B5: Cell Bio Exam 3 FINAL

140-145 mEq/L

What is the typical concentration of sodium within the ECF (interstitium and plasma)?

15 mEq/L

What is the typical concentration of sodium within the ICF?

true

T/F: sodium intake must precisely match its output

less

If sodium excretion is (more/less) than intake:

-(+) Na+ balance

-Na+ is retained within the ECF

-ECF volume expands --> increased blood volume and arterial pressure

-End Result: Edema

more

If sodium excretion is (more/less) than intake:

-(-) Na+ balance

-Na+ is lost from the ECF

-ECF volume contracts --> blood volume and arterial pressure decreases

tubular fluid

What is the ultrafiltrate/urine at any point along the nephron?

tubular fluid to plasma ratio

What ratio compares the [tubular fluid in lumen of nephron] / [plasma] of a given substance?

equal to 1

If the TF/P ratio is _________ then:

-substance is freely filtered, not reabsorbed or secreted

-Ex = Na+, K+ is also around here

less than 1

If the TF/P ratio is _________ then:

-substance is reabsorbed more avidly than water

-less substance in the tubular fluid, more in the plasma

-Ex = bicarb, AAs, glucose

greater than 1

If the TF/P ratio is _________ then:

-substance is secreted

-substance reabsorbed less than water

-more in tubular fluid than in the plasma

-substance is hypotonic!

-Ex = PAH, creatinine, urea, Cl-

0

If a substance is not filtered at the glomerulus, then the tubular fluid (TF) would be ______

true

T/F: sodium is freely filtered at the glomerulus

99%

What percentage of the filtered load of sodium is reabsorbed?

true

T/F: sodium is not secreted into the ultrafiltrate from the plasma

PCT

Where, in the nephron, is Na+ reabsorbed the most?

65-80%

What percentage of Na+ is reabsorbed at the PCT?

27%

What percentage of Na+ is reabsorbed at the thick ascending limb of henle?

5%

What percentage of Na+ is reabsorbed at the DCT?

3%

What percentage of Na+ is reabsorbed at the cortical collecting duct?

PCT

Where in the nephron:

Apical:

-SGLT-2 symporters reabsorb glucose and Na+

-Na+-AA symporter reabsorbs Na+ and AAs

-Na+-H+ exchanger (NHE) will SECRETE and H+ and REABSORB Na+

-Acetazolamide inhibits CA causing excretion of water, Cl-, and bicarb

-AngII stimulates Na-H exchanger; reabsorbs Na+ and secretes H+

Basolateral:

-GLUT transporter allows for glucose to be reabsorbed into the blood

-Na+-K+ ATPase to bring Na+ back towards peritubular capillaries and bring K+ in

thin limb of henle

Where in the nephron:

-no sodium reabsorption

-only water reabsorption

PCT

Where is 100% of glucose and AAs & 99% of Na+ reabsorbed?

acetazolamide

What is a drug that inhibits carbonic anhydrase at the PCT, leading to the excretion of water, Cl-, and bicarb?

angiotensin II

What is a product of the RAAS that stimulates the Na+-H+ exchanger at the PCT, leading to increased reabsorption of Na+ and secretion of H+?

sodium

________ reabsorption drives the passive reabsorption of other substances in permissive segments. For example, this substance's reabsorption drives (1) H2O reabsorption and (2) increases the lumen's negative potential.

(1) H2O reabsorption will increase luminal Cl- and urea concentration

As a result of increased lumen negative potential and Cl- concentration, there will be passive Cl- absorption. As a result of increased lumen urea concentration, more urea will be passively reabsorbed. This is all due to this substance's reabsorption, this substance will passively pull Cl- and urea with it.

diffusion limited

The following substances are __________, sodium reabsorption will drive their passive reabsorption in permissive segments:

-H2O

-Cl-

-Urea

thin limb of henle

Where in the nephron is ONLY water reabsorbed?

