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200 Cards in this Set

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Molality definition
amt of solute per 1 kg of water
Osmolality definition
number of solute particles in a kilogram of water
Colloid osmotic pressure
The osmotic pressure generated by large molecules (especially proteins) in solution. For our purposes: remember theat COP of plasma = osmotic pressure exerted by plasma proteins
What is the major difference between plasma of blood and plasma of interstitiial fluid?
Plasma contains a much higher concentration of plasma proteins. [in most tisues, COP of isf is near zero.]
What are the major ions in ECF?
Na and Cl
Describere permeability of cell membranes to Na
relatively impermable to Na
What is the major cation in ICF?
What are the major anions in ICF?
Organic ions and low concentrations oif Cl-
Compare and contrast bood plasma and ECF?
Essentially the same concentrations of ions
BUT: Plasma of blood has plasma proteins, whereas ECF does not
higher osmolarity than plasma. ECF. or ICf
Approximate value of osmolarity of ECF?
Apx. twice the plasma sodium concentration
What happens when you increase NaCl load in ECF?
Water moves out of cells to normalize osmolarity. ECF volume increases, ICF volume decreases.
What happens when you increase HOH load in ECF?
increases ECV and decreeases osmolality. Water moves into cells and ECV and ICV go up.
a solution that has no effect on cell volume.
solution that causes cell to swell
solution that causes a cell to shrink
How is it that some solutes that can readily cross the PM can be isosmolar but not isotonic?
Because permeable solutes cannot exert an "effective" osmotic pressure.
2 types of nephrons
cortical (loops do not penetrate medulla)
juxtamedullary (loops menetrate medulla)
How much filtered water and Na are exreted?
less than 1%
What is PCT responsible for?
1) tubular reabsorption
2) tubular secretion
What specifically does PCT do?
1) reabsorbs 2/3 of the filtered water and NaCl
2) reabsorbs VIRTUALLY ALL of the filtered glucose AND AA's.
3) Can also secrete organic acids, bases (e.g., drugs)
What does the descending limb do?
1) tubular reabsorption of water
2) tubular secreetion of NaCl into the filtrate
What does the ascending limb do?
1) dubular REABSORPTION of NaCl
2) NO WATER REABBSORPTION: virtually impermeable to water
Does net reabsorption or secretion of water occur in the ascending limb?
What does DCT and collecting duct do?
1) Tubular reabsorption of NaCl and water.
2) responsibe to ADH and Vasopressin, whicih control water permeability
What does ADH do?
it promotes water reabsorption in the DCT/CD
What does aldosterone do?
Controls amount of Na reabsorbed by the DCT and CD--promotes Na reabsorption and K+ secretion.
Describe hydrostatic pressure in the glomereular caps
High: higer than in other systemic cap beds.

this pressure provides the driving force for ultrafiltration.
Describe hydrostatic pressure in peritubular caps?
Low, like other systemic cap beds. This provides optimal situation for peritubular caps to REABSORB filtered hoh
What is GFR
glomerular filtration rate

Volume of FLUID filtered across the glomeruli eevery min (mL/min)
what is the filtered load of solute? How is it calculated?
A measure of the amount of dissolved solute (e.g. glucose or nacl) in plasma that is filtered across the glomerulus every minute.)

FL = GFR * Plasma concentration of the solute
What is excreted load of solute? how is it calculated?
EL = Volume of urine excreted per minute * concentration of solute in the urine
What is renal blood flow, on average? What is renal plasma flow on average?
BF: 1 L/min
PF: .6 L/min
Define CLEARANCE. Give equation.
minimum rate of plasma flow required to provide/supply the amount of a substance that is exreted in the urine in a given amount of time.

Clearance of "y" = (Uy * V)/Py

Where Uy is conc of y in urine, V is urine flow RATE, and Py is concentration of Y in the plasma.
What 3 processes does clearance rate for a substance depend on?
1) GFR
2) tubular reabsorption
3) tubular secretion
What are 2 ways that a substance cna have a clearance of 0?
1) it is not filtered at the glomerulus R secreted by the kidney (e.g. plasma proteins)

2) it is filtered at the glomeruli or screted by the kidney tubules BUT it is COMPLEETELY reabsorbed and so does not enter the final urine (e.g. glucose)
What is the clearance rate of something freely filtered and not reab/metab/or secreted? Name an exogenous and endogenous substance with such properties/
Such a substnace has clearance rate = GFR.

