Renal Week 1 Flashcards
Describe the role of the kidney in a single sentence
The main physiological function of the kidney is the maintenance of the composition and volume of the extracellular fluid
Intracellular compartment
volume
main componenets
aggregate intracellular volume of all cells
⅔ of total body fluid (27 L)
Main ICF = K+, PO4 3-, Mg2+, proteins
Extracellular compartment
volume
main component
2 parts
⅓ of total body fluid (15 L)
Plasma + interstitial fluid (space between cells) → both constantly mixing across capillary membrane, so have same concentration
Main ECF = Na+, Cl-, HCO3-, Ca2+
(GI fluids, urine, lung fluids NOT considered ECF)
Major components and volumes of daily water intake and loss
Input: Total = 2.5 L
- Ingestion in fluids and food = 2.0 L
- Metabolic processes = 0.5 L (e.g. glucose → H2O and CO2)
Output: Total = 2.5 L
- Sweat and feces = 0.1 L
- Respiration, skin “leaks” = 0.9 L
- Urine = 1.5 L
What does the renal system regulate? (3)
1) ECF characteristic: volume, osmolarity, electrolyte composition (e.g. Na+, K+, Ca2+, PO4-), pH (via bicarbonate)
2) Excretion: metabolic wastes (urea, nonvolatile acids, etc.), foreign substances (drugs and their metabolites, etc.)
3) Blood pressure: water and Na+ regulation and renin-angiotensin system
The nephron
- basic unit of renal structure and function
- 2 million nephrons in the renal system
- made up of blood supply (glomerular and peritubular capillaries) and epithelial tubules
function: blood filtration and selective reabsorption
Pathway of blood through the nephron
Blood enters through afferent artery → passes through glomerular capillaries → some fluid filtered into tubules → rest of blood leaves efferent capillaries → peritubular capillaries (surround tubules) → blood then leaves through renal veins
Four process in a nephron
1) Glomerular Filtration
2) Tubular Reabsorption
3) Excretion
4) Tubular secretion
Glomerular filtration
filter plasma into tubule = NONSPECIFIC
Free passage of H2O and solutes into tubule, but retains larger colloids (proteins, lipid aggregates, etc.) and circulating blood cells in blood
-GFR held relatively constant → rates of tubular handling of each regulated substance varied as needed
Tubular Reabsorption
once in tubule, kidney recaptures some filtered components
Transport of substances across epithelial layer
Highly selective transporters
Regulated by kidney - Selective regulation of rate of reabsorption of individual ECF components → just enough ECF components returned to circulating plasma
Excretion
substances in excess of those required to maintain ECF balance pass through tubule and are excreted as urinary output
tubular secretion
movement of substances from peritubular blood capillaries into the tubule
Regulated
Involves specific molecular transporters
Some substances undergo both reabsorption and secretion within the tubule
Normal values for: assuming CO = 5.2 L/min in 70 kg person
Renal Blood Flow
Renal Plasma Flow
Glomerular Filtration Rate
Filtration Fraction
Renal blood flow = 1.3 L/min
-Kidneys get 25% of CO! More blood than any other organ (except lungs)
Renal plasma flow = 0.65 L/min, 650 ml/min
Glomerular filtration rate = 130 ml/min
-Daily rate of 190 L!
