8 Water Homeostasis Flashcards
1
Q
Homeostasis
A
- Ability of the body to maintain a constant internal environment depsite fluctuations in diet, fluid intake, & other environmental conditions
- Maintain a constant volume, stable electrolyte compositoin of body fluids, etc.
- Kidney
- Main organ responsible for homeostasis
- Regulates water balance
2
Q
Normal water content & distribution
- Total body water (TBW)
- TBW distribution
A
- Total body water (TBW)
- 60% of body weight in adult men
- 50% of body weight in adult women due to higher proportion of adipose tissue
- Decreases w/ age
- TBW distribution (70kg adult man: 42L)
- Intracellular fluid (ICF): 2/3 (28L)
- Extracellular fluid (ECF): 1/3 (14L)
- Interstitial fluid (ITF): 3/4 (10.5L)
- Intravascular fluid (IVF): 1/3 (3.5L)
3
Q
Water balance
- Water balance
- Water is added to the body via 3 major sources
- Water is lost from the body via 4 major sources
A
- Water balance
- Water input = water output
- Water is added to the body via 3 major sources
- Ingested liquids
- Ex. pure water
- Ingested solid food
- Ex. peanut butter (low content) & watermelon (high content)
- Synthesized in the body from oxidized carbohydrates
- Ex. metabolic water
- Ingested liquids
- Water is lost from the body via 4 major sources
- Urine (most important)
- Low urine volume (ex. dehydration, 0.5 L/day): need to retain water
- High urine volume (ex. drink a lot of water, 18 L/day): need to excrete water
- Sweat
- Varies w/ physical activity & environmental temperature
- Feces
- Normally: small amt lost
- Can be increased to several liters w/ severe diarrhea
- Insensible losses
- Evaporation in the respiratory tract & skin
- Neither perceived nor directly measured
- Urine (most important)
4
Q
Osmolarity, osmolality, & tonicity
- Osmole
- Osmolarity
- Osmolality
- Tonicity
- Both osmolality & tonicity
A
- Osmole
- # of moles of a compound that contribute to osmotic pressure
- Osmolarity
- # osmoles (mmol) / volume of solution (L)
- Difficult to determine b/c volume changes w/ temperature & pressure
- Osmolality
- # osmoles (mmol) / weight of water (kg)
- Easier to determine b/c amt of solvent remains constant despite changes in temperature & pressure
- Tonicity
- # particles in sol’n that can’t cross a semi-permeable membrane
- # particles that exert an osmotic effect driving water out of cells
- Both osmolality & tonicity
- Refer to the # of particles in 2 soln’s separated by a semi-permeable membrane
5
Q
Plasma tonicity
- Main osmoles in plasma
- Plasma osmolality (Posm) calculation
- Normal plasma osmolality
- Plasma tonicity (Pton) calculation
- Normal plasma tonicity
A
- Main osmoles in plasma
- Na
- Glucose
- Urea (BUN)
- Plasma osmolality (Posm) calculation
- Posm (mmol/kg) = 2*[Na] (mEq/L) + serum glucose/18 (mg/dl) + BUN/2.8 (mg/dl)
- Double Na for negative ions associated w/ na that contribute to plasma osmolality
- Divide serum glucose by 18 & BUN by 2.8 for units
- Normal plasma osmolality
- 280-295 mOsm/kg
- Plasma tonicity (Pton) calculation
- Pton (mmol/L) = 2*[Na] (mEq/L) + serum glucose/18 (mg/dl)
- Exclude BUN b/c urea freely crosses cell membranes & doesn’t contribute to plasma tonicity
- Normal plasma tonicity
- 270-285 mOsm/kg
6
Q
Plasma tonicity
- Main determinant of plasma tonicity
- Plasma tonicity vs. TBW
- Plasma tonicity vs. water shifts among dif body fluid compartments
A
- Main determinant of plasma tonicity
- Na conc
- Decrease Na conc –> plasma becomes hypotonic
- Increase Na conc –> plasma becomes hypertonic
- Plasma tonicity vs. TBW
- Decrease TBW –> water deficit concentrates osmotic particles in plasma –> increase plasma tonicity –> hypertonic plasma
- Increase TBW –> excess water dilute osmotic particles in plasma –> decrease plasma tonicity –> hypotonic plasma
