Unit 8 - 2 Scheme

Front 1

Back 1

Outlined black area impermeable to water; starts at 300 -> 1200> at top you're down to 150

Salt is being pumped out of ascending loop of henle which accounts for half the concentration of sodium (300 -> 150)

Front 2

Back 2

Interstitium; more dilute at top, more concentrated at the bottom

salt and urea gets pumped out into interstitium; why doesn't it diffuse away and equalize gradient?

Front 3

why doesnt interstitial conc just diffuse away?

Back 3

Vasa recta countercurrent system;

blood comes down and goes up but at every moment a gradient exists to maintain the gradient;

1200 is max concentration; gerbils are much more conc (4000); pee out pellet

Front 4

Aquaporins

Back 4

water channels inserted into cell membrane (they can go up or down); facilitate rapid movement of water across membrane

under influence of ADH (from posterior pituitary gland)

Front 5

alternative names for ADH

Back 5

vasopressin or AVP (arginine vasopressin)

Front 6

when is ADH released?

Back 6

changes in extracellular fluid osmolality (cells in hypothalamus detect osmolariy)
nonosmotic factors such as physical pain, stress or a drop in bp

Front 7

Back 7

older people won't get thirst

Front 8

High sodium levels indicates

Back 8

Not even water, thus Na is conc

Front 9

Causes of hypotonic water loss

Back 9

Gastrointestinal losses
• vomiting
• nasogastric suction
• enterocutaneous fistula
• diarrhea

Renal losses
• diuretic use
• osmotic diuresis
• post obstructive diuresis
• non-oliguric acute renal failure

Front 10

Causes of hypotonic water loss

Back 10

Gastrointestinal losses
• vomiting
• nasogastric suction
• enterocutaneous fistula
• diarrhea

Renal losses
• diuretic use
• osmotic diuresis
• post obstructive diuresis
• non-oliguric acute renal failure

Front 11

osmotic diuresis

Back 11

something you've put in that has a high conc that dilutes the blood
natural one: glucose (out of control diabetic pulls water out of cells)

Front 12

Causes of pure water loss

Back 12

Increased insensible loss
• fever


Increased insensible loss with
no fluid replacement

• inability to obtain water,
such as when trapped in a
collapsed building, or
having suffered a stroke

Diabetes insipidus
• nephrogenic
• hypothalamic

Front 13

Na gain

Back 13

Exogenous
• salt ingestion
• intravenous hypertonic saline
• intravenous sodium bicarbonate

Endogenous
• mineralocorticoid excess

Front 14

mineralcorticoid excess

Back 14

make too much of a hormone which causes you to raise minerals (never this)

Front 15

Hypovolemia urine Na>20 mmol/L

Back 15

kidney dumping out salt; should be trying to hold onto them

Front 16

Glucocorticoid deficiency

Back 16

you were on steroids and someone forgot to give you more when you came into hospital

Front 17

SIADH

Back 17

Syndrome of Inappropriate ADH

Front 18

Urine Na <20 mmol/L

Back 18

Kidney is retaining sodium so it's working fine; must be losing salt EXTRArenally

Front 19

Key questions

Back 19

Kidney is either trying to hold onto sodium or remove it

Kidney is either trying to hold onto water or remove it

Get osms

Front 20

Plasma Osmolality Equation

Back 20

2[Na+] + Glucose/18 + BUN/2.8

Front 21

Plasma Osmolar Gap Normal

Back 21

Osmolar Gap = Measured mOsm/l - Calculated mOsm/l

Calculated = 2[Na+] + Glucose/18 + BUN/2.8

10-15 mOsm/l

Front 22

substances that increase the osmolar gap

Back 22

Ethanol, ethylene glycol, methanol, acetone, isopropyl ethanol, propylene glycol

Front 23

What happens to measued sodium levels if lipids or proteins increase too much in plasma?

