Fluid and Electrolyte Balance Flashcards
The body is in a state of ______ flux
constant
how much fluid and ions do we ingest
- ingest ~2L of fluid containing 6-15g of NaCl
- take in varying amounts of other ions
Mass Balance
- whatever comes in must be excreted if not needed
- kidneys main route
How else can fluid be excreted?
- small amounts lost in feces and sweat
- lungs lose water and help remove H+ and HCO3- by excreting CO2
H2O and Na+ Homeostasis
- determine ECF volume and osmolarity
K+ Homeostasis
- K+ balance can because problems with cardiac and muscle function
Ca2+ Homeostasis
- is involved in many processes in the body
H+ and HCO3- Homeostasis
- determines body pH
ECF Osmolarity Affects ____
cell volume
Cells in Hypotonic Solution
- lysed
- cell would burst
- more water outside, so water moves into cell
Cells in Isotonic Solution
- normal
Cells in Hypertonic Solution
- shrinks
- less water outside cell, so water moves out
Independent Mechanisms to Maintain Cell Volume
- renal tubule cells are constantly exposed to hypersonic ECF and produce organic solutes such as sugar alcohols and amino acids to match their intracellular osmolarity to ECF
- some cells use changes in cell volume to initiate cellular responses, liver cells beginning protein and glycogen synthesis (swell)
Fluid and Electrolyte balance is an _______ process involving…
- integrative process
- involves the respiratory, cardiovascular and renal system, also behavioural responses
CV and Renal Systems are under _____ control
- under neural control
- quite rapid
Renal responses occur ___ ____ because…
- occur more slowly
- because kidneys are primarily under endocrine and neuroendocrine control
T/F: no overlap between processes.
FALSE
Water Balance
- water intake must match excretion
- normal conditions: water loss in urine (regulated mechanism)
- other mechanisms become significant conditions like excessive sweating, diarrhea (drop in blood pressure, increase osmolarity)
Kidneys can ____ excess fluid or ____ what is in the body , but ____ replace what is lost to the environment
- remove
- conserve
- cannot
Volume Gain in Kidneys
- will be offset with increase loss
Volume Loss in Kidneys
- results in reduced flow through the “handle”
- v. loss is reduced in urine
- reabsorption is regulated and can be increased
- v. loss must be replaced through behavioural mechanisms to maintain homeostasis
What does the renal medulla create?
- concentrated urine
How do you measure how much water is secreted by the kidneys?
- the concentration or osmolarity of urine
Removal of Excess Water Required
- kidneys produce large volume of dilute urine
- osmolarity as low as 50 mOsM
Diuresis
- removal of excess urine
- high concentration of diluted urine
Need to Conserve Water
- low volume of concentrated urine is produced
- up to 1200 mOsM
How do the kidneys control urine concentration?
- control urine concentration by varying the amounts of water and Na+ reabsorbed in the distal nephron
- distal tubule and collecting duct
How to produce Dilute Urine
- the distal nephron must reabsorb solute without allowing water to follow by osmosis
How to produce Concentrated Urine
- the distal nephron must reabsorb water and little solute
Vasopressin
- control water reabsorption
- AVP
- posterior pituitary hormone
- antidiuretic hormone (ADH)
How do the Distal Tubule and Collecting Duct alter permeability to water?
- by adding or removing water pores in the apical membrane under the direction of the posterior pituitary hormone vasopressin (AVP), aka antidiuretic hormone (ADH)
Maximal Vasopressin
- collecting duct is freely permeable to water
- water leaves by osmosis and is carried away by the vasa recta capillaries
- urine is concentrated
Absence of Vasopressin
- the collecting duct is impermeable to water
- urine is dilute
Vasopressin Receptor
- V2 Receptor
Insertion of AQP2
- graded
- depends on the amount of AVP present
- AVP induced AQP2 insertion
- insertion is all or none
AQP2 Insertion Process
- vasopressin binds to the membrane receptor
- receptor activates cAMP second messenger system
- cell inserts AQP2 water pores into apical membrane
- water is absorbed by osmosis into the blood
What activates Osmoreceptors
- blood volume, pressure, and osmolarity
What is the most potent stimulus of AVP secretion?
- increased osmolarity
AVP secretion also shows _____ _____ (____ at night)
- circadian rhythm
- increase at night
Osmolarity Greater than 280 mOsM
- hypothalamic osmoreceptors
- interneurons to hypothalamus
- hypothalamic that synthesize vasopressin
- vasopressin (released from posterior pituitary)
- collecting duct epithelium
- insertion of water pores in apical membrane
- increased water reabsorption to conserve water
Magnocellular Neurosecretory Cells (MNC’s)
- produce and release AVP
AVP Production and Secretion
- osmolarity is monitored by osmoreceptor neurons
- stretch sensitive neurons that increase firing rate as osmolarity increases (shrink)
- signal to the MNC’s, AP’s fire in MNC’s causing release of AVP vesicles
- baro and atrial receptors also signal to MNC’s
Process of AVP Production/Secretion
- AVP is made and packaged in cell body of neuron
- vesicles are transported down the cell
- vesicles containing AVP are stored in posterior pituitary
- AVP is released into blood
Loop of Henle
- countercurrent multiplier
AVP is important for water _____ out of the _____.