Filtration fraction = 0.2 (20%)
-20% of RPF undergoes glomerular filtration
Non-ECF functions of the renal system
EPO production
Glucogenesis
Produce active vitamin D (calcitriol 1,25-dihydroxyvitamin D)
Renin Angiotensin Axis
Decrease in BP sensed by baroreceptors → kidney increases secretion of renin
→ cleaves angiotensinogen to angiotensin I (biologically inactive)
- Renin level is rate-limiting for production of AgII
- Primary regulatory event is a decrease in BP
AgI → lungs where it is cleaved by ACE to Angiotensin II → arteriolar smooth muscle contraction → increased peripheral resistance → rise in MAP
Function of arterioles of filtration apparatus and special cells there
- on either side of glomerular capillary bed
- Serve as valves that control flow of plasma and blood through the filtration apparatus (and kidney) while regulating GFR
Granular cells: specialized smooth muscle cells of afferent arteriole
-Secrete renin - part of juxtaglomerular apparatus (JGA)
Filterability
concentration of filtrate in Bowman’s capsule vs. concentration in plasma
1 = freely filtered 0 = not filtered
Molecular size cut off of glomerular filtration
size of substances that don’t pass through filter (60,000 D)
Just lower than serum albumin size (67,000 daltons)
How does the ultrafiltrate pass from the glomerular capillaries into the urinary space? (3 things it goes through)
1) Glomerular capillary endothelium (fenestrated holes)
2) Basement membrane
3) Podocytes
Glomerular capillary endothelium
Fenestrated holes in epithelium don’t present resistance to movement of plasma through them - stop RBCs from entering
Podocytes
- sheet of tubular epithelial cells on other side of filter
- visceral epithelium of Bowman’s capsule
- Rounded cell bodies with “feet” (pedicles) projected toward endothelial layer - feet of adjacent podocyte intimately intertwine
- Act as molecular sieves
- most important filter for size
Basement membrane
basement membrane secreted by endothelial and epithelial cells
Important molecular sieve
Composed of mucoproteins (acidic sugars + protein cores), negatively charged → near molecular size cutoff, + charge macromolecules filter much better
What drives filtration in the glomerulus?
Hydrostatic pressure within glomerular capillary
osmotic force in tubule considered to be zero
What opposes filtration in the glomerulus?
1) Pt (hydrostatic backpressure in bowmans capsule)
- caused by filtrate flowing through narrow confines of the tubule
2) Osmotic force in glomerular capillary (πgc)
What generates the osmotic force in the glomerular capillary?
Small ions and solutes filter freely, and are equal on both sides
Large dissolved proteins in plasma (albumin, immunoglobulins) do not filter → water extracted from plasma by filtration → protein concentration rises = Colloid osmotic pressure (COP)
Starling equation for GFR
GFR = K (Pgc - Pt - πgc)
will be tested
What is K
total hydraulic conductivity of kidneys (how much fluid will flow across glomerulus per unit time for each unit of pressure)
Large K due to large GF surface area
What is the Net Filtration pressure (NFP)
Sum of the forces (Pgc - Pt - πgc)
NFP is changing across the glomerular capillary
Why does GFR change? (3)
1) GFR falls in urinary obstruction due to increased Pt
2) GFR falls in severe hypovolemia due to decreased RPF (increased gc)
3) GFR falls in glomerular disease (diabetes, lupus, etc.) due to decreased K
Typical magnitude of starling forces
Pgc =
Pt =
πgc =
NFP =
Pgc = 46 mm Pt = 10 mm πgc = 30 mm NFP = 6 mm
Implications of small NFP: means K is relatively large (large surface area)
Mesangial Cells
cover glomerular capillaries
-Contract and decrease filtration area and thus GFR
Purpose of Autoregulation
If Pgc wasn’t regulated, 15% increase in MAP would cause doubling of NFP → enormous increase in urine flow rate, and electrolyte/metabolite excretion
Changes in MAP do NOT cause proportionate changes in glomerular capillary pressure - Pgc is tightly regulated = autoregulation
Myogenic response
autoregulation
MAP increases → smooth muscle cells of afferent arteriole constrict or dilate to keep downstream flow constant, and maintain Pgc and GFR constant
Intrinsic to vascular SM cells in afferent arteriole
What happens to the myogenic response in malignant HTN
MAP exceeds autoregulatory range, causing dramatic change in RPF/GFR and Pgc as well as damage to delicate glomerular capillaries
What happens to the body during times of hypovolemia?
Hypovolemia → increases resistance of peripheral circulation, shunt blood to essential organs (heart, brain, lungs) → kidney must reduce blood flow, while maintaining function of plasma processing
Complete kidney filtration shutdown can occur if volume loss leads to hypotension and a MAP drop below autoregulatory range
How is GFR maintained during hypovolemia?