Back 23

Artifactual hyponatremia (pseudohyponatremia/factitious hyponatremia)

Front 24

Protein levels of 10 g/dl

Back 24

Exclusively associated with multiple myeloma

Front 25

Flame photometer

Back 25

In patients with elevated proteins or lipids, Na measured with a flame photometer will have low values

Front 26

Ion specific electrodes

Back 26

Will give values corrected for waer phase only

Front 27

How do you treat patients with artifactual hyponatremia?

Back 27

No therapy is needed

Front 28

Hypo-osmolar Hyponatremia

Back 28

True decrease in plasma sodium

Psychogenic water consumption (poly dyspia)

Beer drinkings who eat nothing and become hypoosomoalr -> urine volume increased above normal due to alcohol consumption (carbs in beer become C02 which is blown off an water, so left only w water); they try to excrete as much water as they can but once the urine osmolality reaches its lowest potential vlaue no more water can be excreted and these patients develop edema

Osmostat reset: resetting of how we respond to plasma conc which can lead to hypoosolar hyponatrmiea

Front 29

Hypovolemic Hypo-osomolar hyponatremia

Back 29

Water lost from body (Hemorrhage, GI losses, diuretic therapy, primary adrenal insufficiency, 3rd spacing of fluids)

Front 30

Hypervolemic hypoosomolar hyponatremia

Back 30

Retained water inappropriately (CHF, cirrhosis, nephoritc syndrome, ESRD)

Front 31

Euvolemic hypoosomolar hyponatremia

Back 31

Myxedema: Different compounds added to compounds that produce edema (GAGs, mucopolysaccharides)
SIADH

Front 32

why does the conc of sodium go up slightly as you go down the proximal tubule

Back 32

some water is reabsorbed with concentration of AA, glucose and bicarbs

Front 33

osmolarity of intestitial fluid around proximal tubule

Back 33

300 mOsm/l

Front 34

countercurrent effect

Back 34

the length of the tubule multiplies the horizontal effect

Front 35

urea recycling

Back 35

urea recycling allows us to concentrate urine at the tip of the ascending portion even though there is no active transport in this part of the nephron

Front 36

TF/P ratio of 3

Back 36

GT balance = 1/3

Front 37

osmolarity of the interstitial fluid at the tip of the loop of henle composition

Back 37

made up by urea and sodium

Front 38

ion movement as you move up ascending limb

Back 38

passive reabsorption of sodium (bc conc of sodium higher in tubular lumne into inteterstitial space down its conc gradient)
passive secretion of urea (bc conc of urea in tubule is lower than interstitium)

Front 39

Two key components of concentrated sodium in thick ascending limb

Back 39

ADH and ACTIVE reabsorption of sodium

Front 40

Location of 2Cl/Na cotransporter

Back 40

apical membrane of thick ascending cell; energy provided for this from Na/K ATPase pump; when this pump is working effectively it absorbs lots of sodium but water cannot follow bc thick ascending limb is impermeable to water -> this allows water to be osmotically absorbed in collecting duct IF ADH is present due to large Na content in interstitium

Front 41

what does urea need to get out of collecting duct

Back 41

ADH; if not present the urine will only be 1/2 as concentrated

Front 42

furosemide

Back 42

blocks 2Cl/Na/K transporter in ascending limb; unable to concentrate interstitial fluid surrounding thick ascending limb; cannot withdraw water from descending limb so fluid at the tip of loop will still be 300 mOsm; as we move up ascending limb nothing happens; we would end up producing an isotonic urine w plasma (300 mOsm)

Front 43

Which two pumps are critical for our kidneys ability to produce dilute or concentrated urine?