- reabsorption
2. nephron
What is necessary to create the concentration gradient for osmotic movement of water out of the collecting duct?
- high osmolarity within the medullary insterstitium
What creates the hyperosmotic interstitium
- Countercurrent Exchange System
2. Urea
Countercurrent Exchange System
- evolved in mammal and birds to reduce heat loss from flippers, tails, wings that are poorly insulated and have a high surface-area-to volume ratio
- allows warm blood entering limb to transfer heat directly to blood flowing back into body
- kidneys transfer WATER and SOLUTES instead of heat
Urea
- contributes to hyperosmotic interstitium
Two Components of the Countercurrent Exchange System
- Countercurrent Multiplier (loop of henle)
2. Countercurrent Exchanger (peritubular capillaries)
What structures are responsible for high osmolarity deep in the medulla?
- the nephrons and vasa recta of juxtamedullary nephrons that extend deep into the medulla
Countercurrent Multiplier
- the descending limb of the loop of Henle
- the ascending limb of the loop of of Henle
The Descending Limb of the Loop of Henle
- allows water to follow its osmotic gradient into the increasingly hypertonic interstitial
- doesn’t allow solutes to be transported
The Ascending Limb of the Loop of Henle
- actively transports solutes (Na+, Cl-, K+) into the interstitium
- selective reabsorption of solutes
Active Transport in Loop of Henle
- majority of reabsorption happens in proximal tubule
- NKCC2 transporter uses energy stored to move Na+, K+, 2Cl- into epithelial cells
About ____% of Na+ and K+ _____ occurs in the _____ limb of the loop of henle
- 25%
- reabsorption
- ascending
NKCC2 Transporter
- on apical membrane
- uses energy stored in Na+ concentration gradient to move solutes into epithelial cell
- target of loop diuretic drugs for treatments of hypertension and edema (prevents generation of hyper osmotic medulla)
Na+ is _____ transported _____ concentration gradient on _______ membrane.
- actively
- against
- basolateral
Vasa Recta
- removes water
- picks up some solute and loses some water
Why doesn’t water entering interstitium via descending limb dilute the hypertonic medulla?
- the opposite direction loop of vase recta
- creates a gradient allowing much of the water transported from the descending limb to move into vasa recta
Main job of the Multiplier
- create the hypertonic interstitium
Main job of the Exchanger
- prevent the washout (dilution) of the hypertonic interstitium
Urea Contribution Countercurrent Exchange System
- contributes to the osmolarity of the medullary interstitium
The high solute concentration in the medulla is only partly due to _____
NaCl
About _____ the solute in the medulla interstitium is _____.
- half
2. urea
a ____ amount of urea is _______ in the distal portion of the nephron and create a ______ loop.
- large
- reabsorbed
- recycling
Water Balance Depends on:
- hyperosmotic medullary interstitium
2. AVP mediated insertion of water pores in collecting duct (AQP2)
Na+ is distributed _____ between ____ and _____ fluid thus representing our eCF [Na+]
- freely
- plasma
- interstitial
Normal Plasma Na+ concentration
135-145 mOsM/L
Affect of adding NaCl and no water
- increase total body osmolarity from 300-307 mOsM
- would draw water from cells disrupting normal function
Our ______ mechanisms maintain mass balance
- homeostatic
Homeostatic Responses to Salt Ingestion
- anything extra that enters the body is secreted
- kidneys are responsible for most Na+ excretion
- only Na+ absorption is regulated
- Cl- tends to follow through the electrochemical gradient set up by Na+ movement or co-transported with Na+
Aldosterone
- helps control Na+ balance
- steroid hormone
- responsible for altering Na+ reabsorption and K+ excretion
Renin-Angiotensin-Aldosterone System
- a complicated endocrine pathway
- where the regulation of blood Na+ levels take place
- aldosterone control Na+ balance
- targets the last third of the distal tubule and the portion of the collecting duct located in the cortex of the kidney
Aldosterone acts on ______ cells.
principal cells
Early response phase to aldosterone binding
- aldosterone binding receptor apical Na+ and K+ channels increase their open time through an unknown mechanism
On apical membrane
- Na+ = ENaCs
- K+ = ROMK (renal outer medulla K)
Cytoplasmic Aldosterone Receptor
- mineralocorticoid receptor
Aldosterone binds to what in where?
- binds to cytoplasmic mineralocorticoid receptor in P cells
What does aldosterone binding do?