Hint: concentrating segment

false

T/F: sodium is reabsorbed at the thin limb of henle

thick ascending limb of henle

Where in the nephron:

Apical Side:

-NKCC symporter reabsorbs Na+, 2Cl-, and K+

-K+ channel secretes K+ into lumen of nephron

-Na+-H+ exchanger (NHE) will secrete H+ and reabsorb Na+

-Loop Diuretics block NKCC to prevent reabsorption of Na+, 2Cl-, and K+ --> water will follow Na+, more water excreted

Basolateral Side:

-Cl- and K+ channels to reabsorb Cl- and K+

-Na-K ATPase

loop diuretics

What is a drug that works at the thick ascending limb of henle to block NKCC symporter?

DCT

Where in the nephron:

Apical Side:

-Na+-Cl- symporter to reabsorb Na+ and Cl-

-Thiazide diuretics will block the Na+-Cl- symporter, preventing reabsorption --> water will follow and lead to more water and Na+ excretion

Basolateral Side:

-Cl- channels to reabsorb Cl-

-Na-K ATPase

thiazide diuretic

What is a drug that works at the DCT to block the Na+-Cl- symporter?

collecting duct

Where in the nephron:

Apical Side:

-ENaC (epithelial Na+ channel) reabsorbs Na+

-K+ channel to secrete K+ into urine

-amiloride and triamterine block ENaC to prevent Na+ reabsorption

Basolateral Side:

-Cl- channels to reabsorb Cl-

-Na-K ATPase

-ADH V2 receptors present for ADH binding --> insertion of aquaporins for water reabsorption

-Aldosterone receptors for aldosterone binding --> increased Na+ reabsorption

-Spironolactone and Eplerenone will block Aldosterone receptors to prevent Na+ reabsorption

amiloride and triamterene

What are drugs that work at the collecting ducts to block ENaC channels?

Hint: K+ sparing diuretic

spironolactone and eplerenone

What are drugs that work at the collecting ducts to block aldosterone receptors?

aldosterone

Which hormone involved in tubular reabsorption:

Site of Action: collecting tubule and duct

Effect: increased NaCl, H2O REABSORPTION, increased K+ and H+ SECRETION

angiotensin II

Which hormone involved in tubular reabsorption:

Site of Action: PCT, TAL, DCT, CD

Effect: increased NaCl and H2O reabsorption, increased H+ secretion

antidiuretic hormone

Which hormone involved in tubular reabsorption:

Site of Action: DCT and CD

Effect: increased water reabsorption

atrial/brain natriuretic peptide

Which hormone involved in tubular reabsorption:

Site of Action: DCT and CD

Effect: decreased NaCl reabsorption

parathyroid hormone

Which hormone involved in tubular reabsorption:

Site of Action: PCT, TAL, DCT

Effect: decreased phosphate reabsorption, increased Ca2+ reabsorption

prostaglandins

Which hormone involved in tubular reabsorption:

-Paracrine secretion will cause vasodilation of afferent arterioles to increase renal blood flow

-NSAIDs will block synthesis --> constriction of afferent arteriole and decreased GFR (may result in acute kidney injury in low renal blood flow states)

dopamine

Which hormone involved in tubular reabsorption:

-secreted by PCT cells

-promotes natriuresis (increased sodium secretion/excretion)

-at low doses, it will dilate interlobular arteries, afferent arterioles, AND efferent arterioles --> increased renal blood flow, little to no change in GFR

-at higher doses, it acts as a vasoconstrictor

angiotensin II

1. JG cells are also considered interrenal baroreceptors because they respond to stretch (as well as RBF and [Na+]) by releasing Renin

2. Renin will cleave angiotensinogen (made by liver) to Angiotensin 1

3. ACE (made from ALL endothelial cells but mostly by the lungs b/c the lungs have a ton of endothelial cells) will cleave AngI to AngII

4. __________ stimulates ENaCs & Na-K ATPase

5. ENaCs and Na-K ATPase will increase Na+ reabsorption, increase vasoconstriction, increase aldosterone secretion

true

T/F: there are angII receptors on the apical AND basolateral surface of the PCT

angiotensin II

Within the PCT, there are ________ receptors on the basolateral AND apical surface. When stimulated, they will leads to increased Na-K ATPase, Na+-bicarb symporter, and Na+-H+ exchanger activity, all causing increased Na+ reabsorption.

