Regulation of Body Fluid and Water Balance Flashcards
What must occur for urine to be concentrated as it passes through the collecting duct?
Water reabsorption from tubular fluid
Where is tubule is osmolarity the highest (most concentrated/ saltiest) ?
Inner Medulla ( Loop of Henle and Collecting Duct)
Basic Concept of countercurrent multiplier in Loop of Henle
- movement
- regulation
produce HYPERtonic medulla by pooling NaCl in interstitium
- favors subsequent movement of water out of the collecting duct
- regulated by ADH
How much of difference is between tubular fluid and interstitium along thick, ascending limb?
200 mOsmol/ kg H2O
Maximum osmolarity of interstitium at tip of loop
1200-1400 mOsmol/ Kg H2O
What is the characteristic/value of fluid leaving Loop of Henle?
- HYPOtonic
- 100 mOsmol/ kg H2O
First Step of Counter Current Multiplier
- Tubular Fluid entering descending limb from proximal tubule is isotonic
- Medullary interstitial fluid concentration AND body fluids are uniformly 300 mOsm/L
Second Step of Counter Current Multiplier
- Active salt pump in ascending LOH transports NaCl out of lumen until surrounding interstitial fluid is 200 mOsm/L more concentrated than tubular fluid in this limb
- When ascending LOH starts actively extruding NaCl, medullary interstiial fluid becomes HYPERtonic
- no water flow in ascending LoH bc impermeable to H2O
- Net diffusion of H2O occur from descending limb into interstitial fluid
Third Step of Counter Current Multiplier
- Net diffusion of H2O out of Descending LoH (highly permeable to H2O) into more concentrated interstitial fluid
- passive movement of H2O out of descending LoH continues until osmolarities in descending and interstitial fluid become equilibrated
- Tubular fluid entering ascending LoH immediately becomes more concentrated as it loses H2O
- At equilibrium, osmolarity of ascending limb fluid is 200 mOsm/L
- osmolarities of interstitial fluid and descending limb fluid are equal at 400 mOsm/L
Fourth Step of Counter Current Multiplier
- a mass of 200 mOsm/L fluid exits top of ascending limb into distal tubule -> a new mass of isotonic fluid at 300 mOsm/L enters the top of the descending limb from proximal tubule
- At bottom of the loop, a comparable mass of 400 mOsm/L fluid from descending limb moves forward around tip into ascending limb, placing it opposite a 400 mOsm/L region in descending limb
- additional ions are pumped into interstitium, with water remaining in tubular fluid, until a 200 mOsm/L osmotic gradient
Fifth Step of Counter Current Multiplier
- additional flow of fluid into LoH from proximal tubule -> causes HYPERosmotic fluid previously formed in descending lumb to flow into ascending limb
- ascending limb, additional ions are pumped into interstitium (water stays in tubular fluid) until 200 mOsm/L osmotic gradient is established, with interstitial fluid osmolarity rising to 500 mOsm/L
Seventh Step of Counter Current Multiplier
- Step 4-6 repeated over
- net effect of fluid in descending LoH more hypertonic until max concentration (1200-1400 mOsm/L) at bottom of loop
Where does interstitial fluid achieve equilibrium?
What is final concentration gradient range in counter current multiplier?
- in descending limb
- 300-1200 mOsm/L
After counter current multiplier is complete, what is concentration of tubular fluid? where? how?
- decreases
- in ascending limb as
- NaCl is pumped out but H2O is unable to follow
After counter current multiplier is complete, what is tonicity of tubular fluid?