- increases opening of apical Na+ and possible K+ channels enhancing Na+ reabsorption and K+ excretion
- hormone ligand complex translocate into the cell nucleus
Increased Na+ entry to cell does what?
- speeds up basolateral Na-K pump leading to increased Na+ reabsorption
Increase Na-K pump
- increases intracellular K+ leading to increased K+ secretion
Hormone Ligand Complex
- translocate into the cell nucleus
- binds to hormone response elements that increase transcription of apical Na+ channels
- basolateral Na/K+ pumps and possibly apical K+ channels further enhancing Na+ reabsorption and K+ excretion
What Triggers Aldosterone Secretion
- K+ acts directly on the adrenal cortex protecting the body from hyperkalemia
- decreased blood pressure**
Decreased Blood Pressure and Aldosterone Secretion
- controls aldosterone secretion initiating a pathway that results in the production of angiotensin II which triggers aldosterone release
2 Additional Modifiers of Aldosterone Release
- increased osmolarity acts directly on the adrenal cortex during dehydration to inhibit release
- abnormally large drops in plasma Na+ can directly stimulate aldosterone secretion
Renin-Angiotensin-System (RAS)
- a multi-step pathway for maintaining blood pressure
RAS Process
- begins with Renin Secretion
- Renin converts angiotensinogen into angiotensin I
- angiotensin I is then converted to angiotensin II
- ANGII travel to adrenal cortex and stimulates production of aldosterone
3 Stimuli for Renin Secretion
- low blood pressure in renal arterioles causes granular cells to secrete renin
- sympathetic neurons activated by CVCC when blood pressure decreases terminate on granular cells and stimulate renin secretion
- paracrine feedback (prostaglandins) from macula densa cells signal to the granular cells to secrete renin
Granular cells are also known as…
- Juxtaglomerular cells (JG cells)
Macula Densa Cells
- sense distal tubule flow and release paracrines that affect afferent arteriole diameter
Granular Cells Job
- secrete renin
Renin
- an enzyme
- involved in salt and water balance
- main role: convert inactive plasma protein angiotensinogen into angiotensin I
Angiotensin Converting Enzyme (ACE)
- an enzyme
- produced in blood vessel endothelium ( especially in the lungs)
- converts Angiotensin I to Angiotensin II
Effects of ANGII
- increases vasopressin secretion (ANG receptors in hypothalamus initiate this reflex)
- stimulates thirst
- one of the most potent vasoconstrictors in the body
- ANGII receptors activated in CVCC increase sympathetic output to heart and blood vessels
- increases proximal tubule Na+ reabsorption (stimulate an apical Na+/H+ exchanger)
- all help to restore blood pressure
ACE Inhibitors
- used as a treatment of hypertension
- prevents conversion of ANGI to ANGII leads to relaxation of the vasculature and lower blood pressure
Other Inhibitors
- AT2 receptor antagonists
- renin inhibitors
Atrial Natriuretic Peptide (ANP)
- promotes Na+ and water excretion
- peptide hormone produced and secreted by specialize myocardial cells primarily in the atria of the heart
- increased blood volume causes stretch of atria causing ANP release
Natriuresis
- loss of Na+
Branin Natriuretic Peptide (BNP)
- a second type of natriuretic peptide produced in ventricles and in some neurons in the brain
ANP Receptor
- an enzymatic membrane bound receptor acting through cGMP second messenger system
ANP Jobs
- increased blood volume stretches atrial wall during filling
- atrial myocytes release ANP in response to stretch
ANP in Kidneys
- relaxes afferent arterioles (increases GFR)
- reduces renin release from granular cells (reduces aldosterone)
- reduces Na+ reabsorption at the collecting duct
ANP in Hypothalamus
- reduces AVP release
ANP in Adrenal Cortex
- inhibits aldosterone release
ANP in Medulla
- acts on the CVCC to decrease blood pressure
Potassium Balance
- aldosterone also plays critical role in K+ homeostatic (enhances excretion
Plasma K+
- needs to be maintained within a narrow range (3.5-5mM)
- alterations in body K+ levels affects the resting membrane potential of all cells
Hyperkalemia
- depolarizes cells
- more dangerous
- initially leads to hyperexcitability
- eventually cells are unable to depolarize and become less excitable
- can lead to life threatening arrhythmias in the heart
Hypokalemia
- hyper polarizes cells
- can’t reach threshold
- causes muscle weakness because its more difficult to fire AP’s (failure of respiratory and cardiac muscles)
Disturbances in K+ Balance
- results from kidney disfunction
- eating disorders
- loss of K+ in diarrhea or use of diuretics that prevent kidneys from properly absorbing K+
Behavioural Responses
- critical in restoring the normal state, particularly when ECF volume decreases or osmolarity increases
Drinking Water
- normally the way to replace lost water
