renal final index cards exam I

Question 1

What is the osmotic coefficient?

Answer 1

function of particle interactions in solutions, which decreases the effective #s of osmoles

Question 2

Hypoosmotic urine results in _________ plasma osmolality (increase or decrease)

Answer 2

increased (more water is loss)

Question 3

What are effective osmoles?

Answer 3

impermeable solutes that can sustain osmosis

Question 4

What is free-water clearance (CH2O)?

Answer 4

Amount of water that needs to be added to/substracted from the urine, in order to render it ISO-osmotic with plasma.

Question 5

What are ineffective osmoles?

Answer 5

permeable solutes that cannot sustain osmosis

Question 6

What does a + CH2O value mean?

Answer 6

(+) value means that the kidneys excrete excess water (hypoosmotic urine)

Question 7

reflection coefficient = 100%

Answer 7

particle is reflected back 100% of the time; IMPERMEABLE

Question 8

What does a - CH2O value mean?

Answer 8

(-) value indicates that the kidneys excrete excess solutes from the body (hyperosmotic urine)

Question 9

reflection coefficient = 0

Answer 9

particle is as permeable as water

Question 10

What does a CH2O = 0 value mean?

Answer 10

urine is isoosmotic with plasma

Question 11

Describe the Donnan Effect

Answer 11

behavior of charged particles near a semi-permeable membrane that sometimes fail to distribute evenly across the two sides of the membrane. The usual cause is the presence of a different charged substance that is unable to pass through the membrane and thus creates an uneven electrical charge. Ex: the large anionic proteins in blood plasma are not permeable to capillary walls. Because small cations are attracted, but are not bound to the proteins, small anions will cross capillary walls away from the anionic proteins more readily than small cations.

Question 12

T/F CH2O value distinguishes between effective an ineffective osmoles

Answer 12

False. It does not distinguish between effective and ineffective osmoles

Question 13

What is the 60-40-20 rule?

Answer 13

Total Body Water (TBW) = 60% of body weight
ICFV = 40% of body weight
ECFV = 20% of body weight
ISFV = 15% of body weight (or 3/4 of ECFV)
PV = 5% of body weight (or 1/4 of ECFV)

Question 14

What are the main effective osmoles of ECF/ICF? What about urea?

Answer 14

the main effective osmoles:
ECF: Na and its anions
ICF: K and its anions

Urea, which is the major component of urine osmolality, is an ineffective osmole. the main effective osmoles:

Question 15

Two reasons that account for the high water permeability of cell membranes

Answer 15

1) lipid bilayer has a small, but not negligible water permeability. Since whole cell surface is available for the transport, there is significant water transport
2) presence of aquaporins, which increase the inherent water property of the cells

Question 16

What is the etiology of Diabetes insipidus?

Answer 16

LACK of ADH action on the kidneys

Question 17

What increases the driving force for water entry via Donnan effect in the cell?

Answer 17

1) presence of high intracellular concentrations of macromolecules and metabolic intermediates
2) membrane is impermeable to these molecules, but permeable to water –> results in a significant driving force for osmotic water entry

Question 18

What are the two forms of Diabetes insipidus?

Answer 18

nephrogenic and central Diabetes insipidus

Question 19

What is the active process that counters the tendency of cells to swell? What is the net result on ICF and ECF?

Answer 19

Na/K ATPase - net efflux of Na from the cell in order to maintain cell volume; net result: effective osmolality in ICF becomes equal to that in ECF

Question 20

What is central diabetes insipidus? What often causes this?

Answer 20

ADH production is inadequate; often results from trauma to the hypophyseal stalk

Question 21

T/F @ steady state ICF osmolality = ECF osmolality

Answer 21

True.

Question 22

What is nephrogenic diabetes insipidus? What often causes this?

Answer 22

kidneys can’t respond to ADH, can result from mutations in the AQP2, receptor that mediates ADH in the CD, or from hypokalemia, hypocalcemia

Question 23

T/F @ steady state Plasma osmolality = ISF osmolality

Answer 23

False. Plasma is slightly > than ISF due to the presence of plasma proteins

Question 24

What is polydipsia? What is the cause of this?

Answer 24

condition in which the patient exhibits excessive thirst because the threshold for thirst is lower than the threshold (usually it’s the other way around); may result from hypothalamic lesions.

Question 25

What is the main determinant of plasma osmolality

Answer 25

Na

Question 26

What is SIADH?

Answer 26

Syndrome of Inappropriate ADH secretion (SIADH), result from overproduction of ADH. Production does not respond to normal osmotic stimuli and therefore cannot be suppressed by reduced plasma osmolality.

Question 27

What are the effective osmoles maintained in the ECF and ICF?

Answer 27

ECF: Na and associated anions
ICF: K and associated anions

Question 28

What causes SIADH?

Answer 28

tumors
inadequate suppression of ADH secretion from the neurophypophysis
complication of surgery (excess use of IV fluids)
gain of function mutations in ADH receptor

Question 29

T/F Plasma proteins exert a Donnan Effect

Answer 29

True. They’re negatively charged and can attract counterions.

Question 30

What is the effect of SIADH on plasma osmolality?

Answer 30

low plasma Na because ADH increases water uptake

Question 31

Why is the concentrations of Cl- and HCO3- higher in the ISF?

Answer 31

Donnan Effect. Plasma proteins attract small cations, therefore the concentration of the small cations is 5% higher in the aqueous phase than in the interstitial fluid, and the concentration of small Anions is 5% lower.

Question 32

Do patients experience any symptoms from SIADH?

Answer 32

asymptomatic since the conditions develop slowly, and therefore brain cells adapt by lowering the intracellular concentration of organic osmolytes

Question 33

How do you figure out the effective osmolality?

Answer 33

2 * [Na]

Question 34

What is perceived volume depletion? When does this occur?

Answer 34

occurs in conditions where ECFV is normal or increased, but the blood volume available for tissue perfusion is inadequate, and thus the body responds as if it was volume depleted (triggering ADH release). Occurs in states of heart failure, liver cirrhosis, sepsis, use of vasodilator drugs

Question 35

How do you figure out total plasma osmolality?

Answer 35

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

Question 36

What determines the size of ECFV? How does the kdieny regulate the size of ECFV?

Answer 36

Na. Kidneys regulate the size of ECFV by regulating the Na content of the body. A high blood volume –> kidneys eliminate salt (fluid follows) –> ECFV is returned to normal

Question 37

What is the osmolar gap? What does it mean if it’s increased?

Answer 37

Osmolar gap = measured osmolality - calculated osmolality. An increased osmolar gap indicates the presence of a toxin that contributes to the osmolality

Question 38

Long term control of BP Is primarily achieved by:

Answer 38

adjusting plasma volume via changes in ECFV and RBC volume via EPO

Question 39

What determines the size of any given compartment (ie ECFV, ICFV, etc)

Answer 39

of osmotically active particles present

Question 40

Using Starlings’s law, how is the two subcompartments of ECF regulated if there is an increase/decrease in BV?

Answer 40

Increase BV –> Increase Pcap –> Increase filtration

Decrease BV -> decrease Pcap -> increase reabsorption

Question 41

What accounts for the decrease in Hct after eating a salt-laden meal?

Answer 41

1) Since Na is restricted to the ECF, this draws fluid out of the cells until ECF=ICF osmolality (but the total number of osmoles is higher in the ECF)
2) ECFV is increased, and this extra fluid is redistributed between the ISFV and plasma in a 3:1 ratio since the endothelium is freely permeable to Na.
3) Hct decreases because a) plasma volume is increased and 2) increased osmolality of the plasma (due to ingestion of Na) results in cell shrinkage

Question 42

What is the main determiant of blood pressure?

Answer 42

Blood volume, which determines CO and ultimately BP

Question 43

What are the effective osmoles (main determinant of oncotic pressure) in the plasma?

Answer 43

albumin

Question 44

In hypertensive patients, what is the treatment directed towards?

Answer 44

mechanisms that regulate the renal handling of NaCl

Question 45

What are the two opposing forces on fluid movement in the capillaries?

Answer 45

hydrostatic pressure (promotes fluid exit) and oncotic pressure (draws fluid in)

Question 46

What is the Na appetite? Where do the signals come from?

Answer 46

since NaCl is so scarce, it is a behavioral response that is analgous to the thirst mechanism; signals come from the kidney

Question 47

What is the effective oncotic pressure dependent on?

Answer 47

reflection coefficient of the capillary membrane for protein.

Question 48

What is the difference between high pressure receptors in carotid sinus/aortic arch, baroreceptors in large arteries, and high pressure receptors in the afferent arterioles of the kidney?

Answer 48

high pressure receptors in carotid sinus/aortic arch = important for short-term control of BP and serve to protect the brain from ischemia.

baroreceptors in large arteries = adapt to changes in BP (ie hypertenison) by undergoing anatomical restructuring, and thus a transient increase in wall tension is transient.

High pressure receptors in the afferent arterioles do NOT undergo restructring because they are a single layer of cells.

Question 49

What is the net ultrafiltration pressure (PUF)?

Answer 49

Sum of all hydrostatic and effective oncotic pressures

Question 50

What is the true renal baroreceptors? What about their structure makes them “true” baroreceptors, as opposed to the receptors in the carotid sinus/baroreceptors in the large arteries?

Answer 50

High pressure receptors in the afferent arteriole contain renin-producing ganular cells, which are TRUE renal baroreceptors because

1) they lack contractile fibers
2) they are composed of a single layer of muscle ells
3) always experience a stretch that is proportional to the actual BP

Question 51

If PUF is +, this means

Answer 51

fluid moves out of the capillary (ultrafiltration)

Question 52

What are low pressure receptors and where are they located? How are they similar to high pressure receptors in the large arteries?

Answer 52

Low pressure receptors are important for intermediate regulation of BP. They reside in the cardiac atria, vena cava, and large pulmonary vessels (all of which are much more distensible). They are similar because tey undergo restructuring to accommodate chronic changes in BP (ie hypertension)

Question 53

if PUF is -, this means

Answer 53

fluid moves into the capillary (absorption)

Question 54

Of all of the receptors that you learned about, which one has the greatest response to changes in BV?

Answer 54

low pressure receptors, because they reside in structures that are much more distensible (ie vena cava, atria, pulmonary vessels)

Question 55

What is the filtration coefficient (Kf) a measure of?

Answer 55

measure of water permeability

Question 56

What is the effective circulating volume?

Answer 56

Total blood volume - unmeasurable amount of pooled blood that circulates slugglishly

Question 57

What is the reflection coefficient (s) a measure of?

Answer 57

measure of protein permeability

Question 58

How do kidneys control the effective circulating volume?

Answer 58

1) regulating ECFV

2) regulating RBC volume via EPO

Question 59

What modifies Kf and s?

Answer 59

vasoactive hormones and cytokines

Question 60

In water immersion, how do the low pressure receptors aid in maintaining the effective circulating volume?

Answer 60

in water immersion, the hydrostatic pressure compresses the tissues, thereby increasing venous return to the atria. The low-pressure receptors in the promote natriuesis (get rid of Na, water follows) to restore blood volume back to “normal”

Question 61

How does PUF change throughout the length of a capillary? How does this affect fluid movement?

Answer 61

It goes from + –> - such that most of the ultrafiltrate produced in the initial portion of the capillary gets reabsorbed at the venous end.

Question 62

In congestive heart failure, why is there an increase in Na reabsorption?

Answer 62

even though there is an increase in venous pressure, the renal arterial pressure decreases, which sends signals to increase blood volume (by increasing Na reabsorption)

Question 63

What two forces contribute to the autoregulation of plasma (and thus blood) volume?

Answer 63

hydrostatic pressure (promotes fluid exit) and oncotic pressure (draws fluid in): increases/decreases in capillary hydrostatic pressures will cause fluid to be drawn in or seep out from the capillaries

Question 64

What are the two main mechanisms that promotes Na reabsorption?

Answer 64

RAAS system and renal sympathetic nerves

Question 65

What are 4 things that can contribute to edema?

Answer 65

increase in venous pressure
reduced oncotic pressure (fluids seeps out of capillary)
changes in capillary wall permeability (endothelial injury/inflammation)
obstruction of lymphatics (tumors/parasites)

Question 66

What is the main mechanism that promote natriuresis?

Answer 66

ANP

Question 67

What happens to patients with hypoalbuminemia?

Answer 67

Edema, since there is reduced oncotic pressure, fluid will seep out of the capillary and into the interstitum

Question 68

Where is renin produced?

