Physiology Flashcards
What % of potassium is intracellular? In what cells is it located?
What is considered hypokalemia?
Hyperkalemia?
What percentage is filtered then reabsorbed?
98% is ICF Muscle cells <3.5 mEq/L >5.0 mEq/L 86.1%
A histological slide shows shrunken cells. What can you infer about the K+ concentration?
There’s low levels of ICF plasma Potassium in the cells as well, what might this indicate?
Cell shrinkage = Loss of K+
Cell swelling = Gain of K+
Low plasma [K+] = Cell alkalosis
High plasma [K+] Cell acidosis
Calcium is mostly stored where? What percentage?
How much is bound to plasma proteins?
What effect does hypocalcemia have on muscle tissue?
What percentage is filtered then reabsorbed?
99% in bone
40% bound to plasma proteins
Hypocalcemia: increases excitability (decreased charge makes it easier for Na+ to get across membrane)
Hypercalcemia: decreases excitability
98.2%
Lab test shows elevated serum calcium, what are 2 differentials?
Now it’s low serum calcium. 3 differentials?
Elevated Serum Ca
Primary hyperparathyroidism
Malignancy
Low Serum
Hypoparathyroidism
Renal Disease
Vitamin D Deficiency
Where is phosphate stored? How much is bound to protein? HOw much of the unbound phosphate is filtered? Reabsorbed in PCT? Reabsorbed in PST?
85% in bone
14% ICM
31% is protein bound
90% filtered
70% reabsorbed PCT
15% reabsorbed PST
In phosphate metabolism, what is the dietary role?
Calcitriol?
PTH?
Renal Tubular?
Diet: Intake and absorption
Calcitriol: Increase phosphorus resorption from bone and absorption from intestine
PTH: Phosphorus resorption directly from bone. Sitmulates calcitriol
Renal Tube: Reabsorption of phosphorus. Stimulated by Tubular filtered load and inhibited by PTH.
A patient can present to the clinic with a variety of symptoms such as: Muscle cramps, epilepsy, SIDS, arrhtymia and migraines. What could cause these things?
Magensium deficiency
What is the MOA of pseudohypoparathyroidism?
Crappy GPCR complex
How much Mg is bound to plasma proteins? How much is filtered? Reabsorbed in PCT? Thich ascending LoH? DCT? Where is magnesium stored?
Bound: 20% Filtered: 80% PCT: 30% LoH: 60% DCT: 5%
50% bone, 49% ICF
What is the MOA of calcitonin?
What conditions may lead to stimulation of calcitonin?
- opposes PTH
Hypercalcemia –> Calcitionin –> promotes phosphate and calcium excretion
Osteoporosis
Paget’s disease
Hypercalcemia
What is the MOA of calcitriol?
Calcitriol = Vitamin D
binds to Vitam D receptor –> promotes phosphate and calcium reabsorption
A molecule must use the transcellular route to get through the endothelial cells of the tubules. What does this mean?
Goes straight through the cell, through the apical membrane –>
Diffusion through cytosol –> Transport across basolateral membrane –>
Through the interstitial space
Avoids tight junctions!
A molecule must use the paracellular route to get through the endothelial cells of the tubules. What does this mean?
Goes around the cells and through tight junctions. Mostly in the PCT
A cell needs a carrier to get through a membrane, but ATP is not needed. WHat type of transport is this?
Facilitated diffusion
You get to Wall Street and 26th and notice the one way doesn’t turn green unless there are 2 vehicles going the same direction. It seems the Jopper driver finds it harder to speed up than the California license plated driver. This reminds you of what type of transport? What molecule represents the California driver? What tissues is this found in?
Give 3 examples
Cotransport
ATP used indirectly
Na+ is going downhill, others are uphill.
Renal tubule and small intestine.
SGLT (Na, Glucose)
Na+, amino acid cotransport.
Na, K, 2Cl- cotransport.
What type of transporter is the NXC transporter?
What about hte Ca ATPase?
How do they work?
Countertransporter
Use energy from Na K ATPase. Solutes move opposite directions
3Na for every 1 Ca
Which transporter uses ATP directly?
