P1 Spring Organs 2011-02-17 (Kidney Functions)

Front 1

Collects urine, and transfers it to ureters

Back 1

Calyces (major and minor)

Front 2

Contains glomerulus and bowmans capsule

Back 2

Renal corpuscle

Front 3

How are juxtamedullary nephrons different from cortical nephrons?

Back 3

Juxtamedullary nephrons have:
1. Longer loop of Henle
2. Concentrate more urine
3. Have different type of peritubular capillaries

Front 4

Name of juxtamedullary nephron capillaries

Back 4

Vasa Recta

Front 5

Filtered and +90% reabsorbed

Back 5

-Na+
-H2O

Front 6

Filtered and 100% reabsorbed

Back 6

-Glucose
-Amino acids

Front 7

Filtered and excreted 100% of the time

Back 7

-Creatinine
-Inulin

Front 8

List substances that are actively secreted.

Back 8

-K+ (K+ channel)
-H+ (Na+/H+ counter transporters)
-Para amino hipuric acid (PAH)

Front 9

What is the equation for filtration fraction?

Back 9

GFR / Renal plasma flow
eg 125ml/min / 605ml/min = 0.21

Front 10

What are the renal corpuscle cells that make up the glomerulus membrane?

Back 10

Podocytes

Front 11

List the properties of podocytes

Back 11

-Cells within the Bowman's capsule that wrap around the capillaries
-Have 3 layers that form the glomerulus membrane
-Porous filter due to slit pores and fenestrations
-Have negatively charged layers that repel neg substances

Front 12

Reduces negative charge on glomerulus membrane, allowing negative substances thru

Back 12

-Hypertension (early/mid)
-Diabetes (early/mid)

Front 13

What can thicken the glomerulus membrane, allowing less substances thru, decreasing GFR?

Back 13

Late diabetes, or well established hypertension.

Front 14

What can lower Kf?

Back 14

Thickening of the glomerular membrane during late diabetes, or well established hypertension.

Front 15

What can decrease GFR by increasing Pb?

Back 15

Kidney stone

Front 16

Cause of proteinuria

Back 16

Glomerulus loses negative charge during (early/mid) diabetes, or (early/mid) hypertension, allowing negatively charged proteins through.

Front 17

Net filtration pressure

Back 17

Pg - Pb - πg

Front 18

Whats the GFR equation?

Back 18

Kf x Net filtration pressure

Front 19

What can lower πg?

Back 19

Liver disease (causes less oncotic protein in glomerular capillaries).

Front 20

Why is GFR as high as it is?

Back 20

-To filter toxins out faster
-To maintain proper electrolyte balance

Front 21

List factors that determine Pg, and therefore GFR

Back 21

-Blood pressure
-Afferent arteriolar resistance (Ra)
-Efferent arteriolar resistance (Re)

Front 22

How does SNS stimulation affect arteriolar resistance and GFR?

Back 22

More Ra than Re, so decreased GFR

Front 23

How does catecholamine stimulation affect arteriolar resistance and GFR?

Back 23

More Ra than Re, so decreased GFR

Front 24

How does endothelin stimulation affect arteriolar resistance and GFR?

Back 24

More Ra than Re, so decreased GFR

Front 25

How does prostaglandin stimulation affect arteriolar resistance and GFR?

Back 25

Dilates Ra more than Re, so increased GFR

Front 26

How does EDRF stimulation affect arteriolar resistance and GFR?

Back 26

Dilates Ra more than Re, so increased GFR

Front 27

How does angiotensin 2 stimulation affect arteriolar resistance and GFR?

Back 27

Increases Re if GFR is low (normalizing GFR), otherwise has no effect on Re.

Front 28

Why does early type 1 diabetes causes high GFR?

Back 28

There are increased levels of nitric oxide and prostaglandins (causing ↓↓Ra and ↓Re).

Front 29

List how kidneys regulate their own GFR.

Back 29

Autoregulation:
-Myogenic mechanism (when GFR is high)
-Macula densa feedback (when GFR is high or low)
-Release of renin (to inc angiotensin 2) (when GFR is low)

Front 30

Descrbe the myogenic mechanism.

Back 30

-Autoregulation of kidneys to dampen an inc in GFR.
-When BP rises, afferent and efferent arterioles stretch and release Ca+, which inc contraction of these arterioles (↑Ra and ↑Re), dampening the inc in GFR

Front 31

How does ↑GFR affect urine production?

