JH part 2 Flashcards
What is the osmotic coefficient?
function of particle interactions in solutions, which decreases the effective #s of osmoles
What are effective osmoles?
impermeable solutes that can sustain osmosis
What are ineffective osmoles?
permeable solutes that cannot sustain osmosis
reflection coefficient = 100%
particle is reflected back 100% of the time; IMPERMEABLE
reflection coefficient = 0
particle is as permeable as water
Describe the Donnan Effect
behavior of charged particles near a semi-permeable membrane that sometimes fail to distribute evenly across the two sides of the membrane. The usual cause is the presence of a different charged substance that is unable to pass through the membrane and thus creates an uneven electrical charge. Ex: the large anionic proteins in blood plasma are not permeable to capillary walls. Because small cations are attracted, but are not bound to the proteins, small anions will cross capillary walls away from the anionic proteins more readily than small cations.
What is the 60-40-20 rule?
Total Body Water (TBW) = 60% of body weight
Two reasons that account for the high water permeability of cell membranes
1) lipid bilayer has a small, but not negligible water permeability. Since whole cell surface is available for the transport, there is significant water transport
What increases the driving force for water entry via Donnan effect in the cell?
1) presence of high intracellular concentrations of macromolecules and metabolic intermediates
What is the active process that counters the tendency of cells to swell? What is the net result on ICF and ECF?
Na/K ATPase - net efflux of Na from the cell in order to maintain cell volume; net result: effective osmolality in ICF becomes equal to that in ECF
T/F @ steady state ICF osmolality = ECF osmolality
True.
T/F @ steady state Plasma osmolality = ISF osmolality
False. Plasma is slightly > than ISF due to the presence of plasma proteins
What is the main determinant of plasma osmolality
Na
What are the effective osmoles maintained in the ECF and ICF?
ECF: Na and associated anions
T/F Plasma proteins exert a Donnan Effect
True. They’re negatively charged and can attract counterions.
Why is the concentrations of Cl- and HCO3- higher in the ISF?
Donnan Effect. Plasma proteins attract small cations, therefore the concentration of the small cations is 5% higher in the aqueous phase than in the interstitial fluid, and the concentration of small Anions is 5% lower.
How do you figure out the effective osmolality?
2 * [Na]
How do you figure out total plasma osmolality?
2[Na] + [Glucose]/18 + [BUN]/2.8
What is the osmolar gap? What does it mean if it’s increased?
Osmolar gap = measured osmolality - calculated osmolality. An increased osmolar gap indicates the presence of a toxin that contributes to the osmolality
What determines the size of any given compartment (ie ECFV, ICFV, etc)
of osmotically active particles present
What accounts for the decrease in Hct after eating a salt-laden meal?
1) Since Na is restricted to the ECF, this draws fluid out of the cells until ECF=ICF osmolality (but the total number of osmoles is higher in the ECF)
What are the effective osmoles (main determinant of oncotic pressure) in the plasma?
albumin
What are the two opposing forces on fluid movement in the capillaries?
hydrostatic pressure (promotes fluid exit) and oncotic pressure (draws fluid in)
What is the effective oncotic pressure dependent on?
reflection coefficient of the capillary membrane for protein.
What is the net ultrafiltration pressure (PUF)?
Sum of all hydrostatic and effective oncotic pressures
If PUF is +, this means
fluid moves out of the capillary (ultrafiltration)
if PUF is -, this means
fluid moves into the capillary (absorption)
What is the filtration coefficient (Kf) a measure of?
measure of water permeability
What is the reflection coefficient (s) a measure of?
measure of protein permeability
What modifies Kf and s?
vasoactive hormones and cytokines
How does PUF change throughout the length of a capillary? How does this affect fluid movement?
It goes from + –> - such that most of the ultrafiltrate produced in the initial portion of the capillary gets reabsorbed at the venous end.