Primary active transport
Carriers have to mediate 3 things. What 3 things affect carriers?
- Saturation: Limited number of binding sites, so once saturated, you’ve hit Tm and rate levels off.
- Stereospecificity: Only transports certain conformations of a molecule (simple diffusion takes glucose, stereospecificty says only L-type glucose)
- Competition: Chemically related solutes compete for the spot.
What specific transporter is located on every cell’s membrane?
What is it’s MOA? include shapes and ratios.
Na K ATPase
3Na –> ECF
2K –> ICF
alpha subunit is where things bind.
- E1: Let go of K+
- E1 –P : grabs onto 3 IC Na
- E2-P: Lets go of Na+
- E2: grabs onto EC K+
What specific transporter is found on gastric parietal cells and alpha intercalated (dark cells) in the renal collecting duct?
What is it’s MOA?
H/K+ ATPase
Pumps H+ from ICF to lumen of stomach.
What specific transporter is located on Sarcoplasmic reticulum and Endoplasmic reticulum?include shapes and ratios
Ca++ ATPase
AKA PMCA
1 Ca++ = 1 ATP
E1 binds IC Ca++
E2 releases Ca to EC
A pt presents with frequent urination and elevated glucose levels in blood and glucosuria. What causes glucosuria?
Diabetes Mellitus, Pregnancy, Congenital abnormality of Na- glucose cotransporter.
What is MOA of glucosuria and diabetes mellitis?
Pregnancy?
Crappy Na Glucose cotransporter?
DM: no insulin to uptake glucose –> glucose overwhelms the cotransporter –> not as much reabsorbed
Pregnancy:
GFR increased -> increased filtration –> So much filtered that Cotransporter is overwhelmed.
Crappy Na glucose cotransporter:
Decreased Tm, glucose excreted at lower than normal plasma concentrations.
Why does splay happen?
Reabsorption is aproaching saturation but hasn’t gotten tehre yet, glucose is still excreted. Why?
Low affinity of Na- glucose cotransporter -if glucose falls off, it’s not getting back onto another one because they’re full.
All nephrons do not have the same Tm
Why is the TF:P ratio valuable?
If you have high TF to P, what can you assume?
WHat 4 molecules will have a TF greater than a P?
Helps distinguish how much is being filtered into urine/ultrafiltrate and how much remains in plasma.
Substance is reabsorbed less avidly than water (more excreted)
Inulin, PAH, urea, Cl-
In the Early Proximal COnvoluted Tubule, what is absorbed at 100% 70% 50% 30%
100: glucose and amino acids
70: H2O, PO4, K+, Ca+, Na+
50% urea
30% Mg++
How does water diffuse through the glomerular complex?
Aquaporins
In the late proximal tubule what is absorbed?
Na+ and Cl-
Absorbed via Na - H antiporter and Cl- base antiporter
How is glucose reabsorbed?
In the early PCT
Apical = SGLT
Basolateral = GLUT1
(SGLT = Na/Glucose symporter; secondary active transporter)
What is the apical membrane?
What is the basolateral membrane?
Apical = tubular lumen –> Endothelial cell
Basolateral membrane = Endothelial cell –> Interstitial/blood
If GFR is increased and plasma glucose concentration remained constant, how would this affect the filtered load?
Would the threshold of glucose saturation value change?
Increase filtered load
Theshold would not change, but due to the increased filtration, you may have too much glucose in blood to be reabsorbed.
You administer a drug that inhibits Na K ATPase. What happens to reabsorption of glucose?
Na/K ATPase maintains the low Na+ content inside the cell so the SGLT transporter can use Na/glucose cotransporter to go inside.
So if you messed up the Na/K, you would mess up all SGLT transporters, lowering the glucose reabsorption
You administer a drug that inhibits OATs.
What builds up on the tubule lumen side?
MOA of OAT?
aKG
Organic anions out of the cell for aKG into the cell
What other transporters does Na/K ATPase power?
Na+ /HCO3 /AA /Pi /H+ SGLT anything using Na+ to get in
In what ways does aKG get into an endothelial cell?
OAT4 (1,2,3)
NaDC3
How does an organic anion cross the basolateral membrane, and the apical membrane?