- hypotonic before leaving the ascending limb to enter distal tubule
(100 mOsm/L)- 1/3 the normal concentration of body fluids
Vasa Recta
- function
- signficance
- supply blood to medulla
- highly permeable to solute and water
- remove water and solute that is continuously added to medullary interstitium by different nephron segments
- maintains medullary interstitial gradient (flow DEPENDENT)
- Increase vasa recta blood flow => dissipates the medullary gradient (medullary washout)
- INCREASE blood flow= decrease salt and solute transport by nephron segments in medulla -> reduce ability to concentrate urine
Urea Recycling in thick limb of LoH
little urea reabsorption
impermeable to urea
Urea Recycling in distal tubule and cortical collecting tubule
little urea reabsorption
impermeable to urea
forms concentrated urine
secretes high levels of ADH
increase reabsorption of water
increase tubular fluid concentration of urea
Urea Recycling in inner medullary collecting tubule
Urea transporters:
- UT-A1
- UT- A3
- cause urea to diffuse into medullary interstitium
Mechanism of urea recycling
some of urea that moves into medullary interstitium diffuses into thin LoH -> passes upward through ascending LoH, distal tubule, cortical collecting tubule-> down into medullary collecting duct again
Purpose of Countercurrent exchange
establish salt gradient in medulla of kidney
What created the medullary interstitial osmotic gradient? (2)
1) aquaporins and absence of tight junctions within thin limb provides a pathway for water without sodium from lumen of descending limb to interstitium of renal medulla
2) anatomic arrangement of LoH and collecting ducts contribute to “countercurrent multiplication”
- increases in osmolality as loop dips deeper into medulla
=> due to interstitial gradient, water flows out of descending limb (concentrate remaining tubular filtrate)
=> Na/K ATPase continue to extrude sodium ions and build concentration gradient
Anti-diuretic Hormone
- location
- mechanism of secretion
- aka arginine vasopressin
- Two types of large neurons that synthesize ADH in supraoptic and paraventricular nuclei of hypothalamus
stimulated by increase osmolarity (rapid) -> nerve impulses pass down these nerve ending -> change membrane permeability-> increase calcium entry -> secretory vesicles containing ADH released in nerve ending in posterior pituitary
=> plasma ADH levels increase fast-> rapid changes in renal excretion of water (more water reabsorption)
Mechanism pathway for ADH
- what will inhibit pathway
plasma osmolality-> osmoreceptor activation-> AVP secretion from supraoptic and paraventricular nuclei-> plasma vasopressin-> vasopressin receptor activation -> inhibits water excretion, promotes water reabsorption
- drinking water and water reabsorption will inhibit pathway
How sensitive are osmoreceptors? what do they activate?
- sensitive to small changes in plasma osmolality (1-2%)
- activate ADH pathway and thirst stimulation
Which one is activated first? thirst pathway or ADH pathway?
ADH pathway before thirst pathway
What happens when there is an increase in plasma concentration? How is this significant in daily life?
concentrate urine and later thirst develops
adequate timing allows us to go about our daily activity, conserving water through concentrating urine rather than constantly being thirsty
Two Cell Types found in late distal tubule and collecting duct
Principal cells
Intercalated Cell
Principal Cells
- function
- mechanism (4)
reabsorbs Na+, Cl-, and H2O
secrete K
1) Na reabsorption
- Na actively transported using Na/K ATPase across basolateral membrane
2) H2O absorption occurs in response to effect of ADH on principal cells
3) ADH increase H2O permeability by directing the insertion of H2O via aquaporin-2 channels in luminal membrane
- no ADH= principal cells impermeable to water
4) K secretion
- K uptake across basolateral membrane occurs via Na/K ATPase -> diffusion down its electrochemical gradient across apical membrane into tubular fluid
Intercalated cells
- function
- mechanism
- significance
reabsorbs K
secretes H
Aldosterone increases H+ secretion by intercalated cells by stimulating H+ Atpase
- important for acid-base balance
Aldosterone
- function
- mechanism steps (3)
- effects with K and Na
- salt retaining hormone
- released from adrenal cortex
- responds to angiotensin II or increase plasma K
1) Aldosterone=> increase ENaC channels => increase sodium reabsorption
2) Sodium tranported into interstitial fluid in exhange for K+
3) Potassium exits cells=> increase urinary excretion and excess K elimination
increase K= increase aldosterone
decrease K= decrease aldosterone
decrease plasma Na= increase aldosterone ( via RAAS)
* increase aldosterone= increase NA reabsorption and K secretion
Aquaporin 2 Channel
- location
- function
- what happens when less ADH
- regulates what?
apical membrane of principal cells
- water osmotically pulled from collecting duct into interstitial space=> more concentrated urine
- Less ADH= less aquaporin channels inserterd= less water is recovered => dilute urine
- regulates blood osmolarity, blood pressure, and osmolality of urine
Cortical collecting duct vs medullary collecting duct in relation to water
Cortical CD always permeable to water
Medullary CD depends on ADH secretion (hypothalmic osmoreceptors to plasma osmolality and volume)
What happens when ADH is secreted?
where does it travel to?
what does it stimulate?