- Plasma tonicity vs. water shifts among dif body fluid compartments
- Hypotonic plasma –> water flows from ECF to ICF –> cell swells
- Hypertonic plasma –> water flows from ICF to ECF –> cell shrinks
- Isotonic plasma –> no net water shift –> cell volume remains unchanged
7
Q
Osmoreceptors
- Osmoreceptors
- Central osmoreceptors
- Function
- Location
- Main osmoreceptor
- Special group of structures
- Peripheral osmoreceptors
- Function
- Location
*
A
- Osmoreceptors
- Sense changes in plasma tonicity b/c we don’t have water sensors
- Senses water imbalance since many clinical disorders can arise as a consequence of water excess or deficit
- Activate homeostatic response to small changes in TBW
- Sense changes in plasma tonicity b/c we don’t have water sensors
- Central osmoreceptors
- Sense changes in plasma tonicity
- Located in the CNS
- Organum vasculosum of lamina terminalis (OVLT)
- Main CNS osmoreceptor
- Part of circumventricular organs
- Circumventricular organs
- Lack BBB & are in direct contact w/ the ECF & plasma
- Readily sense minimal changes in its composition (e.g. changes in plasma tonicity)
- Peripheral osmoreceptors
- Anticipate osmotic loads
- Sense osmotic loads in food & trigger a response before actual changes in plasma tonicity occur
- Located in peripheral structures
- Pharynx
- Esophagus
- GI tract
- Portal vein
- Splanchnic mesentery
- Anticipate osmotic loads
8
Q
Homeostatic response to TBW deficit
A
- Decrease TBW
- Water is continuously lost in sweat, stool, etc.
- If not replaced by drinking water, plasma tonicity will increase
- Osmoreceptors in the OVLT sense increased plasma tonicity
- Stimulates thirst
- Drives drinking behavior
- Increases water intake
- Stimulates ADH release by the posterior pituitary
- ADH –> kidneys
- Increases water permeability of principal cells in the collecting duct
- Increased water reabsorption –> decreased urine volume & increased urine osmolality –> concentrated urine
- Stimulates thirst
- Increased thirst + increased water reabsorption in the kidney –> increased TBW back to normal –> decreased plasma tonicity back to normal
9
Q
Homeostatic response to TBW excess
A
- Increase TBW
- Drink water –> water is distributed throughout the body
- Amt of solute doesn’t change
- Excess water –> dilute solutes –> decrease plasma tonicity
- Osmoreceptors in the OVLT sense decreased plasma tonicity
- Inhibits thirst
- Suppresses water drinking
- Decreases water intake
- Inhibits ADH release by the posterior pituitary
- Decreased ADH delivery to kidneys
- Decreased water permeability of principal cells in the collecting duct
- Decreased water reabsorption –> increased urine volume & decreased urine osmolality –> diluted urine
- Inhibits thirst
- Decreased thirst + decreaed water reabsorption in the kidney –> decreased TBW back to normal –> increased plasma tonicity back to normal
10
Q
Antidiuretic hormone (ADH) / vasopressin
- ADH synthesis
- ADH storage
- ADH release vs. plasma tonicity
- ADH release vs. effective arterial blood volume (EABV)
- EABV
- Baroreceptors
- Increase EABV –>
- Decrease EABV –>
- Set point for ADH release
A
- ADH synthesis
- Supraoptic & paraventricular nuclei in the hypothalamus
- ADH storage
- ADH is transported down axons from the hypothalamus to the posterior hypophysis where its stored in nerve terminals
- ADH release vs. plasma tonicity
- Increased plasma tonicity –> ADH release into the circulation
- Plasma osmolality threshold: 280-285 mOsm/kg
- Decreased plasma tonicity –> inhibits ADH release
- Increased plasma tonicity –> ADH release into the circulation
- ADH release vs. effective arterial blood volume (EABV)
- EABV
- Arterial blood volume that effectively perfuses organs
- Can’t be directly measured
- Inferred from other physiological measurements (renin, aldo, urine Na, etc.)