Basolateral: OAT 1,2,3,
Apical Membrane: OAT4
How does an organic cation cross the basolateral membrane, and the apical membrane?
Basolateral: OCT2 (uniporter)
Apical: MDRI ( ATP), MATE (H+)
PAH is filtered, secreted and excreted. Why is so much excreted?
Very low Tm
As the plasma concentration of PAH goes up, what happens to its clearance?
What about inulin?
And glucose?
Which clearance represents GFR?
PAH: Clearance decreases to 125
Glucose increases to 125
Inulin stays at 125
Inulin.
As the plasma concentration increases, what happens to the urinary concentration of PAH, inulin and glucose?
PAH goes up incredibly fast,
Inulin increases at a steadfast rate
glucose increases slowly at first, then faster.
When can acids and bases cross the membrane?
Once they have been neutralized.
You neutralize a weak acid with acid environment.
You charge a weak acid with basic environment.
An acidic environment favors reabsorption of what? What gets trapped in the tubule?
organic weak acids
Organic weak bases
(Vice versa for bases)
Your pt has an acidic environment in his urine. What is your goal and how do you treat this pt?
Keep HCO3- from being reabsorbed or take more H+ out of tubule.
Tx: actiated charcoal and Sodium bicarbonate IV
What are 4 factors that shift K+ into ICF?
What factors shift K+ Out of cells?
In: Insulin Aldosterone beta adrenergic stimulation Alkalosis
Out: Diabetes mellitus Addison's disease (low adlosterone) B adrenergic blockade Cell lysis Strenuous exercise Increased ECF osmolarity
Arrhythmias can result from [K+] variations. What appears on an EKG if you have 1.5 mM of [K+]?? (Normal is 4.5)
What about during hyperkalemia?
Hypokalemia: U waves
Hyperkalemia: High T waves and eventually death via Vfib
The body Potassium is important to regulate. What cells do the regulating? Where are these cells?
What transporters are used?
beta intercalated cells secrete K+ into the collecting tubule and DCT.
Alpha intercalated cells reabsorb K+
Epothelial –> Tubular lumen (Apical) K+ Out
BK, ROMK
Na+ in
Why might K+ be reabsorbed?
K+ deficiency, low K+ diet, hypokalemia, severe diarrhea
What cells secrete K+, HCO3- and Reabsorb H+ Cl-
Beta intercalated cells
What cells secrete H+ and reabsorb K+ HCO3-
a Intercalated cells
What cells secrete K+ and reabsorb Na+, H2O
Principal cells
What is the normal K+ Serum level?
What 4 ways can that level be changed?
4.2 mEq/L
- Na/K ATPase pump messes up
- Reduced leakage of K+ from ICF to renal interstitium
- increased synthesis of K channels and insertion into luminal membrane
- increased Aldosterone secretion
If you eat a high potassium diet, you may see an increase in what kidney function?
Tubular flow rate
What 3 things stimulate potassium secretion?
Increased ECF [K+]
Aldosterone
Increased Tubular Flow Rate
A pt presents in acute alkalosis. What is the body doing to compensate?
Hypokalemia via increased activity of Na/K ATPase and K+ Secretion
A pt presents in acute acidosis. What is the body doing to compensate?
Send the body into hyperkalemia via decreased activity of Na/K ATPase pump and decreaed K secetion
In order to stabilize K+ secretion, there are opposing factors as to not get extreme. In acidosis, what increases K+ Secretion? What decreases it?
Acidosis
Increase: decrease intracellular [K+] content
Decrease: decrease proximal reabsorption and increase distal flow
In order to stabilize K+ secretion, there are opposing factors as to not get extreme. In volume expansion, what increases K+ Secretion? What decreases it?
increase:
decrease proximal reabsorption
Increase distal flow
Decrease:
Decrease aldosterone
In order to stabilize K+ secretion, there are opposing factors as to not get extreme. In volume contraction, what increases K+ Secretion? What decreases it?
increase:
increase renin, AGII and Aldosterone
Decrease:
Lower GFR and distal flow
In order to stabilize K+ secretion, there are opposing factors as to not get extreme. In high water intake, what increases K+ Secretion? What decreases it?