angiotensin II

___________ modulates renal control of BP by:

-stimulating sodium reabsorption in PCT through NHE and Na-K ATPase

-stimulating sodium reabsorption in DCT through Na-Cl symporter

-stimulating sodium reabsorption in CD through ENaC channel

-stimulating constriction of afferent arterioles (decreases GFR)

-stimulating secretion of aldosterone

-stimulating sympathetic outflow from CNS

-stimulating general peripheral vasoconstriction

-stimulating thirst in hypothalamus

-stimulating salt cravings

-stimulating ADH release

hypothalamus

Angiotensin II will work on the __________ to:

-stimulate thirst

posterior pituitary

Angiotensin II will work on the __________ to:

1. stimulate release of ADH

2. ADH will work on principal cells in CD to increase H2O reabsorption via aquaporins

adrenal glands

Angiotensin II will work on the __________ to:

1. induce aldosterone secretion

2. aldosterone will stimulate alpha-intercalated cells and principal cells in the collecting duct

-alpha-intercalated cells will increase H+ secretion through H+-ATPase activity

-principal cells will increase Na+ reabsorption and K+ secretion

PCT

Angiotensin II will work on the __________ to:

-increase Na+-H+ exchanger activity --> Na+, bicarb, and water reabsorption (permits contraction alkalosis)

glomerulus

Angiotensin II will work on the __________ to:

-constrict efferent arteriole --> increase filtration fraction --> preserve GFR when RBF is low

arterioles

Angiotensin II will work on the __________ to:

-increase vasoconstriction by binding to Angiotensin II receptor type 1 --> increase BP

increase

Things that (increase/decrease) sodium EXCRETION include:

-dopamine

-[Na+] in ECF

-ECF volume

-Natriuretic peptides

-intrarenal messengers

decrease

Things that (increase/decrease) sodium EXCRETION include:

-RAAS system

-AngII

-aldosterone

-sympathetic stimulation

-ADH

-intrarenal messengers

type 1

Type ___ renal tubular acidosis:

-classical

-secondary to autoimmune disease (Na-K ATPase or Na-H exchanger defect)

-hyperchloremic acidosis present

-minimum urine pH >5.5

-plasma K+ low to normal

-renal stones present

-reduced H+ excretion in DCT

type 2

Type ___ renal tubular acidosis:

-Bicarb-Na+ defect in PCT

-hyperchloremic acidosis present

-minimum urine pH usually <5.5 (>5.5 before acidosis established)

-plasma K+ low to normal

-NO renal stones

-impaired bicarb reabsorption in PCT!

type 4

Type ___ renal tubular acidosis:

-HYPERKALEMIA

-can be elevated aldosterone defect

-hyperchloremic acidosis present

-minimum urine pH <5.5

-plasma K+ HIGH

-NO renal stones

-due to impaired cation exchange in DCT

Fanconi Syndrome

What transporter defect:

-all transporters defective in the PCT

-growth retardation, osteopenia, rickets

-metabolic alkalosis, phosphatemia, hypokalemia

Bartter Syndrome

What transporter defect:

-NKCC defective in TAL

-presents as loop diuretic use (looks like someone on furosemide and NKCC is being blocked)

-metabolic alkalosis, hypokalemia, hypocalciuria

-normal BP

-increased plasma renin

-increased aldosterone

-normal serum magnesium

Gitelman Syndrome

What transporter defect:

-NaCl defective in DCT

-presents as thiazide use (looks like overuse)

-metabolic alkalosis, hypomagnesemia, hypokalemia, hypocalciuria

-normal BP

-increased plasma renin

-increased aldosterone

-decreased serum magnesium

-decreeased urine Ca@+

Liddle Syndrome

What transporter defect:

