Pbd 2 Renal Exam 3 Part 2

Front 1

Compare the glomerular filtrate to the plasma?

Back 1

It has the same chemical composition but it contains almost no proteins b/c large molecules d not radily cross the glomerular wall.

Front 2

what is the capillary filtration pressure of the glomerulus? how is this different from the rest of the body? how is this pressure regulated?

Back 2

it's about 60mmHg w/c is about 2-3x higher than other capillary beds in the body. The filtration pressure & GFR are regulated by the constriction & relaxation of the afferent & efferent arterioles

Front 3

What is the innervation of the afferent & efferent arterioles?

Back 3

sympathetic nervous system

Front 4

in the mechanism of transport in the nephron, what 2 substances are passively transported along [ ] gradients?

Back 4

urea & water

Front 5

Over half of all reabsorptive & secretory processes that occur in the tubulr system occur in w/c part of the nephron?

Back 5

PCT

Front 6

What is the role of glucose in the nephron?

Back 6

it is freely filtered in the glomerulus & reabsorbed by energy dependent cotransport carrier mechanisms

Front 7

W/c part of the nephron is affected by ADH?

Back 7

Loop of Henle

Front 8

what transport mechanisms are found in PCT?

Back 8

secondary active transport or cotransport of Na w/ glucose or aa from the tubules to the peritubular capillary
There is also a countertransport of Na in for H to go to the tubules.
There is a primary counter transport that allows Na to the blood & K into the PCT cell but K leaks back into the blood. See Fig 30.7

Front 9

The LOH as a whole, reabsorbs what? how is this different from PCT?

Back 9

always reabsorbs more sodium & chloride than water. this in contrast to PCT w/ reabsorbs sodium & water in equal amounts

Front 10

W/c part of the LOH is highly permeable to water?

Back 10

the thin descending limb

Front 11

Where is the highest osmolality of filterate in LOH?

Back 11

at the elbow of the LOH

Front 12

W/c part of the LOH is IMpermeable to water? what happens in this part?

Back 12

ascending limb. solutes are reabsorbed but water cannot follow. As a result, the tubular filtrate becomes more & more dilute

Front 13

what type of transport does the thick ascending LOH contain?

Back 13

Na/K/2Cl cotransport system. The gradient for this cotransport is provided by Na/K ATPase pump on peritbular cap side

Front 14

What does the reabsorption of Na, K, & Cl in the thick LOH do?

Back 14

it leads to the development of a transmembrane potential that favors the passive reabsorption of small divalent cations such as Ca & Mg

Front 15

Besides the ascending limb, what other part is IMpermeable to water

Back 15

DCT

Front 16

What type of transport is found in the DCT

Back 16

There is a Na/Cl cotransport mechanism that allows reabsorption of these ions

Front 17

Where in the tubules is Ca affected?

Back 17

1st in the thick ascending LOH where it's passively reabsorbed. 2nd in the DCT where it is actively reabsorbed in a process that is largely regulated by PTH

Front 18

Where in the tubule does aldesterone exert its action? what does it do?

Back 18

in the late distal tubule & cortical collecting tubule. it exerts its action on Na reabsorption & K elimination

Front 19

The cells in the thick ascending limb closest to Bowman's capsule (between the afferent and efferent arterioles) are specialized cells known as

Back 19

the macula densa

Front 20

What marks the end of the thick ascending limb and the beginning of the distal convoluted tubule?

Back 20

The macula densa

Front 21

collecting ducts eventually empty where

Back 21

each empties into a calyx of the renal pelvis.

Front 22

Each renal calyx is continuous with?

Back 22

the ureter

Front 23

w/c part of the nephron passes right between the afferent & efferent arterioles?

Back 23

thick ascending limb of the nephron

Front 24

T/F: afferent arterioles & glomeruli are found in the cortex and medulla

Back 24

False: they are only found in the cortex

Front 25

Substances that are present in the filtrate at the same concentration as found in the plasma are said to be?

Back 25

freely filtered.

Front 26

Give examples of things that are freely filtered?