Back 43

2Cl/Na/K pump and Na/K exchanger

Front 44

If you knock out thick ascnending limb what will urine conc be

Back 44

Low, 300 mOsm

Front 45

excessive water intake

Back 45

goes into ECF -> descreased plasma conc -> decreased ADH release -> decreased plasma ADH conc -> decreased water reabsorption in kidney -> increased "free water" excretion

Front 46

primary control effector of ADH release

Back 46

decreased plasma volume; determined by receptors in hypothalamus

decreased venous pressure, venous return and atrial pressure would also lead to increased ADH release

Front 47

Production/storage of ADH

Back 47

Produced in 3rd ventricle of brain in supraoptic nuclei -> stored in posterior pituitary

Front 48

Primary and secondary stimulus for release of ADH

Back 48

1. Increased ECF concentration
2. a. Increased circulation angiotensin
b. decreased pressure in left atrium of heart
c. decreased pressure in aortic arch

Front 49

Hypertonic ECF causes what

Back 49

ADH release

this could also be mimicked by hemorrhage or cardiac failure

Front 50

cellcular action of ADH

Back 50

ADH binding -> AC -> cAMP -> AQP2 tranporters in CD = increased free water absorption -> free water returned to ECF -> ECF tonicity decreases -> decreased ADH release

Front 51

which anatomical site collects the reabsorbed water in descending limb and collecting duct?

Back 51

vasa recta -> renal vein

Front 52

1. if producing dilute urine (artery vs vein conc)

2. if producing conc urine (artery vs vein conc)

Back 52

renal vein must be more conc than renal artery

renal vein must be less conc than renal artery (bc youre absorbing fluid)

Front 53

what is reabsorbed in collecting duct

Back 53

water and urea (as part of the urea recycling system)

Front 54

free water clearance equation

Back 54

Cosm = Uosm x V / Posm

CH20 = V - Cosm = free water clearance

Front 55

Free water clearance in concentrated urine (above 300 mOsm/l)

Back 55

Negative free water clearance (bc we're absorbing water)

Front 56

Free water clearance in isomotic urine

Back 56

Free water clearance of 0

Front 57

Free water clearance in dilute urine (below 300 mOsm/l)

Back 57

will result in a positive free water clearance (bc we're excreting water)

Front 58

free water clearance definition

Back 58

volume of water that would need to be added to or substracted from each minutes of urines production to make it iso-osmotic with plasma (300)

Front 59

primary cation in ecf

Back 59

sodium; makes up most of the osmolality

Front 60

donnon effect

Back 60

proteins in plasma provide negative charge in plasma (more proteins in plasma than interstitial space); VERY slight disequilibrium between the sodium in the plasma and sodium in the interstitium; negative charge of proteins in plasma helps retain some sodium ions in circulating plasma in a conc in excess of what you would see in the interstitial space

Front 61

main cation in icf

Back 61

potassium (very little sodium); this balance is maintained by Na/K/ATPase pump located on cell membranes

If we destroy this pump we will have significant abnormalities in the function of the heart/nerves/intracellular hydration

Front 62

Intracellular K in acidosis

Back 62

Low; H+ ions move into cell and K move out of cell; can cause hyperkalemia

Front 63

Intracellular K in alkalosis

Back 63

High; H+ ions move out of cell and K moves into cell; can cause hypokalemia

Front 64

Intracellular H in acidosis

Back 64

High; H+ ions move into cell and K moves out of cell; can cause hyperkalemia

Front 65

Intracellular H in alkalosis

Back 65

Low; H+ move out of cell and K moves into cell; can cause hypokalemia

Front 66

The effect of high or low insulin on intracellular K+

Back 66

Low insulin: K+ leaves cell

High insulin: K+ enters cells (esp. when glucose is present)

Front 67

stop-gap measure to tx hyperkalemia

Back 67

Give potassium and glucose; will drive potassium into cell; however potassium WILL eventually leak back out of cell

Front 68

effect of high or low aldosterone on intracellular K+

Back 68

Low aldosterone: K+ leaves cell

High aldosterone: K+ enters cell

Front 69

hyperkalemia promotes the release of what to drive it back into cell

Back 69

Insulin, aldosterone, epinephrine (B-agonists)