Answer 68

granular cells of afferent arterioles

Question 69

How does inflammation/endothelial cell injury change Kf and s?

Answer 69

Increase Kf (increase water permeability)
decrease s (capillary becomes more permeable to proteins)

Question 70

What are the main renal effects induced by AII? (4)

Answer 70

1) stimulates Na reabsorption in the PCT via Na/H exchanger
2) lowers the set point and heightens sensitivity to TGF (an increase in NaCl load –> MD will trigger a more robust decrease in GFR)
3) constricts efferent arteriole, thus tilting the peritubular starling forces in favor of reabsorption by PCT (due to decreased hydrostatic/increased oncotic pressure)
4) reduces medullary blood flow, which enhances urine conc. ability and increases Na reabsorption in thin ascending limb (not to be confused with TALH -> thick ascending limb)

Question 71

What are crystalloids? Examples?

Answer 71

Na and glucose

Question 72

What are the main extra-renal effects of AII? (3)

Answer 72

stimulate aldosterone secretion, thirst, and to a lesser degree Na appetitestimulate aldosterone secretion, thirst, and to a lesser degree Na appetitestimulate aldosterone secretion, thirst, and to a lesser degree Na appetitestimulate aldosterone secretion, thirst, and to a lesser degree Na appetitestimulate aldosterone secretion, thirst, and to a lesser degree Na appetitestimulate aldosterone secretion, thirst, and to a lesser degree Na appetitestimulate aldosterone secretion, thirst, and to a lesser degree Na appetitestimulate aldosterone secretion, thirst, and to a lesser degree Na appetitestimulate aldosterone secretion, thirst, and to a lesser degree Na appetitestimulate aldosterone secretion, thirst, and to a lesser degree Na appetitestimulate aldosterone secretion, thirst, and to a lesser degree Na appetitestimulate aldosterone secretion, thirst, and to a lesser degree Na appetitestimulate aldosterone secretion, thirst, and to a lesser degree Na appetitestimulate aldosterone secretion, thirst, and to a lesser degree Na appetitestimulate aldosterone secretion, thirst, and to a lesser degree Na appetite

Question 73

What is the effect of administering a hypertonic saline solution?

Answer 73

expand ECFV, reduce ICFV

Question 74

What are the effects of AII on GFR?

Answer 74

It helps to maintain GFR, NOT increase it. Counterintuitive because one would think that it would increase it, but AII is only produced when the blood pressure declines, and thus AII helps to preserve GFR

Question 75

What is the effect of administering a hypotonic saline solution?

Answer 75

expand ECFV and ICFV

Question 76

What is the main driver of Na appeitite?

Answer 76

aldosterone

1) stimulates salt appetite
2) heightens sensitivity of taste buds to salt by reducing the salivary Na concentration

Question 77

What is the effect of administering a normal saline solution?

Answer 77

nothing, ECF stays the same

Question 78

What is the main driver of thirst?

Answer 78

angiotensin II

Question 79

What is the effect of administering glucose?

Answer 79

hemolysis

Question 80

What are the effects of aldosterone?

Answer 80

Increases Na reabsorption by:

1) upregulates ENaC and Na/K-ATPase in CD
2) upregulating NaCl cotransporter in the DT

also enhances Na reabsorption in the colon and sweat glands

main driver of Na intake (salt appetite, sensitivity)

Question 81

What is the effect of administering pure water?

Answer 81

hemolysis

Question 82

The CD is the site of convergance of 4 Na-conserving mechanisms. What are they?

Answer 82

1) TGF (increased Na delivery to MD –> afferent arteriole constriction –> reduce GFR)
2) AII –> afferent arteriole constriction in TGF/Na reabsorption in PCT via Na/H exchanger
3) catecholamines (Epi) - Na/reabsorption in PCT/ via Na/H exchanger
4) aldosterone - Na reabsorption in DCT

Question 83

What are colloids? Examples?

Answer 83

plasma expanders (ie albumin, gelatins, dextrans, starches)

Question 84

What is the RAA Axis?

Answer 84

Low BP/NaCl or high sympathetic activity –> Renin Release.

Renin –> AII

AII –> provides NEGATIVE FEEDBACK control for renin production (increased level of pressor hormones inhibit renin release) but STIMULATES aldosterone secretion

Question 85

What is ORT? What is it made of?

Answer 85

oral rehydration therapy: Na w. glucose in a slightly hypotonic solution (net: expand ECFV and ICFV)

Question 86

What are the two things that stimulate aldosterone production?

Answer 86

AII and high plasma K (in the CCD, Na reabsorption is coupled to K secretion)

Question 87

What is the main energy consumer in the kidney?

Answer 87

active reabsorption of the ultrafiltrate, specifically Na (via Na/K ATPase)

Question 88

In the proximal tubules, what regulates Na reabsorption?

Answer 88

AII, catecholamines (sympathetic innervation)

Question 89

T/F O2 consumption determines renal blood flow

Answer 89

False. In the kindey, blood flow drives O2 consumption (because more blood flow = more active reabsorption = more O2 consumption)

Question 90

What is ANP?

Answer 90

ANP is made in the heart and released in distension of the atria. Promotes natriuresis

Question 91

Why is the kidney an ideal site to monitor changes in arterial O2 content?

Answer 91

Unlike other organs, renal tissue pO2 is independent of blood flow and is thus proportional to arterial pO2 content. Therefore, RBC production is regulated by the kidneys

Question 92

How does ANP promote natriuresis? (4)

Answer 92

1) increase GFR, and medullary blood flow
2) inhibit Na reabsorption in medullary CD
3) block renin/aldosterone production
4) antagonize ADH in CD, thus inhibiting Na reabsorption and promoting water excretion

Question 93

How is the renal vasculature arranged in terms of capillary beds and arterioles?

Answer 93

afferent arteriole –> glomeruli –> efferent arteriole –> peritubular capillaries

Question 94

What is pressure natriuresis?

Answer 94

a back-up system for regulating ECFV. Kidneys have an intrinsic capacity to increase Na excretion in response to an increase in BP. With an increase in perfusion pressure, Na reabsorption is inhibited, which results in an exponential increase in Na excretion in spite of a constant GFR

Question 95

Where is blood flow the highest in the kidneys? Lowest? Why is this important?

Answer 95

Blood flow is highest in the superficial cortex. The medulla has no direct arterial blood supply, but it does receive blood from juxtamedullary glomeruli thrrough the peritubular network in the outer medulla and vasa recta in the inner medulla. Blood flow in outer medulla is 6-10% of cortical flow, and only 1/10 of that is transmitted to the vasa recta. The low blood flow in medulla and the coutnercurrent arrangement of flow in the vasa recta is critical for conserving the medullary hyperosmolality required for concentration of urine.

Question 96

During ECFV expansion/contraction (during regulation), what happens to the O2 carrying capacity of the blood and PCT O2 consumption, and what is the net effect of this regulation on EPO secretion?

Answer 96

ECFV Expansion:
- O2 carrying capacity decreases (due to hemodilution)
- PCT O2 consumption decreases (less being absorbed to return ECFV to normal).
NET: PO2 is constant, and therefore no change in EPO.

ECFV Contraction
- O2 carrying capacity increases (due to hemocontraction)
- PCT O2 consumption increases (more being absorbed to increase ECFV to normal).
NET: PO2 is constant, and therefore no change in EPO.

Question 97

What are the forces that govern ultrafiltration?

Answer 97

ultrafiltration is drive by hydrostatic pressure in glomerular capillary (PGC), opposed by hydrostatic pressure in bowman’s space (PBS), and the oncotic pressure in the glomerular capillary (pGC)

Question 98

How does polycythemia affect PO2 and EPO production?

Answer 98

Polycythemia (increase in RBC volume, which increases O2 carrying capacity)

• PCT Na reabsorption (and O2 consumption) is normal or low
• tissue PO2 is elevated, and therefore EPO is suppressed

Question 99

What determines GFR?

Answer 99

hydrostatic pressure in glomerular capillary (PGC)
hydrostatic pressure in bowman’s space (PBS)
oncotic pressure in the glomerular capillary (pGC)
permeability of the membrane for small molecules (filtration coefficient Kf)

Question 100

How does anemia affect PO2 and EPO production?

Answer 100

Tissue PO2 is reduced and therefore more EPO is released

Question 101

What is the equation for GFR?

Answer 101

GFR = Kf [(PGC-PBS)-pGC]

pBS is not included because the reflection coefficient for glomerular filtration barrier for protein is ~1 and thus fluid in BS under physiological conditions is practically protein free

Question 102

What is the chief determinant of cell volume?

Answer 102

K

Question 103

Why is GFR so high in the kidneys?

Answer 103

It has a high Kf (filtration coefficient)

Question 104

How does K affect cell volume?

Answer 104

Uptake of K -> swelling

Loss of K -> shrinking

Question 105

Why is Kf so high in the kidneys?

Answer 105

Because glomerular capillaries have large fenestrations that allow the passage of small molecules (and therefore a much larger fraction of the total surface area is available for the passage of H2O/small molecules)

Question 106

Transmembrane K gradient is a key determinant of:

Answer 106

RMP and excitability

Question 107

How does one calculate filtration fraction (FF)?

Answer 107

FF = GFR/RPF (renal plasma flow)

Question 108

a high plasma K causes: (vasoconstriction or vasodilation)

Answer 108

vasoconstriction

Question 109

How does RBF and GFR change with changes in afferent tone?

Answer 109

Since PGC is the main determinant of GFR: RBF, GFR, and FF changes in parallel with changes in afferent tone (ie afferent constriction –> decrease RBF, GFR, and FF)

Question 110

a low plasma K causes: (vasoconstriction or vasodilation)

Answer 110

vasodilation

Question 111

How does RBF and GFR change with changes in efferent tone?

Answer 111

Since PGC is the main determinant of GFR, GFR and FF changes in opposite directions with changes in efferent tone (ie efferent constriction –> increase GFR and FF), but RBF will change in parallel (efferent constriction –> decrease RBF)

Question 112

Why are K disturbances not manifested in the brain?

Answer 112

the BBB/glial cells/CSF shelter the brain from changes in plasma K (since minor changes in extracellular K can cause major disruptions in neuronal function

Question 113

How does constriction of the efferent arteriole affect RBF/GFR/fluid reabsorption?

Answer 113

Increase GFR, decrease RBF, increase fluid reabsorption from the tubules by decreasing hydrostatic pressure and increasing oncotic pressure in the peritubular capillaries

Question 114

What generates the uneven distribution of K and Na

Answer 114

Na/K ATPase

Question 115

What about the glomerulus prevents albumin and Igs from being filtered?

Answer 115

Filtration barrier rejects Igs based on their large size. Albumin is rejected based on charge (the filtration barrier carries a significant negative surface charge, which restricts the passage of negatively charged proteins)

Question 116

What does a low Km mean?

Answer 116

high affinity for substrate; therefore the receptor is usually saturated and increasing the substrate concentration doesn’t change the activity very much.

Question 117

How does proteinuria occur?

Answer 117

damage to the filtration barrier

Question 118

What does a high Km mean?

Answer 118

low affinity for substrate; therefore the receptor is usually NOT saturated and increasing the substrate concentration changes the enzyme activity substantially

Question 119

What is minimal change nephropathy?

Answer 119

kidney disease –> proteinuria

Question 120

Na/K ATPase has two different Kms. What are they and what does this mean?

Answer 120

Km for K = 1, which means that changes in plasma K within the physiological rage (3-5mM) has marginal effect on the activity of the transporter.

Km for Na = 4, which means that changes in plasma Na within the physiological rage (3-5mM) has a large effect on the activity of the transporter. Thus changes in the activity of Na-coupled transporters (ie Na/H exchanger) that alter intracellular Na have a large influence on Na/K ATPase activity, and consequently, K distribution

Question 121

What is renal clearance?

Answer 121

virtual volume of plasma completely cleared from a substance (s) per unit time

Question 122

What are some factors that affect internal K balance?

Answer 122

Insulin
Exercise and catecholamines
Acid/Base balance
Plasma osmolality

Question 123

How do you calculate renal clearance?

Answer 123

Clearance = (Us x V)/(PaS)  
Us = conc. of urine in substance 
V = urine flow rate
PaS = concentration of substance in arterial plasma

Question 124

What are insulin’s effects on internal K balance?

Answer 124

2/3 increases intracellular Na, which increases the Na/K ATPase activity to dump Na out, which results in K uptake

NET: increases K uptake via

1) stimulating Na/K ATPase
2) increase glucose uptake, which requires phosphate intake with Na (turnover)
3) activates Na/H exchanger

Question 125

How do you calculate GFR using inulin?