GFR maintained by coordinated constriction of afferent and efferent arterioles
Constriction of efferent arteriole → flow diverter, restoring Pgc to normal value, and GFR resumes a normal flow
-Also increases renal vascular resistance → decrease RBF further
Usual baroreceptors in main arteries and effect on GFR
Sense decline in MAP that is significant and long lasting → increase renal sympathetic nerve activity → cause arteriolar muscle to contract → decreases RBF, keep GFR constant
External baroreceptor reflex and effect on GFR
-hormone constriction of arterioles
Neural stimulation of afferent arteriole → increase renin release from granular cells of JG apparatus → increase AgII
→ directly constricts arterioles (afferent and efferent) of kidney
**AgII acts more strongly on efferent arteriole
Intrarenal baroreceptors and effect on GFR
reside in granular cells, stimulate renin-angiotensin axis by detection of reduced arteriolar pressure
A decrease in MAP causes stimulation of what two pathways
1) Arterial baroreceptor reflex –> increase firing rate of renal sympathetic nerve –> JGA renin secretion and constriction of afferent/efferent arterioles
2) JGA baroreceptor stimulation –> renin and angiotensin II
Angiotensin II and hypovolemia
AgII production stimulated by two limbs of hypovolemic response (causes afferent/efferent arteriole constriction)
AND
Essential to systemic circulatory response because AgII causes ALL arterioles to constrict → raise central perfusion and pressure
Filtration equilibrium
point at which NFP = 0 before plasma exits the capillary → no further filtration takes place until end of glomerular capillary
Filtration equilibrium in hypovolemia
During hypovolemia…GFR takes a “double hit” - filtration starts off with a lowered NFP due to hypotension AND effective area for filtration is reduced (equilibrium reached sooner)
What happens if you increase efferent constriction too much?
decrease RBF, increase pressure in glomerular capillary (increase FF) BUT if efferent arteriole constricted too much, πgc increases → decrease GFR
This is what happens in severe hypovolemia
What happens if you increase afferent constriction too much?
decrease RBF, decrease pressure in glomerular capillary (decrease FF), πgc increases → decrease GFR
Renal prostaglandins
-produced by renal interstitial cells in response to AgII
- Local dilatory effect on renal arterioles - antagonizes AgII!
- Pgs maintain adequate renal blood flow by blunting affect of AgII on renal arteriolar constriction
- Provide protection against acute renal failure in hypovolemia
**Dilatory effect of Pgs is selective for AFFERENT arteriole
**DOES NOT eliminate hypovolemic mechanisms, merely blunt them a bit so RBF and GFR reductions aren’t purely vasoconstrictive
Medullary Pyramids
conical functional units, consist of series of tubular elements of nephrons and their associated collecting ducts)
Collecting ducts
empty urine at tip of each cone or pyramid (papilla) into a calyx
Calices
urinary drainage conduits that connect sections of kidney together at the renal pelvis –> ureter at hilum
Blood flow into and within the kidney finishing with entry into glomeruli
Abdomina aorta –> Renal arteries –> anterior and posterior branches –> interlobar arteries (between medullary pyramids)
–> Arcuate arteries (parallel to outer capsule) –> interlobular arteries (towards capsule) –> afferent arterioles
–> glomeruli
Blood flow out of the glomeruli finishing with exit in renal vein
glomeruli –> efferent arterioles
–> interlobular veins –> arcuate veins –> interlobar veins –> renal vein
OR
–> VASA RECTA (capillary plexus where important shit happens)
Renal corpuscles
- initial blood filtering component of nephron
- glomerulus (capillaries) + bowman’s capsule (epithelial capsule)
- located in the cortex
Proximal convoluted and straight tubule
- Cuboidal epithelium, extensive brush border of tall microvilli on luminal side
- Connected by tight junctions
-Basolateral side → extensive basal and lateral infolds with Na+K+ ATPase for pumping Na+ out basolateral side
→ drive uptake of Na+, glucose, and amino acids by facilitated diffusion at microvilli luminal side
-75-85% of filtrate volume absorbed by the time it enters thin portion of loop of henle
Thin descending loop of Henle and thin ascending loop of henle are composed of what cell type?