Front 70

Potassium levels levels in proximal tubule

Back 70

2/3 of potassium is reabsorbed in proximal tubule, along w/ sodium

Front 71

potassium transport in low K+ diet

Back 71

Its all reabsorbed

Front 72

potassium transport in high K+ diet

Back 72

much more is excreted; still 2/3 absorbed in prox tubule, we can secrete much of the filtered load in an attempt to bring the high plasma potassium back to normal

Front 73

How do loop diuretics and thiazides cause hypokalemia

Back 73

Drugs in the descending loop (furosemide) and distal convoluted tubule (thiazide) inhibit sodium reabsorption; it is later reabsorbed by aldosterone which secretes potassium into the lumen

Front 74

CHF effect on aldosterone

Back 74

Increased aldosterone; causes Na reabsorption and K secretion; if pt is tx with diuretic MUST watch for hypokalemia since this can compound the hypokalemic efectf

Front 75

Amiloride

Back 75

Potassium sparing diuretic; inhibits sodium reabsorption in collecting tubules and thus inhibits potassium secretion into lumen

Front 76

Thiazide

Back 76

Blocks active Na and Cl reabsorption in early distal convoluted tubule

Front 77

Furosemide

Back 77

Blocks NKCC pump in the ascending loop of Henle

Front 78

Intercalated cell

Back 78

Alternative to principal cell in the collecting tubules

One of its jobs is to reabsorb K and secrete H+

If the intercalated cell is not working properly we will be unable to properly acidify our urine; this is one of the conditions that will give rise to a renal tubular acidosis

Front 79

RTA Type I

Back 79

Renal tubular acidosis due to damaged intercalated cells (can't secrete H+ into lumen)

Front 80

RTA Type II

Back 80

renal tubular acidosis type II

decreased bicarb reabsorption in the proximal tubule

increased HC03 (and Na+) excretion will result in volume constriction and the increased release of aldosterone. This will increase K+ excretion

Front 81

chronic metabolic acidosis effect on renal potassium

Back 81

Increased renal loss of K+

Front 82

chronic respiratory acidosis effect on renal potassium

Back 82

increased renal loss of K+ -- due to increased distal delivery of HC03 (high circulating biarb = beyond its transport maximum = distal delivery = potassium losses in body)

Front 83

chronic metabolic alkalosis effect on renal potassium

Back 83

increased renal excretion of K+ due to decreased amount of hydrogen in cells and increased amount of K; this will increase potassium losses; if plasma bicarb levels are high in chronic metabolic alkalosis we will increase transport maximum, increasing distal Na/bicarb delivery

Front 84

chronic respiratory alkalosis effect on renal potassium levels

Back 84

increases renal loss of K+ -- usually not severe and not well understood

Front 85

effects of acidosis on potassium balance

Back 85

H+ in principal cell, decreased intracellular K+ content, decreased proximal reabsorption

Front 86

effect of water intake on potassium balance

Back 86

high water intake inhibits ADH which decreases distal potassium secretion; decreased reabsorption of water increases distal flow which could increase the distal excretion of potassium

Front 87

effect of volume constriction on potassium

Back 87

leads to decresaed GFR, decreased GFR, decreases K secretion

BUT also leads to increased Renin, AII, increased Aldosterone -> increased potassium excretion

Front 88

the effect of volume expansion on potassium balance

Back 88

volumee expansion decresaed aldosterone which would decrease K secretion/excretion

it also decresaes proximal reabsorption bc changes GT balance, increase distal flow rate and increase potassium secretion

Front 89

Addisons disease (opposite of cushings)

Back 89

Lack of aldosterone -> sodium and water lost in urine

ppl w addisons have reduced extracellular volume

can become hyponatremic, hyperkalemic and mild acidosis

Front 90

tumor related hyponatremia

Back 90

pituitary tumors

SIADH type often in lung, breast, head and neck

Front 91

small cell carcinoma

Back 91

tumors found in lung that lead to production of pseudo-ADH or ACTH

these tumors do not respond to feedback and continue to produce ADH or ACTH regardless of the body fluid volume or concentration