Answer 125

GFR = (Uinulin x V)/PaInulin

U = conc. of inulin in urine 
V = urine flow rate
Pa = concentration of inulin in arterial plasma

Question 126

A person with diabetes mellitus is given insulin. What happens to their K?

Answer 126

plasma K decreases because insulin stimulates K uptake

Question 127

What is PAH and what is it used to measure?

Answer 127

PAH is used to measure RPF. It is actively secreted into tubular fluid from the peritubular capillaries and is almost completely cleared from the blood after a single passage (renal concentration ~0)

Question 128

How does an action potential result in a local dilation of blood vessels?

Answer 128

During an action potential, the depolarization (Na influx) is shorter than the repolarization/hyperpolarization (K efflux), resulting in a net K efflux from the cell.

This K accumulates and causes local vasodilation.

Question 129

What is Inulin and what is it used to measure?

Answer 129

Inulin is used to measure GFR. It is freely filtered by the glomerulus and is neither reabsorbed nor secreted by the tubules.

Question 130

What is the effect of norepinephrine and epineprhien on internal K balance?

Answer 130

Norepineprhine inhibits Na/K ATPase, thus promoting K loss from the cells.

Epinephrine stimulates Na/K ATPase, thus promoting K uptake from the cells. EPI = INSULIN on K balance

Question 131

What is the endogenous marker of GFR?

Answer 131

creatinine, because it is produced in the body at a relatively constant rate and is eliminated primarily by glomerular filtration

Question 132

How does exercise affect internal K balance? How does the body response?

Answer 132

exercise results in a large increase of K from muscle cells (lots of APs –> hyperkalemia). Body anticipates this by secreting epinephrine at the onset of exercise (which stimulates Na/K ATPase, thus lowering plasma K levels)

Question 133

What does a high plasma creatinine level indicate?

Answer 133

low GFR (they’re inversely related)

Question 134

What is rebound hypokalemia?

Answer 134

After the cessation of exercise, the mechanisms that stimulate K uptake (epinephrine) cannot be turned off immediately. However, the increased norepinephrine levels released from sympathetic nerve endings buffer this effect by promotes K efflux by (inhibiting Na/K ATPase)

Question 135

At what point does autoregulation of RBF and GFR breakdown?

Answer 135

180mmHg

Question 136

How does b-blockers and b-agonists affect plasma K levels?

Answer 136

Epinephrine stimulates their insulin-like effects on K uptake via beta-receptors.

b-blocker would result in hypERkalemia

b-agonist can be used to treat hyperkalemia (b-agonist will stimuate K uptake) to lower K levels

Question 137

How does autoregulation affect RBF in the kidneys?

Answer 137

RBF remains relatively constant over a wide range of mean arterial pressure (~80-180)

Question 138

How does K transport affect acid-base balance?

Answer 138

Due to the H/K exchanger, cellular K depletion results in intracellular acidosis, while K depletion results in intracellular alkalkination.

(H/K exchanger = antiport. K in = H out and vice versa).

Question 139

Where does autoregulation in the kidneys occur?

Answer 139

afferent arteriole, which stabilizes glomerular capillary pressure (the main determinant of GFR)

Question 140

How does hyperosmolality affect internal K balance?

Answer 140

In hyperosmolality, cell shrinks –> intracellular K concentrates –> K leaks out –> increased plasma K

Question 141

How is autoregulation achieved? (2 mxns)

Answer 141

1) myogenic response

2) tubuloglomerular feedback (TGF)

Question 142

How does hypo-osmolality affect internal K balance?

Answer 142

In hypo-osmolality, cell enlarges –> intracellular K becomes diluted –> K enters -> decreased plasma K

note: this occurs to a lesser degree

Question 143

What is the myogenic response?

Answer 143

when the afferent arteriole contracts in response to an increase in blood pressure (stretching of the vessel)

Question 144

In a patient with diabetes mellitus, what are the two factors that contribute to and/or excerbate hyperkalemia?

Answer 144

Insulin promotes K and glucose uptake.

In DM patients, they lack insulin, which result in a reduction of K intake –> hyperkalemia.

Also, since there is no insulin, glucose is an effective osmole, which its accumulation in the ECF increases osmolality. This results in cell shrinkage, and thus K concentrates and leaks out –> hyperkalemia

Question 145

What is TGF?

Answer 145

tubuloglomerular feedback (TGF) - an increase in arterial pressure temporarily increases GFR, and thus more salt and water is delivered to the tubules. In response to an increased NaCl load, the macula densa sends a humoral signal to the neighboring afferent arteriole to contract and thus decrease GFR.

Question 146

What is the main mechanism for achieving K balance?

Answer 146

regulating renal K excretion

Question 147

What is the signal that activates TGF?

Answer 147

increased NaCl load detected by the macula densa

Question 148

How is K transport along the nephron different than N transport?

Answer 148

Na transport along the nephron is unidirectional (i.e. reabsorption), renal K transport involves both reabsorption and secretion by different nephron segments.

Question 149

What is the TGF response?

Answer 149

macula densa sends a humoral signal to the neighboring afferent arteriole to CONTRACT, thereby decreasing GFR

Question 150

How is K transported in the PCT?

Answer 150

it is reabsorbed: passive, paracellular and is mediated by solvent drag and by the lumen-positive voltage in the second half of the PT

Question 151

What is the effect of a vasoconstrictive hormone?

Answer 151

reabsorption

Question 152

How is K transported in the LOH?

Answer 152

In the thin ascending limb, K is secreted into the tubular fluid passively and is driven by the high [K] in the medullary interstitium.

Some of the K in the tubular fluid is reabsorbed in the TALH, which establishes a cortico-papillary gradient for K, with the highest in the medullary interstitium, which is important to minimize K back-leak from the medullary collecting duct

Question 153

What is the effect of a vasocondilator hormone?

Answer 153

inhibit reabsorption

Question 154

What are 3 things that help establish the corticopapillary gradient for K? why is this important?

Answer 154

1) In the thin ascending limb, K is secreted into the tubular fluid passively (due to high medullary concentration)
2) some (~20%) K is reabsorbed in the TALH
3) active K reabsorption of K via luminal H/K ATPase in the medullary CD

All 3 help to establish the cortico-papillary gradient for K, with the highest in the medullary interstitium, which is important to minimize K back-leak from the medullary collecting duct

Question 155

What are the 4 things that induce renin RELEASE?

Answer 155

1) decreased stretch of granular cells in afferent arteriole
2) decreased Na load to macula densa
3) increased sympathetic tone in response to reduced systemic BP
4) increased AII

Question 156

How does K transport change from the DCT to the LOH?

Answer 156

On normal intake, K transport in the DT and cortical CD is bidirectional, but in the medullary CD, it reabsorbs K

Question 157

What is the negative feedback loop on renin release?

Answer 157

Angiotensin II

Question 158

What does the principle cells in terms of K and Na transport?

Answer 158

It reabsorbs Na via ENaC and secretes K. This is energized by the Na/K ATPase

Question 159

What is the action of AII?

Answer 159

preserve GFR by counteracting the direct effects of reduced perfusion

Question 160

What does the alpha-intercalated cells do in terms of K and Na transport?

Answer 160

It reabsorbs K and secretes H. This is energized by the K/H ATPase

Question 161

What are some vasoconstrictors that act on the afferent arteriole?

Answer 161

sympathetic nervous system, adenosine

Question 162

Where are the a-ICC and principle cells present?

Answer 162

cortical collecting duct

Question 163

What is the effect of a vasoconstrictor acting on the afferent arteriole?

Answer 163

decrease RBF, GFR, and FF

Question 164

Where is K mostly being reabsorbed in the nephron?

Answer 164

medullary collecting duct - this helps to establish the corticopapillary gradient for K, which prevents back-leak from the medullary collecting duct

Question 165

What are some vasoconstrictors that act on the efferent arteriole?

Answer 165

angiotensin II, endothelin, ADH

Question 166

What secretes K in the CCD?

Answer 166

principle cells (Principle K Kicks Kids Out)

Question 167

What is the effect of a vasoconstrictor acting on the efferent arteriole?

Answer 167

decrease RBF, but increase GFR and FF

Question 168

What reabsorbs K in the CCD?

Answer 168

a-ICC (think “ICK for taking K in”

Question 169

What are some vasodilators that act on the afferent arteriole?

Answer 169

dopamine, ANP

Question 170

How does plasma K affect aldosterone secretion?

Answer 170

Increase in plasma K stimulates aldosterone secreton (potent stimulus).

Question 171

What is the effect of a vasodilator on the afferent arteriole?

Answer 171

Increase RBF, GFR, FF

Question 172

What 2 things stimulate K secretion in the late DCT and CCD?

Answer 172

1) increase in plasma K
2) aldosterone (which is stimulated by the increase in plasma K)
3) K is coupled to Na transport; aldosterone increases plasma reabsorption, which promotes K secretion

Question 173

What are some global vasodilators?

Answer 173

prostaglandins, NOs, kinins

Question 174

How does using a diuretic that acts in preceding nephron segments stimulate K secretion?

Answer 174

Diuretics prevent less from being reabsorbed, and therefore more Na is delivered to the late DCT and CCD. This results in an increase in Na reabsorption, but more K secretion

Question 175

What are unique about Kinins?

Answer 175

they are degraded by the same enzyme (ACE) that generates Angiotensin II. Thus, AII and kinins have opposing effects

Question 176

How does anion concentration in the CD affect K transport?

Answer 176

Cl- in the CCD is reabsorbed primarily through the paracellular pathway, creating a less (-) (or more +) lumen voltage, thereby creating a LESS favorable driving force for K secretion.

Therefore more Cl –> more reasorbed –> more + lumen charge –> less K secretion

Question 177

What is the effect of NSAIDs in a person with congestive heart failure?

Answer 177

NSAIDs block prostglandins production (which is a normal vasodilator). NSAIDs normally have no significant effects on GFR in healthy patients, but in a person with congestive heart failure (which is already hypertensive), this can cause renal insufficiency.

Question 178

how does an increase in tubular flow rate stimulate K secretion?

Answer 178

1) high flow rate washes away K, and prevents tubular K from equilibrating with intracellular K. Thus K to be secreted continually.
2) high flow rate bends the cilia on principle cells, which stimulates K secretion (Principal K kicks Kids out)

Question 179

What is renal insufficiency?

Answer 179

Renal failure - condition in which the kidneys fail to adequately filter waste products from the blood

Question 180

What is the effect of ADH on K transport?

Answer 180

stimulates K secretion

Question 181

What is the effect on ACE inhibitors on blood pressure?

Answer 181

It is a hypertensive drug (ACE normally breaks down Kinins, which are vasodilators. If ACE is blocked, then you get unapposed effects of AII, which is an efferent constrictor)

Question 182

What is the effect of pH on K channels?

Answer 182

closes them

Question 183

What are the two mediators of TGF?

Answer 183

endothelin and NO.
Endothelin is potent vasoconstrictor on the efferent arteriole.
NO is a vasodilator

think “TEN”

Question 184

What is TTKG?

Answer 184

used to diagnose the causes of hyperkalemia or hypokalemia

Question 185

What is the effect of ANP on RBF and GFR?

Answer 185

ANP is a vasodilator and acts on the afferent arteriole. Therefore RBF and GFR will increase

Question 186

What is a low TTKG value (<3) indicate?

Answer 186

hypokalemia (either non-renal or cause of K depletion)

Question 187

What is the effect of Sympathetic Nervous System on RBF and GFR?

Answer 187

SNS is a vasoconstrictor of the afferent arteriole. Therefore RBF and GFR will decrease

Question 188

What is a low TTKG value (>10) indicate?

Answer 188

hyperkalemia

Question 189

What is the effect of Angiotensin II on RBF and GFR?

Answer 189

Angiotensin II is a vasoconstrictor of the efferent arteriole. Therefore RBF will decrease, but GFR will increase

Question 190

What is the normal [H] in the ECF?

Answer 190

40nM

Question 191

What is the effect of dopamine on RBF and GFR?

Answer 191

Adenosine is a vasodilator of the afferent arteriole. Therefore RBF and GFR will increase

Question 192

What is the main buffer in the body?

Answer 192

CO2-bicarbonate buffer system

Question 193

What is the effect of endothelin on RBF and GFR?

Answer 193

Endothelin is a vasoconstrictor of the efferent arteriole. Therefore RBF will decrease, but GFR will increase

Question 194

At physiological pH, what does carbonic acid do?