simple squamous epithelium
Ascending thick loop of henle
Cuboidal epithelium
Active transporters of sodium, numerous mitochondria, extensive basolateral infolds
Distal convoluted tubule
Continuation of thick ascending loop after it enters cortex
Cuboidal epithelium
Short microvilli on luminal side
Major role in acid/base balance
Respond to aldosterone and ADH (?? - not sure if this is right)
Numerous mitochondria, basolateral infolds with Na+K+ ATPase
Collecting tubules and ducts
Collecting tubules of several nephrons join collecting ducts
- ADH acts on cells to increase permeability to water of collecting ducts and tubules via increase in aqua-pores → more concentrated urine
- Columnar
Principal clear cells
active transporters
Couple Na+ uptake with K+ secretion
Function: Na+ reabsorption, K+ secretion, H2O reabsorption
Intercalated cells
stain more darkly
- Secrete H+, reabsorb bicarbonate
- Acid-base balance
A-intercalated cells: H+ secretion, HCO3- synthesis, K+ absorption
B-Intercalated cells: HCO3- secretion, Cl- absorption
Epithelium of ureters and bladder
Transitional epithelium - contains unique lamina propria with folded elastic CT that enables marked stretch of entire epithelium
Highly elastic basal lamina
Range of Water and Salt Handling by the Kidneys
Max excretion of either salt or water is only a small fraction of the filtered load
→ MOST of filtered load of water and salt is obligatorily reabsorbed, with only a small fraction under homeostatic control
At least 92% of filtered water and 98% of filtered NaCl MUST be reabsorbed
- Nearly all obligatory recapture in proximal segments (proximal tubule and loop of Henle)
- Homeostatically varied reabsorption takes place in “fine tuning” segments (distal tubule and collecting duct)
Possible to overwhelm excretory abilities?
salt
water
Water:
Difficult to ingest large volume of water sufficient to overwhelm excretory abilities of kidneys in maintaining water balance
-Water intoxication - possible with drugs like ecstasy
Salt:
Upper limit of salt excretion can be exceeded with high salt diet
Epithelial transport of sodium
Na+ actively extruded from interior of tubular epithelium by basolateral Na+/K+ ATPase ion pump = primary energetic event
→ reduce [Na+] inside cell, increase [K+] in cell
-Na+ moved to serosal side of epithelium
-Na+ passes from tubular lumen into cell through Na+ channels on apical membrane (passive) - large driving gradient due to pumping
_______, _________, and _________ are coupled to the active reabsorption of ______
chloride, water, and other solutes
Na+
Chloride and water transport across tubular epithelium
Chloride:
- paracellular - through tight junctions
- moves with Na+ gradient
- accumulates with Na+ and serosal side of membrane
→ osmotic gradient across epithelium → WATER then moves from lumen to serosal side (paracellular/tight junctions or transcellular/aquaporins)
Transport of glucose across tubular epithelium
reabsorbed in “secondary” active transport
Na+/glucose co transporter → concentrate glucose in the cell → passive movement from cell into serosa
Role of Proximal tubule in NaCl and water reabsorption
-“big bite” of filtered load of water and NaCl, and recapture important metabolites in filtrate
- Obligatorily reabsorbs 65% of filtered water and NaCl regardless of homeostatic requirements
- Aquaporins allow H2O passage transcellularly
- Absorption of essentially ALL filtered glucose and amino acids
- Via Na+ co transporters
*Absorption of filtered bicarb/H+ secretion
Capacity for reabsorption is finite (mediated by discrete transporters)
Loop of Henle role in NaCl and water reabsorption
creates hypertonic interstitium, hypotonic tubular fluid (urine dilution)
- more NaCl than water is reabsorbed
- Obligatory processes
- Crucial for water reabsorption in fine tuning segments
Descending limb of the loop of Henle role in NaCl and water reabsorption
highly permeable to H2O, impermeable to NaCl
Osmotic gradient established in ascending limb brings H2O in at descending limb
Ascending limb of the loop of Henle role in NaCl and water reabsorption
NaCl reabsorption (25% of original filtered load from lumen) → highly hypertonic interstitium
- Impermeable to water
- Increases medullary osmolarity
- Calcium and magnesium ion reabsorption
- Apical membrane: Na/K/2Cl cotransporter for reabsorption
Role of distal convoluted tubule and collecting ducts in NaCl and water reabsorption
“fine tuning” segments
Na/K pump Na+ into serosa → Na+ channels on lumen side bring Na+ down gradient into the cell
Na/Cl cotransporter - Thiazide diuretic site of action
Ca and Mg reabsorption (Ca2+-Mg2+-ATPase)
Aldosterone and ADH active here
Aldosterone actions in collecting ducts
upregulates sodium reabsorption on principal cells in collecting duct
Mechanism by which aldosterone upregulates sodium reabsorption
Aldosterone enters principal cell (lipid soluble) → bind intracellular receptor → hormone/receptor complex diffuses to nucleus → turns on genes to increase synthesis of transporter proteins
-Takes an hour or more
Rapid insertion of pre-existing pools of transporters within vesicles near cell membrane
-Occurs in tens of minutes
Why is there such a high driving osmotic force for water reabsorption at distal tubule and collecting duct?