For this substance, a volume of plasma = volume of plasmar/water that is filtered every minute can be cleared of such a substance.

Exogenous substance: inulin
Endogenous substane: creatinine
What is an endogenous substance that generally is freely filtered from plasma and not reabsorbed, metabolized or secreted?
What must the maximum possible clearance of a substance equal?
renal plasma flow.
How much plasma is filtered at the kidney?
How can a substance be completely cleared from plasma flowing through the kidney?
it must be filtered AND secreted
Name a substance that is freely filtered AND is very actively secreted by the renal tubules?
PAH (paraaminohippurate)
What does the clearance rate of PAH approximate?
renal plasma flow (&thus renal blood flow)
What are normal GFR values fo radult men and women?
95 for women
120 for men
What might happen if you lose one half of your functioning nephrons?
GFR declines, but electrolyte balance and urinary compensation can be OK due to unknown mechanisms of compensatory hyperfiiltration by the function al nephrons
What is a unique property of substances that are freely filtered and not secreted or reabsorbed by the renal tubule?
Filtered load = secreted load
Why is plasma cratinine concentration most often used as a measure of GFR?
There is a direct inverse relationship between changes in GFR and plasma concentration.

If GFR is reduced, the filtered load of creatinine is reduced transiently--plasma creatinine rises in proportion to the GFR drop. The proportionate increase in plasma creatiniene (to the decline in GFR) means that filtered load returns to the same value as before. Excreted load also returns to the same value.
What is a unique property of substances that are freely filtered and not secreted or reabsorbed by the renal tubule?
Filtered load = secreted load
What happens to plama creatinine and excreted and filtered load of creatinine when GFR drops?
GFR drop causes transient drop in filtered load and excreted load. But because of this drop, plasma creatinine rises proportionately. Thus, with time, the proportionate rise in plasma creatinine concentration causes the filtered load and the excreted load of creatinine to rise back to normal levels, even though the GFR has dropped.
what factors affect creatinine levels (other than GFR)?
Age and sex influence muscle mass.

Old people have lower creatinien level even w/ormal GFR

High meat inflences creatinine level

Women have lower creatinine level
how much PAH is removed from plasma in a single pass through the kidney?
What is "renal extraction" (E)
The fraction of a substance tha tis removed from the blood by the kidneys
What then is the E of PAH?
How can you calculate renal plasma flow with PAH?
RPF = clearance of PAH / E of PAH

normally this comes to 600 mL/min
How do you calculate renal blood flow?
RBF = RPB / 1-hematocrit

hematorcrit is approximately .4 of blood volume
How do you calculate the rate of reabsorption?
= filtered load - excreted load

= (GFR * Plasma concentration) - (Urine flow rate - concentration in urine)
If the amount of subsstance excreted in the urine is less than the amount filtered, the substance...
has been REABSORBED by te renal tubules
If the clearance of substance z is LESS than GFR or inulin clearance, thee has been...
net tubular reabsorption
How do you calculate the rate of secretion?
=excreted load - filtered load
What makes up the filtration barrier in the glomerulus?
1) the endothelial cell layer of the glomerular capps (fenestrated)

2) a NEGATIVELY charged basement membrane that lies between the endothelial layer and the epithelial cells of bowmans space

3) a specialized epithelial layer of bowman's capsule composed of specialized cells called podocytes.
In a healthy kidney, the filtration barrier is freely permeable to:
The glomerular filtration barrier as limited permeabilitey to:
Larger solutes, like:

The filtration barrier is essentially impermeable to:
cellular components of blood
what is the biggest size of something that can pass thru the filtration barrier?
40 Angstrom

Though there is dropoff in filtration above 20 angstrom, and filtration is nearly nonexistant at 40.
Given the same radius for theree particles, filterability based on charge follow this order:
cationic > neutral > anionic
What are 4 possible components of glomeruluar disease?
1) proliferative: increased glomeruluar cellullarity

2) membranous: any increase in thickness of the glomerular cap wall

3) necrotizing: death of tissue

4) sclerotic - fibrosis and scarring
What is glomerular disease marked by? Why?
Note: GFR can be variable

Due to focal disruptions in the glomerular membrane OR due to loss of negative charge on the membrane
What is one component of glomerular disease in DM?
High blood glucose leads to abnormal glycation of BM, reducing its negative charge and leading to greater "filterability" - protein is filtered and appears in urine
Commpare hydrostatic presssure of glom caps compared to SM caps:
Glomerular caps have a higher hydrostatic pressure.