- Baroreceptors
- Stretch-sensitive receptors in carotid & aortic sinus sense changes in EABV
- Potent stimulus for ADH release even when plasma tonicity is decreased
- Increase EABV –> neural impulses inhibit ADH release
- Decrease EABV –> decrease discharge rate of stretch receptors –> ADH release
- EABV
- Set point for ADH release
- As blood volume decreases (ex. hemorrhage), rates of ADH secretion increase
- Set poitn for ADH release shifts to a lower plasma osmolality
11
Q
ADH effect on distant organs
- ADH effect on aquaporins
- Main determinant of water flow through principal cells
- ADH effect on Na/K/2Cl
- ADH effect on urea
- ADH effect on blood vessels
A
- ADH effect on aquaporins
- ADH binds to V2 receptors in the basolateral membrane of princiapl cells in the CD
- Receptor is coupled to adenylylcyclase through G stimulatory protein (Gs)
- Bindings increases intracellular cAMP –> activates protein kinase A (PKA) –> increases # of aquaporin 2 water (AQP2) channels in the apical membrane of principal cells
- Allows water to move from tubules into principal cells
- Water exits princiapl cells via AQP3 & AQP4 channels on the basolateral membrane
- Not dependent on ADH
- ADH binds to V2 receptors in the basolateral membrane of princiapl cells in the CD
- Main determinant of water flow through principal cells
- Hyeprtonic medullary interstitium
- Water: tubules –> principal cells –> medullary interstitium by osmosis
- Driven by high tonicity of the renal medulla
- ADH effect on Na/K/2Cl
- ADH increases Na/K/2Cl activity in the TkAL
- Increases NaCl transport into the medullary interstitium
- Contributes to medullayr ypertonicity
- ADH effect on urea
- ADH increases expression of urea transporters (UTA1) –> increases permeability of the inner medullary CD to urea
- ADH increases transport of urea into medullary interstitium & contribues to medullary hyeprtonicity
- ADH effect on blood vessels
- ADH binds to V1 receptors in smooth muscl ecells –> vasoconstriction
12
Q
Thirst
- Originates in…
- Triggered by…
- Thirst vs. age
A
- Originates in thirst centers int eh brain
- Triggered by an increase in plasma tonicity of as little as 2-3%
- Plasma osmolality threshold = 295 mOsm/kg
- Ability to feel thirsty decrease w/ age
13
Q
Renal water handling: absence vs. presence of ADH
A
14
Q
Renal water handling: proximal tubule
- GFR
- PT water reabsorption
- PT permeability to water
- Accumulation of fluid & solutes within the renal interstitium
- Osmolality of reabsorbed fluid
A
- GFR = 125 ml plasma / min (93% = water)
- PT reabsorbes 65-80% of filtered water
- PT reabsorbs Na & other solutes from tubular fluid into lateral intercellular spaces
- Decreases the osmolality of tubular fluid
- Increases the osmolality of hte lateral intercellular space
- PT is highly permeable to water
