Renal Phys- Muster Flashcards
What are the 3 primary signaling pathways that stimulate renin release?
- sympathetic imput (increased NE)
- Decreased stretch in the afferent arteriole
- Decreased chloride (Na+) delivery to the Macula Densa
What are the primary actions of angiotensin II?
- Stimulates ALDOSTERONE
- Systemic Vasoconstrictor
- Stimulates Proximal Tubule Reabsorption of Na+
- Increases sympathetic activity
Where is aldosterone secreted from?
Cortex glomerulosa of adrenal gland
What does aldosterone do once it leaves the cortex glomerulosa of the adrenal gland?
Lipophillic
Crosses membrane, and binds steroid response element
Increases transcription of:
- Na/K ATPase on basolateral side
- ENac channel on luminal side (Na gets reabsorbed)
- ROMK channel (K+ leaves cell)
What is Liddle Syndrome?
Gain of function mutation
Increases ENaC channels
Increased Na+ reabsorption in collecting tubules
Autosomal dominant
Results in hypertension, hypokalemia, metabolic alkalosis, decreased aldosterone
What is Gitelman Syndrome?
Reabsorptive defect of NaCl in DCT
Autosomal recessive
Leads to hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria
Bartter Syndrome
Reabsorptive defect in thick ascending loop of Henle
Autosomal recessive
Affects NKCC cotransporter
Results in hypokalemia and metabolic alkalosis with hypercalciuria
What symptoms would you expect with a low serum concentration of Na+
Nausea Malaise Stupor Coma Seizures
What usually causes hyponatremia with low urinary osmolarity
Almost always due to excessive water intake (primary polydipsia) - typically a psych disorder
What is normal serum sodium concentration?
135-145 meq/L
What equation can you use to estimate the plasma/serum osmolarity? What should it be at?
Serum osmolarity = 2[Na] + BUN/2.8+ Glucose/18
Should be 285-300
Where does ADH bind? Then what happens?
V2 receptor in collecting tubules
- activates a protein kinase
- causes Aquaporin 2 to move from cytoplasm to luminal membrane
- forms water channels
ADH is released in response to?
Serum hyperosmolarity
Hypovolemia
What should you do if patient has hyponatremia and the urinary osmolarity is > 100? (Concentrated urine)
Looks at urinary Na+ concentration and volume status (on physical exam)
How do you treat hyponatremia if patient is also volume depleted?
Give normal saline to replenish volume and turn off ADH
How do you treat hyponatremia when neutral volume or volume expanded?
Restrict fluid intake!! or treat states of poor perfusion
May also give ADH antagonist
MOA of Tolvaptan and Conivaptan?
ADH antagonists –> target ADH receptors
Indicated in volume expanded hyponatremia
At what rate should you correct hyponatremia out of the “danger range”?
0.5 meq/L/hour
What is the “danger range” of hyponatremia?
115-120
What treatment should you use if hyponatremia and serum sodium is 115-120?
3% NaCl solution
If siezures - 100 cc over 10 mins IV
If just other neuro symptoms- 30-50 cc/hr for several hours
In what circumstances would you see hypernatremia?
due to excessive water losses and inadequate intake
What is the difference between Central diabetes insipidus and nephrogenic diabetes insipidus?
central = hypothalamus/pituitary axis not releasing ADH so kidney can’t reabsorb free water
nephrogenic = collecting tubules don’t respond to ADH so kidney can’t reabsorb free water
*can be partial or complete!
What medication can induce nephrogenic diabetes insipidus?
LITHIUM!
What fluids would you give for hypernatremia?
Free water orally
D5W IV
1/4 NaCl for hypernatremia due to volume depletion (Na+ is also depleted)
NS if patient is hypotensive with fluid losses
What is normal serum K+ concentration?
4-5 meq/L
What are the two primary functions of potassium?
Cell metabolism (protein and glycogen synthesis)
The RATIO of intracellular/extracellular is primary determinate of resting membrane potentials
How much K+ is stored intracellularly?
98%
How does Insulin affect the activity of the Na/K+ ATPase?
Increases its activity!
Promotes skeletal and muscle uptake
When we eat, we stimulate insulin, which alleviates a sharp rise in concomitant K+ serum levels
How does catecholemines affect the Na/K ATPase?
B2 receptors stimulate the Na-K ATPase inducing cellular uptake
Immediate treatment for hyperkalemic patient
INSULIN! (and glucose)
Give Ca+ to stabalize cardiac membrane (lasts 45 minutes)
Which part of the nephron is the primary site for K+ excretion?
Principle cell in the collecting duct!
Which two channels facilitate the excretion of K? Are they always in the membrane?
