarity (↑ amount of solutes per V of water & hypertonic)
• ascending limb
  
  • actively transports Na out of tubular lumen into surrounding interstitial fluid
  • is impermeable to water ➔ salt leaves without water following
  • hypotonic going into collecting duct

Question 31

renin

Answer 31

enzyme secreted by juxtaglomerular cells that ↑ BP

• part of renin-angiotensin-aldosterone system (RAS)

Question 32

JG cells

Answer 32

juxtaglomerular cells = mechanoreceptors that sense ↓ BP in AA & secrete renin in response

• surround AA

Question 33

macula densa cells

Answer 33

• tall & closely-packed
• adjacent to JG cells
• chemoreceptors in the lining of the distal tubule of the juxtaglomerular apparatus
• respond to changes in NaCl of filtrate ➔ regulate AP & osmotic balance
• release renin in response to ↓ NaCl in tubular lumen
• secrete nitric oxide = vasodilator that stops ATP & adenosine at the AA

Question 34

mesangial cells

Answer 34

btwn macula densa & AA/EE

• engulf macromolecules stuck in filtration
• structure

Question 35

renin triggered by:

Answer 35

1. ↓BP
2. sympathetics nerves
3. macula densa cells sense ↓Na = filtration pressure in glomerulus is too low

Question 36

vasopressin aka anti-diuretic hormone

Answer 36

• released from posterior pituitary in response to hypertonic ECF (dehydration)
• inserts aquaporins via G coupled protein receptors that ↑ water permeability in distal & collecting tubules ➔ body is reabsorbing water
  
  • vasopressin binds to G coupled protein receptor in basolateral membrane & activates adenylate cyclase ➔ converts ATP to cAMP ➔ activates protein kinase A ➔ protein phosphorylation ➔ aquaporin vesicle fuses with tubular (apical) membrane to create aquaporin channels
• promotes arteriolar vasoconstriction

Question 37

water absorption in distal convoluted tubule & collecting duct

Answer 37

• impermeable to water under stable conditions
• permeable to water when stimulated by vasopressin/anti-diuretic hormone (ADH) in response to dehydration ➔ body can reabsorb more water

Question 38

aldosterone

Answer 38

• ↑ Na reabsorption in distal & collecting tubules by inserting Na channels in luminal membranes & Na/K ATPase carriers in basolateral membranes
• ↑ K excretion
• triggered by ↑ [K] in plasma ➔ activates adrenal cortex to secrete aldosterone ➔ cortical collecting ducts ↑ rate of K secretion & Na & H2O reabsorption ➔ ↑ K excretion in urine ∴ less K in plasma

Question 39

aquaporins

Answer 39

• always open in proximal tubule
• regulated by vasopressin (ADH) in distal & collecting tubules
• ↑ permeability to water in distal & collecting tubules when activated by G-proteun coupled receptors

Question 40

Baroreceptor Control of Vasopressin Secretion

Answer 40

↓ plasma V = ↓ in BP aortic arch & carotid sinus baroreceptors stimulate secretion of vasopressin ➔ ↑ water permeability in collecting ducts so more water can be absorbed & less is excreted

• vasopressin ↑ BP & ECF

Question 41

Osmoreceptor Control of Vasopressin Secretion

Answer 41

too much water ↓ ECF osmolarity (hypotonic) ➔ ↓ hypothalamic osmoreceptors that inhibit vasopressin secretion & makes collecting ducts less permeable to water so less water is reabsorbed & more is excreted

Question 42

micturition

Answer 42

urination

• peristaltic contractions move urine
• as bladder fills pressure against ureters prevents backflow, but urine can still enter
• bladder SM inhibited by sympathetic stimulation & stimulated by paraym to contract
• can occur by reflex action or voluntary control
• 2 sphincters prevent continuous emptying
  
  1. internal urethral sphincter made of SM ≠ voluntary: when bladder relaxes sphincter closes, contracts sphincter opens
  2. external urethral sphincter made of skeletal muscle = voluntary: motor neurons continuously firing (keeping closed) until they are inhibited
• micturition reflex (spinal cord reflex) initiated when stretch receptors in bladder wall stimulate parasympathetic pathway
  
  • parasympathetic stimulation = contraction
  • deliberately tightening external sphincter can prevent contraction & emptying

Question 43

internal urethral sphincter

Answer 43

prevents continuous emptying

• made of SM ≠ voluntary
• when bladder relaxes sphincter closes
• when bladded contracts sphincter opens

Question 44

external urethral sphincter

Answer 44

prevents continuous emptying

• made of skeletal muscle = voluntary
• motor neurons continuously firing (keeping closed) until they are inhibited

Question 45

micturition reflex

Answer 45

spinal cord reflex initiated when stretch receptors in bladder wall stimulate parasympathetic pathway

• parasympathetic stimulation = contraction
• deliberately tightening external sphincter can prevent contraction & emptying

Question 46

cardio & renal hormones

Answer 46

• Alsosterone ↑ Na reabsorption, BP & K+ secretion,
• ANP inhibits aldosterone & renin secretion, ↓ BP & Na+ reabsorption ➞ ↓ECF & BP
• vasopressin (ADH) ↑ BP through a G coupled receptor cascade that adds aquaporins to the luminal membrane of the collecting tubule cells