Addition of more solute to interstitium around fine tuning segments by loop of henle process → increasing osmotic gradient between lumen and interstitium
→ HIGH driving force of water reabsorption
ADH/Vasopression action on collecting duct and mechanism
dramatically increases water permeability of segments
Small vesicles with aquaporins fuse to apical membrane of epithelial cells in presence of ADH
-ADH binds V2 receptor on basolateral membrane of epithelial cells of collecting duct→ initiate intracellular cAMP phosphorylation cascade → initiate de novo synthesis of aquaporins
In absence of vasopressin, collecting duct relatively impermeable to water
RAPID response
Countercurrent multiplication
- generates medullary osmotic gradient
- Deeper from cortex into medulla, osmotic gradient in kidney increases
- Established by U-shaped loop of Henle and Vasa recta
Descending permeability: H2O > NaCl
Ascending permeability: NaCl»_space;» H2O (impermeable)
–> Concentrates the interstitium
Allows for fine tuning of water excretion distally in collecting ducts
Vasa recta in countercurrent multiplication
U shaped - maintain osmotic gradient
Passive movement of H2O and solute
Blood in Vasa recta becomes more concentrated as it descend deeper into the medulla
As blood ascends, water will return into blood vessel and solutes will move from blood vessel into interstitium
Descending vs. ascending capillaries of vasa recta
Descending capillaries:
-Blood enters hypertonic interstitium → H2O movies out of blood into interstitium and solute moves from interstitium into blood
Ascending capillaries:
-Blood enters less hypertonic interstitium → H2O moves back into blood, solute moves back into interstitium
Starling forces for bulk recapture flow - why do we need it?
Huge amount of water and NaCl pumped across tubular epithelium re-enters capillaries to be returned to the ECF via bulk flow of interstitial fluid into the peritubular capillaries - governed by Starling’s principles
What is the main driving force for flow of reabsorbed fluid back into capillaries?
high osmotic pressure of capillary plasma
Due to colloid osmotic pressure of plasma: High because plasma had lots of H2O extracted from it upstream when it was subjected to glomerular filtration → only cells and big things left in blood
Starling forces for bulk recapture flow (equation + normal values)
Fic = K (Pint + πcap - Pcap - πint)
Pint = 7 mm πcap = 35 mm Pcap = 11 mm πint = 6mm
→ NFP = 25
How does flow rate effect reabsorption
Proportional reabsorption changes with flow RATE:
Increased tubular flow → allow more tubular substance to escape reabsorption → increase excretion rate with tubular flow
Opposite is true for reduced tubular flow
How do diuretics effect tubular flow and excretion?