ROMK - stored intracellularly and inserted
BK - always in membrane, but only open at HIGH [K+]
What symptoms would you see in hypo/hyper kalemia?
-symptoms relate to inability to generate action potentials in muscles
Cramps
Muscle weakness/ paralysis (starts in the legs)
EKG changes
Cardiac arrhythmias
List the primary solutes of the different body compartments
Intracellular = K+, PO4, and anions
Intravascular (plasma) = Na+
Interstitial = Na+
What percent of your body is water? How much is intracellular? interstitial? Plasma?
60% (50% in females)
2/3 of that is intracellular
Of the remain 1/3
3/4 of that is interstitial
1/4 of that is plasma
What compartments does normal saline distribute to?
Interstitial & Plasma!
Extracellular volume will increase
No effect on intracellular volume or osmolality –> cannot enter cells!*
If you drink water, how will it distribute in your compartments?
It will distribute proportionately according to the volume of the compartments
How does 1/2 normal saline distribute to the compartments?
Basically half acts like normal saline and half of it acts like you drank water
Extracellular volume increases
Slight increase in intracellular volume
Osmolality slightly decreases
USE FOR SWEAT LOSSES
How will D5 Fluid distribute among the compartments?
5% dextrose
will distribute just like water because glucose is taken up by cells, water follows, and then the sugar is degraded completely
If can’t drink water, then give D5
Distinguish between volume depletion and dehydration
Volume depletion = extracellular volume loss for ANY CAUSE (most often loss of salt and water)
Dehydration = presence of HYPERNATREMIA due to pure water loss
What fluids would you give for diabetetic ketoacidosis? sepsis? secretory diarrhea?
Normal Saline
What fluids would you give for sweat losses? Or sick old people in the hospital?
1/2 normal saline (replace sweat with sweat!)
What fluids would you give for diabetes insipidus or severe hypoglycemia?
D5
How many L of water does a normal healthy young 70 kg person contain?
42 L of water (60% of body weight!)
How many liters does the kidney filter in one day (normal GFR)?
What is this per minute?
180 L/ day
125 mL/min
What are the three things that limit size of particle filtrated through the glomerulus?
Capillary Endothelium (has fenestrations) Basement membrane Podocytes (small negatively charged slits)
Do anionic or cationic particles get filtered less? why?
anionic particles get filtered less because the GBM and the slit diaphragms of podocytes are negatively charged
What equation describes the fluid/solute movement from the capillary lumen into bowman’s space?
GFR = K [Hydrostatic P in capillary + Oncotic P in BS) - (hydrostatic P in BS - oncotic P in capillary)
GFR = (forces favoring filtration) - (forces favoring reabsorption)
What happens to RPF, GFR, and FF when there is constriction of the efferent arteriole?
Decreased RPF
Increased GFR (capillary hydrostatic pressure increases due to fluid “backing up” into the glomerulus)
Increased FF
What is filtration fraction?
FF = GFR/RPF
What happens to RPF, GFR, and FF when there is constriction of the afferent arteriole?
Decreased RPF
Decreased GFR
No change in FF (since both RPF and GFR are decreased)
What happens to RPF, GFR, and FF when there is dilation of the efferent arteriole?
Dilation of efferent arteriole causes a drop in glomerular hydrostatic pressure decreasing GFR
RPF is increased
Filtration Fraction is decreased
Does plasma protein concentration affect GFR or RPF? FF?
Increased [plasma proteins] = increased capillary oncotic pressure –> decreased GFR –> decreased FF
Decreased [plasma proteins] = decreased capillary oncotic pressure –> increased GFR –> increased FF
NEITHER affect the renal plasma flow
How does angiotensin II affect the arterioles of the glomerulus?
Preferentially constricts the EFFERENT arteriole
How does NE affect the arterioles of the glomerulus?
Constricts EFFERENT and AFFERENT arterioles
Decreased RPF
Decreased hydrostatic pressure and greatly decreased GFR
Describe glucose reabsorption in the proximal tubule….. what kind of transporter is it? Can it be saturated?
SLGT = sodium linked glucose transporter
CAN be saturated = Tm (transport maximum)
Will start to see glucose in the urine at 200 mg/dL (threshold)
All transporters are fully saturated at 375 mg/dL
NOTE* pregnancy will decrease threshold!
In the absence of ADH, which part of the tubule will the lumen have the highest osmolarity? How concentrated can the urine become?
Medullary segment of the loop of Henle
Will reach 600 osms
**will be most dilute at collecting ducts in absence of ADH!
What part of the nephron does ADH act on?
The collecting ducts!!!! Increases permeability to water, and concentrates urine
Loop diuretics such as furosemide and bumetanide inhibit the NKCC pumps, but to compound their diuretic effect, what else do they do?