- Expresses AQP1 channels in the apical & basolateral membranes
- Water is reabsorbed transcellularly by osmosis due to higher osmolality of fluid in the lateral intercellular space 9renal interstitium) than tubular fluid
- Some water is also reabsorbed paracellularly
- Accumulation of fluid & solutes within the renal interstitium
- Increases hydrostatic pressure in this compartment
- Forces fluid & solutes into peritubular capillaries
- Osmolality of reabsorbed fluid
- Reabsorbed fluid is iso-osmotic to plasma
15
Q
Renal water handling: proximal tubule
- Net water reabsorption force in the renal interstitium
- Pc
- During hypovolemia
- πc
A
- Net water reabsorption force in the renal interstitium
- Filtration = Kf [(Pc - Pi) - (πc - πi)]
- Kf = filtration coefficient
- Pc = peritubular capillary hydrostatic pressure
- Pi = renal interstitium hydrostatic pressure
- πc = peritubular capillary oncotic pressure
- πi = renal itnerstitium oncotic pressure
- Pc
- Determined by arteiral BP & vasuclar resistance in AffAs & EffAs
- Increase arterial BP –> increase Pc –> decrease water reabsorption in PT
- Increase vascular resistance in AffAs & EffAs –> decrease Pc –> increase water reabsorption in PT
- During hypovolemia
- Decrease arterial BP –> decrease Pc
- Release AII –> AffA & EffA constriction –> decrease Pc
- Net effect: increase water reabsorption in Pt
- πc
- Determiend by serum albumin conc & FF
- Increase serum albumin –> increase πc –> increase water reabsorption in PT
- Increase FF –> more plasma filtered through glomerulus –> more concentrated albumin –> increase water reabsorption in PT
16
Q
Normal hydrostatic & oncotic forces that determine water reabsorption by peritubular capillaries
- Normal hydrostatic pressure in peritubular capillaries vs. renal interstitium
- Normal oncotic pressure in peritubular capillaries vs. renal interstitium
- Net result
A
- Normal hydrostatic pressure in peritubular capillaries vs. renal interstitium
- Peritubular capillaries: 13 mmHg
- Renal interstitium: 6 mmHg
- Net result: hydrostatic pressure gradient of 7 mmHg opposes water reabsorption
- Normal oncotic pressure in peritubular capillaries vs. renal interstitium
- Peritubular capillaries: 32 mmHg
- Renal interstitium: 15 mmHg
- Net result: oncotic pressure gradient of 17 mmHg favors water reabsorption
- Net result
- Net oncotic forces that favor reabsorption (17 mmHg) - net hydrostatic forces that oppose water reabsorption (7 mmHg) = net water reabsorption (10 mmHg)
17
Q
Renal water handling: water permeability
- LOH
- TDL
- TnAL
- TkAL
- DCT
- CD
A
- LOH
- TDL: has AQP1 & reabsorbs 15% of filtered water
- NaCl transporter: absent
- NaCl permeability: no
- Osmolality: increase
- TnAL: lacks AQP1 & is impermeable to water
- NaCl transporter: Cl channel, Na channel?