Increases: Decreased ADH decreases distal water reabsorption while increasing distal flow
Decreased:
Decreased ADH decreases K+ Secretion.
A pt presents in acute acidosis. Do you expect urine concentration of Ca to increase or decrease?
In acidosis, less Ca binds to protein because H+ is in higher concentration. Since there is now more free Ca, you expect Urine concentration to increase.
What is hypocalcemic tetany caused by?
Less Calcium bound to plasma proteins
When Ca++ Gets reabsorbed in the PCT, what type of transport does it use? (energy-wise)
What about in the thick ascending limb?
passive transport
via positive voltage gradient paracellularly.
The DCT only reabsorbs 8% of Calcium, so why it is important?
What apical channel does it have for Calcium?
Basolateral for calcium?
What does calbindin do?
Only step where Ca++ is not coupled to Na+.
TRPV5
Na/Ca antiporter NCE
Prevents apoptosis from excessive IC [Ca]
How does the peritubular know how much calcium to reabsorb?
on the DCT there are CaSR - calcium sensing receptors that increase or decrease peritubular Ca++ reabsorption
Calcium goes through the Proximal Tubule primarily through which path? What transporters might it use?
How much Calcium is reabsorbed here?
Paracellular
Ca++ ATPase and Na/Ca antiporter
67%
A pt has increased arterial blood flow. Without compensatory mechanisms, How would this affect the Ca++ in the tubule?
Increased blood flow = increased hydrostatic pressure = more water pushed into tubule = volume expansion of tubule = decreased Ca Reabsorption
This is because if you already have an increase in fluid, then you don’t want more Na+ cause then it’d follow it!
inteh thick ascending LoH, how much calcium is absorbed? How does it pass through the endothelium?
What is the driving force behind reabsorption here?
What can stimulate reabsorption?
25%
paracellular
Na/K/2Cl cortanasport makes positive charge in lumen, pushes it back into blood.
ADH
What do loop diuretics cause?
What conditions can be treated with loop diuretics
inhibits Na/K/Cl cotransporter –> inhibited Calcium and Na Reabsorption in Thick Ascending
and also inhibit Mg2+ reabsorption in thick ascending.
Hypercalcemia
While on rotation you see your attending give a pt with idiopathic hypercalciuria a drug called thiazide. What is the MOA for thiazide?
Inhibit Na/Cl transporter on the DCT, which inhibits Na+ reabsorption thereby increasing Na excretion.
It also decreases Ca excretion and increases Ca reabsorption.
Watch for this. It’s an “exception” so HY.
If you needed to increae Calcium reabsorption, what 4 things could you use?
PTH,
Vit D
Calcitriol
Thiazide
A pt presents in acidosis, what concentration of calcium do you expect in your pt’s urine?
Alkalosis?
increased Calcium because it inhibits TRPV5, which is the apical transporter. Less reabsorption
Also H+ Competes with Calcium for spots on albumin, and if ther’s more H+, Ca is more free.
Alkalosis stimulates TRPV5
How much Phosphate is reabsorbed by the proximal tubule? Where is it stored?
How much is bound to plasma?
How much is filtered?
How much is reabsorbed?
80%
85% is in bone and muscle, 15% is in ICM
31% is bound
90%
70%
What growth factor is release by bone to increase phosphate excretion? What factor not released by bone can also increase phosphate excretino? How?
FGF 23
PTH - inhibits Na/P transporters and Na/H antiporter in apical membrne of PT.
I,25(OH)2D3 has what effect on serum phosphorus?
insulin?
Increases intestinal phosphate absorption
Insulin: lowers serum levels by shifting phosphate into cells
When is FGF 23 secreted?
ACidosis has what effect on phosphate regualtion?
increased PTH, calcitriol and hyperphosphetemia
Increase [P]PO4 (reabsorption)
What pathway does the phosphate take to reach the capillary from the proximal tubule?
Apical? Basolateral?
Apical: Na/P symporter
Basolateral: Na/K ATPase
Unknown actual channel - but I guess this drives it.
How much magnesium is filterd?
How much magnesium is excreted?