Back 26

ions sodium, potassium, chloride, and bicarbonate; the neutral organics glucose and urea; amino acids; and peptides like insulin and antidiuretic hormone (ADH).

Front 27

in the PCT, secretion of what occurs?

Back 27

It is the site of secretion of a number of organic substances that are either metabolic waste products (eg, urate, creatinine) or drugs (eg, penicillin)

Front 28

how do you calculate RPF?

Back 28

it's RBF of 1.1L/min * .55 (plasma) The renal plasma flow (RPF) = 0.55 x 1.1 L/min = 605 mL/min

Front 29

what is the equation for net filtration pressure

Back 29

NFP = (PGC – GC) – (PBC – BC),

Front 30

what is the equation for GFR?

Back 30

GFR = Kf (PGC – PBC – GC).

Front 31

Ridding the body of a substance is often called?

Back 31

clearance

Front 32

The units of renal clearance are volume per time (not amount per time). Explain by example what this means?

Back 32

The easiest way to think of this is to ask what volume of plasma contains the amount excreted in a given time. Suppose 5 mg of a substance is excreted per hour and 200 mL of plasma contains 5 mg. Then the clearance of the substance is 200 mL/h, ie, 200 mL of volume has been completely cleared of the substance. Again, note the units: volume per time (ie, the volume of plasma from which a substance is completely removed [cleared]).

Front 33

Can something have a clearance greater than the GFR?

Back 33

Indeed, yes. One such substance is para-aminohippurate (PAH).

Front 34

What substance can approximately measure RBF? how?

Back 34

PAH. It is freely filtered and also avidly secreted by the proximal tubule epithelium (via the transcellular route). The secretion rate is saturable. (That is, there is a maximum rate of PAH secretion into the tubule. However, at low plasma concentrations, about 90% of the PAH entering the kidney is removed from the plasma and excreted in the urine. Its clearance, therefore, is nearly as great as the renal plasma flow.

Front 35

Can a freely filtered substance have a clearance value less than the GFR? give examples

Back 35

Yes. insulin & glucose have 0 clearance b/c the first is completely degraded & the latter is completely reabsorbed. Ions have clearance less than GFR b/c most of their amount is reabsorbed back.

Front 36

What can the clearance of a substance tell us, in another words, be familiar w/ secretion, reabsorption, & filtration of a substance?

Back 36

If we know the GFR (as assessed from inulin clearance) and the clearance of a given substance, then any difference between clearance and GFR represents net secretion or reabsorption (or, in a few rare cases, renal synthesis). If the clearance of a substance exactly equals the GFR, then there has been no net reabsorption or secretion. If the clearance is greater than the GFR, there must have been net secretion. Finally, if the clearance is less than the GFR, there must have been net reabsorption

Front 37

Define filtered load?

Back 37

It’s the amount that is filtered per unit time.

Front 38

The _________ __________ is what is presented to the rest of the nephron to handle?

Back 38

Filtered load

Front 39

What does a high filtered load mean?

Back 39

It indicates a substantial amount of material to reabsorb

Front 40

This term a mechanism through which renal blood flow and glomerular filtration rate are kept relatively constant across a wide range of systemic arterial pressures?

Back 40

Autoregulation

Front 41

What happens if autoregulation is absent? How would abesence of autoregulation affect the glomerular capillaries?

Back 41

Urinary output would vary widely with changes in blood pressure produced by normal daily activities. glomerular capillaries (which have higher basal pressure than capillaries elsewhere in the body) would be at high risk of hypertensive damage during periods of exertion.

Front 42

As mean arterial pressure goes up, smooth muscle in the walls of the arterioles is stretched. This induces the smooth muscle to constrict, thereby increasing vascular resistance?

Back 42

Myogenic response

Front 43

Cells of the macula densa respond to the level _______ in the distal tubule?

Back 43

Na

Front 44

Relate [Na] in distal tubule to GFR?

Back 44

[Na+] in the distal tubule is high when GFR is high, and low when GFR is low.

Front 45

High [Na+] in the distal tubule causes release of ‘transmitter agents’ from the JGA. These agents lower GFR in two ways, what are they?