Note: it exceeds COP along the length of the cap, leading to net filtration along the length of the cap
Compare Kf in glom cap and SM cap
Glom cap has Kf 100 - 200x higher than in SM
What happens to COP along the length of the glomerular cap? Why?
It rises along the length of the cap--because there is filtration along the length of the cap, then COP rises because the colloid particles essnetially becomme more concentrated becase fliud is filtered but they stay in the plasma
A formula to calculate GFR by pressure measurement is:
GFR = Kf * MFP (mean filtration pressure)
Name the following pressures:

P in afferent artery
P in Glom cap
P in efferent arteriole
COP in the glom cap
COP in bowmans space
Pressure in BS
Paff = 60
P glom cap = about 60
P eff = ~59
COPgc = 30
COPbs = ~0
Pbs = 15
describe generally the equation for MFP
Net filtration pressure (Pgc - Pbs) less the mean COP opposing it.

Mean COP = COPaff + COPeff /2
What is the difference between filtration pressure equilibrium and disequilibrium?
In FP equilibrium, Difference in Pgc and Pbs = COPgc BEFORE the end of the cap. That is, COPgc rises to meet the net FP difference of Pgc - Pbs (which is constant) BEFORE the end of the cap (rising asymptotically).

In FP disequalibrium, Pgc - Pbs is ALWAYS above COPgc along the full length of the cap
What factors can increase GFR?
1) increased Pgc (this depend on arterial BP and resistance of the afferent and efferent arterioles)

2) decreased COPO in the plasma

3) inreased Kf (drugs, size of glomeruli increases/hypertrophy)
How do glom caps differ from caps in other bed wrt vessels on either side?
They have resistance vessels (can change their diameter/resistance) on both input and output sides.
name some physiological mediators of vasoconstriction?
sympathetic nerves
angiotensin II
Name some physiological mediators of vasodilation
Most physiological mediators of laltered resistance affect the diameter (resistance) of the ____ arterioles more than the _____ arterioles because _____
afferent; efferent

the wall of the afferent arterioles is thicker and more reactive to physiological modulators
Increased afferent resistance does what to Pgc, GFR, and RBF
decreases all of them
Increased efferent resistance does what to Pgc, GFR, and RBF?
It Increases Pgc AND GFR but decreases RBF
More than 99% of all energy consumption by the kidney is expended on _______
Active transport of salt, mainly NaCl
How does water get transported transcellularly in the nephron?
It moves thru apical and basolateral surfaces via small hydrophilic pores formed by AQUAPORINS that allow water but exclude all solutes.
Why are peritubular capps very effecient at taking up reabsorbed water?
Plasma in these caps has a very high COP due to los of protein free fluid at the glomeruili. Water then moves readily from interstituium to peritubular caps
What ions constitute the majority of the total solute of te tubular fluid and the major ions reabsorbed?
Na+, Cl-
In which segments are sodium ions reabsorbed?
all EXCEPT descending limb of Henle's loob
Why does the descending loop of henle not reabsorb Na+?
One reason is that it lascks the Na+/k+ ATPase transporters that transport Na out across the basolateral surface of tubule cells
How does Na get from tubule lumen to interstitium?
1) passive diffusion down concentration and electrical gradients into the tubule endothelium

2) active transport against concentration gradient using a Na/K ATPase on the basolateral surface of the cells. (TRANSCELLULAR movement of Na)
Correction on the previous card re: transport of Na from lumen to interstitium:

that dealt only with the TRANCELLULAR movement of NaCl, which is tnot the only way.
What is an additionla way that Na is transported out of lumen?
Describe how paracellular movement of sodium occurs?
1) occurs via passvie diffusion

2) can be from lumen to interstitutm (reabsorption) or interstitium to lumen (secretion or PASSIVE LEAK BACK)
What determines the degree of leak back in a given nephron segment?
1) electrochemical gradient