Back 31

Causes more urine production

Front 32

What happens when kidneys stop working/filtering

Back 32

Little/no urine production

Front 33

Location of the macula densa

Back 33

Early distal tubule

Front 34

Juxtaglomerular apparatus consists of?

Back 34

Macula densa + juxtaglomerular cells

Front 35

What does the macula densa do when it senses low Na+ ?

Back 35

1. Normalizes GFR:
Tells juxtaglomerular cells to ↑renin (↑angio 2, ↑Re, ↑GFR to normal), and also ↓Ra (dilation to ↑GFR to normal).
2. Raises BP:
Angio 2 increases Na+ and water retention, and stimulates aldosterone production, which does the same.

Front 36

Why does a decrease in GFR cause the macula densa to sense less Na+ ?

Back 36

A decrease in GFR slows the movement of filtrate, allowing for more Na+ reabsorption prior to macula densa (and less to sense)

Front 37

Another name for juxtaglomerular cells?

Back 37

Granular cells

Front 38

Location of juxtaglomerular cells?

Back 38

In afferent arteriole

Front 39

List what happens when macula densa senses high Na+ ?

Back 39

1. Normalized GFR:
Tells juxtaglomerular cells to ↓renin (↓angio 2, ↓Re, ↓GFR), and also does not ↓Ra (no dilation as with low Na+) (IBLV).
2. Lowers BP:
IBLV the macula densa supports pressure natriuresis by increasing the pericap pressure (by ↓Re), which ↓reabsorption in general, causing Na+ and water excretion.

Front 40

What is the equation for filtered load?

Back 40

FL = GFR x plasma conc of substance

Front 41

List transporters in proximal tubule.

Back 41

-Na+/glucose
-Na+/amino acid
-Na+/K+
-Na+/H+

Front 42

What stimulates the Na+/K+ pump?

Back 42

-Angiotensin 2
-SNS
-Aldosterone

Front 43

What inhibits the Na+/K+ pump?

Back 43

-Dopamine
-Aldosterone antagonists
-SNS antagonists? (me)
-Angiotensin 2 antagonists? (me)

Front 44

What does stimulation of the Na+/K+ pump cause?

Back 44

-Na+/water reabsorption
-K+ wasting

Front 45

What does inhibition of the Na+/K+ pump cause?

Back 45

-Natriuresis/diuresis
-K+ sparing

Front 46

What do carbonic anhydrase inhibitors do, and where?

Back 46

Inhibits H+ from binding with HCO3- in the tubular lumen.
Therefore HCO3- and H+ are excreted, preventing reabsorption of HCO3- back into the blood.
It's also a diuretic IBLV because the HCO3- lost contains the H2O that most likely would've been reabsorbed, also where electrolytes go, water tends to follow.
This occurs in the proximal tubule, and thick ascending loop of Henle.

Front 47

What can cause glucose in the urine?

Back 47

During diabetes, the high blood glucose saturates the Na+/glucose transporters, causing the excess to be excreted.

Front 48

What is the percentage of Na+ and water reabsorbed in the thin loop of Henle?

Back 48

0% Na+
10% water

Front 49

What is the percentage of Na+ and water reabsorbed in the proximal tubule?

Back 49

65-70% Na+
65-70% water

Front 50

What is the percentage of Na+ and water reabsorbed in the thick ascending loop?

Back 50

25% Na+
0% water

Front 51

What is the percentage of Na+ and water reabsorbed in the early distal tubule?

Back 51

5-7% Na+
0% water

Front 52

What is the percentage of Na+ and water reabsorbed in the late distal tubule?

Back 52

Up to 2.4% Na+ (with aldosterone)
5-24% water (with ADH)
0% water (without ADH)

Front 53

What is the percentage of Na+ and water reabsorbed in the cortical and medullary collecting tubules/ducts?

Back 53

Same as in the late distal tubule:
Up to 2.4% Na+ (with aldosterone)
5-24% water (with ADH)
0% water (without ADH)

Front 54

List the transporters in the thin loop of henle.

Back 54

None?
No Na+ reabsorption.
No mention of K+ or Cl- either

Front 55

List the transporters in the thick ascending loop of henle.

Back 55

-NK2Cl
-Na+/H+
-Na+/K+

Front 56

What does Lasix/furosemide do?