Back 45

1)By causing constriction of the afferent arteriole. 2) By causing contraction of the glomerular mesangial cells (decreasing surface area of the capillaries and thus KF).

Front 46

T/F: Renal clearance does not indicate the amount of substance excreted per unit time.

Back 46

True

Front 47

How to calculate clearance in the proper units?

Back 47

CS = US*V / PS Where: CS = clearance of S US = urine concentration of S V = volume of urine per unit time PS= plasma concentration of S.

Front 48

What is the equation from excretion rate?

Back 48

(US * V) is the excretion rate

Front 49

renal clearance deals specifically with clearance performed by the ________. It should not be confused with _______ clearance rate, which may involve many additional processes.

Back 49

Kidneys, metabolic clearance

Front 50

In order to provide an accurate measure of GFR, a compound must meet the following criteria (5)?

Back 50

1. freely filterable 2. not reabsorbed 3. not secreted 4. not synthesized by the tubules 5. not metabolized by the tubules.

Front 51

What is the gold standard for accurate measurement of GFR? Why is this not used clinically?

Back 51

Inulin. inulin clearance is cumbersome due to the requirement to infuse inulin to obtain constant plasma concentration.

Front 52

What is used instead of inulin to measure GFR?

Back 52

Creatinine clearance

Front 53

Where do we get creatinine from?

Back 53

Creatinine (end product of creatine metabolism) is constantly exported into our blood at a rate proportional to skeletal muscle mass

Front 54

Does creatinin meat all five criteria for GFR measurement? Why or why not?

Back 54

creatinine does not meet all five criteria; it is freely filtered, and not reabsorbed, however, it is secreted by the tubules in small amounts (10-20% of what is excreted).

Front 55

B/c of its clearance, creatinine clearance slightly _________ GFR.

Back 55

Overestimates GFR since it’s freely filtered but some is also secreted so its number is actually higher than GFR.

Front 56

Rising plasma creatinine over time indicates what?

Back 56

It’s a red flag that indicates a potential renal dysfxn

Front 57

What happens to creatinine if one day GFR suddenly decreases by 50%?

Back 57

This means that there is a possible blockage like a blood clot w/c will increase plasma creatinine

Front 58

The epithelial cells between the tubule lumen & peritublular capillary have what names to those sides?

Back 58

Apical membrane is to the side next to the lumen & basolateral membrane is to the side facing the capillary

Front 59

Reabsorption thru the epithelial cells occurs thru what 2 mechanisms?

Back 59

Either thru gaps between cells called paracellular reabsorption or thru the cells called transcellular reabsorption.

Front 60

There is a lesser role for transepithelial voltage in paracellular transport. Where is this voltage difference & what does it do?

Back 60

1) early in proximal tubule lumen is slightly negative of interstitium.
2) late in proximal tubule it is slightly positive.
This enhances anion reabsorption early in the tubule, and diminishes it later.

Front 61

Transport mechanisms can be categorized by the properties of their limits as: what are the 2 transport mechanisms?

Back 61

Tubular maximum-limited (Tm limited) systems
Gradient limited systems

Front 62

How does the Tm transport system work?

Back 62

Tm systems reach an upper limit because transporters are saturated. From that point, increased plasma concentration does not produce increased reabsorption.

Front 63

How does the gradient transport limited system work?

Back 63

Gradient limited systems reach a limit because tight junctions are leaky, and any significant lowering of luminal concentration relative to the interstitum results in a leak back into the lumen as fast as the substance is transported out.

Front 64

Increased sympathetic activity causes ____________ of the afferent & efferent arterioles & thus a ________ in RBF.

Back 64

constriction, decrease

Front 65

these are special hairpin shaped capillaries along the loops of Henle & found in the juxtamedullary nephrons

Back 65

vasa recta w/c descend into the medullary portion of the kidney.

Front 66

The __________ __________ is thought to prepresent a feedback control system that links changes in the GFR w/ RBF?