2) how leaky or tight the junctions are between the epithelial cells.
Which nephron segemnts have leaky epithelia?
Proximal tubule
Descending limb of loop of Henle
What happens then in the descending limb wrt Na movement?
1) no transcellular movement of Na out of the lumen, due to lack of Na/K atpase transporters in basolateral membrane

2) Na Leakback back into the lumen due to leasky epithelium and fact that Na concentration in interstitium is high and in lumen it is low
What is the pump/leak ratio?
The ability of an epithelium or nephron segment to pmp Na relative to the degree to which the epithelium allows paracellular leakage
Describe relationship of water permeability to epithelium leakiness
1) leaky: high water permeability, due tp paracellular transport AND due to transcellular transport via Aquaporin 1

2) tight: low water permeabilit, due to no paracellular movement and different expression of aquaporins (2, 3, other...that have lower water transport rate)
Describe the Na transport capacity of leaky v. tight epithelia (?)
Leaky: high (?)
Tight: low (?)
Which segment absorbs the most water? How?
proximal tubule via aquaporin 1 that is constitutively expressed in apical membrane of cells
Which segment reabsorbs te least water? How much?
Ascending loop of henle: absorbs ZERO water
Describe water reabsorption in distal tubule/collecting duct?
Depends on ADH. These segments express aquaporin 2, which is regulated by ADH.

ADH present: DT and CD reabsorb water
ADH absent: DT and CD reabsorb much less water
Describe fluid and solute concentrations at beginning and end of proximal tubule
Same, same as filtrate and to the plasma. Absorbs roughly equal quantities of water and solute, so you just reduce the volume of the filtrate but do not alter its concentration
Describe water/solute reabsorption in the loop of Henle?
Overall, it reabsorbs more solute than water. Thus, this dilutes the filtrate, since reabsorbate is hyperosmolar to plasma and the tubule fluid at the end is hypo-osmolar.
Describe the reabsorptionin the distal tubule/collecting duct
If ADH present: reabsorbs more water than solute, so the fluid becomes more concentrated.
What is sodium reabsorption coupled to in the proximal tubule?
Cl reabsorption (passively)

glucose, AA reabsorption

Secretion of H+ and Bicarbonate
How much glucose and AA is reabsorbed by the end of the proximal tubule?
What is the driving force to move Cl ions out of the limen and into the interstituim?
Wen Na moves across epithelium, it creates a charge difference such that lumen is neg to the interstitium. This drives the negative Cl- out of the lumen and into the interstitium
What is water movement driven by in the proximal tubule?
It is all passive diffusion through aquaporins/paracellular xport driven by OSMOTIC GRADIENTS set up by the transport of solute.
What would happen if you have an osmotically active solue in the proximal tubule that is NOT reabsorbed from the ultrafiltrate?
It can restrict water movement out of the proximal tubule and reuslt in an osmotic diuresis
Name such a substance(s) that can cause osmotic diuresis
glucose in diabetics
what happens to bicarbonate in the proximl tubule?
PT reabsorbs most of the filtered bicarbonate to preserve normal a/b balance
Describe the bicarbonate reabsorption process in the PCT
1) Epithelium secretes H+ ions
2) h+ combines with bicrobonate to form carbonic acid
3) carbonic acid associates with carbonic anhydrase on the lumen side of the apical membrane, forming H20 and CO2
4) CO2 rapidle enters cell by passive diffusion
5) inside cells, CO2 and H20 combine, in association with intracellular carbonic anhydrase, to form H+ and HCO3. H+ is secreted into the lumen in exchange for Na. The HCO3 is excreted out basolateral membrane in exhange for Cl- or passively.
what happens to urea in the PCT?
approximately 50% of filtered urea is reabsorbed here by PASSIVE DIFFUSION (PCT is very permeable to urea and filters 50% regardless of ADH presence.)

As water is reabsorbed in PCT, urea concentration rises and favors passive diffusion out of the PCT
What happens wrt drugs in the PCT?
Man drugs are secreted ito the filtrate here (PAH, penicillin, salicylate, morphine, wuinine) via specific transporters
How does inulin concentration show what happens with respect to water movement in PCT?
Inulin is not secreted or reabsorbed.