Answer 194

dissociate into H2O + CO2

Question 195

What is the effect of Adenosine on RBF and GFR?

Answer 195

Adenosine is a vasoconstrictor of the afferent arteriole. Therefore RBF and GFR will decrease

Question 196

The CO2-bicarbonate system operates as an open system. What does “open” mean? Why is this important?

Answer 196

“Open” means that CO2 can be eliminated or retained via the lungs whenever an acid or alkali load is added to the system.

During an acid load, CO2 is leaves the system.

During an alkali load, additional CO2 can be retained to generate more HCO3-

Question 197

Give an example of a vasoconstrictor that is buffered by the simultaneous release of vasodilators.

Answer 197

Increase in AII/NE (vasoconstrictors) promote the release of prostaglandins (vasodilators)

Question 198

What’s the difference between respiratory buffering and respiratory compensation?

Answer 198

Respiratory Buffering = CO2 can be eliminated or retained via the lungs whenever an acid or alkali load is added to the system.

Respiratory Compensation = hyper-/hypo-ventilation that ensues to adjust PCO2 in attempt to normalize blood pH after a fixed acid/base challenge

Question 199

What is the effect of ADH on RBF and GFR?

Answer 199

ADH is a vasoconstrictor of the efferent arteriole. But because it selectively targets a tiny population of nephrons, it has no significant effects on total RBF and GFR

Question 200

How does the fact that CO2 can readily cross the cell membrane affect pH intracellularly and extracellularly?

Answer 200

CO2 can cross cell membranes, and thus changes in extracelluar pH typically parallel those in the ECF (ECF=ICF), but not always

Question 201

How does RBF and GFR change with pregnancy?

Answer 201

they both increase

Question 202

What are examples of intracelluluar buffers?

Answer 202

phosphate, creatine phopshate

Question 203

How does RBF and GFR change with a (chronic) protein diet?

Answer 203

they both increase, but due to certain a.a. that serve as substrates for NO production. Increased NO –> vasodilation –> increased glomerular hypertension and acceleration of renal disease

Question 204

What are examples of some bone buffers?

Answer 204

Acute setting: bone acts as an ion exchange resin: H+ are exchanged for Na, K ions.

The bone contains a readily exchangable pool of of HCO3- and CO3(2-) ions.

Surface of bone contains crystalline alkaline salts (hydroxyapatite, carbonate)

Question 205

What are the two main purposes of the kidney?

Answer 205

1) Eliminate metabolic end products (urea, creatinine) via ultrafiltration
2) keep volume/electrolyte composition of ECF/ICF constant

Question 206

How does chronic acidosis affect bone?

Answer 206

leads to breakdown of bone matrix and mobilization of alkali supply (hycroxyapatite, carbonate)

Question 207

What is the main energy consumer in the kidney?

Answer 207

reabsorption of Na by the tubules (Na/K ATPase, ENaC)

Question 208

Why is HCO3- not a relevant buffer in urine?

Answer 208

practically all of it is reabsorbed in the tubules

Question 209

Why is the macula densa stragetically placed at the beginning of the DCT?

Answer 209

the DCT has limited reabsorption capacity, and therefore the MD is located at the beginning of the DCT to ensure a constant Na load via the tubuloglomerular feedback mechanism

Question 210

What is the key urinary buffer?

Answer 210

phosphate (via HPO4-), urate, creatinine, citrate, ketoacids, NH3/NH4

Question 211

How is the PCT/LOH different than the DCT in terms of function?

Answer 211

the PCT/LOH function more along the lines of Na reabsoprtion (energetically favorable) whereas the DCT has limited reabsorption capacity and functions to establish the steep concentration gradients (energetically demanding)

Question 212

How does the kidneys regulate acid-base balance?

Answer 212

excretion of NH4

Question 213

What are the two main transport mechanisms that occur in the proximal tubules?

Answer 213

1) reabsorption of 2/3 of the filtered water and Na, 80% of bicarbonate and phopshate, and all nutrients.
2) Secretion of xenobiotics

Question 214

CO2 is generated during metabolism of carbs, fats, carbon skeleton of a.a.; why is its removal from the system critical?

Answer 214

any disruptions of CO2 removal can lead to profound ACIDOSIS

Question 215

Where and how is HCO3 primarily reabsorbed?

Answer 215

HCO3 is primarily reabsorbed in the PT, and this process is indirect.

1) PT secretes H+, which combines with filtered HCO3- to form carbonic acid (catalyzed by carbonic anhydrase), which dissociates into CO2 and H2O and is reabsorbed into the PCT cells
2) In the cell, CO2 and H2O are converted back to carbonic acid by an intracellular carbonic anhydrase and H2CO3 spontaenously dissociates into H+ and HCO3-.
3) HCO3- is exported to the blood by an Na/HCO3 on the basolateral side, while the H+ is secreted into the tubular fluid by the Na/H exchanger for another round

Question 216

Under normal conditions, what drives respiration?

Answer 216

pH. (NOT PO2)Any disruptions of CO2 removal can lead to profound ACIDOSISpH. (NOT PO2)Any disruptions of CO2 removal can lead to profound ACIDOSISpH. (NOT PO2)Any disruptions of CO2 removal can lead to profound ACIDOSISpH. (NOT PO2)Any disruptions of CO2 removal can lead to profound ACIDOSISpH. (NOT PO2)Any disruptions of CO2 removal can lead to profound ACIDOSISpH. (NOT PO2)Any disruptions of CO2 removal can lead to profound ACIDOSISpH. (NOT PO2)Any disruptions of CO2 removal can lead to profound ACIDOSISpH. (NOT PO2)Any disruptions of CO2 removal can lead to profound ACIDOSISpH. (NOT PO2)Any disruptions of CO2 removal can lead to profound ACIDOSISpH. (NOT PO2)Any disruptions of CO2 removal can lead to profound ACIDOSIS

Question 217

What is acetazolamide?

Answer 217

It is a carbonic anhydrase inhibitor, and therefore it increases Na excretion (and is therefore, a potent diuretic)

Question 218

Why is CO2 considered a “volatile” acid?

Answer 218

it’s eliminated via lungs

Question 219

What influences the solvent drag in the PCT?

Answer 219

1) reabsorption of Na, glucose, lactate, and inorganic phosphates increases the osmolality of the interstitial fluid (while reducing the osmolality of the tubular fluid).
2) Due to preferential reabsorption of Na with HCO3-, phosphates, and other ions, the concentration of Cl- in the tubular fluid gradually increases towards the later segments of Cl-, and this differene allows Cl- to diffuse through the paracellular pathway, which creates a luminal (+) voltage

Question 220

What happens during incomplete metabolism of carbs, fats, carbon skeleton of a.a.? Under what physiological conditions do these intermediate accumulate?

Answer 220

a fixed acid load is generated

• lactic acid from carbohydrates
• ketoacids from fats

accumulates during vigorous exercise or starvation

Question 221

What is non-ionic diffusion?

Answer 221

passive movement of lipid soluble weak acid and bases in their undissociated forms through the cell membrane.

Question 222

Catabolism of carboxyl moiety of organic acids generates this:

Answer 222

OH

Question 223

How are is Cl- reabsorbed in the PCT?

Answer 223

Transport of Cl- is mediated by the Cl-/A- and Na/H exchangers.

1) Uphill movement of Cl- into the cell is driven by the higher concentrations of organic anions (formate) inside the cell than in the tubular fluid.
2) Secretion of H+ neutralizes the secreted organic anions, the neutralized organic acid becomes lipophilic and diffuses into the cell
3) resulting cellular alkalination (due to the H+ secretion) aids the dissociation of organic acid into an anion and H+ inside the cell.
4) Na is then transported into the blood via basolateral Na/K ATPase, while Cl- exits via basolateral K/Cl cotransporter.

Question 224

How would you correct the acidosis associated with renal failure?

Answer 224

Add Na-acetate (CH3COONa) to the dialysis fluid, which catabolism of the carboxyl moiety will generate OH to correct renal failure

Question 225

What is the purpose of the Na/K ATPase?

Answer 225

to keep the intracellular concentrations of Na low so that Na can be reabsorbed (energetically favorable movement of ions down its concentration gradient)

Question 226

What is the citrus juice paradox?

Answer 226

Citrus juice contains citric acid and citrate. Metabolism of citric acid results in an equal amount of base that fully neutralizes the added H+, while metabolism of citrate anions generates additional base. Thus, the net effect of ingesting citrus juice is alkalinzation of body fluids.

Question 227

What are the advantages/disadvantages of the transport events in the PCT?

Answer 227

Pro: the PCT is relatively leaky and therefore large amounts of Na/H2O are reabsorbed with relatively little energy expenditure
Cons: since the PCT is so permeable, it is prone to back-leak

Net: since the PCT is so leaky, its rate of transport is so high that the rate of uptake into the peritubular capillary can become limiting

Question 228

Catabolism of amino moiety of a.a. generates this:

Answer 228

H+

Question 229

What are two ways that salt/water transport is regulated in the PT?

Answer 229

1) glomerulotubular balance

2) Hormonal and neural regulation (AII, dopamine, ANP)

Question 230

Catabolism of carboxy moiety of a.a. generates this:

Answer 230

OH-

Question 231

What is glomerulotubular balance?

Answer 231

balance between reabsorption of solutes in the proximal renal tubules and glomerular filtration, which must be as constant as possible. The PT always reabsorbs a constant fraction of the filtered load. The purpose is to stabilize the rate at which Na and water is delivered to the LOH and ultimately to the distal nephron, which has limited transport capacity. Balance is maintained by neural, hormonal, and other mechanisms

Question 232

What happens to NH4+ generated from a.a. catabolism?

Answer 232

It is converted to urea and H+ in the liver

Question 233

What is the net effect of the GT feedback under the influence of AII or endothelin?

Answer 233

AII/endothelin is present during low ECFV, and they act to constrict the efferent arteriole. This results in

1) increased hydrostatic pressure in the glomerulus bed, which enhances filtration of a protein-free filtrate and thus leads to increased oncotic pressure entering the peritubular capillaries.
2) increased oncotic pressure + decreased hydrostatic pressure in the peritubular bed results in an enhanced reabsorption of fluid from the tubular fluid/interstitium, thereby reducing the likelihood of backflow in the PCT

Question 234

What do you generate when you catabolize neutral a.a.? Diabasic a.a.? Dicarboxylic a.a.? Sulfur-containing a.a.?

Answer 234

neutral = equal amounts of acid + base generated
dibasic = H+ generated
dicarboxylic = OH generated
Sulfur-containing a.a. = sulfuric acid generated

Question 235

Since the PCT is so leaky, how is backflow minimized?

Answer 235

AII/endothelin constricts the efferent arteriole under low ECFV. This results in

1) increased hydrostatic pressure in the glomerulus bed, which enhances filtration of a protein-free filtrate and thus leads to increased oncotic pressure entering the peritubular capillaries.
2) increased oncotic pressure + decreased hydrostatic pressure in the peritubular bed (due to constriction of efferent arteriole) results in an enhanced reabsorption of fluid from the tubular fluid/interstitium, thereby reducing the likelihood of backflow in the PCT

Question 236

What happens when you catabolize organic phosphates (nucleic acids + phospholipids)

Answer 236

phosphoric acid is generated, which contributes to the daily acid load

Question 237

What are the main hormones that stimulate Na reabsorption in the PCT? What transporter do they act on?

Answer 237

Angiotensin II (but also catecholamines/sympathetic) via the Na/H exchanger

Question 238

What is a common feature of transepithelial H+ transport?

Answer 238

for every H secreted, an HCO3- exits on the basolateral side and enters the blood

Question 239

Which receptors sense and respond to ECFV depletion?

Answer 239

low-pressure receptors in the atria/large veins

Question 240

What happens to your blood pH when you’re eating?

Answer 240

During food ingestion, gastric acid is produced, and H+ ions derived from intracellular H2CO3 are secreted into the stomach lumen while HCO3- enters the blood

Question 241

What happens under severe ECFV depletion?

Answer 241

increased renal sympathetic activity -> increased secretion of catecholamines -> increased Na/H activity to stimulate water and salt reabsorption

Question 242

What is alkaline tide?

Answer 242

increase in plasma HCO3- after a meal. During food ingestion, gastric acid is produced, and H+ ions derived from intracellular H2CO3 are secreted into the stomach lumen while HCO3- enters the blood

Question 243

What are the two main inhibitors of Na reabsorption in the PCT?