How much is bound to plasma proteins?
How much is reabsorbed in the PCT? via what path?
How much is reabsorbed in TAL?
DCT?
80%
5%
20%
20% Paracellular. Follows Na and H2O
TAL: 70%. Paracellular.
DCT: 10%
Mg reabsorption is increased when:
How much calcium? How much PTH? How much ECV? Alkalosis or Acidosis? Diuretics or antidiuretics?
Calcium depletion Elevated PTH Decreased ECV Alkalosis Diuretics
What are the Trans epithelial charge differences in the following:
PCT PST TS? Thick Ascending Loop Distal Convoluted CCD (Cortical Collecting Duct) OMCD (Outer medullary collecting duct)? IMCD (Inner medullary collecting duct)?
PCT -2 PST+2 TS? 0 Thick Ascending Loop +10 Distal Convoluted -50 CCD -70 OMCD +10 IMCD 0
What is the MOA for Carbonic anhydrase inhibitors?
Decreases bicarbonate reabsorption via Na+ H+ antiporter in proximal tubule.
What is the MOA for Loop diuretics?
Inhibits NKCC2 transporter = increases Ca++ and Mg++ excretion in Loop of Henle
What is the MOA for Thiazides?
inhibit Na Cl symporter which inhibits NaCl reabsorption and enahnces Ca rebasorption in the Distal Tubule
What is the MOA for K+ Sparing diuretics?
inhibits Na+ reabsorption and increases K+ reabsorption
- Inhibits aldosterone
- inhibits ENAC (Sodium endothelial channel on the apical side. Allows rebasorption of Na)
in the late distal tubule and CCD
What is the MOA for Osmotic diuretics?
Describe mannitol
inhibit reabsorption of water and solutes by altering osmotic forces along nephron in the PT and Loop of Henle
Mannitol: Freely filtered, but not reabsorbed. Oncotic pressure increases in tubule, so water reabsorption is reduced
When you give an osmotic diuretic, what happens to urine volume? Sodium excretion?
Urine volume increases (less water reabsorption)
Sodium excretion increases
Na+ maintains osmolar gradient by staying in tubule
MOA for Pi when given diuretics?
Mg?
Pi:
Increase Pi excretion
Mg: decreased Reabsorption in the TAL, increase Mg excretion
MOA for K+ when given diuretics?
Increase secretion of K+ (besides K-sparing diuretics)
MOA: Increased tubular fluid flow rate –> Stimulates K+ secetion
Decreased ECFv –> RAAS and ADH –> increased K+ secretion from principal cells
MOA for Ca+ when given
loop diuretics?
Thiazide diuretics?
Loop: increased Ca++ excretion
Inhibition of water reabsorption –> Reduced transepithelial voltage –> Ca does not get reabsorbed –> Excreted
Thiazide: Increase Ca reabsorption
Stimulates TRPV5 in DT to reabsorb Ca
When the arterial pressure increases, what senses it?
What is signaled to decrease it?
When arterial pressure decreases what sense it?
What is signaled to increase?
Senses:
Cardiac atria
Pulmonary vasculature
Decrease BP Signals:
Natriuretic (ANP, BNP)
Senses:
Carotid sinus
Aortic arch
JG apparatus
Increase BP signals:
RAAS
ADH/Vasopressin
Prostaglandins
A pt has been checkin the sodium content of their urine and notices that the concentration has dropped. What stimulates change in sodium balance? Why did the Sodium drop?
ECF volume is probably high, so more Na+ is excreted (in DCT) so that water will follow
What 4 substances/fluid changes increase sodium excretion?
Decrease sodium excretion? (3)
Increase excretion: Dopamine High ECF [Na] Natriuretic peptides Prostaglandins
Decrease excretion:
RAAS (AGII and aldosterone)
Sympathetics
ADH
When renal sympathetic nerves are activated, 3 things happen.
1) constrict afferent arterioles, decreasing GFR
2. Increase tubular reabsorption of water and salt
3. Activate RAAS, increasing reabsorption
What 3 ways can we stimulate renin secretion?