Inulin concentration goes up 3x in the PCT.

This must mean that water concentration is reduced to 1/3 of original, or redued by 2/3.
Characterize the fluid leaving the loop of henle
It is ALWAYS hypoosmolar to plasma and to the fluid that entered the loop of Henle from the proximal tubule
normal K concentration in the ECK
3.5 - 5
Normal Na concentration in the ECF:
what is the horizontal gradient int he loop of henle, ADH+ and ADH -
either one it is 200 (300 in DL, 100 in AL)
What causes the horizontal gradient?
Since on the AL, water is NOT reabsorbed, but Na is actively reabsorbed, dilution occurs in the AL compared to the DL
Describe longitudinal osmotic gradient along LOH, ADH+ and ADH -
ADH+, the longitudinal gradient is higher than in ADH-
what is the osmolarity of fluid in the descending LOH, ADH + and -.
either one, it is isosmolar to plasma, essentially.
describe urea concentration in LOH interstitium, + and - ADH
adh + : urea high (due to collecting duct mechanisms)

ADH - : urea low.
how does Na go back into tubule cells in the ascending limb?
via a Na/K/2C1 tranporter that transports all 3 ions oout of the lumen
What drug tarkets the na/k/cl cotransporter?
Furosemide (Lasix)
what is a side effect of lasix? why?

because there is not as much transport of K from the lumen into the tubule cells due to inhibition of the na/k/2cl cotransporter, and too much K is lost in the urine
describe steps of countercurrent multiplication
1) Pump/equil step: ascending limb pumps out Na+ into the intertitium to create a 200 gradient between AL and interstitium. Descending limb equilibrates to this new higher interstitial osmolarity
2) shift/equil step. new, lower osmo fluid enters descending limb. Mushes higher osmo fluid around bottom of loop. Bottom still high osmo, but top equilibrates with the isoosmolar new stuff.
3) pump equil step: AL pumps out Na into the interstitium, again setting up a 200 osmo gradient. Now osmo at bottom of loop is even higher
4) shif equil step: isoosmo new comes in top and equils with interstitium. new hyperosmo stuff is pushed round the bend....
what determines the magnitude of the longitudinal osmotic gratddient within the medullary interstitium?
1) lengths of LOH. Longer loop, more concentrating power

2) amount of urea in the interstitium. more wen ADH is present.
add one to the previous list
rate of flow thru the LOH. Increase flow rate reduces equil time and prevents maximal concentration
what is the functional significance of countercurrent exchange in the vasa recta?
countercurrent exhange of water and solute prevents the blood flowing through the vasa recta from dissipating the longitudinal osmotic gradients within the medullary interstitium.

note tho that ther is some net gain of solute and water by the vasa recta.
what are the functions of the distal tubule and cortical collecting duct
1) aldosterone independent NaCl reabsorption (early distal tubule)

2) ADH dependent water reabsorption
3) aldosterone dependent NaCl reabsorption
4) Aldosterone dependent K secretion
5) H+ secretion or HCO3 reabsorption regulated by acid/base status
does the early distal tubule dilute or concentrate?
dilutes. absorbs nacl but no water
what determines whether the hypoosmolar water in the early distal tubule is reabsorbed in the DT/CCD?
physio status and ADH concentration
what are the major roles of the medullary collecting duct?
1) ADH dependent water reabsorption
2) ADH dependent urea reabsorption
3) ADH dependent ability to excrete a max concentrated urine
4) aldosterone dependent Na reabsorption
how does ADH lead to urea exit from the Medullary CD?
Causes H20 to be reabsorbed. This effectively concentrates the remaining 50% of the Urea, causing it to move out passively from the MCD, via the ADH ACTIVATED UREA TRANSPORTER, UT1
what is ENaC
Sodium transporter on apical surface of principal cells of mid/late DCT and CCD.

Insertion in membrane an effect of aldosterone.
structure of ENaC
3 subunits
2 membrane spanning domains
functional properties of ENaC
1) high Na specificit
2) functional dependence on aldo for channel activation
3) specific expression in DCT, CCD, and a bit in the MCD
4) inhibition by amiloride
types and functions of intercalated cells in the DCT/CCD
1) alpha: secrete HCO3 and reabsorb H
2) beta: secrete HCO3 and reabsorb H
how is bicarbonate reabsorption different in alpha intercalated cells than in proximal tubule cells?
H+ is secreted not in exchange for NA, but either by an ATPase H+ transporter or an ATPas K+ antiporter.