Answer 243

dopamine and ANP

Question 244

What happens to blood pH later during digestion?

Answer 244

HCO3- secretions neutralize the acid in the duodenum (H+ ions are delivered to the blood) which results in a lowering of blood pH

Question 245

How are xenobiotics normally eliminated?

Answer 245

they are actively taken up through the PCT basolateral membrane via high affinity transporters and then secreted into the tubular fluid. Thus, they are cleared at a rate comparable to RBF.

Question 246

What are the limitations imposed on renal acid/base excretion?

Answer 246

urinary pH cannot be lowered below 4.5 or increased above 8.0

Question 247

How are xenobiotics related to PAH?

Answer 247

they are actively taken up through the PCT basolateral membrane via high affinity transporters and then secreted into the tubular fluid. Thus, they are cleared at a rate comparable to RBF. This is the basis of PAH clearance and is used to measure RBF

Question 248

How are H+ secreted from the kidneys?

Answer 248

~30% of H+ ions are excreted in buffered form (buffer = phosphate), which is called titratable acid excretion. The rest are eliminated indirectly via NH4

Question 249

How are filtered proteins eliminated from the tubular fluid?

Answer 249

1) oligopeptides are degraded by ectopeptidases in the brush border
2) larger proteins are taken up by the cell via receptor mediated endocytosis and degraded intracellularly.

–> amino acids are returned to blood through the basolateral membrane

Question 250

HCO3- is filtered through the glomeruli. How is it reabsorbed?

Answer 250

indirect transepithelial pathway; linked to H+ ion secretion because HCO3- does not actually traverse the apical membrane.

Question 251

Where is water reabsorbed in the LOH?

Answer 251

descending limb

Question 252

What are the two main transporters that function in HCO3- reabsorption? Where are they located? Describe the pathway that HCO3 is reabsorbed in the PCT

Answer 252

Na/H exchanger and luminal H-ATPase in PCT - together, they reabsorb 80% of the filtered HCO3 (via carbonic anhydrase in the lumen)

Na/H exchanger in the TALH (no carbonic anhydrase in lumen)

H-ATPase and H/K-ATPase in the CD (no carbonic anhydrase in lumen)

All of these dump H+ into the tubular lumen, which combines together with the filtered HCO3- to form H2CO3, which will spontaneously dissociate into H2O and CO2, which diffuses into the cell. Once in the cell, intracellular carbonic acid catalyzes the formation of HCO3 and H+. HCO3 reenters the blood stream via the basal side, while the H+ is transprted back into the lumen for another round of HCO3 reabsorption

Question 253

Where is Na reabsorbed in the LOH?

Answer 253

thick ascending limb (TALH)

Question 254

How does the bicarbonate concentration change as it flows down the descending limb?

Answer 254

increases because water is reabsorbed (H2O + CO2 –> HCO3- + H)

Question 255

T/F the acending limb of LOH is water permeable

Answer 255

False. It is water impermeable

Question 256

During conditions of HCO3- excess, how is HCO3 excreted?

Answer 256

1) reduced fractional reabsorption of HCO3- in proximal tubule. HCO3- reabsorption in the proximal tubule has a transport maximum (Tm), thus when filtered HCO3- load exceeds this Tm, more HCO3- is delivered downstream and ultimately excreted
2) active HCO3- secretion in CD (via b-intercalated cells)

Question 257

Why does the tubular fluid become hypoosmotic as it moves through the LOH?

Answer 257

The descending limb is where most water is absorbed, but the TALH is where it is water impermeable, and therefore water cannot follow the reabsorbed salt in the TALH. Thus:

• > tubular fluid becomes hypo-osmotic
• > the medullary interstitium becomes hyperosmotic due to accumulation of reabsorbed salt)

Question 258

Only a fraction of acid load (30%) is excreted as titrable acid. How is the rest excreted?

Answer 258

via NH4+

Question 259

What is the effect of a hyperosmotic medullary environment?

Answer 259

drives the reabsorption of water from the thin ascending limb and from the collecting ducts if ADH is present

Question 260

What is the signficance of the pK value of NH3 + H+ NH4+ reaction being 9.2?

Answer 260

at physiological pH, NH3 is fully protonated (reaction is shifted towards the left)

Question 261

What is the main route of entry for Na in the TALH?

Answer 261

Na/K/2Cl cotransporter

Question 262

What happens when NH4+ is excreted?

Answer 262

HCO3 is reabsorbed, thus “replenishing” body stores

Question 263

How are cations (Na/Mg/Ca) reabsorbed in the TALH? What facilitates this?

Answer 263

Na/K/2Cl cotransporter is an electroneutral transporter, but it facilitates reabsorption of Na. K is returned to the tubular lumen, which generates a lumen (+) voltage. This drives the reabsorption of cations through the paracellular pathway.

Question 264

Why is the excretion of NH4+ equivalent to the excretion of H+?

Answer 264

excreted NH4+ is no longer available to generate H+ in the urea cycle

Question 265

What do loop diuretics act on?

Answer 265

Na/K/2Cl cotransporter; prevents the reabsorption of Na, resulting in an ablation of the countercurrent multiplier gradient, and can result in isoosmotic urine production (because there is no concentration capability of the kidneys)

Question 266

NH4+ is very toxic. How does the body resolve this so that it can be transported and excreted in the kidneys?

Answer 266

The problem is solved through a cooperative effort between the liver and kidneys. The liver converts NH4+ into glutamine (non-toxic intermediate), which is transported to the kidney. The kidney converts it to NH4+ and a-ketoglutarate.

a-ketoglutarate is converted to 2 molecules of HCO3 “new bicarbonate”, which is ultimately returned to the blood circulation

Question 267

What happens with chronic use of loop diuretics?

Answer 267

Chronic use prevents the reabsorption of Na, resulting

1) increases Na load arriving to the DT, which results in an upregulation of the NaCl cotransporters in the DT.
2) an ablation of the countercurrent multiplier gradient, and can result in isoosmotic urine production (because there is no concentration capability of the kidneys)

Question 268

Where is “new bicarbonate” formed?

Answer 268

The kidney converts glutamine (from the liver) to NH4+ and a-ketoglutarate.

a-ketoglutarate is converted to 2 molecules of HCO3 “new bicarbonate”, which is ultimately returned to the blood circulation

Question 269

How is the TAL auto-regulated? Whats the purpose this autoregulation?

Answer 269

TAL increases the rate of Na reabsorption with an increase in salt delivery, and its purpose is to buffer changes in salt load arriving to the distal tubule (which has limited transport capacity)

Question 270

Describe the excretion of NH4+ in the PCT

Answer 270

Glutamine from the blood and the tubular fluid and converted to NH4+ ions, which is secreted into the tubular fluid through two separate pathways:

1) Na+/NH4+ exchanger (NH4+ substitutes for H+ ions on the Na+/H+ exchanger) on the apical membrane
2) a fraction of NH4+ ions dissociate into NH3 and H+ inside the cell. NH3 is a gas and diffuses through the apical membrane AND basolateral membrane is considerable.

In the tubular fluid NH3 is converted back into NH4+ by secreted H+ ions.

Question 271

What is the purpose of the Ca sensor in the TAL?

Answer 271

The TAL reabsorbs significant amounts of Ca and Mg without water into the medullary interstitium. These cations have limited solubility and are prone to precipitate at high concentrations. When activated, this sensor inhibits the apical K channels in the TAL, which eliminates the (+) luminal voltage that drives the paracellular reabsorption of Ca.

Question 272

Describe the excretion of NH4+ in the descending limb

Answer 272

As water is reabsorbed in the descending limb of the Henle’s loop, the concentration of HCO3-, and with it, the pH of the tubular fluid increases. This alkalinization favors the dissociation of NH4+ into NH3 and H+, and some NH3 may diffuse out into the medullary interstitium

Question 273

What does the Ca sensor in the TAL act on?

Answer 273

K channels (allows K to leave the cell into the lumen)

Question 274

Describe the excretion of NH4+ in the ascending limb

Answer 274

NH4+ reabsorption is mediated primarily by the Na/K/2Cl cotransporter, where NH4+ masquerades as a K+ ion.

Additional NH4+ is reabsorbed paracellularly and through apical K channels in both cases driven by a favorable electrical gradient.

The result is the accumulation of NH4+ in the medullary interstitium and the development of a corticopapillary gradient.

Practically all of the NH4+ secreted by the proximal tubule is reabsorbed in the loop.

Question 275

What type of feedback is the MD involved in?

Answer 275

Tubuloglomerular feedback. The MD senses the increased NaCl load arriving to the distal tubule, and inihits the TGF to ensure that the downstream segments are not overwhelmed by a Na load

Question 276

What is unusual about the ascending limb of LOH in terms of NH3/NH4?

Answer 276

An unusual property of the ascending limb is that it is impermeable to NH3, but it actively reabsorbs NH4+.

Question 277

What are two process that the MD is involved in?

Answer 277

TGF and Renin secretion

Question 278

What is diffusion trapping, and where does this occur?

Answer 278

Occurs in the CD, where the final step in the excretion of NH4+ is its transfer from the medullary interstitium –> urine.

Ongoing HCO3- reabsorption in the ascending limb and collecting duct alkalinizes the medullary interstitium, which promotes conversion of NH4+ –> NH3 (recall that practically all of the NH4+ secreted by the proximal tubule is reabsorbed in the loop.)

Unlike the ascending limb, the collecting duct is highly permeable to NH3, but is impermeable to NH4+. As NH3 diffuses into the tubular fluid, it is converted to NH4+ by secreted H+ and thus is “trapped” and excreted.

In the deep medulla, levels of interstitial NH4+ are high enough to allow active NH4+ uptake into the cell, conversion to NH3, diffusion of NH3 into the tubular fluid and its subsequent trapping as NH4+.

Question 279

Which two parts of the nephron is impermeable to water?

Answer 279

TALH and DCT

Question 280

What is the main determinant of the activity of acid-base transporters?

Answer 280

intracellular pH.

Acidification of tubule cells → increases H+ secretion (want to get rid of H+)
Alkalinization of tubule cells → inhibits H+ secretion

Question 281

How is Na reabsorbed in the DCT?

Answer 281

through a NaCl cotransporter

Question 282

What are the short/long term regulators of acid/base transport?

Answer 282

Short-term:

• allosteric regulation/postsynthetic modifications to increase the activity of transporters existing in the membrane
• insertion of new transporters from an intracellular pool of vesicles.

Long-term:

• synthesis of transporters
• cellular remodeling in the collecting duct that affects the ratio of α- vs β-intercalated cells.

Question 283

What do thiazides do? What happens with chronic thiazide use?

Answer 283

They block the NaCl cotransporter in the DCT, which results in decreased Na reabsorption; chronic use leads to salt wasting.

Question 284

Why does the long-term regulators of acid/base transport exist (from an evolution stand-point)

Answer 284

Evolutionarily the two main acid challenges are:
- lactic acidosis (vigorous exercise) “acid cough” - happens quickly and is resolved spontaneously when the accumulated lactate anions are metabolized into HCO3-. Excretion of acid is not desirable, as it would result in alkalosis following recovery from anaerobic metabolism.

• ketoacidosis during starvation - develops slowly during starvation and thus there is ample time for the kidneys to adjust.

Question 285

What transporter is responsible for Na transport in the CD?

Answer 285

ENaC - highly selective for Na

Question 286

NH4+ secretion in the PCT and diffusion trapping in the CD are dependent on this:

Answer 286

ongoing H+ secretion

Question 287

What drives the ENaC?

Answer 287

low intracellular Na concentration (due to basolateral Na/K/ATPase) and negative potential inside of cell

Question 288

How does chronic acidosis affect NH4+ secretion?

Answer 288

increase

Question 289

Which two ions are coupled in the CD?

Answer 289

Na reabsorption (via ENaC) and K secretion (via K channels)

Question 290

How does chronic alkalosis affect NH4+ secretion?

Answer 290

decrease

Question 291

What are K sparing diuretics? What do they act on?

Answer 291

blocks ENaC or blocks the effects of aldosterone, therefore K excretion is reduced due to the coupling of Na reabsorption to K secretion in the CD

Question 292

Where is H+ secretion is directly coupled to Na reabsorption?

Answer 292

proximal tubule + ascending limb via the Na/H exchanger

Question 293

What are the effects of aldosterone?

Answer 293

Increases Na reabsorption by:

1) upregulates ENaC in CD
2) upregulating NaCl cotransporter in the DT

Question 294

How does AII and catecholamines contribute to acid-base chemistry in the PCT?