Stimulate PGE release, this vasodilates the afferent arteriole
This increases the RPF and increases the GFR complementing the diuretic effect
What is the equation for determining clearance?
Clr = [x in urine]*[urine flow rate]/[x in plasma]
How do prostaglandins effect GFR?
They vasodilate
Decreased glomerulus hydrostatic pressure
Decreased GFR
What % of fluid is intracellular and extracellular when you give 1/2 NS?
66 % is extracellular and 33 % is intracellular.
How much blood do the kidneys take in per minute?
1000 mL/min
Vasoconstricting agents constricts what 2 vessels?
It has a greater effect on which one? Why?
Afferent and Efferent Arterioles
Has a greater effect on the efferent arteriole because it is smaller!
How do you determine Filtered Load?
[x serum] x GFR
Equation for excretion rate?
[urine concentration of x] x urine flow rate
What are the properties of the ideal solute you’d want to use to measure GFR?
Filtered load = excretion rate
Solute is completely filtered, not secreted, or reabsorbed
Describe the formate recycling process. Location, direction of ion travel, etc.
Most of the formate anti-porters are in the LATE proximal tubule.
Chloride accumulates and by the time it reaches the late proximal tubule, there is a gradient for it to move inward through the antiporter that moves formate outward.
What are the directions of the ions flowing in the Na+/H+ pump?
Sodium into the cell
H+ into the lumen
2 places where there are no aquaporins?
Thick ascending limb of loop
Distal tubule
Why do we see metabolic alkalosis in Bartter and Gitleman’s syndromes?
Because there is a huge drive to pull Na+ in in the proximal tubule since it is not being reabsorbed later on. This occurs via the Na+/H+ antiporter, so we are losing H+ in the process!
In what situation would your FeNa look high and be un-interpretable?
After you give a diuretic!
What are the 3 active transporters in the alpha-intercalated cell?
Na+/K+ ATPase on the basolateral membrane
K+/H+ antiporter on the lumenal side (K+ in, H+ out)
H+ ATPase lumenal side (H+ out)
What antiporter is also present on the basolateral membrane of alpha-intercalated cells?
Bicarbonate/Chloride antiporter
bicarbonate to interstitium/chloride into cell
What are the effects of PTH on the kidney?
What part of the kidney?
Increased Vitamin D production (increases gut absorption of calcium)
Increased calcium reabsorption
Decreases renal phorphorous absorption
-Distal Convoluted Tubule
Where does glutamine uptake occur?
Proximal Tubule
1/3 of urinary H+ is buffered by what?
Phosphorous
What 2 major things are getting reabsorbed in the alpha-intercalated cell?
K+
Bicarbonate
What effect could an opioid have as far as acid/base problems go?
Respiratory acidosis because they decrease respirations–build up of CO2
What 2 renal enzymes would be upregulated in the case of a respiratory acidosis?
Glutaminase
Carbonic anhydrase
Describe what would happen during a panic attack.
What does the kidney do?
Too much breathing–>CO2 given off–>Respiratory Alkalosis
Beta-intercalated cells will appear in the kidney to excrete bicarbonate
Hypokalemia can induce what sort of acid/base imbalance?
Metabolic Alkalosis
Lose H+ ions if hypokalemic.
Alpha-intercalated cells are going to try to Reabsorb more K+, in which case H+ is excreted
(K+ in, H+ out into lumen)
Is osmolality in the interstitium usually the same, hypo, or hyperosmolar to the tubule?
Hyperosmolar
Where is 50 % of urea reabsorbed?
Proximal Tubule
How is urea absorbed in the proximal tubule?
PARACELLULARLY! (through tight junctions…. NOT transporters on the membrane!)
Which urea transporter is stimulated by ADH production and helps reabsorb urea?
UT1
Which urea transporter contributes to urea recycling by secreting urea back in to the thin segments of loop of henle?
UT2
Where would you find the UT1 transporter along the nephron? (in response to ADH of course!)
in the MEDULLARY collecting duct!! (the distal 1/3 of the collecting duct)
What is glutamine split into? Why is its uptake up-regulated in acidosis?
Glutaminase splits glutamine into NH4 and 2 bicarbs.
Up-regulated in acidosis to increase bicarb levels in blood
(bicarb gets sent out the backside with Na+ with a 3:1 ratio)
Why would you see proteinuria in DKA?
Patient becomes hyponatremic.
Sodium/AA transporters in PROXIMAL TUBULE cannot function properly.
AA stays in the lumen and is excreted in urine
Where is K+ reabsorbed?
Alpha-intercalated cell
Where is calcium reabsorbed?
Distal convoluted tubule!