-effects
travels to kidney
stimulates insertion of aquaporins into tubular membrane
allow water to move by osmosis into hypertonic interstitium
What causes stimulation ADH secretion? cessation of ADH secretion?
increase plasma osmolality = stimulate ADH secretion (collecting tubule permeable to water)
- water goes into hypertonic interstitium via osmosis
- less water excreted=> decreased osmolality
decrease plasma osmolality= decrease ADH secretion (collecting tubule impermeable to water)
- excess water excreted into urine=> increase plasma osmolarity
What is simple rules of ADH?
- normal plasma osmolality value
- value for dehydrates
Overhydrated=> ADH inhibited
Dehydrated=> ADH released
normal= 275-295 mOsm/kg
dehydrated > 300 mOsm/kg
Diabetes Insipidus
2 types
1) Failure to produce ADH
- Central Neurogenic Diabetes Insipidus
2) Inability of Kidneys to respond to ADH
- Nephrogenic Diabetes Insipidus
Central Neurogenic Diabetes Insipidus
- causes
- mechanism
- treatment
- can’t produce/release ADH in posterior pituitary
- caused by head injury/infection, congenital, or unconsciousness ( severe dehydration can rapidly occur)
- no ADH= distal tubular segments cannot reabsorb water
- > diluted urine
Treatment:
- water restriction
- desmopressin (acts selectively on V2 receptors -> increase water permeability in late distal and collecting tubules-> restore urine output to normal
Nephrogenic Diabetes Insipidus
- causes
- effects
ADH present but renal tubular segments cannot respond appropriately
Causes
- failure of countercurrent mechanism that would normally lead to a hyperosmotic renal medullary interstitium
- failure of distal and collecting tubules and CD to respond to ADH
- drugs ( lithium/ tetracyclines) impair ability of distal nephron to respond to ADH
Effects
- diluted urine
- body= dehydration
- compromised urine-concentrating ability
Central vs. Nephrogenic diabetes
** distinguished by administration of desmopressin
injection of desmopressin => 2 hours later=> decrease of urine volume and increase of urine osmolarity
- if this effect doesn’t show up => will indicate nephrogenic diabetes insipidus
** low sodium diet and thiazide diuretic will help hypernatremia of nephrogenic DI
SIADH
Such Immense Anti Diuretic Hormone Secretion
- excessive release of ADH => excessive water retention ( Increase ECF)
- > decreased plasma osmolality, hyponatremia, diminished aldosterone secretion, increased GFR
- > increased Na excretion
ECF is hypotonic to cell
Cell is hypertonic to ECF
- fluid shift to cells => cells swell ( water intoxication)
Diabetes Insipidus vs SIADH
DI
- high urinary output
- low ADH levels
- hypernatremia
- dehydrated
- lose too much fluid
- Excessive thirst
SIADH
- low urinary output
- high levels of ADH
- hyponatremia
- overhydrate
- retain too much fluid
- Excessive Thirst
What part of the nephron depends on Dilution? Why?
thick ascending limb of loop of Henle
- solutes (Na, Cl, K) are reabsorbed here without water
- impermeable to water
Water Excess
- large volume of dilute urine
- no ADH is secreted
- urine flow rate is increased
Water Deficit
- small volume of concentrated urine
- ADH secretion increased
- H2O reabsorption
Hyponatremia
- causes
- excess of water relative to solute in body
- develops as a result of ADH in kidney to diminish free water excretion
- drugs, pain, nausea, decreased effective arterial volume, strenuous exercise
- water intoxication <100 mOsm/kg (urine osmolality)
- low solute intake
Hypernatremia
deficit of free water relative to solute
due to impaire access/ thirst
- inadequate free water intake
- volume depletion
high salt intoxication
diabetes insipidus
Polyuria
- mechanism (4)
- passage of excessive quantity of urine
- water/solute diuresis of 2.5-3L/ day
- urine volume of more than 40 ml/kg/day
associated with polydipsia (water intake of more than 6L/day)
1) increase intake of fluid (psychogenic causes, stress, anxiety)
2) increased GFR
(hyperthyroidism, fever, hypermetabolic states)
3) increased output of solute ( DM, hyperthyroidism, hyperparathyroidism, diuretics)
4) inability of kidney to reabsorb water in DCT (CDI, NDI, drugs, chronic renal failure)
Water diuresis
- causes
- increased water excretion without corresponding increase in salt excretion
Causes:
- increase intake of water
- polydipsia
- diabetes insipidus
Solute (osmotic) diuresis
- causes
- increased water excretion concurrent with increased salt excretion
Causes:
- significant increase in salt in tubular fluid
- NaCl
- hyperglycemia
- high protein intake
- recovery from AKI
Minimum amount of solute human must excrete
700 -1000 mOsm/ day
Maximal volume of concentrated urine
1200 mOSm/L
Obligatory Urine Volume
- minimal volume of urine that must be excrete
0. 5 L/ day
if less than 0. 5 L/ day=> oliguria
Free Water Clearance
- if (+)? (-)?