Back 66

juxtaglomerular complex

Front 67

The distal tubular site that is nearest the glomerulus is characterized by densely nucleated cells called _________ _________. in the adjacent afferent arteriole, the sm mm cells are modified as special secretory cells called ____________ cells

Back 67

macula densa, juxtaglomerular cells

Front 68

What is found in the juxtaglomerular cells?

Back 68

granules of inactive renin

Front 69

what is the function of renin?

Back 69

it's an enzyme that fxns in the conversion of angiotensinogen to AG

Front 70

How does tubular secretion occur?

Back 70

like reabsorption, this an occur by diffusion or by transcellular transport mechanisms.

Front 71

What does tubular secretion require?

Back 71

Active transport across the basolateral or luminal membrane of epithelial cells

Front 72

What happens in the kidneys during a fast?

Back 72

cells of the renal tubules synthesize glucose and add it to the blood.

Front 73

What type of metabolism occurs in the tubules?

Back 73

They can also catabolize peptides, and a number of organic substances present in the tubular lumen or peritubular capillaries. This is also a form of excretion as catabolized substances are effectively eliminated from the body.

Front 74

abnormality in the Na+ glucose cotransporter that mediates reabsorption of glucose in the proximal tubule. Leads to appearance of glucose in the urine.

Back 74

familial renal glucosuria:

Front 75

ability to absorb glucose is usually normal, but filtered load of glucose exceeds the threshold for the tubule to reabsorb. (lack of insulin or failure to respond to insulin leads to high blood sugar).

Back 75

Diabetes mellitus:

Front 76

What is the primary role of the PCT?

Back 76

Reabsorb most the filtered water & non waste solutes

Front 77

Urinary water excretion can vary from approximately 0.4 L/day to___________?

Back 77

25 L/day!

Front 78

Na+ reabsorption is an active process occurring in all tubular segments except where?

Back 78

descending limb of the loop of Henle.

Front 79

T/F: glucose is reabsorbed by the paracellular route?

Back 79

False: transcellular route

Front 80

T/F: Both Na+ and water undergo considerable reabsorption, but no secretion.

Back 80

True

Front 81

How does Na reabsorption achieve reabsorption of phosphate & sulfate?

Back 81

Cotransport across the luminal membrane

Front 82

How does Na achieve H ions secretion?

Back 82

By countertransport across the luminal membrane

Front 83

What are the secretion of H ions required for?

Back 83

Reabsorption of bicarbonate

Front 84

What is Na’s affect on Cl?

Back 84

Achieves reabsorption of Cl by indirect cotransport (Cl-/base countertrasnporters depend on Na+/H+ countertrasnporters)

Front 85

It can be said that the PCT promotes ________ osmotic volume reabsorption?

Back 85

Iso-osmotic

Front 86

What can be said about the transporters in the kidneys?

Back 86

a given transporter selectively takes up one or a few substrates and ignores all others. However, there is not a separate transporter for every solute in the body. Two or more closely related substances may use the same transporter. For example, the amino acid transporters are distinct from those for glucose and other monosaccharides

Front 87

w/ what mechanism is glucose reabsorbed in the PCT?

Back 87

This involves removing glucose from the tubular lumen along with sodium via a sodium-dependent glucose symporter (SGLUT) across the apical membrane of proximal convoluted tubule epithelial cells, followed by its exit across the basolateral membrane into the interstitium via a GLUT uniporter

Front 88

Although we sometimes say that the glomerular filtrate is protein-free, it is not truly free of all protein since small and medium-size proteins (eg, angiotensin, insulin) are filtered in considerable quantities. What eventually happens to these filtered proteins?

Back 88

The proximal tubule is capable of taking up filtered albumin and other proteins, and we treat this protein uptake separately here to emphasize its importance. We use the word uptake rather than reabsorption because the proteins, although they are transported intact out of the lumen into the epithelial cells, are degraded into their constituent amino acids before being transported into the cortical interstitium. Thus, the term reabsorption in the context of proteins and peptides, although widely used, is actually a misnomer.

Front 89

What are the steps for the reuptake of the proteins that filter thru?