-due to increased Na+ transporter expression in CD

-presents as hyperaldosteronism but is not supported by labs

-metabolic alkalosis, hypokalemia, HTN, low/normal serum aldosterone

-increased BP

-decreased plasma renin

-decreased aldosterone

-normal serum magnesium and urine Ca2+

SIADH

What transporter defect:

-BP normal or high

-decreased plasma renin

-decrease aldosterone

normal serum magnesium and urine Ca2+

primary hyperaldosteronism

What disorder:

-increased BP

-decreased plasma renin

-increased aldosterone

-normal serum magnesium

-normal urine Ca2+

renin-secreting tumor

What disorder:

-increased BP

-increased plasma renin

-increased aldosterone

-normal serum magnesium

-normal urine Ca2+

3.5-5 mEq/L

What is the typical concentration of potassium within the ECF (interstitium and plasma)?

120 mEq/L

What is the typical concentration of potassium within the ICF?

ICF

98% of K+ is found in the ______, and this depends on:

-total [K+] in the body

-distribution of K+ between the ECF and ICF

shrinkage

A net loss of K+ will lead to cell (shrinkage/swelling)

swelling

A net gain of K+ will lead to cell (shrinkage/swelling)

acidosis

low plasma [K+] will lead to cell (acidosis/alkalosis)

alkalosis

higher plasma [K+] will lead to cell (acidosis/alkalosis)

true

T/F: some cell enzymes are dependent on K+

potassium

__________ is an important component of DNA/protein synthesis and growth. Without it, there will be a reduction of protein synthesis and stunted growth

hyperkalemia

What disorder:

Etiology

-due to consumption of too much of a K+ salt

-most commonly due to failure of kidneys to normally excrete K+ ions into the urine

-leakage of K+ from cells and tissues into the bloodstream (e.g., severe muscle/tissue damage, burns, infection)

-acidosis, hypotension

-addison's disease (adrenal dysfunction)

EKG:

-wide and flat P wave

-prolonged PR interval

-widened QRS

-depressed ST segment

-narrow, peaked T wave

hypokalemia

What disorder:

Etiology:

-abnormal GI loss (e.g., d/v, diuresis, cancers)

-diuretics

-intracellular shift of K+ (e.g., insulin administration, insulin release stimulation, stimulation of SNS, genetic causes)

-increased renal excretion of K+

-medications

EKG:

-slightly peaked P wave

-slightly prolonged PR interval

-QRS normal but comes down into a suppressed or long ST segment

-ST depressed and prolonged

-T wave may be depressed or inverted

-U wave

into

Potassium shifts (into/out of) cell:

-decreasing ECF K+

-Hypokalemia

-hypo-osmolarity

-alkalosis

-dobutamine --> beta1 adrenergic agonist (increase Na-K ATPase)

-insulin (inc. Na-K ATPase)

-Aldosterone

-beta2 adrenergic agonists

out of

Potassium shifts (into/out of) cell:

-increasing ECF K+

-hyperkalemia

-digoxin (blocks Na-K ATPase)

-hyperosmolarity

-lysis of cells (e.g., crush injury, rhabdomyolysis, tumor lysis syndrome)

-acidosis

-beta1 blocker (metorolol/propanolol)

-high blood sugar (insulin deficiency)

-succinylcholine (inc. risk of burns/muscle trauma)

-alpha adrenergic agonists

acidosis

K+ shifts in (acidosis/alkalosis) involves in the collecting duct:

-alpha intercalated cells!!!!!!! --> H+ ATPase and K+-H+ exchanger

-carbonic anhydrase works here to make bicarb and H+ from carbonic acid. Bicarb will be transported into the peritubular capillaries (and K+ will follow) --> pH of peritubular capillaries will rise, giving us a more alkalotic state to get us back to normal pH

-increased H+ excretion into ultrafiltrate

-pt at greater risk for hyperkalemia/tend toward hyperkalemia

-K+ and bicarb reabsorbed into plasma!!!

alkalosis

K+ shifts in (acidosis/alkalosis) involves in the collecting duct:

-beta-intercalated cells!!!!!!!!!