What two forces contribute to the autoregulation of plasma (and thus blood) volume?
hydrostatic pressure (promotes fluid exit) and oncotic pressure (draws fluid in): increases/decreases in capillary hydrostatic pressures will cause fluid to be drawn in or seep out from the capillaries
What are 4 things that can contribute to edema?
increase in venous pressure
What happens to patients with hypoalbuminemia?
Edema, since there is reduced oncotic pressure, fluid will seep out of the capillary and into the interstitum
How does inflammation/endothelial cell injury change Kf and s?
Increase Kf (increase water permeability)
What are crystalloids? Examples?
Na and glucose
What is the effect of administering a hypertonic saline solution?
expand ECFV, reduce ICFV
What is the effect of administering a hypotonic saline solution?
expand ECFV and ICFV
What is the effect of administering a normal saline solution?
ECFV increases, but no change in ICFV (since isotonic saline was used, there was no change in osmolality and therefore no water shift between ICFV and ECFV)
What is the effect of administering glucose?
hemolysis
What is the effect of administering pure water?
hemolysis
What are colloids? Examples?
plasma expanders (ie albumin, gelatins, dextrans, starches)
What is ORT? What is it made of?
oral rehydration therapy: Na w. glucose in a slightly hypotonic solution (net: expand ECFV and ICFV)
What is the main energy consumer in the kidney?
active reabsorption of the ultrafiltrate, specifically Na (via Na/K ATPase)
T/F O2 consumption determines renal blood flow
False. In the kindey, blood flow drives O2 consumption (because more blood flow = more active reabsorption = more O2 consumption)
Why is the kidney an ideal site to monitor changes in arterial O2 content?
Unlike other organs, renal tissue pO2 is independent of blood flow and is thus proportional to arterial pO2 content. Therefore, RBC production is regulated by the kidneys
How is the renal vasculature arranged in terms of capillary beds and arterioles?
afferent arteriole –> glomeruli –> efferent arteriole –> peritubular capillaries
Where is blood flow the highest in the kidneys? Lowest? Why is this important?
Blood flow is highest in the superficial cortex. The medulla has no direct arterial blood supply, but it does receive blood from juxtamedullary glomeruli thrrough the peritubular network in the outer medulla and vasa recta in the inner medulla. Blood flow in outer medulla is 6-10% of cortical flow, and only 1/10 of that is transmitted to the vasa recta. The low blood flow in medulla and the coutnercurrent arrangement of flow in the vasa recta is critical for conserving the medullary hyperosmolality required for concentration of urine.
What are the forces that govern ultrafiltration?
ultrafiltration is drive by hydrostatic pressure in glomerular capillary (PGC), opposed by hydrostatic pressure in bowman’s space (PBS), and the oncotic pressure in the glomerular capillary (pGC)
What determines GFR?
hydrostatic pressure in glomerular capillary (PGC)
What is the equation for GFR?
GFR = Kf [(PGC-PBS)-pGC]
Why is GFR so high in the kidneys?
It has a high Kf (filtration coefficient)
Why is Kf so high in the kidneys?
Because glomerular capillaries have large fenestrations that allow the passage of small molecules (and therefore a much larger fraction of the total surface area is available for the passage of H2O/small molecules)
How does one calculate filtration fraction (FF)?
FF = GFR/RPF (renal plasma flow)
How does RBF and GFR change with changes in afferent tone?
Since PGC is the main determinant of GFR: RBF, GFR, and FF changes in parallel with changes in afferent tone (ie afferent constriction –> decrease RBF, GFR, and FF)
How does RBF and GFR change with changes in efferent tone?
Since PGC is the main determinant of GFR, GFR and FF changes in opposite directions with changes in efferent tone (ie efferent constriction –> increase GFR and FF), but RBF will change in parallel (efferent constriction –> decrease RBF)
How does constriction of the efferent arteriole affect RBF/GFR/fluid reabsorption?
Increase GFR, decrease RBF, increase fluid reabsorption from the tubules by decreasing hydrostatic pressure and increasing oncotic pressure in the peritubular capillaries
What about the glomerulus prevents albumin and Igs from being filtered?
