Renal- Applied Renal Physiolgy

Front 1

Generalized defect of PCT function

Back 1

Fanconi's Syndrome

Front 2

1) 1/3 of Na flux across the apical PCT membrane is via the _____ pump

2) 2/3 of Na flux across the apical PCT membrane is via______

Back 2

1) Na/H exchange
2) Various Na/solute exchangers (Na/gucose, Na/AA, Na/HPO4)

Front 3

1) 90% of filtered bicarb is reclaimed where?
2) 10% of filtered bicarb is reclaimed where?

Back 3

1) PCT

2) Intercalated cells of DCT and CD

Front 4

Modulators of PCT transport
1) Angiotensin 2 causes?
2) PTH

Back 4

1) Increased Na/H exchange
2) decreased Na/HPO4 transport

Front 5

Describe how PCT reclaimes HCO3-

Back 5

Filtered Bicarb cannot cross apical membrane so the PCT pumps out H+ and with Na+ uptake. H+ in lumen combines with H+ to form CO2 and water. CO2 moves into the PCT cell. Here CO2 combines with water to form carbonic acid which then dissociates into bicarb and H+. H+ is pumped back into the tubular lumen (across the apical membrane) via the Na/H antiporter. Bicarbonate is then transported across basolateral membrane via the Na/2HCO3- symporter. All reactions are catalyzed by Carbonic Anhydrase.

Front 6

The transcellular movement of salt and water is all driven by the______

Back 6

Na/K ATPase which maintains low intracellular Na+ concentration to force salt and water absorption, and then pumps the salt into the pericapillary space where water follows it to.

Front 7

What forces drive capillary uptake of reabsorbate?

Back 7

NA/K ATPase pumps salt into the pericapillary space. THe water which follows causes hydrostatic pressure in the space. The albumin in the capilaries causes high oncotic pressure pulling the water into the capillaries.

Front 8

What are the two possible fates of protein that makes it into Glomerular filrate

Back 8

Albumin is transcytosed into pericapilary space OR proteolyzed in proteasome for reuse as AAs

Front 9

What specific kidney location is responsible 1-alpha hydroxylation 25-OH D3?

Back 9

PCT

Front 10

What are the 6 symptoms of Fanconi's Syndrome?
be sure to include acid/base

Back 10

Glycosuria
Aminoaciduria
Phosphaturia
Kaliuresis
Metabolic Acidosis (Due to absence of PCT Na+/H+ exchangers)
Natriuresis

Hint 10

GAPKMN

Front 11

Why does Fanconi's cause metabolic acidosis?

Back 11

Cannot reclaim bicarb and loss of Na/H exchanger in PCT

Front 12

Reason why K+ is wasted in Fanconi's syndrome

Back 12

K+ is usually reabsorbed in the PCT and TLH. THe PCT is non-functional here, and TALH K+ reabsorbtion is normally done by exchange for Na+. BUT If more Na+ is presented then, then this favors the opposite direction where Na+ is reabsorbed, and K+ pumped back into tubular lumen.

Front 13

Histology of Fanconi's

Back 13

PCT atrophy

Front 14

Fanconi's: Choose Low or High
1) ____ Na+ intracelularly
2) _____ ATP prodcuction
3) _____Number of solute transporters

Back 14

1) high
2) Low
3) Low

Front 15

Possible etiology of Fanconi's

Back 15

1) Genetic defect of production of something in mitochondria that gives decreased ATP production (poorly oxidative). This may be aquired when the damage is caused by a filtered drug

Front 16

What causes nephrogenic Diabetes Insipidus

Back 16

Unresponsiveness of the CD to ADH such that apical Aquaporins cannot be added to membrane to allow water uptake.

Front 17

ADH causes the insertion of ___1____ aquaporins in the CD, ____2____ aquaporins are always present

Back 17

1) apical
2) basolateral

Front 18

Mechanism by which ADH causes aquaporin exocytosis?

Back 18

In kidney, V2 receptor (in response to ADH) stimulates via GPCR to raise cAMP to activate PKA to cause cigar shaped membrane vesicles full of aquaporins to fuse into membrane (for this to happen, vesicles must fall off tracks by being phosphorylated and have increase in intracellular calcium, both of which are caused by ADH)

Front 19

1) Childhood presentation if DI
2) milder presentation of DI

Back 19

1) frequent urination and nocturnal enuresis
2) headache and change in mental status after water deprivation due to brain shrinkage

Front 20

defects that can cause DI.

Back 20

1. A signal transduction defect (basolateral V2 receptor)
2. Defect in aquaporin itself
3. General- cannot respond to ADH causing inability to reabsorb water.

Front 21

Unusual urinary finding in ADI

Back 21

AQP channels in urine

Front 22

Describe interesting treatment of nephrogenic DI.