Diuretics: increase tubular flow and excretion of most substances
Increase urine output by decreasing water reabsorption → more water in tubule → increased tubular flow → increased excretion of all solutes
Glomerulotubular Balance
ability of obligatory reabsorption mechanisms in proximal tubule to compensate for changes in filtered load
Fixed proportion of filtered load of water and NaCl is ALWAYS reabsorbed (65%)
**There will still be a surplus
Increased GFR → Higher volume of ultrafiltrate
→ oncotic pressure in capillary increases → more water and solute reabsorbed
Tubuloglomerular Feedback
direct regulation of GFR of each nephron in response to changes in NaCl concentration at macula densa
-done by macula densa
Macula densa
specialized epithelial cells in direct contact with cells of afferent arteriole (Can cause arteriole to constrict or dilate)
Placed at start of distal tubule → monitor status of obligatory reabsorption just before the tubular fluid enters fine tuning segments
How does tubuloglomerular feedback work? 4 steps
1) Rise in GFR → initial rise in tubular fluid flow → compensated by glomerular tubular balance in proximal tubule, but uncompensated part causes fluid to move faster in loop of Henle
2) → reduction in proportion of NaCl reabsorbed in ascending limb → NaCl concentration increases in lumen of ascending limb
3) → fluid exits loop and encounters macula densa → sense rise in NaC concentration → signal afferent arteriole to contract
4) → Pgc drops to return GFR to normal level
ECF volume is determined more by _______ than _______
ECF osmolarity is determined more by _______ than ________
ECF volume is determined more so by sodium balance than water balance
ECF osmolarity is determined more so by water balance than sodium balance
ECF volume is sensed by _______ via what receptors?
What is the response?
effective vascular volume
Sensors: stretch receptors
EABV increases → increase renal excretion of Na, “natriuresis”
EABV decreases → decrease renal excretion of Na (increase reabsorption of Na)
Response: renal Na absorption/excretion
ECF osmolarity is sensed by _______ via what receptors?
What is the response?
plasma osmolarity
osmoreceptors
Response: urine osm/H2O excretion, thirst/H2O intake
What happens to ECF volume and sodium concentration when you eat a big salty meal?
EX) eat big salty meal → increase ECF osmolarity → water flows rapidly from cells to ECF to balance osmolarity between the two compartments
→ decrease osmolarity of ECF and increase osmolarity of cellular compartment as water leaves
NO change in sodium concentration, just pure increase in ECF volume
Why do *Losses or gains in ECF sodium cause greater changes in ECF VOLUME than they do in sodium concentration? consequences?
Two-fold greater volume of cellular over ECF compartment → gains (or losses) of sodium in ECF result in TWO-FOLD greater changes in ECF volume than they do in ECF sodium concentration
→ sensors of sodium regulation monitor changes in ECF volume NOT sodium concentration
4 types of sensors of sodium regulation
1) High pressure baroreceptors
2) Low pressure baroreceptors
3) Intra-renal sensors (JGA - glomerular afferent arteriole, macula densa)
4) Hepatic and CNS sensors
High pressure baroreceptor sensors of Na+ regulation
sense effective arterial blood volume (EABV) in aortic arch and carotid sinus by monitoring MAP
-EABV does not always correspond to ECF volume
E.g. heart failure → high ECF volume, low EABV
Low pressure baroreceptor sensors of Na+ regulation
in cardiac atria, LV, and pulmonary vasculature
Sense stretch in cardiac chamber walls or pulmonary vessels caused by increased ECF volumes
Renin-angiotensin-aldosterone system effect on renal absorption of sodium
Activated by low ECF fluid volume –> activate ECF volume sensors
Angiotensinogen → AgI → AgII → adrenal gland (zona glomerulosa) → increase secretion of ALDOSTERONE → MR in collecting duct (principal cells) → SODIUM RETENTION and increased BP
SNS effect on renal absorption of sodium
Reduced arterial pressure and vascular volume → VASOCONSTRICTION, release of renin, decreased RBF and GFR, and increased RENAL REABSORPTION of NaCl
Direct innervation of renin secreting cells in JGA and catecholamines → stimulate renin release and RAAS → increased RENAL REABSORPTION of sodium
What effector molecules are activated during times of high ECF volume (help renal excretion of sodium and vasodilation)