1) Sympathetic stimulation
2) Low NaCl delivered past macula densa
3) Low pressure at granular cells (caused by afferent arteriol constriction)
What 4 ways can we inhibit renin secretion?
1) Increased NaCl across macula densa
2) Increase affereent arteriol pressure
3) ADH
4) negative feedback loop with AGII
What is the overall goal of AGII?
In what ways does it accomplish this goal?
Increase BP
1) Renal efferent cosntriction > and afferent constriction
2) Na+ reabsorption in PT > TAL and CCD
3) increase thrist
4) ADH secretion (Vasopressin)
5) Aldosterone secretion from adrenal cortex
What does aldosterone do for the basolateral membrane? (part of Nephron?)
Apical?
Basolateral (DT):
Increase synthesis of Na/K ATPase
Apical:
Increase Na+ Channels
Overall:
- Increase Na+ reabasorption
- Increase K+ Excretion
What does ADH do? (3 things)
1) Increase water permeability of principal cells (CCD) via aquaporins!
2) Increase urea permeability in inner medullary collectin gudcts (NOT any other CD)
3) Increase NKCC cotransporter activity in TAL
How does ADH increase permeability of CD to water?
Include the receptors
ADH (AVP) binds to AVPR2 to stimulate GPCR. which pushes an AQP2 (aquaporin) onto the apical membrane to be reabsorbed!
(G –> Adnelyl Cyclase –> cAMP –> PKA)
The body senses a low effective circulating volume/high concentration of solutes, what series of steps to make ADH?
(include receptors)
OVLT and SFO are osmoreceptors that sense the water volume –> Mangocellular neurons in hypothalamus –> supraoptic nucleus and paraventricular nuclei –> ADH carried from hypo to posterior pituitary where it is released
What else besides low effective circulating volume may stimulate ADH secretion?
Inhibit ADH?
Increase:
Nausea,
AGII
Nicotine
Decrease:
ANP
Ethanol
A pt presents dehydrated from a 12 hour stunt lost in the desert. What is the ADH pathway that compensates for this?
Decreased H2O –> increased osmolarity –> Osmoreceptors in anterior hypothalamus –> Increased ADH secretion from Post pituitary –> Increased H2O permeability via AVPR2 and AQP2 –> Increased H2O reabsorption –>
Increased urine osmolarity = plasma osmolarity normal
What is the MOA of prostaglandin?
Inhibits K+ Channels in TAL –> increases Cl- –> decreasing NKCC channels –> Reduces NaCl reabsorption
which buffers vasoconstrictive effects of SNS/RAAS and protects RBF and GFR
A patient is on diuretics, has renal stenosis and is hypertensive. What Tx would worsen the Sx?
NSAIDS
What do ANP and BNP do?
Urodilatin?
What do these molecules inhibit?
In response to increased intravascular volume, cardiac myocyte stretch receptors: Promote NaCl and water secretion.
Elevates GFR.
Urodilatin: Promotes NaCl Secretion, but doesn’t have systemic vasoactivity effect
RAAS, SNS, ADH
ANP's affect on GFR? Renin? Aldosterone secetion? Na and H2O reabsorption? ADH?
increase GFR
Decrease Renin –> inhibits release from JG cells
decrease Aldosterone –> inhibit release from adrenal gland
Na and H2O reabsorption –> inhibits apical Na+ channels
Decreased ADH –> INhibit release from pituitiary gland and inhibits ADH from acting on CD
Increase/Decrease
There is a salt deficit. \_\_\_\_ osmolarity \_\_\_\_ diuresis \_\_\_\_ Plasma volume \_\_\_\_ Blood pressure \_\_\_\_ Sympathetic Activity \_\_\_\_ ANP \_\_\_\_ Oncotic capillary pressure \_\_\_\_ RAAS activity
Know this would be opposite for salt excess.
Decreased Osmolarity
Increased water diuresis
Decreased plasma volume
Decreased BP
Increased Sympathetic
Decrease ANP
Increased Oncotic capillary
Increased RAAS
There is a volume expansion in the arterial system. This causes the heart to release what?
Baroreceptors are stimulated, this causes?
the Osmolarity in DT decreases, this causes?
Urodilatin is stimulated, this causes?