Back 89

The initial step for the uptake of larger proteins is endocytosis at the luminal membrane. This energy-requiring process is triggered by the binding of filtered protein molecules to specific receptors on the luminal membrane. Therefore, the rate of endocytosis is increased in proportion to the concentration of protein in the glomerular filtrate until a maximal rate of vesicle formation, and thus the Tm for protein uptake, is reached. The pinched-off intracellular vesicles resulting from endocytosis merge with lysosomes, whose enzymes degrade the protein to low-molecular-weight fragments, mainly individual amino acids. These end products then exit the cells across the basolateral membrane into the interstitial fluid, from which they gain entry to the peritubular capillaries

Front 90

What happens if there is an increase in protein filtration?

Back 90

The endocytic mechanism by which protein is taken up is easily saturated; however, any large increase in filtered protein resulting from increased glomerular permeability can cause the excretion of large quantities of protein

Front 91

Where does ADH act in the tubules?

Back 91

Cortical collecting ducts

Front 92

How does ADH act in reabsorbing water?

Back 92

It stimulates insertion of specific aquaporins into the luminal membrane. When aquaporins are present, water reabsorption is high, and urine concentration is increased.

Front 93

w/ maximum reabsorption of water, final urine volume would be what compared to filtered water? Compare its osmolarity to plasma?

Back 93

With maximum reabsorption, final urine volume can contain less than 1% of filtered water. In this situation urine is very hyperosmotic relative to plasma (as high as 1400 mOsmol /L vs. 285-300 mOsm /L).

Front 94

What type of Na transport is seen in the thick & thin ascending limb?

Back 94

In the thick: Na transport depends on Na-Cl co-transporters. In the thin: there is no Na-Cl co-transporters so Na reabsorption depends on simple diffusion

Front 95

What is the permeability of water in the thick & thin limbs?

Back 95

Both thick and thin ascending limbs of the loop of Henle are relatively impermeant to water, so in the entire ascending limb, salt is reabsorbed, but water is not.

Front 96

What happens w/ water & Na in the the descending limb?

Back 96

does not reabsorb Na+ but is highly permeant to water.

Front 97

W/c 2 areas of the tubules are diluting segments?

Back 97

Ascending limb & DCT

Front 98

What channels are found in the DCT?

Back 98

Na/K pump on basolateral membrane, Na/Cl symport on apical membrane, & Na channels on apical membrane

Front 99

Where do thiazide diuretics target?

Back 99

Na Cl symport in DCT

Front 100

What is the osmolarity of the tubular lumen when it reaches the collecting ducts?

Back 100

w/ the absence of vasopressin, water is not allowed to leave & therefore lumen will be hypo-osmotic in relation to the plasma

Front 101

What is the permeability & transport of urea?

Back 101

It’s small, polar, & water soluble. b/c it’s polar, it’s not very membrane permeant so movment across membranes is facilitated by uniporters

Front 102

How does urea get into the tubules?

Back 102

It’s freely filtered but ½ gets reabsorbed in the PCT. The amount reabsorbed gets secreted in the LOH. ½ of that gets reabsorbed in the medullary collecting duct.

Front 103

What is the reabsorption mechanism of urea in the PCT?

Back 103

By diffusion & paracellular

Front 104

How does urea work in concentrating urine?

Back 104

Since some of the urea gets reabsorbed, it is in the interstitial space & therefore contributes to the hyperosmotic conditions that are necessary to [ ] urine in the presence of ADH

Front 105

Aldosterone is a steroid hormone produced by the_________ __________?

Back 105

adrenal cortex

Front 106

Function of Aldosterone & where does it act?

Back 106

Aldosterone stimulates Na+ reabsorption by the distal convoluted tubule and the cortical collecting ducts.

Front 107

In what situation would aldosterone be released?

Back 107

Adrenal secretion of aldosterone is high when Na+ intake or blood volume is low

Front 108

How is aldosterone regulated?

Back 108

Aldosterone secretion can be regulated through several systems, however the core regulation is via the renin angiotensin system.

Front 109

What cells release renin?