The rest is the same: H+ combines with HCO3- in the lumen to form H2CO3. Carbonic anhydrase causes this to form H20 and CO2. Co2 diffuses into tubule cell. Carbonic anhdrasse causes it to combine wiht water to form H2CO3. Dissociates into H+ and HCO3-. HCO3 transported across basolateral membrane in exchange for CL. H+ is secreted into the lumen to start the cycle again.
why does urine pH not go below 4.5, even in acidosis and even after all the bicarbonate is "consumed"?
h+ combines wiht ammonia, or is excreted with phosphate buffers
What are the 2 general antidiuretic effects of ADH?
1) vasopressin effect: vasoconstriction
2) etc....?????????
does ADH effect total urinary solute excretion
NO. It just makes the same amt of solute be xcreted in a smaller volume of water
where is ADH made and stored?
made in magnocellular neurons in the hypothalamus

Stored in the posterior pituitary.
what triggers ADH release
increases in plasma osmolarity
what is normal plasma osmolatity?
280-295 mOsm/L
what happens when plasma osmolarity goes lower than normal
ADH plasma rapidly goes to zero
what is aquaporin 4's role in this
expressed by glial cells in the region of the hypothalamic osmoreceptors; thought to play a role in osmoreception
how might that aqp 4 related osmoreception work
glial cells take up water when osmolarity decreases. They constrict around the osmoreceptors, initiating neural input to the nurons what reduce ADH secretion
relationship of blood volume and ADH
Lower blood volume triggers ADH release through atrial stretch receptors.

HOWEVER: if blood volume alone is lost, ADH alone is not effective to maintan volume. ADH will be released, triggereing water reabsorption. However, if salt is not also reabsorbed, then this dilutes the plasma below normal. This blunts the ADH response, since low osmolarity triggers ADH inhibition fromm the hypothalamus
ADH and blood pressure
Blood pressure sensed by baroreceptors in the carotid sinus.

Decreased bp-->activates ADH secretion.

ADH causes vasoconstriction, which increases BP.

ADH also causes H20 Retention, to help increase BV and increase BP. Note though you run into the samme blunting effefct if ONLY ADH is used.
what does BP or blood volume do to thie curve regarding plasma osmolarity?
A decrease in blood pressure or blood volume shifts the ascending plasma osmolarity v plasma ADH to the left. Thus, at a given osmolarity, ADH will be higher if the blood volume or pressure is lower.
the slope of that curve increases in low BP/BV situation. That is, for a given change in osmolarity, the effect in terms of change of ADH will be GREATEER in times of low BV or BP
half life of ADH?
short. 20-30 minutes. this is important, because when we ingest water, we need to rapidly shut of ADH so we can diurese.
where is the V2 ADH receptor expressed in high levels?
Distal tubule and the collecting ducts
what is the overall effect of ADH:
increase in water permeability in the DT and CD, and increase in urea permeability in the MCD
how does ADH work exactly in the DT and the CD?
Binds to g protein receptor. Leads to increase in cAMP, which leads to activation of PKA, which phosphorylates AQP2, which is loaded on intracellular vesicles. Phosphorylation causes vesicles to be trafficked to apical membrane. Thus, AQP2 is added to the apical membrane. In these regions, AQP3 is consitutvely expressed on the basolateral membrane.
what are the additional effects of ADH in the medullary collecting duct
here it also causes increased shuttling of UT! to the apical membranes. Probably a mechanism similar to shuttling of AQP2 vesicles.

Urea leaves via AQP3.
summary of the aquapporins:
1) on apical and basolateral surfaces of the PCT and descending limb of LOH. Consitutive H20 transport

2) On apical surfaces of DCT and CD. Upregulated/activated by ADH dependent phosphorlyation

3) On basolateral membranes f disatal tubule and CDs. constitutively active. Also allows urea to leave in the MCD when ADH has induced UT1.