Release ANP to increase GFR.
Baroreceptors –. inhibit sympathetic, decrease Renin, vasodilate system
Osmolarity= decreased renin
Urodilatin: decreased Na+ reabsorption
What is euvolemia?
normal blood amount in body
What senses an abnormal effective circulating volume (4)?
What do these stimulate (4)?
Macula densa
Afferent arterioles
Atria
Carotid sinus
RAAS
ANP
NE
ADH
What senses an abnormal plasmas osmolarity?
What do these stimulate?
Hypothalamic osmoreceptors
ADH
thirst.
How does PTH regulate Ca+?
PO4?
- increase Serum Ca+
via: Increase renal reasbsorption
Release calcium from bones
Simulate TRPV5
Stimulates Calcitriol - Lowers serum PO4 by increasing renal excretion
Via: Inhibits NaP transport (apical of PT, reabsorbs)
Alkalosis decreases PO4 excretion
In the PCT, what receptor does glucose use to get from the lumen to the blood?
Somatically how are these receptors useful?
APical: SGLT4 Na+ Glucose symporter
Basolateral: GLUT4 glucose facilitated diffusion
Gets glucose into skeletal muscel and adipose tissue
What types of diuretics are there?
Loop diuretic
Thiazide
Oncotic/Osmotic diuretics
K+Sparing Diuretic
Which segment of the nephron is only permeable to water?
Thin segment of Loop of Henle
The ascending thick segment of the Loop of Henle is responsible for what?
Non permeable to water, but has NCC channels to concentrate the interstitum and dilute the urine
What is ADH’s affect on the loop of Henle and CCD?
- Increase permeabilty of principal cells to water
- INcreases NKCC transporter - enhances corticopapillary osmotic gradient
- stimulate UT1, which transports urea into interstitial
NKCC cotransporter is important for ?
NaCl reabsorption in the ascending limb of loop of Henle
The early distal tubule is responsible for what?
Late distal tubule?
Early distal tubule never permeable to water. Reabsorbs NaCl and Calcium. Contains juxtaglomerular apparatus
Late segment permeable to water in presence of ADH.
Principal cells and beta intercalated increase K+ Secretion. alpha intercalated reabsorb K+ for acid base balance
We all know aldosterone increases Na+ Reabsorption, but how?
antagonizes the Na/K ATPase so the gradient isn’t maintained?
The alpha intercalated cells use what transporters? What is the cell’s function? In what metabolic state is this stimulated?
H+ Excretion and HCO3- reabsorption
Use HCO3- and H+ to use H+ ATPase and H/KATPase transporters to move hydrogen into lumen.
Acidosis
The beta intercalated cells use what transporters? What is the cell’s function? In what metabolic state is this stimulated?
H+ Reabsorption and bicarb secretion
Use HCO3- and H+ to use H+ ATPase and H/KATPase transporters to move hydrogen into interstitial fluid.
Alkalosis
What is the renal effect of ANP?
Secreted in response to high atrial pressure. Causes increased GFR and increased Sodium filtration, but no Sodium rebasorption
What is the renal effect of Angiotensin II?
Secreted in rresponse to low BP. Efferent arteriole constriction, increased GFR and Increased FF. Compensatory Sodium rebasorption in proximal and distal nephronto maintain circulating volume
What is the renal effect of PTH
Secreted in resopnse to low plasma clcium and high plasma phosphate or low plasma 1,25 OH2D3.
Calcium is reabsorbed, phosophate is secreted, and 1,25OHD is produced.
A pt has hypervolemia hyponatremia, what do you expect the past medical history to show?
Congestive heart failure
Renal impairment
cirrhosis
A pt has euvolemic hyponatremia, what do you expect the past medical history to show?
SIADH
COPD
Malignancy
What is the difference between Central diabetes insipidus and nephrogenic insipidus
Central: Deficient secretion of ADH from hypothalamus or pituitary
Nephrogenic: Renal insensitivity to ADH
You know this person has Diabetes insipidus. What steps do you use to find out if it’s central or nephrogenic?
Test urine output
Challenge with ADH
Retest urine output.