Back 56

-Inhibits the NK2Cl pump, which prevents Na+, K+, and Cl- reabsorption
-Promotes natriuresis/diuresis
-Promotes K+ wasting

Front 57

Which tubule are diuretics most effective?

Back 57

The thick ascending loop of Henle.

Front 58

List things that can cause diuresis without natriuresis.

Back 58

-Excess water intake with no Na+ intake
-ADH deficiency (diabetes insipitus)
-ADH present but unable to act on late distal tubules or collecting tubules (diabetes insipitus)
End result of these is that water is not reabsorbed, but any Na+ present is.

Front 59

Where is ADH made and stored?

Back 59

ADH/vasopressin is made in the hypothalamus, and stored in the posterior pituitary (wiki).

Front 60

What does ADH do (generally), and where?

Back 60

-Increases water absorption (up to 24%) in the late distal tubules and collecting tubules.
-Does not affect Na+ reabsorption

Front 61

List three ways that pressure natriuresis favors Na+ and water excretion.

Back 61

1. ↑BP causes less pressure difference between tubular lumen and pericaps. (↓Na+ and water reabsorption). Causes natriuresis and diuresis, lowering blood volume (and BP).
2. Causes a decrease in renin, angio2, and aldosterone. Less Na+ reabsorbed means more Na+ detected by macula densa in the EDT, which tells juxtaglomerular cells to produce less renin (less angio 2). Less angio 2 ↓Re (further increasing pericap pressure via positive feedback), and less angio 2 also decreases aldosterone production.
3. The ↑BP causes the release of ANP, prostaglandins, and EDRF (NO), all of which ↑GFR and excretion.

Front 62

What does thiazide do, and where does it act?

Back 62

-Promotes natriuresis (and therefore diuresis)
-Inhibits the Na+/Cl- cotransporter in the early distal tubule

Front 63

List the transporters at the early distal tubule.

Back 63

-Na+/Cl-
-Na+/K+

Front 64

What are principal cells, and their location?

Back 64

-Make up 70% of cells in the late distal tubule and collecting tubules
-These cells are sensitive to both aldosterone and ADH

Front 65

What are intercalated cells, and their location?

Back 65

-Make up 30% of cells in the late distal tubule and medullary collecting tubules
-These cells actively secrete H+ (Na+/H+ counter transporter IBLV)

Front 66

List things aldosterone does, and where it does it.

Back 66

-Stimulates K+ channel (out), Na+ channel (in), and Na+/K+ pump
-This increases Na+ reabsorption (and therefore water reabs), and promotes K+ secretion (kaliuresis)
-Aldosterone only operates on principal cells (LDT and collecting tubules)

Front 67

When do ADH levels increase?

Back 67

During dehydration (to retain more water).

Front 68

Whats the big difference between diuretics acting on the thick ascending loop, and ones acting on the late distal tubule (or later)?

Back 68

The diuretics acting on the TAL, cause K+ wasting, while the diuretics acting later cause K+ sparing.

Front 69

Where does K+ secretion occur? Due to?

Back 69

-Late distal tubule and collecting tubules
-Due to aldosterone

Front 70

What does amiloride do, and where?

Back 70

-Na+ channel blocker of principal cells (LDT and collecting ducts)
-Promotes natriuresis
-Promotes K+ sparing (inhibiting Na+ channel indirectly inhibits K+ channel out)

Front 71

When is there no ADH present?

Back 71

When your body has excess water.

Front 72

What causes a small volume of concentrated urine?

Back 72

High ADH levels.

Front 73

List all the diuretics mentioned in this lecture, and their principal location of action.

Back 73

-Lasix/furosemide (TAL)
-Aldosterone antagonists (principal cells)
-Amiloride (principal cells)
-Thiazide (EDT)
-Carbonic anhydrase inhibitors? (proximal tubules and TAL)
-Angiotensin 2 antagonists? (on any Na+/K+ and Na+/H+ transporters?)

Front 74

List the K+ sparers.

Back 74

-Amiloride
-Aldosterone antagonists
-Angiotensin 2 antagonists? (me)
-SNS antagonists? (me)

Front 75

List the K+ wasters.

Back 75

-Aldosterone/agonists
-Lasix/furosemide (loop diuretics)
-Angiotensin 2
-SNS? (me)

Front 76

Where is urea reabsorbed?