- NaCl permeability: yes
- Osmolality: decrease
- TkAL: lacks AQP1 & is impermeable to water
- NaCl transporter: Na/K/2Cl co-transporter
- NaCl permeability: yes
- Osomlality: decrease
- TDL: has AQP1 & reabsorbs 15% of filtered water
- DCT
- Lacks AQP1 & is impermeable to water
- CD
- Segments: cortical, outer medullayr, & inner medullary CD
- Absence of ADH: impermeable to water
- Presence of ADH: permeable to water
19
Q
Urea recycling
- Urea recyling contributes to…
- Urea contributes to…
- Plasma urea filration & reabsorption under normal GFR
- Urea reabsorption in the PT
- Urea conc in the TDL
- Urea conc in the TnAL
- Urea conc in the TkAL & DCT
- Urea conc int he CCD, OMCD, & IMCD in the presence of ADH
- Cycle continuation
A
- Urea recyling contributes to…
- Generation of the corticopapillary osmotic gradient
- Urea contributes to…
- 50% of the medullary interstitium osmolality when hte kidney forms max concentrated urine in the presence of ADH
- Esp true in the IMCD where osmolality reaches 1200 mOsm/L
- Plasma urea filration & reabsorption under normal GFR
- All plasma urea is filtered
- Urea reabsorption in the PT
- 50% is reabsorbed
- Urea conc in the TDL
- Conc increases due to water reabsorption & urea secretion into the TDL via UT-A2 urea transporters
- Urea conc in the TnAL
- Conc increases due to urea secretion into the TnAL
- Urea conc in the TkAL & DCT
- Unchanged b/c tubules are impermeable to water
- Urea conc int he CCD, OMCD, & IMCD in the presence of ADH
- CCD & OMCD are permeable to water but impermeable to urea
- Urea conc increases due to water reabsorption
- IMCD is permeable to urea
- High urea conc when fluid reaches IMCD
- Urea is tranpsored out via UT-A1 urea transporters
- Favors urea diffusion into the medullayr interstitium
- CCD & OMCD are permeable to water but impermeable to urea
- Cycle continuation
- A moderate share of the urea that moves into the interstitium eventually diffuses into the DTL and ATL,
20
Q
Countercurrent exchanger
- Purpose
- Histological structure responsible for the countercurrent exchanger
- Blood flow
- Energy: active vs. passive process
- Osmolality
- Blood entering TDL
- As blood descends…
- Bend of vasa recta
- As blood ascends…
A
- Purpose
- Maintain the medullayr gradient by mitigating washout
- Histological structure responsible for the countercurrent exchanger
- Vasa recta: capillaries that serve the medulla
- Branch off EffA of juxtamedullary nephrons
- Follow the LOH
- Blood flow
- RBF = 20% * CO
- Medulla receives 5% of total RBF
- Blood flow through the vasa recta is slow & has a low oxygen conc
- Energy: active vs. passive process
- Purely passive so no energy is spent
- Contrasts countercurrent multiplication: energy is spent
- Osmolality
- Blood entering TDL: 300 mOsm/L
- As blood descends, it’s exposed to interstitial fluid w/ increased osmolality
- Capillaries are freely permeable to water & solutes, so small solutes (ex. NaCl, urea) diffuse from the medulla –> descending capillary limb
- Allows blood to equilibrate osmotically
- Bend of vasa recta: osmolality = interstitial fluid = 1200 mOsm/L
- Hairpin config doesn’t allow medullary gradient to be washed out by solute leaving & water coming
- As blood ascends the TnAL & TkAL, blood is exposed to interstitial fluid w/ decreasing osmolality
- Solutes diffuse out into the interstitium & water diffuses into the TALs
- Blood in the ascending limb equilibrates w/ surrounding interstitial fluid
21
Q
Renal water handling during TBW deficit
- Main job of kidneys during TBW deficit
- PT
- TDL
- TnAL
- TkAL
- DCT
- CD
A
- Main job of kidneys during TBW deficit
- Produce concentrated urine to maximize water reabsorption & preserve water balance
- PT
- Osmolality of glomerular filtrate = blood (300 mOsm/L0
- Osmolarity remains at 300 mOsm/L b/c water is reabsorbed in proportion to solutes (iso-osmotic)
- TBW deficit + total body Na deficit (hypovolemia): increase % of water reabsorbed (90%)
- Osmolality of glomerular filtrate = blood (300 mOsm/L0
- TDL