If the ADH fixes the problem, it’ll be central
If the blood flwo in the vasa recta icnresaes too much, what happens?
The gradient in the loop of henle is messed up, then the urine can’t get concentrated
Formula sheet
Osmolar Clearance
Olbigatory urine volume
Free Water Clearance
Fractional Excretion
Cosm = Uosm (V)/Posm
OUV = Max slute excretion per day/Max urine concetrating ability
Ch2O = V - Cosm
FE= Amount of X excreted/Amount of X filtered = Ux (v)/ Px (GFR) = Ux Pcr/Px*Ucr
Hypoxia = Acute Renal injury. Inflammation can be a cause of that! Which is why in steril erenal inflammation, What type of alarmins are secreted? What are those released by?
DAMPs
Parenchymal cells,
HMGB1, Uric acid, HSP
Kidney cells express what CD??
Ischemic kidney cells express what CD?
If these are stimulated, what happens?
TLR
TLR4
Proinflammatory cytokines (Dendrites, Mascrphage, endothelial cell). Exacerbates kidney damage due to massive leukocyte and cytotoxic stuff
When TLR4 is stimulated, the Dendritic cell release what?
Macrohpage?
Endothelial cell?
Dendrite: Type I IFNs, IL12, IL1
Macrophage: IL 1 IL6
Endothelial cell;: TNF, IL6, IFN gam
Acute kidney infection stimualtes what immune response?
Chronic Kidney disease?
Macrophages M1–> TNF alpha and IL6 INFLAMMATION
Macrophage 2 –> IL 10 NOT INFLAMMATORY
Kidney is ischemic, so it releases _____. The Damps activate teh _______. This activates Cytokines, which activates ______. Inflammation ensues. Until chronic, and you get FIRROSIS!
DAMPs
Complement
Macrophages
This ischemia just happened, the immune response is just kicking in, what cytokines are ifrst responders?
Th17 cells, then Th1 cells
TH1 activate Macrophages
Treg also prouce IL10
What stimulates Th1? What does it relaease?
Stimualtes TH2? What does it release?
Stimulates TH17? What does it release?
IL12 –> TH1 –> IFNg
IL4> TH2 > IL4, IL5, IL13
IL23 > TH17 > IL17
What does IL 17 do?
Stimulates resident renalcells to produce chemokine
- Leads to neutrophil recruitment
What hypersensitivities can arise in the kidney?
II and III
End stage renal failure. Treatment is transplant.
There are types of rejection, name them and describe.
Hyperacute rejection: Immediate; via antibody
Acute rejection: Caused by T cells. dasys to weeks
Chronic: months to years. caused by vascular trauma and inflammation
What are these types of graphs? Autograft Isograft Allograft Xenograft
Autograft - same individual
Isograft: Twins
Allograft: nonidentical members of same species
Xenograft: Different species
What non-immunological facotrs are at risk with transplants?
Mechanical trauma to graft tissues
- Clottin gcascade = fibrinogepeptides –> Vascular permeability increases and attracts neutrophils and macrophages –> Bradykini produces, vasodilation –> proinflammatory response, if uncontrolled result in yperacute
If you’re getting what type of transplant, it doesn’t matter your ABO?
Corneal,
Heart Valve,
Bone and tendon grfat
With HLA, how does that work?
1) Have donor cells, stick them with pt cells. If pt cells proliferate then it does not work. There was a reaction
In acute Rejections, which type of Tcell is humoral vascular? What about cellular?
TH2
Th1
Hyperacute Graft rejection involves what tpye of antibodies?
Preexisting ABS. Within minutes.
- Blood type, previous transplants, Classic complemetn
Acute Graft rejection involves what?
Primary activation of T cells
days to weeks.
Generation of cytotoxic T cells
Chronic Graft Rejection involves what?
Macrophages and T cells
months to years
Occlusion of blood vessels and ischemia of organ = inflammation, macrophages, indirect complement pathway
What is GVHD?
What is it caused by?
Grafted mature T cells react in immunocompromised pts. The immune system is unable to reject teh allogenic cells?
Acute: Epithelial cells get killed (rash, jaudice diarrhea)
Chronic: Fibrosis and atrophy of affected organ