Front 92

SIAD

Back 92

more common in hospital patients and rare in outpatient populations

asymptomatic as long as serum osmols is above 240 msOsm/kg of water

mcc of hypotonic (slightly increased plasma volume), euvolemic hyponatremia in children

Front 93

kidney response to CHF

Back 93

release of renin secondary to decresaed perfusion

promotes aldosterone, increased reabsorption of sodium and water in kidney; increased release of ADH to increase water reabsorption

tx w drugs to increase cardiac performance and decrease water reabsorption/rid excess water (diuretic)

Front 94

Back 94

GFR and RBF held pretty constant; (80-160)

there will be an increase in urine formation despite this constant flow; this is called pressure diuresis

point: urine flow/excretion of salt increase despite constant GFR and RBF

Front 95

aldosterone escape

Back 95

if aldosterone admin exogenously you will see an increase in weight gain bc aldosterone increases sodium/water retention; early phase shortly after administration where excretion of sodium drops (even though intake is constant) - area indicated by hashed line is the amount of sodium retained in the body; along w that sodium is water; therefore plasma sodium conc would not change substantially

after 3-4 days intake/excretion goes back to being equal before aldosterone admin;

after we quit giving aldosterone the amount of sodium excreted increases and the extra sodium will be alleviated from body along w water, as noted by the weight returning to normal levels after aldosterone admin stops

reasons not well known (maybe naturetic hormone, Na+ regulatory hormone)

Front 96

ANP/BNP effect on GFR

Back 96

increases GFR; increases glomerular pressure by dilating afferent arterioles, constricting efferent arterioles

Front 97

Angiontensin II in proximal tubule

Back 97

In low concentrations will increase sodium reabosprtion

In high conc. will inhibit reabsorption

Front 98

ANP in prox tubule

Back 98

Inhibits sodium reabsorption via interaction w other hormones

Front 99

ADH in Loop of Henle

Back 99

Stimulates NKCC transporter; also increases transepithelial NC transport

Front 100

Paracellin-1 in loop of henle

Back 100

Increases Na+ permeability

Front 101

PGE2 in DCT

Back 101

Inhibits NC transport

Front 102

Aldosterone in connecting tubule

Back 102

Stimulates ENaC channels in principal cells

Front 103

Aldosterone in cortical collecting tubule

Back 103

Aldosterone stimulates ENaC channels

Front 104

Aldosterone in medullary collecting duct

Back 104

stimulates ENaC channels

Front 105

Regulation o fK transport in prox tubule?

Back 105

No; no hormones involved; K+ reabsorbed through "pseudosolvent drag" along paracellular pathway

Front 106

Regulation of potassium transport in loop of henle

Back 106

Active transepithelial K transport across TAL

Front 107

ADH K transport regulation

Back 107

Activates ENaC increases K+ secretion to inhibit hyperkalemia during dehydration when distal Na delivery is low

Front 108

AQP2 in DCT

AQP3 in DCT

Back 108

On apical membrane (2)

On baseolateral membrane (3)

Front 109

regulation of calcium and phosphate by calcitriol

Back 109

Front 110

Regulation of calcium balance

Back 110

Front 111

calcium levels in proximal tubule

Back 111

Front 112

Where is PTH and calcitonin produced?

Back 112

PTH: chief cells of parathyroid

Calcitonin: parafollicular cells of thyroid

Front 113

The Effect of Increased Plasma Phosphate on Bone

Back 113

Plasma phosphate complexes w/ calciu -> decreased serum calcium -> stimulation of PTH -> bone resorption

also decreases calcitriol (since plasma senses enough phosphate) -> less calcium resorption from gut -> further hypocalcemia -> more PTH release

weak bones due to increased plasma phosphate