Answer 294

AII increases the activity of Na/H exchanger in the PCT, which increases H+ secretion (coupled to Na reabsorption)

Question 295

What is the effect of ADH?

Answer 295

It caues the insertion of AQP2 water channels in the apical side of the priniciple cells, which allows water to be reabsorbed.

Question 296

How is H+ secretion is directly coupled to Na reabsorption in the PCT?

Answer 296

Mxn #1: Na+ reabsorption in principal cells occur through ENaC, which renders the lumen negative as Na+ exit. This voltage creates a favorable electrical gradient for the operation of the H-ATPase in the neighboring α-ICC cells As the rate of Na+ reabsorption increases, the lumen becomes more negative, which enhances H+ secretion from the α-cells.

Mxn #2: In principal cells, an increase in Na reabsorption via ENaC is typically accompanied by an increase in K+ secretion. Some of this K is reabsorbed via the H/K-ATPase cotransporter by α-ICC cells, thereby leading to further stimulation of H+ secretion.

Mxn #3: Aldosterone, stimulates Na and K transport, and also acts on α-ICC cells to increase the # of apical H-ATPase.

Question 297

What antagonizes ADH?

Answer 297

ANP, prostaglandins, divalent cations (Ca/Mg)

Question 298

How would volume depletion or primary hyperaldosteronism affect acid/base balance?

Answer 298

volume depletion triggers the RAAS system, which increases the # of apical H-ATPase (thus promoting H+ secretion)

Primary hyperaldosteronism makes patients more susceptible to the development of alkalosis

In both cases, aldosterone causes more H-ATPase to be inserted into the luminal side of the a-ICC cells

Question 299

Under normal conditions, how much of filtered urea is excreted?

Answer 299

~70%

Question 300

How does K depletion affect acid/base balance in general?

Answer 300

K depletion leads to cellular acidification and extracellular alkalemia (because H can’t be removed from the cell if there isn’t K) K depletion leads to cellular acidification and extracellular alkalemia (because H can’t be removed from the cell if there isn’t K) K depletion leads to cellular acidification and extracellular alkalemia (because H can’t be removed from the cell if there isn’t K) K depletion leads to cellular acidification and extracellular alkalemia (because H can’t be removed from the cell if there isn’t K) K depletion leads to cellular acidification and extracellular alkalemia (because H can’t be removed from the cell if there isn’t K) K depletion leads to cellular acidification and extracellular alkalemia (because H can’t be removed from the cell if there isn’t K) K depletion leads to cellular acidification and extracellular alkalemia (because H can’t be removed from the cell if there isn’t K) K depletion leads to cellular acidification and extracellular alkalemia (because H can’t be removed from the cell if there isn’t K)

Question 301

Under water deprivation, how much of filtered urea is excreted?

Answer 301

~15%

Question 302

How does K loading affect acid/base balance in general?

Answer 302

K depletion leads to cellular alkalemia and extracellular acidificaiton (because H is removed from the cell in exchange for K) K depletion leads to cellular alkalemia and extracellular acidificaiton (because H is removed from the cell in exchange for K) K depletion leads to cellular alkalemia and extracellular acidificaiton (because H is removed from the cell in exchange for K) K depletion leads to cellular alkalemia and extracellular acidificaiton (because H is removed from the cell in exchange for K) K depletion leads to cellular alkalemia and extracellular acidificaiton (because H is removed from the cell in exchange for K) K depletion leads to cellular alkalemia and extracellular acidificaiton (because H is removed from the cell in exchange for K) K depletion leads to cellular alkalemia and extracellular acidificaiton (because H is removed from the cell in exchange for K) K depletion leads to cellular alkalemia and extracellular acidificaiton (because H is removed from the cell in exchange for K)

Question 303

What happens to urea transport in the nephron under severe ECFV depletion? What hormone regulates this?

Answer 303

ADH increases urea permeability of the inner medullary CD (which is normally impermeable to urea), which allows urea to be reabsorbed. This is to maximize water conservation during dehydration (since water follows urea reabsorption): if the CD is impermeable to urea but permeable to water, urea excretion would require the excretion of additional water.

Question 304

How does hypokalemia affect acid/base balance in the kidney?

Answer 304

hypokalemia increases H+ excretion throughout the nephron and also stimulates NH4+ transport and excretion in the proximal tubule, so that K can be reabsorbed in order to maintain a normal plasma K concentration. This can lead to extracellular alkalosis.

This process occurs via Na/K/2Cl in the TALH and the H/K ATPase in the CD. **Remember that K can be substituted for NH4

Question 305

Under normal conditions, how is urea transported in the nephron?

Answer 305

50% is reabosrbed in the PCT by paracellular diffusion and solvent drag, and about 20% is reabsorbed in the thin limb of LOH. The rest of the nephron has low urea permeability.

Question 306

How does hyperkalemia affect acid/base balance in the kidney?

Answer 306

hyperkalemia results in diminished acid and NH4+ excretion (so that K can be excreted in order to maintain a normal plasma K concentration), leading to extracellular acidosis.

Question 307

Why is acute cell volume regulation limited to a few organs?

Answer 307

Extrusion or uptake of electrolytes in every tissue would dramatically change the electrolyte composition of the ECF

Question 308

What is a potent stimulus for respiration?

Answer 308

acidosis

Question 309

Which two organs can regulate their cell volume during osmotic challenge?

Answer 309

brain and intestines

Question 310

How is metabolic acidosis compensated for?

Answer 310

respiratory compensation

Question 311

What limits the brain from responding to an osmotic challenge? What does it do in response?

Answer 311

It’s limited by changes in excitability that result from transmembrane ion fluxes. The brain cells eventually adapt to an abnormal osmolality by regulating the conc. of small organic molecules that do not disturb cell function (ie taurine, sorbitol, etc)

Question 312

T/F hyperchloremia metabolic acidosis results in hyperkalemia

Answer 312

True.

Question 313

What is the solute that significantly affects tonicity?

Answer 313

Na

Question 314

What is the ultimate consequence of metabolic acidosis?

Answer 314

Bone dissolution because remember that in the acute setting: bone acts as an ion exchange resin: H+ are exchanged for Na, K ions. (bone contains a readily exchangable pool of of HCO3- and CO3(2-) ions.)

Question 315

What is principle ion in osmoregulation? How is it regulated?

Answer 315

Na, by regulating the Na concentration (via adjusting the amount of water)

Question 316

T/F respiratory acidosis leads to bone dissolution

Answer 316

False. Can be remedied through breathing

Question 317

How is an abnormal Na plasma corrected?

Answer 317

by adjusting the amount of water (because it changes much more readily than the amount of Na)

Question 318

T/F respiratory acidosis leads to neuromuscular excitability

Answer 318

True. It may also lead to tetany

Question 319

What is hyponatremia an indication of?

Answer 319

water excess/overhydration (NOT a Na problem)

Question 320

How do you determine HCO3 in blood plasma?

Answer 320

measure arterial bood gas, which should give you pH and pCO2. Use Hendersen-Hasselbalch eqn to figure out HCO3-

Question 321

What is hypernatremia an indication of?

Answer 321

water deficit/dehydration (NOT a Na problem)

Question 322

What are normal pH levels?

Answer 322

7.35-7.45

Question 323

Why is hyponatremia associated with oligoura, even though the expected response would be polyuria?

Answer 323

because the kidneys ability to excrete H2O is compromised. Therefore oligouria is the cause, not consequence, of hyponatremia

Question 324

What are normal pCO2 levels?

Answer 324

35-45

Question 325

What is the expected urine output in response to hypernatremia due to dehydration?

Answer 325

oligouria

Question 326

What are normal HCO3 levels?

Answer 326

22-26

Question 327

What is the expected urine output in response to hypernatremia that’s caused by a renal concentrating defect?

Answer 327

polyuria

Question 328

Acid-base disturbances are conventionally categorized as respiratory if they are initiated by an abnormal _______, and metabolic if they result from an abnormal _______. Thus, there are four cardinal disturbancesAcid-base disturbances are conventionally categorized as respiratory if they are initiated by an abnormal _______, and metabolic if they result from an abnormal _______. Thus, there are four cardinal disturbancesAcid-base disturbances are conventionally categorized as respiratory if they are initiated by an abnormal _______, and metabolic if they result from an abnormal _______. Thus, there are four cardinal disturbancesAcid-base disturbances are conventionally categorized as respiratory if they are initiated by an abnormal _______, and metabolic if they result from an abnormal _______. Thus, there are four cardinal disturbancesAcid-base disturbances are conventionally categorized as respiratory if they are initiated by an abnormal _______, and metabolic if they result from an abnormal _______. Thus, there are four cardinal disturbancesAcid-base disturbances are conventionally categorized as respiratory if they are initiated by an abnormal _______, and metabolic if they result from an abnormal _______. Thus, there are four cardinal disturbancesAcid-base disturbances are conventionally categorized as respiratory if they are initiated by an abnormal _______, and metabolic if they result from an abnormal _______. Thus, there are four cardinal disturbances

Answer 328

PCO2, HCO3-

Question 329

Oligouria

Answer 329

low urine volume

Question 330

What are the 4 cardinal acid/base disturbances?

Answer 330

respiratory acidosis
respiratory alkalosis
metabolic acidosis
metabolic alkalosis

Question 331

Polyuria

Answer 331

high urine volume

Question 332

T/F An excess of CO2 can be converted to a fixed acid and excreted by the kidneys.

Answer 332

Although CO2 and HCO3- are linked in the acid-base disturbances, they are regulated independently by the lungs and the kidneys, respectively.

An excess of CO2 cannot be converted to a fixed acid and excreted by the kidneys.

Similarly, a decline in [HCO3-] resulting from the addition of a fixed acid cannot be corrected by the lung because there is no mechanism to convert a fixed acid into CO2.

Question 333

What is insensible water loss?

Answer 333

water loss that you can’t measure (water lost via evaporation from the lungs and skin)

Question 334

How do you compensate metabolic disturbances?

Answer 334

adjustments in PCO2

Question 335

Which receptors sense and response to changes in osmolality? Where are they located?

Answer 335

osmoreceptors - located in the CNS in an area where it is “leaky. This allows neurons to sense a change in plasma Na concentration (since these neurons are sensitive to changes in cell volume)

Question 336

How do you compensate respiratory disturbances?

Answer 336

adjustments in HCO3-

Question 337

Under normal conditions, what governs water balance?

Answer 337

ADH secretion and consequently water secretion

Question 338

both the lungs and the kidneys respond to this common variable. How do you determine this variable?

Answer 338

pH. determined by the ratio of [HCO3-] and PCO2

Question 339

Under conditions of excessive water loss (ie hot weather, exercise), what governs water balance?

Answer 339

The kidneys ability to conserve water becomes exhausted (it can only conserve up to 1L/day via ADH) and therefore water balance depends almost exclusively on the thirst mechanism

Question 340

Metabolic disturbances are compensated by adjustments in PCO2, but this is always INCOMPLETE. Why is that?

Answer 340

because the compensatory response is initiated by the change in pH, and thus full restoration of pH would eliminate the signal that drives the compensation.

Question 341

Is the threshold for ADH secretion lower or higher than the threshold for thirst response?

Answer 341

lower. Thus, under normal conditions, water balance is maintained by regulating ADH secretion and consequently water secretion

Question 342

What is the time scale of respiratory compensation of metabolic disturbances?

Answer 342

Respiratory compensation begins almost instantly through changes in the activity of peripheral chemoreceptors.

However, the full response, which includes central chemoreceptors, takes a few hours to develop because HCO3- penetrates only slowly through the blood-brain barrier.

Question 343

How is water balance regulated?

Answer 343

behavioral response of thirst determines water intake

ADH regulates renal water excretion by altering permeability of the collecting duct

Question 344

What is the time scale of renal compensation of metabolic disturbances?

Answer 344

Renal compensation of respiratory disturbances takes several days. Consequently, acute and chronic respiratory disorders can be distinguished based on the degree of renal compensation (i.e. change in [HCO3-]).

Question 345

What role do cold receptors in the mouth and stretch receptors in the esophagus and stomch play in water regulation?

Answer 345

they temporarily inhibit the sensation of thirst to prevent overhydration. This is because the osmoreceptors regulation of water intake is insufficient.

Question 346

What is the time scale of metabolic/renal compensation of respiratory disturbances?

Answer 346

respiratory disturbances can develop much more quickly but the metabolic/renal compensation can take several days

Question 347

What is the primary function of ADH and thirst?