Back 76

ONLY in the medullary collecting tubules, everywhere else is impermeable to urea reabsorption.

Front 77

H+ excretion occurs in which tubules?

Back 77

-Proximal tubule
-(NOT) loop of Henle
-TAL
-(NOT) EDT
-LDT
-(NOT) Cortical collecting tubule
-Medullary collecting tubule

Front 78

List everything angiotensin 2 does.

Back 78

-Stimulates the Na+/K+ and Na+/H+ counter transporters.
-Normalizes Re
-Promotes Na+ and water retention
-Stimulates production of aldosterone by the adrenal cortex.

Front 79

List what dopamine does in the kidneys.

Back 79

-Inhibits the Na+/K+ counter transporter
-Inhibits the Na+/H+ counter transporter

Front 80

List the substances that cause a decrease in Na+ retention.

Back 80

-Natriuretic hormones (ANF/ANP)
-Dopamine

Front 81

What does an increase in Re cause?

Back 81

Increases GFR, but decreases the pericap pressure, creating a steeping pressure gradient, which facilitates more reabsorption (eg Na+ and water).

Front 82

What inhibits angiotensin 2?

Back 82

ACE inhibitor

Front 83

How does ADH work?

Back 83

-ADH (in blood) attaches to V2 receptors on basolateral side of epithelial cells.
-Binding causes translocation of aquaporins to both the luminal and basolateral sides, allowing water to pass from the tubular lumen to the blood/circulation.

Front 84

How is ANP released, what does it do, and where does it do it?

Back 84

-ANP is released by the atria when they stretch due to ↑BP.
-ANP travels in the blood to the kidneys.
-ANP causes ↑GFR and ↑pericap pressure, ↓renin/angio2/aldosterone.
All these result in natriuresis and diuresis, lowering BP.

Front 85

List everything the SNS does in relation to the kidneys.

Back 85

-Stimulates Na+/K+ and Na+/H+ counter transporters
-Stimulates juxtaglomerular cells to produce renin (angio 2)
-SNS increases Na+ and water retention, and BP.

Front 86

How does the SNS and angio 2 stimulate Na+/K+ and Na+/H+ counter transporters?

Back 86

They attach to alpha receptors on the epithelial cells containing these transporters.

Front 87

Why does diabetes mellitus cause polyuria?

Back 87

Glucose is excreted in the urine, glucose transporters are saturated so it cant all be reabsorbed, water follows glucose/solute out of the body.

Front 88

Whats the equation for renal clearance?

Back 88

Cx = (Ux)(V) / Px
where Cx is renal clearance (in ml plasma cleared/min)
Ux is conc of substance X in urine (in mg X/ml urine)
V is urine rate of flow (in ml urine/min)
Px is conc of X in plasma (in mg X/ml plasma)

Front 89

How would you represent the amount of drug cleared from plasma per minute?

Back 89

(Px)(Cx)

Front 90

How would you represent the amount of drug excreted in urine per minute?

Back 90

(Ux)(V)

Front 91

How would you represent the amount of drug filtered per minute?

Back 91

That would be the filtered load (FL):
FL = (GFR)(Px)

Front 92

How would you represent the amount of drug cleared per minute?

Back 92

Amount cleared = amount excreted
And since amt excreted = amt filtered + amt secreted = amt reabsorbed:
amt cleared = amt filtered + amt secreted = amt reabsorbed
Note: whatever is reabsorbed (back into blood) is not cleared from plasma

Front 93

Can the clearance of a substance ever be higher than the GFR?

Back 93

Yes, when its secreted.
Note: any reabsorption must be less than the amount secreted for this to be true.

Front 94

When does clearance (Cx) = GFR?

Back 94

For substances like inulin and creatinine that are 100% filtered (0% secreted, 0% reabsorbed) and 100% excreted.

Front 95

How much of inulin and creatinine is filtered, secreted, reabsorbed, and excreted?

Back 95

100% filtered
0% secreted
0% reabsorbed
100% excreted

Front 96

What substance(s) can be used to calculate renal plasma flow, and why?

Back 96

PAH (para amino hipuric acid).
It is filtered and secreted, but not absorbed, so its renal clearance Cpah = renal plasma flow.

Front 97

What substance(s) cannot be cleared, and why?

Back 97

Glucose and amino acids.
They are 100% reabsorbed, which means they have 0% clearance.