Filtration barrier rejects Igs based on their large size. Albumin is rejected based on charge (the filtration barrier carries a significant negative surface charge, which restricts the passage of negatively charged proteins)
How does proteinuria occur?
damage to the filtration barrier
What is minimal change nephropathy?
kidney disease –> proteinuria
What is renal clearance?
virtual volume of plasma completely cleared from a substance (s) per unit time
How do you calculate renal clearance?
Clearance = (Us x V)/(PaS)
How do you calculate GFR using inulin?
GFR = (Uinulin x V)/PaInulin
What is PAH and what is it used to measure?
PAH is used to measure RPF. It is actively secreted into tubular fluid from the peritubular capillaries and is almost completely cleared from the blood after a single passage (renal concentration ~0)
What is Inulin and what is it used to measure?
Inulin is used to measure GFR. It is freely filtered by the glomerulus and is neither reabsorbed nor secreted by the tubules.
What is the endogenous marker of GFR?
creatinine, because it is produced in the body at a relatively constant rate and is eliminated primarily by glomerular filtration
What does a high plasma creatinine level indicate?
low GFR (they’re inversely related)
At what point does autoregulation of RBF and GFR breakdown?
180mmHg
How does autoregulation affect RBF in the kidneys?
RBF remains relatively constant over a wide range of mean arterial pressure (~80-180)
Where does autoregulation in the kidneys occur?
afferent arteriole, which stabilizes glomerular capillary pressure (the main determinant of GFR)
How is autoregulation achieved? (2 mxns)
1) myogenic response
What is the myogenic response?
when the afferent arteriole contracts in response to an increase in blood pressure (stretching of the vessel)
What is TGF?
tubuloglomerular feedback (TGF) - an increase in arterial pressure temporarily increases GFR, and thus more salt and water is delivered to the tubules. In response to an increased NaCl load, the macula densa sends a humoral signal to the neighboring afferent arteriole to contract and thus decrease GFR.
What is the signal that activates TGF?
increased NaCl load detected by the macula densa
What is the TGF response?
macula densa sends a humoral signal to the neighboring afferent arteriole to CONTRACT, thereby decreasing GFR
What is the effect of a vasoconstrictive hormone?
reabsorption
What is the effect of a vasocondilator hormone?
inhibit reabsorption
What are the 4 things that induce renin RELEASE?
1) decreased stretch of granular cells in afferent arteriole
What is the negative feedback loop on renin release?
Angiotensin II
What is the action of AII?
preserve GFR by counteracting the direct effects of reduced perfusion
What are some vasoconstrictors that act on the afferent arteriole?
sympathetic nervous system, adenosine
What is the effect of a vasoconstrictor acting on the afferent arteriole?
decrease RBF, GFR, and FF
What are some vasoconstrictors that act on the efferent arteriole?
angiotensin II, endothelin, ADH
What is the effect of a vasoconstrictor acting on the efferent arteriole?
decrease RBF, but increase GFR and FF (filtering more, but since protein doesn’t get filtered, oncotic pressure is increased in the blood vessels, which pulls water out of the tubules)
What are some vasodilators that act on the afferent arteriole?
dopamine, ANP
What is the effect of a vasodilator on the afferent arteriole?
Increase RBF, GFR, FF
What are some global vasodilators?
prostaglandins, NOs, kinins
What are unique about Kinins?
they are degraded by the same enzyme (ACE) that generates Angiotensin II. Thus, AII and kinins have opposing effects
What is the effect of NSAIDs in a person with congestive heart failure?
NSAIDs block prostglandins production (which is a normal vasodilator). NSAIDs normally have no significant effects on GFR in healthy patients, but in a person with congestive heart failure (which is already hypertensive), this can cause renal insufficiency.
What is renal insufficiency?
Renal failure - condition in which the kidneys fail to adequately filter waste products from the blood
What is the effect on ACE inhibitors on blood pressure?
It is a hypertensive drug (ACE normally breaks down Kinins, which are vasodilators. If ACE is blocked, then you get unapposed effects of AII, which is an efferent constrictor)
What are the two mediators of TGF?
endothelin and NO.