Answer 347

prevent changes in plasma osmolality, and therefore cell volume

Question 348

How do you distinguish between acute and chronic respiratory disorders?

Answer 348

degree of renal compensation (change in [HCO3-])

Question 349

Under normal conditions, what is the #1 priority of volumetric control?

Answer 349

under normal conditions, regulation of cell volume takes precedence over regulation of ECFV. But with extreme disturbances of ECFV (ie hypovolemic/hemorrhagic shock, the body tolerates changes in plasma osmolality to prevent circulatory collapse.

Question 350

What is the first line of defense against any acid or base load?

Answer 350

physicochemical buffering

Question 351

What is a potent inducer of thirst?

Answer 351

AII

Question 352

Metabolic disturbance: a fixed acid or base load is buffered primarily by

Answer 352

CO2-bicarbonate system

Question 353

How can diluted urine be produced? How does this affect the medulla? Where is this normally occuring? What is this process called?

Answer 353

reabsorbing solute without H2O generates dilute urine, but generates a hyperosmotic medulla. This occurs in the TALH, and this is called the “single effect” of urinary concentration

Question 354

Metabolic disturbance: a fixed acid load (HCl) does this

Answer 354

generates CO2

H + HCO3 => H2O + CO2

Question 355

In what parts of the nephron contributes to the formation of dilute urine?

Answer 355

ascending limb of LOH, DT, and in the absence of ADH, the CD (since all of these areas are water-impermeable)

Question 356

Metabolic disturbance: a fixed alkali load (NaOH) does this

Answer 356

requires input/consumption of CO2, but generates HCO3

NaOH + CO2 => Na + HCO3-

Question 357

What is respiratory alkalosis caused by?

Answer 357

removal of CO2

Question 358

What is the “single effect” of urinary concentration?

Answer 358

deposition of Na into the interstitium (without water)

Question 359

What is respiratory acidosis caused by?

Answer 359

retention of CO2

Question 360

What does the countercurrent multiplier result in?

Answer 360

at any one level in the medulla, there is only a modest difference in the salt concentration of the tubular fluid in the ascending limb of LH and the interstitium, but the counterflow arrangement generates a large axial (corticopapillary) salt gradient

Question 361

respiratory disturbances can only be buffered by:

Answer 361

non-bicarbonate buffers, including intracellular proteins

Question 362

How does the medullary maintain its hyperosmotic environment?

Answer 362

blood flow through the vasa recta in the medulla at a sluggish rate and in opposite directions.

Question 363

How do you compensate for respiratory acidosis?

Answer 363

buffering with intracellular proteins, or non-bicarbonate buffers

the CO2-bicarbonate system cannot be used because in this case the source of H+ ions is H2CO3. Remember that in respiratory acidosis, CO2 accumulates (due to hypoventilation) and causes the reaction (H + HCO3 => H2O + CO2) to go in the opposite direction, thus generating H+. These H+ are taken up by proteins, which ultimately affects protein structure and function.

Question 364

What is “medullary washout”?

Answer 364

an increased medullary blood flow results in an incomplete equilibration between the ascending and descending blood, and thus the vasa recta carries away more salt from the medulla than what the TAL can produce

Question 365

Why do respiratory disorders tend to have more severe functional consequences than metabolic ones at a comparabe pH?

Answer 365

Respiratory disturbances can only be buffered by non-bicarbonate buffers, including intracellular proteins. This problem is intensified by the ease with which CO2 (diffusion) can enter cells relative to HCO3- (requires transporter)

Question 366

What are some things that can reduce the kidney’s concentrating ability?

Answer 366

1) increased medullary blood flow
2) increased luminal flow
3) loop diuretics (block salt reabsorption in TALH, thereby abolishing the corticopapillary salt gradient)

all three reduces the time available for equilibration with the interstitium, which increase tubular flow, and consequently diminishes renal concentrating ability

Question 367

Metabolic acidosis can result from…

Answer 367

loss of bicarbonate or gain of fixed acid

Question 368

In the presence of ADH, the bulk of water reabsorption occurs in the cortical CD. Why is that?

Answer 368

to maintain the medullary osmotic gradient

Question 369

How does metabolic acidosis affect pH, [HCO3-] and PCO2?

Answer 369

decrease, decrease, decrease

Question 370

What is the effect of ADH on the nephron?

Answer 370

1) increase H2O permeability along the entire length of the CD.
2) increase urea permeability in the terminal portion of the CD. NET: corticopapillary urea gradient established

Question 371

In metabolic acidosis, what is the primary event and what is the compensatory event in terms of pH, [HCO3-] and PCO2, hypo/hyperventilation?

Answer 371

primary event: HCO3 loss

compensation event: PCO2 (hyperventilation)

Question 372

What is the rapid vs chronic effect of ADH?

Answer 372

rapid: increase AQP2 transcription
chronic: increase AQP2 transcription

Question 373

in metabolic acidosis, what is the significance of the respiratory compensation?

Answer 373

prevent large decreases in PH

Question 374

Where is the bulk of water reabsorption in the CD occur?

Answer 374

cortical collecting duct

Question 375

What is PAG?

Answer 375

PAG = [Na+] - [Cl-] - [HCO3-]

PAG is the difference between the concentrations of anions and cations that were not measured or are not included in the formula

Question 376

How is urea permeability changed under the influence of ADH? Whats the purpose of the change?

Answer 376

ADH increases urea permeability of the inner medullary CD (which is normally impermeable to urea), which allows urea to be reabsorbed. Urea deposited into the medullary interstitium is taken up by the thin limbs of LH, which has constitutively high urea permeability. During anti-diuresis, tubular fluid exiting the LH contains more urea than what was filtered. The subsequent segments up to the point of the terminally medullary CD are impermeable to urea, and due to water reabsorption under the influence of ADH, urea concentration increases in the cortical and outer medullary.

Question 377

What is the normal value of PAG. What is this largely attributed to?

Answer 377

8-10 mEq/L. largely attributed to the presence of albumin

Question 378

What two compounds undergo the counter-current multiplier process?

Answer 378

Na and urea

Question 379

What is the utility of the PAG?

Answer 379

diagnosis of metabolic acidosis

Question 380

What happens to urea under chronically high levels of ADH?

Answer 380

rate of urea excretion is reduced, and therefore urea concentration in the blood increases. Since urea is not an effective osmole, the increased blood urea does not change ICFV, and the accumulated urea can be excreted upon rehydration?

Question 381

How does metabolic acidosis affect the PAG?

Answer 381

Its value increases during metabolic acidosis, or whenever an acid other than HCl is added to plasma:

• ketoacids in diabetes mellitus
• lactate during exercise
• unusual anions resulting from the ingestion of certain toxins (ex: formic acid from methanol)

Question 382

Is urea an effective or ineffective osmole?

Answer 382

ineffective osmole - increased blood urea does not change ICFV

Question 383

What is Renal Tubular Acidosis (RTA) and how does this affect PAG?

Answer 383

renal defect in H+ ion secretion –> acidosis. Increases PAG

Question 384

How would you expect BUN and creatinine to change during renal plasma failure?

Answer 384

In renal failure plasma creatinine and BUN increase in parallel (because the problem lies within the ability of the urine to filter/reabsorb stuff)

Question 385

How does volume expansion with normal saline result in metabolic acidosis?

Answer 385

[HCO3-] declines by dilution, thus fooling the body to think that there is less buffering capacity (blood becomes more acidic).

Ventilation increases to get rid of CO2 to make the body “less acidic” but in reality, you’re decreasing the HCO3, or buffering capacity even more due to ventilation

H + HCO3 => H2O + CO2 (expelled)

Question 386

How would you expect BUN and creatinine to change during dehydration?

Answer 386

During dehydration (as long as GFR is maintained) creatinine excretion and thus plasma creatinine remain constant whereas BUN increases. (because ADH causes increased urea permeability, whereas creatinine is not affected by ADH)

Question 387

Metabolic alkalosis can result from…

Answer 387

too much bicarbonate retention

Question 388

What is the effect of ANP on water permeability?

Answer 388

ANP inhibits Na reabsorption in the CD and antagonizes the effect of ADH. This results in rapid reduction of the ECFV.

Question 389

How does metabolic alkalosis affect pH, [HCO3-] and PCO2?

Answer 389

increase, increase, increase

Question 390

What is the effect of prostaglandins on water permeability?

Answer 390

it antagonizes the effect of ADH.

Question 391

In metabolic alkalosis, what is the primary event and what is the compensatory event in terms of pH, [HCO3-] and PCO2, hypo/hyperventilation?

Answer 391

primary event: HCO3

compensation event: PCO2 (hypoventilation)

Question 392

What is the effect of NSAIDs on water permeability?

Answer 392

ADH-like effects (because they inhibit prostaglandins, which normally antagonize ADH). As a result, ADH can act on the CDs, resulting in increased urine osmolality

Question 393

How do kidneys respond to metabolic alkalosis?

Answer 393

bicarbonaturia (excretion of HCO3)

Question 394

What is the purpose of the Ca sensor in the CD?

Answer 394

The CD monitors urinary [Ca] via luminal Ca++ receptors. If the urine Ca concentration is too high (which increases risk of precipitation, these receptors are activated to inhibit the effect of ADH on the CD, thus generating more dilute urine.

Question 395

in metabolic alkalosis, what is the significance of the respiratory compensation?

Answer 395

to decrease pH and HCO3 levels

Question 396

Where are two places in the kidneys were Ca sensors are placed?

Answer 396

TALH and cortical CD

Question 397

How does metabolic alkalosis affect HCO3 transport in the kidneys?

Answer 397

1) transport maximum for bicarbonate reabsorption in the proximal tubule is only slightly above the normal filtered load, and thus an increase in plasma [HCO3-] results in increased bicarbonate delivery out of the proximal tubule
2) alkalosis suppresses HCO3- reabsorption in other segments, and also stimulates HCO3- secretion by β-intercalated cells

Question 398

Hyperosmotic urine results in ___________ plasma osmolality (increase or decrease)

Answer 398

decreased (more water is retained)

Question 399

Why is the most common cause of metabolic alkalosis?

Answer 399

repeated vomiting, which also leads loss of Na/K in the urine (resulting in a negative Na and K balance). It is the secondary effects of Na and K depletion that are responsible for perpetuating the alkalosis.

Question 400

Why is the most common cause of metabolic alkalosis?

Answer 400

repeated vomiting, which also leads loss of Na/K in the urine (resulting in a negative Na and K balance). It is the secondary effects of Na and K depletion that are responsible for perpetuating the alkalosis.

Question 401

How would the kidneys respond to a bulemic person? What would the HCO3/Na/K profile of this person look like?

Answer 401

Increased HCO3 + Negative Na and K balances

The kidney responds to the initial loss of HCl (vomiting) and the resulting alkalosis by bicarbonaturia (HCO3 secreted in urine). Due to the coupling of Na and HCO3- reabsorption in the nephron, HCO3 secretion results in the loss of Na.

Less HCO3 and Na reabsorption means that there is greater tubular flow, which enhances K secretion in the CD.

Reduced intake of Na and K due to the upset stomach also contributes to the negative Na and K balance.

Question 402

What would the nervous/hormonal response of a bulemic person be?

Answer 402

In a bulemic person (repeated vomiting), Na and K loss occurs, resulting in activation of the sympathetic nervous system and RAAS.

Question 403

How does a bulemic person become hypokalemic?

Answer 403

1) increase HCO3 –> loss of Na (due to coupling of transport)
2) less HCO3 and Na reabsorption –> greater tubular flow, which enhances K secretion in the CD.
3) Reduced intake of Na and K due to the upset stomach –> negative Na and K balance
4) activation of the sympathetic nervous system and the RAAS. Catecholamines and AII stimulate the apical Na/H exchanger (HCO3- reabsorption) in the proximal tubule. Aldosterone acts on Na/H exchanger in the CD to stimulate Na reabsorption, H secretion, and K secretion, thereby aggravating the K depletion.

Question 404

How do tubular cells respond to hypokalemia?

Answer 404

hypokalemia leads to intracellular acidosis due to enhanced H/K exchange, to which tubule cells respond accordingly:

• increased NH4+ production and excretion
• increase in HCO3- reabsorption

Question 405

How would you treat a bulemic person?

Answer 405

administer K and NaCl levels

Question 406

What is contraction alkalosis?

Answer 406

dehydration (loss of water) or treatment with diuretics can result in contraction alkalosis.

Question 407

What is respiratory acidosis caused by?