-K+ and bicarb freely filtered

-reabsorbing H+ --> pH will decrease and plasma K+ falls (can tend towards hypokalemia)

aldosterone

When we have increased K+ intake, the plasma concentration of K+ will increase. An increase in [plasma K+] will cause increased _________ release. This will lead to an increase in K+ secretion from cortical collecting tubules and K+ excretion.

reabsorbed

K+ is (reabsorbed/secreted) in the PCT

reabsorbed

K+ is (reabsorbed/secreted) in the TAL of Henle

a. reabsorbed

b. secreted

secreted

K+ is (reabsorbed/secreted) in the late DCT and CCD

reabsorbed

K+ is (reabsorbed/secreted) in the principal cells (late CD)

increase

Things that (increase/decrease) potassium secretion in the distal nephron (principal cells of the collecting duct):

-alkalosis

-AVP/ADH

-high plasma K+

-aldosterone

-high Na+ delivery to principal cells

-high K+ diet

decrease

Things that (increase/decrease) potassium secretion in the distal nephron (principal cells of the collecting duct):

-angII

-low K+ diet

-acidosis

-epinephrine

bicarb

K+ follows ________

hydrogen ions (acid)

K+ moves opposite of ________

normal or high

during a(n) (normal or high/low) K+ diet:

-Reabsorption of K+ in PCT

-Reabsorption of K+ in TAL of Henle

-Secretion in DCT, principal cells, CCT

-Reabsorption of K+ in H-K-ATPase containing intercalated cells in CCT

-Reabsorption of K+ in H-K-ATPase containing cells in medullay collecting duct ~5%

-final urine 20-150% K+

low

during a(n) (normal or high/low) K+ diet:

-Reabsorption of K+ in PCT

-Reabsorption of K+ in TAL of Henle

-LITTLE Secretion in DCT, principal cells, CCT

-Reabsorption of K+ in H-K-ATPase containing intercalated cells in CCT

-Reabsorption of K+ in H-K-ATPase containing cells in medullay collecting duct ~3%

-final urine 2% K+

principal

K+ handling in the _________ cells:

-aldosterone/angII will increase ENaC activity

-Na-K ATPase activity is increased (bringing in more K+ to the cell)

-increased K+ secretion via K+ channels on lumenal side

true

T/F: during times of low plasma [K+] the principal cells do NOT secrete K+

renal outer medulla K+ (ROMK)

Under normal conditions, ENaC channels bring in Na+ to the principal cell. The Na-K ATPase functions to pump Na+ out of the cell and into peritubular capillaries while pumping K+ into the cell to maintain electrochemical gradient. However, K+ needs to be excreted. The ___________ channel helps excrete K+ into the tubular lumen and is is blocked by AngII.

angiotensin II

Under normal conditions, ENaC channels bring in Na+ to the principal cell. The Na-K ATPase functions to pump Na+ out of the cell and into peritubular capillaries while pumping K+ into the cell to maintain electrochemical gradient. However, K+ needs to be excreted. The renal outer medulla K+ (ROMK) channel helps excrete K+ into the tubular lumen and is is blocked by ____________.

big potassium (BK)

The ____________ channel helps ROMK secrete K+ into the tubular lumen when [plasma K+] is high and ROMK gets overwhelmed

increased

Renal secretion and excretion of K+ is (increased/decreased) when:

-high K+ diet

-hyperaldosteronism (Conn's Syndrome)

-alkalosis

-thiazide diuretics

-loop diuretics

decreased

Renal secretion and excretion of K+ is (increased/decreased) when:

-low K+ diet

-hypoaldosteronism (Addison's disease)

-acidosis

-K+ sparing diuretics

osmotic diuretics (mannitol)

What type of diuretic:

MOA: inhibit H2O and solute reabsorption by increasing osmolarity of tubular fluid

Tubular Site of Action: mainly PCT

loop diuretics

What type of diuretic:

MOA: inhibit NKCC co-transporter in luminal membrane

Tubular Site of Action: TAL of Henle

thiazide diuretics

What type of diuretic:

MOA: inhibit NaCl co transporter in luminal membrane

Tubular Site of Action: early DCT