What is the effect of ANP on RBF and GFR?
ANP is a vasodilator and acts on the afferent arteriole. Therefore RBF and GFR will increase
What is the effect of Sympathetic Nervous System on RBF and GFR?
SNS is a vasoconstrictor of the afferent arteriole. Therefore RBF and GFR will decrease
What is the effect of Angiotensin II on RBF and GFR?
Angiotensin II is a vasoconstrictor of the efferent arteriole. Therefore RBF will decrease, but GFR will increase
What is the effect of dopamine on RBF and GFR?
Adenosine is a vasodilator of the afferent arteriole. Therefore RBF and GFR will increase
What is the effect of endothelin on RBF and GFR?
Endothelin is a vasoconstrictor of the efferent arteriole. Therefore RBF will decrease, but GFR will increase
What is the effect of Adenosine on RBF and GFR?
Adenosine is a vasoconstrictor of the afferent arteriole. Therefore RBF and GFR will decrease
Give an example of a vasoconstrictor that is buffered by the simultaneous release of vasodilators.
Increase in AII/NE (vasoconstrictors) promote the release of prostaglandins (vasodilators)
What is the effect of ADH on RBF and GFR?
ADH is a vasoconstrictor of the efferent arteriole. But because it selectively targets a tiny population of nephrons, it has no significant effects on total RBF and GFR
How does RBF and GFR change with pregnancy?
they both increase
How does RBF and GFR change with a (chronic) protein diet?
they both increase, but due to certain a.a. that serve as substrates for NO production. Increased NO –> vasodilation –> increased glomerular hypertension and acceleration of renal disease
What are the two main purposes of the kidney?
1) Eliminate metabolic end products (urea, creatinine) via ultrafiltration
What is the main energy consumer in the kidney?
reabsorption of Na by the tubules (Na/K ATPase, ENaC)
Why is the macula densa stragetically placed at the beginning of the DCT?
the DCT has limited reabsorption capacity, and therefore the MD is located at the beginning of the DCT to ensure a constant Na load via the tubuloglomerular feedback mechanism
How is the PCT/LOH different than the DCT in terms of function?
the PCT/LOH function more along the lines of Na reabsoprtion (energetically favorable) whereas the DCT has limited reabsorption capacity and functions to establish the steep concentration gradients (energetically demanding)
What are the two main transport mechanisms that occur in the proximal tubules?
1) reabsorption of 2/3 of the filtered water and Na, 80% of bicarbonate and phopshate, and all nutrients.
Where and how is HCO3 primarily reabsorbed?
HCO3 is primarily reabsorbed in the PT, and this process is indirect.
What is acetazolamide?
It is a carbonic anhydrase inhibitor, and therefore it increases Na excretion (and is therefore, a potent diuretic)
What influences the solvent drag in the PCT?
1) reabsorption of Na, glucose, lactate, and inorganic phosphates increases the osmolality of the interstitial fluid (while reducing the osmolality of the tubular fluid).
What is non-ionic diffusion?
passive movement of lipid soluble weak acid and bases in their undissociated forms through the cell membrane.
How are is Cl- reabsorbed in the PCT?
Transport of Cl- is mediated by the Cl-/A- and Na/H exchangers.
What is the purpose of the Na/K ATPase?
to keep the intracellular concentrations of Na low so that Na can be reabsorbed (energetically favorable movement of ions down its concentration gradient)
What are the advantages/disadvantages of the transport events in the PCT?
Pro: the PCT is relatively leaky and therefore large amounts of Na/H2O are reabsorbed with relatively little energy expenditure
What are two ways that salt/water transport is regulated in the PT?
1) glomerulotubular balance
What is glomerulotubular balance?
balance between reabsorption of solutes in the proximal renal tubules and glomerular filtration, which must be as constant as possible. The PT always reabsorbs a constant fraction of the filtered load. The purpose is to stabilize the rate at which Na and water is delivered to the LOH and ultimately to the distal nephron, which has limited transport capacity. Balance is maintained by neural, hormonal, and other mechanisms
What is the net effect of the GT feedback under the influence of AII or endothelin?