Natriuretic peptides, prostaglandins, bradykinin, and dopamine
Act directly on tubules or indirectly via renal vasculature to change glomerular hemodynamics
Feedback Loop: Renal Control of ECF Volume (Na Balance)
Negative sodium balance –>
Positive sodium balance –>
Negative sodium balance = more sodium leaving the body than entering (sweat, diarrhea, diuretics)
-Body is volume contracted → volume sensors → renal effector mechanisms → anti-natriuresis
Positive sodium balance = more sodium entering the body than leaving
-Body volume is expanded → volume sensors → renal effector mechanisms → natriuresis
Mechanisms of Na and H2O regulation are ______ of one another
INDEPENDENT
Feedback mechanisms of water balance:
Negative water balance
Negative water balance (H2Oin less than H2Oout) = hypertonicity
Negative water balance → ECF osmolarity increases (hypertonic)
1) → osmostat (hypothalamus) → stimulate SON to produce ADH and release ADH from posterior pituitary, stimulate thirst
→ increase water reabsorption from collecting duct
→ increase H2O intake
Feedback mechanisms of water balance:
Positive water balance
Positive water balance (H2Oin > H2Oout) = hypotonicity
Positive water balance → Hypotonic ECF
1) → osmostat (hypothalamus) → suppress ADH synthesis (decrease renal H2O excretion) and decrease thirst and water intake
2) → stretch of atrial cells → release proANP → increase ANP in plasma → block ADH, decrease secretion of ADH → decrease water reabsorption, and increase excretion
* *Only active when volume less than 10%
Changes in ECF tonicity are reflected by changes in _________
[Na] plasma
What is the target serum osmolarity?
Goal is to maintain serum osmolarity (Sosm) between 280-290 mOsm/kg
What effectors control water balance (3)
1) Thirst
2) Vasopressin
3) ANP
When is thirst typically stimulated?
Thirst is stimulated when maximal effective vasopressin levels have been reached (urine osmolarity of about 1200)
Vasopressin
synthesized in hypothalamus, packaged into vesicles, and transmitted via axons to posterior pituitary where it is stored and released
When ECF osmolarity increases, or ECF volume decreased → vasopressin released from posterior pituitary
Stimuli for release of vasopressin
osmotic vs. non-osmotic
Osmotic → hypertonicity (elevated PNa)
Non-osmotic → unrelated to tonicity
- Decreased EABV (overrides tonicity)
- Pain, nausea, medications, drugs (ecstasy), etc. → Syndrome of inappropriate ADH (SIADH)
Osmoreceptors in the hypothalamus
(Neurons in supraoptic nucleus (SON) of hypothalamus)
Sense serum osmolarity, which is primarily determined by [Na]plasma
-[Na]plasma is determined by water content and sodium content
ECF volume receptors
- Sense filling pressure in LA of heart
- Sense ECF osmolarity through changes in their cell volume
**Triggered when EABV declines by > 10%
With low EABV, ADH release stimulated even if Sosm/SNa low
ECF sensors for water (osmolarity)
1) Osmoreceptors in the hypothalamus
2) ECF volume receptors (sense filling pressures in LA)
what determines ECF water regulation under normal physiologic conditions vs. more severe conditions?
ECF osmolarity determines renal regulation of water balance (osmoregulatory loop is VERY sensitive)
When ECF volume is significantly decreased (>10%) → ECF volume overrides osmotic control of renal water handling
**ECF water regulation is primarily an osmoregulatory system with an emergency low-volume override
What happens to your water regulation during severe sweating
→ decrease in blood volume, increase osmolarity of ECF
Decreased ECF volume → low filling pressure in LA of heart (sensitive indication of circulating volume/preload) → baroreceptor reflex → ADH-synthesizing hypothalamic neurons release ADH from terminals in posterior pituitary → kidney → aquaporins and water reabsorption
Hypotonic composition of sweat → hypertonic ECF → activate osmoreceptors in hypothalamus → ADH synthesis activated
What happens when you have severe diarrhea and lose 3L of volume
Decrease in blood volume (3 L)→ ADH synthesis and secretion
Diarrhea is isotonic, so does NOT change osmolarity and thus does NOT activate osmoreceptors in hypothalamus
When patient recovers:
-Patient drinks 2 L of water → decrease osmolarity of blood, but total blood volume is still down by 1 L
→ inhibit ADH secretion
**ECF volume has little effect on ADH levels, except when ECF volume falls severely