- Permeable to water, impermeable to NaCl
- Water is reabsorbed following the osmotic gradient of th ehypertonic medulla
- As water –> medulla, tubular fluid osmolality increases & equilibrates w/ the osmolality of the medulla at the hairpin of the LOH (1200 mOsm/L)
- TnAL
- Impermeable to water so no osmotic equilibrium
- Permeable to NaCl: passive process
- NaCl conc in the medullayr interstitium has been diluted by water from the TDL
- NaCl conc in TnAL > medulla
- NaCl moves passivley down conc gradient –> decrease TnAL osmolality
- TkAL (aka medullayr diluting segment, aka concentrating segment)
- Impermeable to water
- Permeable to NaCl: active process
- NaCl is reabsorbed down its conc gradient into the medulla via the N/K/2Cl co-transporter
- Gradient is produced by Na/K ATPase actively pumping Na out of the cell
- ADh stimulates Na/K/2CL to contribute to the increasing gradient
- osmolality of fluid leaving this segment = 100 mOsm/L
- NaCl is reabsorbed down its conc gradient into the medulla via the N/K/2Cl co-transporter
- DCT (aka cortical diluting segment)
- Impermeable to water
- Permeable to NaCl
- Osmolality of tubular fluid decreases to 80 mOsm/L
- CD
- Permeable to water only in the presence of ADH
- As tubular fluids flow down, it’s exposed to interstitial fluid w/ increasingly higher osmolality (corticopapillary osmotic gradient)
- Water will be reabsorbed until tubular fluid equilibrates osmotically w/ surrounding medullary interstitial fluid
- Final urine osmolality at the tip of the papilla = 1200 mOsm/L
- ADH also increases urea permeability in the IMCD to facilitate urea transport
- Urea contributes to the medullayr gradient in the inner medulla
- Permeable to water only in the presence of ADH
22
Q
Renal water handling during TBW excess
- Main job of kidneys during TBW excess
- PT
- TDL
- TnAL
- TkAL
- DCT
- CD
A
- Main job of kidneys during TBW deficit
- Produce diluted urine to maximize water excretion & preserve water balance
- PT
- Osmolality of glomerular filtrate = blood (300 mOsm/L0
- Osmolarity remains at 300 mOsm/L b/c water is reabsorbed in proportion to solutes (iso-osmotic)
- TBW deficit + total body Na deficit (hypovolemia): decrease % of water reabsorbed (65%)
- Osmolality of glomerular filtrate = blood (300 mOsm/L0
- TDL
- Permeable to water, impermeable to NaCl
- Water is reabsorbed following the osmotic gradient of the hypertonic medulla
- As water –> medulla, tubular fluid osmolality increases & equilibrates w/ the osmolality of the medulla at the hairpin of the LOH (600 mOsm/L)
- Lower than in TBW deficit
- TnAL
- Impermeable to water so no osmotic equilibrium
- Permeable to NaCl: passive process
- NaCl conc in the medullary interstitium has been diluted by water from the TDL
- NaCl conc in TnAL > medulla
- NaCl moves passivley down conc gradient –> decrease TnAL osmolality
- TkAL (aka medullary diluting segment, aka concentrating segment)
- Impermeable to water
- Permeable to NaCl: active process
- NaCl is reabsorbed down its conc gradient into the medulla via the N/K/2Cl co-transporter
- Gradient is produced by Na/K ATPase actively pumping Na out of the cell
- ADh stimulates Na/K/2CL to contribute to the increasing gradient
- Osmolality of fluid leaving this segment = 120 mOsm/L
- Higher than in TBW deficit b/c dilution step is diminished w/o ADH due to lack of N/K/2Cl stimulation
- NaCl is reabsorbed down its conc gradient into the medulla via the N/K/2Cl co-transporter
- DCT (aka cortical diluting segment)
- Impermeable to water
- Permeable to NaCl
- Osmolality of tubular fluid decreases to 100 mOsm/L
- Higher than in TBW deficit
- CD
- Imermeable to water in the absence of ADH
- As tubular fluids flow down, no osmotic equilibration is possible
- NaCl continues to get reabsorbed
- Urine osmolality decreases to 50 mOsm/L
- ADH can’t increase urea permeability in the IMCD
- Urea doesn’t contribute to the medullary gradient
- Final urine osmolality at the tip of the papilla = 600 mOsm/L
- Lower than in TBW deficit
- Imermeable to water in the absence of ADH