4) in glial cells around the hypothalamus, may be involved in osmoreception.
does ADH affect the ascendging LOH
maybe: some studies suggest that ADH upregulates the actions of the tri-ionic NA/K/2cl co transporter. This would increase the ability of the limb to make linear osmotic gradients.
symptoms of diabetes insipidus
hypernatremia (elevated plasma osmolarity)
cause of central diabetes insipidus. treatment?
posterior pituitary does not produce adequate ADH (pituitary tumor, trauma to the HYPOTHALAMUS (not pituitary))

can be treated by administering ADH.
Typical disease course of central DI following head injury
1) initial polyuria due to shock of nurons that prevents hormone release

2) 1-2 week period of appropriate release of ADH from damage deurons

3) then permanend DI develops as those neurons die.
Treatment of people with hypertonic hypovolemia
Given slow infusion of isotonic saluine. Why? Glia in the brain in times of high plasma osmolarity will retain a bunch of protein to keep fromm losing more water to the interstitium. If you give hypoosmolar salinee, water can enter neurons and cause cerebral swelling.
cause of nephrogenic DI
mutations in the V2 ADH receptor, or in the aquaporin 2 gene. Causes lack of responsiveness to ADH.
name a therapy for nephrogenic diabetes insipidus
paradoxically involves administering low dose diuretics. This induecs mild hypovolemia, which makes mechanisms OTHER THAN ADH kcik in to conserve salt and water, reducing the river like flood of piss that is passing through this persons nephrons
what hormone might be a mediator of thirst
why is renal autoregulation important?
it prevents or minimizes changes in GFR and RBF in response to transient BP changes that occur frequently throughout the day.
in what BP range does renal autoregulation operate?
what is the basic gist of autoregulation?
Renal vascular resistance increases in direct proportion to aortic blood pressure. Involves changes in the radius of the afferent arteriole and probaby the interlobular arteries. the adjustments are rapid and efficient.
what are 2 mechanisms responsible for autorgulation of renal blood flow and GFR
1) myogenic response:when SM in the arteries tension/pressure increases, it triggers contraction of the SM, decrease in radius, increase in resistance.

2) tubuloglomerular feedback mechanism involving the JGA
what is the JGA composed of
1) macula densa cells
2) extraglomerular mesangial cells
3) granular cells of the afferent arterials
is renein-angiotensin involved in tubuloglomerular feedback and autoregulation?
probably not
when is/isn't autoregulation effective?
It is good to prevent major changes when BP changes in the ABSENCE of alteration in na balance or ECV.

If there IS a change in sodium balance or ECV, other mechanisms overcome this.
is renein-angiotensin involved in tubuloglomerular feedback and autoregulation?
probably not
When is/isn't autoregulation effective?
It is good to prevent major changes in GFR/RBF when BP changes in the absence of Na level change or ECV change.

If that IS the case, then other mechanisms take over.
How does the JGA system work?
Cells in the macula densa, whiich is at the top of the ascending limb of the LOH, sense the "delivered load" of NaCL to that part of the tubule. If it is going up, as it woudl in increased BP, it sends signal to the granular cells around the afferent arteriole to constrict.
what is the idea of glomerulotubular balance?
refers to idea that at a CONSTANT ECV, changes in GFR are matched by proportionately similar changes in reabsorption of NaCL and H20.
so what is the basic deal with GTB
basically it means that the amount of NaCL reabsorbed is always a PERCENTAGE of the amount filtered, and is not just a constant amount. duh.
what drives glomeulotubular balance
Starling forces.

If you increase GFR, more filtrate is filtered out. What is left in the cap has an even higher oncotic pressure--proteins are more concentrated. Thus, there is an eeven bigger driving force to get H2O and salt out of the lumen, into the interstitium, and into the cap.