Back 109

release of renin from the granular cells of the juxtaglomerular apparatus.

Front 110

What 3 primary factors cause the release of renin?

Back 110

1) arterial BP, 2) sympathetic input to the JGA, & 3) Na content in DCT as sensed by the cells of the macula densa.

Front 111

What regulates vasopressin?

Back 111

Depends on activity of discrete group of hypothalamic neurons; the input to these neurons comes from osmoR & baroR.

Front 112

When do osmoR activated?

Back 112

When there is excess water so they help to increase water excretion

Front 113

Where are BaroR found & when do they decrease their firing?

Back 113

Baroreceptors in the cardiovascular system decrease their firing rate when cardiovascular pressure deceases.

Front 114

How is ADH affected when baroR are firing?

Back 114

Baroreceptor firing normally reduces vasopressin secretion (through an inhibitory interneuron), so a reduction in baroreceptor firing leads to an increase in vasopressin release.

Front 115

What is the major extracellular buffer in human physiology?

Back 115

CO2/HCO3 system

Front 116

How does the kidney maintain plasma pH?

Back 116

by regulating excretion or reabsorption of bicarbonate as necessary to maintain proper plasma hydrogen concentration

Front 117

What is the relationship of HCO3 & H in the kidneys?

Back 117

excretion of bicarbonate increases plasma hydrogen ion concentration. addition of bicarbonate to the plasma lowers plasma hydrogen concentration.

Front 118

What is the fate of bicarbonate in the kidneys?

Back 118

Bicarbonate is freely filtered and normally is completely ‘reabsorbed’.

Front 119

What happens to the filtered HCO3?

Back 119

It’s converted to water & CO2 in the lumen of the tubules by carbonic anhydrase. For this reaction to occur, H must combine w/ bicarb.

Front 120

How is bicarb reabsorbed & where in the tubule does it occur?

Back 120

For each H that combines w/ bicarb in the lumen, a different bicarb is reabsorbed from the epithelial cell into the interstitium. see part 5 slide 8

Front 121

How does the kidney prevent acidosis? 2 mechanisms

Back 121

Mechanism 1: If plasma begins to become too acidic, there will be more hydrogen secreted into the tubule than is necessary to reabsorb all the filtered bicarbonate. This leads excretion of hydrogen bound to non-bicarbonate buffers (and thus produces a net increase in bicarbonate in the plasma (preventing acidosis).
Mechanism 2:
Glutamine is released from the liver as an additional byproduct of protein catabolism.
Filtered glutamine enters tubular epithelial cells through both the basolateral and tubular membrane.
Inside the epithelial cells, glutamine is metabolized producing both ammonium and bicarbonate.
The ammonium is actively secreted via a sodium/ammonium antiporter.
The bicarbonate is reabsorbed, causing a net increase in plasma bicarbonate.
As before, this reduced plasma hydrogen ion concentration and helps prevent acidosis.

Front 122

How do the kidneys prevent alkalosis?

Back 122

As alkalosis begins to occur, hydrogen ion secretion from the tubular epithelial cells will become insufficient to reabsorb all the filtered bicarbonate.
As a result significant bicarbonate will be secreted in the urine, and there will be little or no secretion of hydrogen on non-bicarbonate buffers.
Similarly, glutamine metabolism can be temporarily slowed to prevent contribution of bicarbonate to the plasma from this source.
Collectively, these mechanisms reduce plasma bicarbonate, raising plasma hydrogen ion concentration, and prevent alkalosis.

Front 123

What is the fate of K in the kidney? Where is it excreted?

Back 123

K+ is freely filtered and heavily reabsorbed (normally not much K+ in urine). However if K+ intake exceeds needs, K+ can be excreted in the cortical collecting ducts.

Front 124

What causes K to excreted? (2 mechanisms)

Back 124

2 mechanisms: 1. increased activity of basolateral N+/K+ ATPase. 2. depolarization of cells in the adrenal cortex, and subsequent release of aldosterone.

Front 125

Relate the activity of excitable cells to amount of K levels?

Back 125

Both an increase & decrease in K will cause heart arrhythmias