- equation
rate at which solute-free water is excreted by kidneys
(+)= excess water is being excreted by kidneys
(-) = excess solutes are being removed by blood by kidneys and water is being conserved
- urine osmolarity > plasma osmolarity
- water conservation
C= V (urine flow rate)- C = V- (Ux V)/P
Ratio of Urine Osmolality to plasma osmolality
determine ability of kidneys to concentrate/dilute urine
if >1= concentrated urine
if 1= isoosmotic with plasma
if <1= dilute urine
Conditions that increased osmolality
- Serum
- Urine
Serum
- dehydration/ sepsis/ fever/ sweating/ burns
- DM
- DI
- uremia
- hypernatremia
- ethanol, methanol, ethylene glycol ingestion
- mannitol therapy
Urine
- dehydration
- SIADH
- adrenal insufficiency
- glycosuria
- hypernatremia
- high protein diet
Conditions that decrease osmolality
- Serum
- Urine
Serum
- excess hydration
- hyponatremia
- SIADH
Urine
- DI
- excess fluid intake
- acute renal insufficiency
- glomerulonephritis
Negative C H2O
excess solutes are removed
water conservation
Positive C H2O
water is being excreted
dilute urine
water excess
What is the mechanism for when plasma osmolality if high?
think in relation to K+
- Water is being removed from plasma by kidneys meaning plasma is becoming more concentrated
- Plasma becomes more concentrated than more k channels are created from principals cells on apical surface
- More K leave inside of principal cells ( high to low concentration ) and becomes excreted in urine
- MORE potassium being excreted in urine
Head Trauma
Neurogenic diabetes insipidus
- Dysfunction of hypothalamic- pituitary axis attributed to direct mechanical impact to acceleration-deceleration effect in motor vehicle accidents
- Changes in rotational velocity of head are the main mechanism of post- traumatic damage of hypothalamo-pituitary unit
-Damage of hypothalamic ADH producing neurons, their axons or posterior pituitary leads to post-traumatic central DI
What happens when you have too much H2O? (think plasma osmolality)
Plasma osmolality decrease -> hypothalamic osmoreceptors will turn ADH off -> dilute urine -> water excreted -> plasma osmolarity increased back to normal
What happens when you have too much solute?
Plasma osmolality increase -> hypothalamic osmoreceptors will turn ADH on AND increase thirst -> concentrate urine -> solute excreted -> plasma osmolarity decreased back to normal
Adenosine receptor antagonists
- Caffeine and theophylline
- Modest non-specific inhibition of adenosine receptors
○ NHE3 ( na/h exchanger) in proximal convoluted tubule
○ Interfere with adenosine-mediated enhancement of the collecting tubule K secretion - Basis for new pharmacological research
Viable selective A1 antagonist
Polyuria
- definition
- Volume
- causes
excessive urine production
> 2.5 L/day
Diabetes Mellitus Diabetes insipidus excess caffeine or alcohol kidney disease certain drugs (diuretics) sickle cell anemia excessive water intake
Oliguria
- definition
- Volume
- causes
Output below minimum volume
300-500 ml/day
Dehydration Blood loss diarrhea cardiogenic shock kidney disease enlarged prostate
Anuria
- definition
- Volume
- causes
Virtual Absence of urine
<50ml/day
Kidney failure
Obstruction such kidney stone or tumor
Enlarged prostate
ADH characteristics
- is it measurable
- effect of high ADH? what is sodium controlled by now?
- what does increase intake mean?
- cannot measure ADH directly
- high ADH can cause hyponatremia
- sodium is no longer controlled by ADH, will be by free water
-increase intake mean diluted plasma equal hyponatremia
Hyponatremia
- definition
- values
urine diluted
more free water than solutes
low urine osmolality
low urinary sodium
serum Na <135
serum osmolality <280
How do you know if kidney is responding appropriately during hyponatremia?
1) if urine diluted = good
- bc ADH levels are low
- problem outside kidney
2) if urine NOT diluted
- too much ADH
- problem within kidney
SIADH
- definition
- symptoms
too much ADH
hyponatremia - high urinary Na (>40 meq/L)
high urinary osmolality (>100 mOsm/kg)