AII/endothelin is present during low ECFV, and they act to constrict the efferent arteriole. This results in
Since the PCT is so leaky, how is backflow minimized?
AII/endothelin constricts the efferent arteriole under low ECFV. This results in
What are the main hormones that stimulate Na reabsorption in the PCT? What transporter do they act on?
Angiotensin II (but also catecholamines/sympathetic) via the Na/H exchanger
Which receptors sense and respond to ECFV depletion?
low-pressure receptors in the atria/large veins
What happens under severe ECFV depletion?
increased renal sympathetic activity -> increased secretion of catecholamines -> increased Na/H activity to stimulate water and salt reabsorption
What are the two main inhibitors of Na reabsorption in the PCT?
dopamine and ANP
How are xenobiotics normally eliminated?
they are actively taken up through the PCT basolateral membrane via high affinity transporters and then secreted into the tubular fluid. Thus, they are cleared at a rate comparable to RBF.
How are xenobiotics related to PAH?
they are actively taken up through the PCT basolateral membrane via high affinity transporters and then secreted into the tubular fluid. Thus, they are cleared at a rate comparable to RBF. This is the basis of PAH clearance and is used to measure RBF
How are filtered proteins eliminated from the tubular fluid?
1) oligopeptides are degraded by ectopeptidases in the brush border
Where is water reabsorbed in the LOH?
descending limb
Where is Na reabsorbed in the LOH?
thick ascending limb (TALH)
T/F the acending limb of LOH is water permeable
False. It is water impermeable
Why does the tubular fluid become hypoosmotic as it moves through the LOH?
The descending limb is where most water is absorbed, but the TALH is where it is water impermeable, and therefore water cannot follow the reabsorbed salt in the TALH. Thus:
What is the effect of a hyperosmotic medullary environment?
drives the reabsorption of water from the thin ascending limb and from the collecting ducts if ADH is present
What is the main route of entry for Na in the TALH?
Na/K/2Cl cotransporter
How are cations (Na/Mg/Ca) reabsorbed in the TALH? What facilitates this?
Na/K/2Cl cotransporter is an electroneutral transporter, but it facilitates reabsorption of Na. K is returned to the tubular lumen, which generates a lumen (+) voltage. This drives the reabsorption of cations through the paracellular pathway.
What do loop diuretics act on?
Na/K/2Cl cotransporter; prevents the reabsorption of Na, resulting in an ablation of the countercurrent multiplier gradient, and can result in isoosmotic urine production (because there is no concentration capability of the kidneys)
What happens with chronic use of loop diuretics?
Chronic use prevents the reabsorption of Na, resulting
How is the TAL auto-regulated? Whats the purpose this autoregulation?
TAL increases the rate of Na reabsorption with an increase in salt delivery, and its purpose is to buffer changes in salt load arriving to the distal tubule (which has limited transport capacity)
What is the purpose of the Ca sensor in the TAL?
The TAL reabsorbs significant amounts of Ca and Mg without water into the medullary interstitium. These cations have limited solubility and are prone to precipitate at high concentrations. When activated, this sensor inhibits the apical K channels in the TAL, which eliminates the (+) luminal voltage that drives the paracellular reabsorption of Ca.
What does the Ca sensor in the TAL act on?
K channels (allows K to leave the cell into the lumen)
What type of feedback is the MD involved in?
Tubuloglomerular feedback. The MD senses the increased NaCl load arriving to the distal tubule, and inihits the TGF to ensure that the downstream segments are not overwhelmed by a Na load
What are two process that the MD is involved in?
TGF and Renin secretion
Which two parts of the nephron is impermeable to water?
TALH and DCT
How is Na reabsorbed in the DCT?
through a NaCl cotransporter
What do thiazides do? What happens with chronic thiazide use?
They block the NaCl cotransporter in the DCT, which results in decreased Na reabsorption; chronic use leads to salt wasting.