The reverse is true. When GFR drops, the efferent arterioles are more dilute. There is less COP that is driving stuff from interstitum into the Cap. Thus, there is more passive leakback back into the lumen, and less H20 and NaCl is absorbed.
how the body regulates ECV changes due to NaCL intake changes
(if you ingest NaCL, your ECV increases)

1) this causes BP to rise, which iinceases the pressure in the peritubular caps, and ddisfavors uptake of water and salt, and you lose the water and salt in the urine

2) causes blood proteins to be diluted due to the new volume. there is less COP, which disfavors uptake of water and salt, and they end up getting excreted
what is the net effect of this on the fractional reabsorption of NaCL
it effectively DECREASES the fractional reabsorption. But note--in the abselce of salt load or ECV changes, changes in GFR do NOT change the fractional reabsorption.
what does cardiopulmonary volume receptors in atria detect
circulating volume
what do baroreceptors in the carotid sinus detect?
arterial pressure
what do
granular cells or JG cells detect?
renal perfusion pressure
what do Macula Densa cells detect?
NaCL delivery to the distal tubule
describe the workings of granular cells in the JGA
When they sense decreased renal perfusion pressure, they increase RENIN release.

when they sense increased renal prefusion pressure, they decrease renin release.
How do the macula densa cells operate?
Increased NaCL delivery causes:

1) signal to be sent to granular cells arond the afferent arteriole to constrict

2) signal sent to granular cells to decreasae renin release.
How does ANP work?
Synthesized by cells in the cardiac atria in response to increased volume detection.

1) Acts to INHIBIT Na Reabsorption in the collecting duct.

2) Dilates afferent arteerioles to increase GFR
How Do the renal sympathetic nerves work?
1) when ECV or BP decreases, sympathetic drive increases

2) this causes constriction of afferent arteriole. This decreases GFR.

3) it also causes increase in Na/H antiporter in proximal tubule, leading to more Na retention.
describe the renin-angiotensin-aldosterone system
Decreased ECV or BP causes renin release from granular cells, due to both sympathetic drive and to signals from the macula densa which senses decreased Na delivery.

This causes renin to convert angiotensinogen to ang I, and ACE then converts Ang I to Ang II.

Ang II Stimulates adrenal cortex to make aldosterone
Ang II effects:
1) stimulates smooth muscle contraction, increasing TPR and blood pressure.

2) causes contraction of efferent (and afferent) arteriole. Even though other things (sympathetiic drive) are causeing DECREASE in RBF, this helps maintain adequate GFR so that kidney fxn doesn't cmopletely fail

3) causes stimulatino of Na/H antiporter in the proximal tubule, increasing Na and H20 reabsorption

4) stimulates aldoterone secretion

5) stimulates ADH secretion, which causes reabsorption of urea and water in the distal segments, allowing for maximal water conservation

6) stimulates thirst center
What all stimulates renin release
1) ECV contraction (low volume, increased sympathetic drive from carotid body)

2) NaCL load detected lower by the macula densa, which in turn gets granule cells to secrete more renin.

3) decreased afferent arteriole pressure in the granule cells itself senses low pressuer and stimulates renin releease
What does aldosterone do?
1) synthesis in the zona glomeulosa in the adrenal gland is stimulated by ang II.

2) STEROID HORMONE that acs on the DT/CD and the colon. Thus there is a latent period that requires that new proteins be synthesized: probable Enac, among other things (like CAP--channel activating protein, and something like ROMK but for the distal segments)

3) increases reabsoption of Na in the kidney and in the colon
Known renal causes of hypertension:
1) renal artery stenosis. If it happens proximal to the glomeulus, then the granule cells will sense DECERASED pressure and will trigger renin release...Angiotensin will trigger its constriction of blood vessels, retention of Na, retention of water (via ADH), increasing BP. BUT: if you give ACE inhibitors, then you lose the Ang II constiction of the efferent arteriole, and GFR may drop too far!!

2) Hyperaldosteronism. Adrenal tumor-->too much Aldosterone-->too much Enac, etc and retention of Na.

3) Glucocorticoid remediable aldoosteronism: feedback mechanism for aldosterone messed up. Give glucocorticoid (cortisol) to supress the ACTH that is incorrectly upregulating the aldosterone.

4) ENaC mutations (Liddles). Causes overpresent, overactive ENaC.

5) Mineralocorticoid excess. Present with aldosteroneexcess...too much cortisol, and it is acting inapropriately on the receptor.
Diuretic that acts on PROXIMAL TUBULE. Inhibits carbonic anhydrase, decreases Na/H exchange
Furosemide (Lasix)
Inhibits Na/K/2Cl transporter in loop of henle. Increases K excretion!
Acts on distal tubule Na/Cl cotransporter
Acts on ENac in the DT/CD
Antaonist of the mineralocortocoid receptor. Decreases ENac activation by aldosterone.