- relieves thirst, doesn’t actually need to be absorbed
- unknown receptors in mouth/pharynx respond to water by decreasing thirst and decreasing VP release
Behavioural Responses
- critical in restoring the normal state
- particularly when ECF volume decreases or osmolarity increases
Avoidance Behaviours
- helps prevent dehydration
Control of Volume and Osmolarity
- CV and Renal systems
- can be kept within narrow range
- can change independently to cause diff. scenarios
Increase volume, Increase osmolarity
- when eating salty foods and drinking liquids at same time
- net results = ingestion of hypertonic saline (salt > water)
- need to excrete solute and liquid to match what was taken in
Increase volume, no change in osmolarity
- salt and water ingested is equivalent to isotonic solution
Increase volume, Decrease osmolarity
- simply drinking pure water without ingesting solute
- kidneys can’t excrete pure water
- some solute would be lost
- compensation is imperfect
no change in volume, Increase osmolarity
- eating salty foods without drinking water
- increases ECF osmolarity shifting water from cells to ECF
- triggers intense thirst and kidneys make concentrated urine
no change in volume, Decrease osmolarity
- water and solutes would be lost in sweat
- only water is replaced
- can lead to hypoklemia or hyponatremia
- sports drinks help
Decrease volume, Increase osmolarity
- dehydration could be due to heavy exercise
- water loss from lungs can double, sweat loss, or diarrhea
- result in inadequate perfusion (decrease blood volume) and cell dysfunction
- increase water intake
Decrease volume, no change osmolarity
- hemorrhage
- need blood transfusion or ingestion of isotonic solution
Decrease volume, Decrease osmolarity
- may result from incomplete compensation for dehydration but is uncommon
Direct Effects of Decreased Blood Pressure/Volume
- granular cells (renin secretion)
- glomerulus (decreased GFR)
Reflexes of Decreased Blood Pressure/Volume
- carotid and aortic baroreceptors (CVCC; increased sympathetic output, decreased parasympathetic output)
- carotid and aortic baroreceptors (thirst stimulation)
- carotid and aortic baroreceptors (vasopressin secretion)
- Atrial volume receptors (thirst stimulation)
- Atrial volume receptors (vasopressin secretion)
Direct Effects of Increased Blood Pressure
- glomerulus (increased GFR - transient)
- myocardial cells (natruieuretic peptide secretion)
Reflexes of of Increased Blood Pressure
- carotid and aortic baroreceptors (CVCC; decreased sympathetic output, increased parasympathetic output)
- carotid and aortic baroreceptors (thirst inhibition)
- carotid and aortic baroreceptors (vasopressin inhibition)
- Atrial volume receptors (thirst inhibition)
- Atrial volume receptors (vasopressin inhibition)
Direct Effects of Increased Osmolarity
- pathological hyponatremia –> adrenal cortex –> decreased aldosterone secretion
Reflexes of Increased Osmolarity
- osmoreceptors (hypothalamus; thirst stimulation)
2. osmoreceptors (hypothalamus; vasopressin secretion)
Direct Effects of Decreased Osmolarity
- pathological hyponatremia –> adrenal cortex –> increased aldosterone secretion
Reflexes of Increased Osmolarity
- osmoreceptors (hypothalamus; decreased vasopressin secretion)
Severe Dehydration
- results in a loss of ECF volume, decrease in blood pressure and increase in osmolarity
Compensatory Mechanisms that Restore the 3 Factors
- conserving fluid to prevent additional loss
- trigger CV reflexes to increase blood pressure
- stimulate thirst so normal fluid volume and osmolarity can be restored
4 Compensatory Mechanisms with Redundant Overlap Overcome the Symptoms of Dehydration
- Cardiovascular mechanisms
- Renin-angiotensin system
- Renal mechanisms
- Hypothalamic mechanisms
During Severe Dehydration
- decreased ECF volume (blood pressure) would signal to increase aldosterone release but at same time an increased osmolarity inhibits aldosterone release
- osmolarity control wins
Aldosterone Release during Severe Dehydration
- would because Na+ reabsorption which would worsen the already high osmolarity
Homeostatic Compensation for Severe Dehydration Process
- Carotid and aortic baroreceptors signal CVCC
- decreased blood pressure directly decreases GFR
- paracrine feedback at macula densa cells causes granular cells to release renin
- Granular cells respond to decreased blood pressure by releasing renin
- Decreased blood pressure, volume, increased osmolarity, and increased ANGII all stimulate vasopressin and the thirst centers of the hypothalamus
Compensation Process Results in:
- Rapid attempt by the CVCC to maintain blood pressure (depending on volume loss CVCC response may not completely
restore pressure) - Restoration of volume by water conservation and fluid intake
- Restoration of normal osmolarity by decreased Na+ reabsorption and increased water reabsorption and intake