Front 98

What does a high level of inulin in the plasma indicate, and why?

Back 98

Kidney failure, hypertension, diabetes.
Because amt filtered = amt excreted for inulin:
GFR = Cin = (Uin)(V) / Pin
so high Pin indicated low GFR, which indicates kidney problems.

Front 99

What is required by the kidneys to concentrate urine?

Back 99

1. High ADH level
2. High osmolarity in medullary interstitium

Front 100

If the tubular lumen osmolarity is 300mOsm/L and the interstitium is 250mOsm/L, can water be reabsorbed in the presence of ADH?

Back 100

No, the interstitial osmolarity must be higher than the tubular lumen for movement of water.

Front 101

LIst what makes the interstitium hyperosmotic enough for ADH to cause water reabsorption.

Back 101

1. Loop of Henle
2. Vasa recta
3. Urea

Front 102

What is the counter-current multiplier?

Back 102

The loop of Henle

Front 103

What is the counter-current exchanger?

Back 103

The vasa recta

Front 104

Where is the vasa recta?

Back 104

They are the specialized pericaps around the juxtamedually nephrons loop of Henle.

Front 105

What are the basic steps of a counter current multiplier?

Back 105

1. Na+ leaving ascending loop, making interstitium more osmotic and lumen less so.
2. Water leaving descending loop, making lumen more osmotic until it equilizes with interstitium.
3. Slow movement of filtrate from descending to ascending loop, creating osmolarity gradient.
4. Repeat of 1 - 3 until interstitium gets up to 1200mOsm/L at the base of loop (hyperosmotic).

Front 106

Why cant the cortical collecting tubules (from cortical nephrons) form concentrated urine?

Back 106

The filtrate flow through their loop of Henle is too fast to form a gradient.
They dont have vasa recta.

Front 107

Is ADH all thats necessary to form concentrated urine?

Back 107

No, even though ADH does work on the LDT onward, including cortical collecting tubules, forming concentrated urine requires much more than just ADH like:
-Slow flow of filtrate through the loop of Henle
-Pericap blood flow to be low and slow enough to NOT pull the solutes out of the interstitium
-Sufficient urea produced to further increase hyperosmolarity.

Front 108

Characterize Central Diabetes Insipidus.

Back 108

-Lots of dilute urine produced
-Low/no ADH produced
-Treatment: ADH/vasopressin

Front 109

Characterize Nephrogenic Diabetes Insipidus.

Back 109

-Lots of dilute urine produced
-Normal to high ADH produced
-Treatment: NOT ADH/vasopressin

Front 110

List causes of short term nephrogenic diabetes insipidus

Back 110

-Loop diuretics that inhibit Na+ pumps (no osmotic gradient)
-Vasodilators (inc blood flow in vasa recta)
-Low protein diet (low urea)
-Drugs that prevent water reabsorption at medullary duct (tetracyclin, lithium)

Front 111

List causes of long term nephrogenic diabetes insipidus

Back 111

-ADH receptors not working
-Infection (disrupts hyperosm interstitium)

Front 112

List the regulatory controls for ADH secretion

Back 112

-Osmoreceptors
-Baroreceptors

Front 113

What do osmoreceptors do, and where?

Back 113

They sense the blood osmolarity in the brain.

Front 114

What do baroreceptors do, and where?

Back 114

They sense the blood pressure in the carotid artery and bifurcation.

Front 115

List anything that can cause an increase in ADH.

Back 115

-↓BP
-↓blood volume
-↑blood osmolarity
-Angiotensin 2
-Nausea
-Vomiting
-Fear

Front 116

List anything that can cause a decrease in ADH.

Back 116

-↑BP
-↑blood volume
-↓blood osmolarity
-Alcohol

Front 117

List anything that can cause an increase in thirst.

Back 117

-↓BP
-↓blood volume
-↑blood osmolarity
-↑Angiotensin 2
-Dryness in mouth

Front 118

List anything that can cause a decrease in thirst.

Back 118

-↑BP
-↑blood volume
-↓blood osmolarity
-↓Angiotensin 2
-Gastric distention

Front 119

What can diabetes insipidus cause without enough water intake?

Back 119

Hypernatremia

Front 120

What can cause hyponatremia?

Back 120

SIADH (Syndrome of inappropriate ADH)
High ADH → hyponatremia