Back 22

Vasopressin AND Chemical chaperones which can favor folding and insertion of AQP channels

Front 23

Define Liddle's syndrome

Back 23

isolated gain of function of epithelial Na channel (ENaC

Front 24

ENaC are found in the _______

Back 24

collecting duct

Front 25

Symptoms of Liddle's
1) ___natremia
2) ___kalemia
3) acid/base status

Back 25

high Na+ (hypernatremia)
Low K+ (hypokalemia)
Metabolic Alkalosis

Front 26

1) Cell in the CD where ENaCs are located?

Back 26

Principle cell

Front 27

1) Function of Alpha cell of the CD?
1) Function of Beta cell of the CD?

These two can have thier levels regulated in response to diet

Back 27

1)H/K ATPase secrees acid and reclaims K+
2) H/K ATPase secretetes K+ and reabsorbs H+ (sometimes said to secrete bicarb, but this is just a functional description, really is absorbs H+)

Front 28

1) what causes the TEP to be lumen negative and how does this effect H+ transport?

Back 28

The lumen negative TEP is caused by the Na/K ATPase which brings a net positive charge into the cell. This lumen negative potential favors H+ exit from the alpha-intercalated cell

Front 29

How does aldosterone stimualte Na+ reabsorbtion?

Back 29

stimulates making of new ENaC channels, insertion of ENaC Channels, and stimulates insertion of basolateral Na/K ATPase's

Front 30

How does ANP stimulate natriuresis?

Back 30

stimulates adenylatate cyclases to make cGMP that bind on ENaC channels to plug them up from the inside

Front 31

Alternate name for Liddle's syndrome

Back 31

Pseudohypoaldosteronism of Collecting duct origin

Front 32

Symptoms of Liddle's syndrome
1) ______natremia
2) metabolic ______osis
3) ____ aldo levels
4) ____kalemia
5) ____urinary H+ and K+

Back 32

1) salt dependant hypertension in the young
2) metabolic alkalosis
3) low aldosterone levels
4) hypokalemia
5) High urinary H and K

Front 33

Tx of Liddle's?

Back 33

ENaC blocker (amiloride)

Front 34

Does Liddle's recur post-transplant?

Back 34

No

Front 35

What is the response of a pt. with Liddle's to:
1)Aldosterone administration
2) ANP administration

Back 35

1) even MORE sodium retention becaue
2) relief because ANP causes ENaC phosphorylation and inactivation

Front 36

What is the molecular basis of Liddle's syndrome

Back 36

1. ENaC inserted exocytotically into apical membrane but truncation of Cytoplasmic domain of ENaC (PY region) → slow channel removal of channel for endocytosis targeted to channel destruction by proteosomes (faulty binding of Nedd4, a ubiquitin-ligase)

Front 37

Amiloride (used for Liddle's)
1) action?
2) K + sparing?

Back 37

1) flicker block of ENaC causing less reabsorbtion of Na+
2) yes

Front 38

1)What general event causes Acute Renal Failure?
2) What is the histological description of this condition

Back 38

1) Hypoxic Kidney insult
2) reversible epithelial disorganization after hypoxic injury

Front 39

what areas is most vulnerable to hypoxic insult?

Back 39

corticomedullary junction (TALH and PCT) because these already have marginal bloodflood and are a little hypoxic at baseline

Front 40

Changes in renal epithelium during acute renal failure?

Back 40

Unstable brush border
leaky tight juntions
loss of integrin attachment to ECM
cell slouging off BM

Front 41

Time scale of recovery from acute renal failure
1) no need to regenerate from stem cells
2) need to regenerate from stem cells
3) bad damage

Back 41

1) days
2) weeks
3) lifetime

Front 42

Three general legs of the CVMP in the face of needing to preserve ECF and IV volume

Back 42

1) thirst activation
2) sympathetic drive
3) endocrine and neural input to kidney

Front 43

Describe the CVMP input to the kidney in the face of hypovolemia, whenblood is being shunted away from kidney.
1) where does this input act in the kidney, causing production of what hormone?
2) how does this hormone lead to downstream maintentance of GFR (increase in filtration fraction) in the face of decreased renal perfusion?

Back 43

1) Sympathetic input stimulates JGA which stimulates Renin and eventually Angiotenstin production.
2) AII constricts afferent and efferent arterioles directly, BUT stimulates PCT cells to make a local vasodilator (PGE2) which works only on the afferent arterioles yielding NET increase in filtration fraction and maintenance of GFR. Due to dilation of afferent and constriction of efferent.

Front 44

CVMP is inhibited by what?

Back 44

Carotic barorceptor activity (sufficient pressure)

Front 45

In the case of high BP, what hormone will be secreted and how is this controlled?

Back 45

High BP causes atrial stretch which causes ANP secretion, allowing Na+ diuresis