Answer 407

increased arterial PCO2; usually due to depressed alveolar ventilation or, rarely, because of excessive CO2 production.

Question 408

Why does acute respiratory acidosis lead to a small rise in PCO2?

Answer 408

the H+ ions derived from H2CO3 are buffered by non-bicarbonate buffers (Hb, proteins, etc)

Question 409

In chronic disturbances with full-blown renal compensation, what is the net pH and HCO3?

Answer 409

large increase in [HCO3-] and pH is returned to near normal values

Question 410

What is respiratory alkalosis caused by?

Answer 410

alveolar hyperventilation. As with respiratory acidosis, the change in [HCO3-] is relatively small acutely, but is substantial if hyperventilation persists for several days.

Question 411

T/F A normal pH is indicative of a normal acid/base balance

Answer 411

False. Mixed acid/base disturbances can either amplify or neutralize each other.

Question 412

How do you analyze acid base disorders?

Answer 412

1) arterial pH - acidemia or alkalemia is present?
2) HCO3/PCO2: low HCO3 = metabolic acidosis; low PCO2 = respiratory alkalosis, and vice versa.
3) if the compensation response is excessive or inadequate, then a second disorder is present. For instance, in a patient with metabolic acidosis and [HCO3-] of 14mEq/L, you expect PCO2 of ~30 mmHg. A higher PCO2 indicates coexistent respiratory acidosis, while a lower value suggests concurrent respiratory alkalosis.
4) Calculate PAG = [Na+] - [Cl-] - [HCO3-]. A elevated PAG indicates a coexistent metabolic acidosis even if pH is normal or alkalemic.
5) If the PAG is wide, compare the ΔPAG to ΔHCO3-. A 1:1 ratio is expected with a “pure” organic metabolic acidosis. If the ΔPAG > ΔHCO3, a concurrent metabolic alkalosis may be present. If the Δ PAG < Δ [HCO3-], a concurrent metabolic acidosis may be present

Question 413

What is the urinary anion gap?

Answer 413

UAG = UAG = [Na+] + [K+] - [Cl-]

used to indirectly measure urinary NH4+ excretion. The logic behind UAG is that the difference between unmeasured anions and cations is attributable mainly to [NH4+]

Question 414

What is the UAG in normal people?

Answer 414

near zero or is positive

Question 415

What is the UAG in metabolic acidosis with a normal kidney function?

Answer 415

negative

Question 416

How does PAG and UAG affeted in persons with metabolic acidosis?

Answer 416

PAG increases, UAG becomes negative (P+, U-)

Question 417

Why is it important to regulate Ca in the ECF?

Answer 417

Extracellular Ca2+ and Pi are near to levels where they tend to precipitate

Question 418

Why is it important to keep intracellular levels of Ca low?

Answer 418

Ca is an important 2nd messenger and this function requires that intracellular [Ca2+] be kept very low.

Question 419

Where is the majority of Ca in the body? What is the relevance of this?

Answer 419

bone. It is in an insoluble form that exchanges with the ECF very slowly (months); acts as a buffer against changes in plasma [Ca2+].

Question 420

Why are half of the Ca in the body not filtered?

Answer 420

~50% is complexed with small anions (~10%) and to albumin (40%) and cannot be filtered by the glomeruli

Question 421

What % of the Ca in the body is the biologically active form?

Answer 421

50% (free, not complexed)

Question 422

Since there is a large electrochemical gradient for Ca2+ entry into cells, cells are equipped with transporter mechanisms to extrude Ca2?

Answer 422

Ca2+/Na+ exchanger

plasma membrane Ca-ATPase.

Question 423

What happens in long-term hypocalcemia?

Answer 423

demineralization of bones, and may result in fractures or the development of rickets.

Question 424

What happens in long-term hypercalcemia?

Answer 424

increased blood pressure, muscle weakness, and constipation. During hypercalcemia Ca salts may precipitate in soft tissues, leading to their calcification and the development of kidney stones.

Question 425

How does Ca cause tetany?

Answer 425

Ca2+ negatively affects voltage-gated Na channels (prevents them from opening). Hypocalcemia results in less inhibition of the VG Na channels, thus resulting in spontaneous firing of motor neurons that may result in tetany and bronchospasm.

Question 426

What is internal Ca balance governed by?

Answer 426

the distribution of Ca between ECF and bone.

Question 427

How does the renal handle Ca?

Answer 427

majority is reabsorbed in the PCT and ascending loop (via passive, paracellular transport).
In the DCT, Ca is reabsorbed via an active transcellular route, and is the prime site of regulation

Question 428

Where is Ca reabsorption regulated in the nephron?

Answer 428

DCT

Question 429

What is calbindin and what is the role in Ca reabsorption? Where can you find this?

Answer 429

Ca ions enter DCT cells via a luminal Ca-channel and are pumped out at the basolateral side by a Ca-ATPase and a Na/Ca exchanger. The intracellular free [Ca2+] needs to be kept very low in order for Ca entry into the cell, otherwise an increased intracellular Ca would limit transport. Therefore, distal tubule cells (as well as epithelial cells of the small intestine) have calbindin, which binds to Ca to maintain a high total intracellular [Ca] thereby allowing a high rate of intracellular diffusion, while maintaining normal ionized [Ca2+] Ca ions enter DCT cells via a luminal Ca-channel and are pumped out at the basolateral side by a Ca-ATPase and a Na/Ca exchanger. The intracellular free [Ca2+] needs to be kept very low in order for Ca entry into the cell, otherwise an increased intracellular Ca would limit transport. Therefore, distal tubule cells (as well as epithelial cells of the small intestine) have calbindin, which binds to Ca to maintain a high total intracellular [Ca] thereby allowing a high rate of intracellular diffusion, while maintaining normal ionized [Ca2+] Ca ions enter DCT cells via a luminal Ca-channel and are pumped out at the basolateral side by a Ca-ATPase and a Na/Ca exchanger. The intracellular free [Ca2+] needs to be kept very low in order for Ca entry into the cell, otherwise an increased intracellular Ca would limit transport. Therefore, distal tubule cells (as well as epithelial cells of the small intestine) have calbindin, which binds to Ca to maintain a high total intracellular [Ca] thereby allowing a high rate of intracellular diffusion, while maintaining normal ionized [Ca2+]

Question 430

Where is Na and Ca transport different in various parts of the nephron? Where is it the same?

Answer 430

Paracellular Ca reabsorption in the proximal tubule and the loop of Henle is driven by Na reabsorption. Consequently, factors that alter Na reabsorption in these segments, like changes in ECFV or diuretics that act here, result in corresponding changes in Ca reabsorption.

Question 431

Where/How do thizaides work? What are they also known as?

Answer 431

DCT, blocks NaCl cotransporter (and thereby Na reabsorption), which stimulates Ca reabsorption. AKA Ca sparing

Question 432

Where/How do K sparing diuretics work? What are they also known as?

Answer 432

Stimulate Na reabsorption in the collecting duct

Question 433

In an acute alkalemic epsiode, what happens to plasma free-Ca levels? What happens in chronic alkalemia?

Answer 433

Decreases, because Ca2+ binds to albumin at alkaline pH. In a chronic setting, this has no effect on plasma ionized Ca because regulation via parathyroid hormone (PTH) maintains Ca concentrations constant.Decreases, because Ca2+ binds to albumin at alkaline pH. In a chronic setting, this has no effect on plasma ionized Ca because regulation via parathyroid hormone (PTH) maintains Ca concentrations constant.

Question 434

What happens to the luminal Ca channels that mediate Ca reabsorption in the DCT at an acidic pH? (metabolic acidosis)

Answer 434

close, therefore Ca excretion increases

Question 435

What happens to the luminal Ca channels that mediate Ca reabsorption in the DCT at an alkalemic pH? (metabolic alkalosis)

Answer 435

opens, therefore Ca excretion decreases

Question 436

What happens to plasma phosphate (Pi) levels in alkalosis?

Answer 436

Alkalosis results in a shift of Pi from extracellular fluid into cells (reduction of plasma Pi)

Question 437

Where is the main site of phosphate (Pi) reabsorption regulation in the nephron?

Answer 437

PCT (85% of phosphate (Pi) is reabsorbed here)

Question 438

What are the two most important regulators of Ca and Pi homeostasis ?

Answer 438

PTH and calcitriol (active form of Vitamin D)

Question 439

What is the stimulus for PTH release in chief cells?

Answer 439

low plasma Ca

Question 440

How is PTH release in chief cells regulated?

Answer 440

Chief cells express a Ca-sensing receptor (CaSR; a typical G-protein-coupled receptor). CaSR is a negative regulator of PTH release. PTH secretion is under tonic inhibition by the Ca-bound CaSR, and hypocalcemia relieves the chief cells from this inhibition.

Question 441

What are the actions of PTH?

Answer 441

1) induces Ca and Pi release from bone
2) stimulates Ca reabsorption in the distal tubule
3) inhibits Pi reabsorption in the PCT by retrieving Na/Pi transporters from the luminal (thus lowering the TM)
4) activates the enzyme to convert Vit-D3 to its active form, calcitriol (1,25‐(OH)2‐vitamin D3).

Question 442

Where is the enzyme that converts Vit-D3 to its active form, calcitriol (1,25‐(OH)2‐vitamin D3) located?

Answer 442

PCT

Question 443

What is calcitriol?

Answer 443

active form of vitamin D3

Question 444

What is the primary role of calcitriol?

Answer 444

stimulates Ca absorption in the gut

Question 445

What is phosphatonin? (ie FGF23)

Answer 445

hormone produced by bone, which is a potent inhibitor of Pi reabsorption

Question 446

How does plasma Pi affect the TM (transport maximum)?

Answer 446

hyperphosphatemia lowers (more reabsorbed) and hypophosphatemia increases (more reabsorbed) the Tm for Pi

Question 447

What is the second most abundant intracellular cation?

Answer 447

Mg

Question 448

How does Mg affect K channels?

Answer 448

closes them

Question 449

How does Mg deficiency associated with K depletion?

Answer 449

Mg channels normally induce K channels to close. Mg depletion thus increases the open probability of the apical K channels in the cortical collecting that mediate K secretion

Question 450

How does Mg affect Ca channels?

Answer 450

opens them

Question 451

How does Mg deficiency associated with elevated intracellular levels?

Answer 451

Mg decreases the open probability of several Ca channels, and thus, Mg deficiency results in elevated intracellular [Ca2+] (less is transported out of the cell)

Question 452

The Ca-sensing receptors require which two ions to be active?

Answer 452

Mg/Ca

Question 453

Where is the majority of Mg reabsorbed?

Answer 453

LOH, via a paracellular pathway

Question 454

Where is the main site of Mg reabsorption regulation in the nephron?

Answer 454

DCT because Mg reabsorption in this segment occurs by a transcellular mechanism

Question 455

What regulates renal excretion of Mg?

Answer 455

Mg plasma conc.

Question 456

The kidney uses these several mechanisms to guard against the formation of ion precipitates:

Answer 456

1) regulation of reabsorption for the three ions: PCT = Pi, early DCT = Mg, late DCT = Ca
2) CaSRs in the basolateral side of the TALH and in the luminal side of collecting duct cells (principle and a-ICC)

Question 457

How does CaSRs work?

Answer 457

An increase in local [Ca] activates CaSR, and initiates a signaling cascade that results in decreased Ca and Mg transport, thereby protecting against nephrocalcinosis.

Question 458

How do the CaSRs differ in function in the TALH and CD?

Answer 458

In the TALH, Ca and Mg are reabsorbed without water. An increase in local interstitial [Ca] activates CaSR, which inhibits further Ca and Mg reabsorption.

In principal cells, CaSRs inhibit ADH-dependent water reabsorption, thereby preventing concentration of the tubular fluid.

In a-ICC cells, CaSRs stimulate H+ secretion, thereby inhibiting the formation of salts (CaPO4, Mg/NH4PO4) that tend to precipitate at alkaline pH.

Question 459

Why is citrate mostly excreted? How does citrate affect Ca and Mg?

Answer 459

Citrate is a natural Ca-and Mg-chelator, and thereby increases the solubility of these ions in the urine

Question 460

What are the main components of bone matrix?

Answer 460

Ca and Pi

Question 461

Why is it important to keep Ca and Pi near their solubility limits?

Answer 461

Ca and Pi are the main components of the bone matrix. Extracellular [Ca2+] and [Pi] need to be kept near their solubility limits for normal bone function. If the solubility limits for Ca and Pi are exceeded, calcification of soft tissues may take place.