Ifc Test 4: Renal

Front 1

In a 100 kg man, how many liters of water in body? How liters of that is ICF? How many liters of that is ECF?

Back 1

60 liters.
40 L are ICF.
20 L are ECF.

Front 2

What fraction of ECF is ISF? What fraction is plasma?

Back 2

3/4 is ISF.
1/4 is plasma.

Front 3

What happens in H2O load?

Back 3

increases ECV and decreases osmolality. Water moves into cell. Increases ECV and ICV.

Front 4

What happens in H2O loss?

Back 4

Decreases ECV and increases osmolality. Water moves out of cell. Decreases ECV and ICV.

Front 5

What effect would an isomolar NaCl load intravenous have on ECV and ECF osmolarity?

Back 5

Increase ECV but wouldn't change ECF osmolarity.

Front 6

What are the major ions of the ECF?

Back 6

Na+ and Cl-

Front 7

What is the major cation of the ICF? What balances this?

Back 7

K+. Organic anions and Cl- are the major intracellular aniones.

Front 8

Can water move freely between ECF and ISF?

Back 8

Yes.

Front 9

When kidney output is less than intake, you are in ___ balance. when kidney output is greater than intake, you are in ___ balance.

Back 9

positive; negative

Front 10

Define ultrafiltration

Back 10

Fluid from plasma of glomerular capillaries squeezed into Bowman's space.

Front 11

Define reabsorption

Back 11

Moving something from tubule lumen of nephrons back into plasma.

Front 12

Define Excretion

Back 12

Moving something outside of the body

Front 13

Normal GFR

Back 13

100 - 120 ml/min

Front 14

Normal Renal blood flow (RBF)

Back 14

1000 ml/min

Front 15

How to calculate RPF (renal plasma flow)

Back 15

RBF x (1 - hematocrit) = 1000 x (1-0.4) = 600 ml/min

Front 16

How to calculate filtered load

Back 16

GFR x Py

Py= concentration of substance being filtered.

Front 17

How to calculate excreted load

Back 17

V x Uy

V- volume of excreted urine
Uy= concentration of substance in urine

Front 18

How to calculate reabsportion

Back 18

Filtered load - excreted load

Front 19

How to calculate secretion

Back 19

Excreted load - filtered load

Front 20

What is clearance? How is it calculated?

Back 20

volume of plasma cleared of a substance per unit time (ml/min).

Cy= (V x Uy)/Py

Cy= clearance of substance y in ml/min
V= urine flow in ml/min
Uy= Urinary concentration of y (mg/mL)
Py= plasma concentration of y (mg/mL)

V x Uy= excreted load y (mg/min)

Front 21

Give two situations when clearance = 0.

Back 21

1. Substance is neither filtered, nor secreted (plasma protein).
2. Substance is freely filtered, but completely reabsorbed (glucose).

Front 22

When does clearance = GFR?

Back 22

No reabsorption or secretion (inulin and creatinine).

Front 23

How can there be maximum clearance? AKA how can all plasma be cleared of the solute in one pass through the kidney?

Back 23

Because GFR is only 120 ml/min and RPF is 600 ml/min, there must also be secretion.

Front 24

When is clearance less than GFR but greater than 0?

Back 24

Substance is filtered but also reabsorbed slightly (Na+ and H20).

Front 25

How do you calculate extraction?

Back 25

([Renal artery] - [renal vein])/[renal artery]

Front 26

How do you calculate renal plasma flow using extraction?

Back 26

RPF = Clearance of PAH x (1/extraction of PAH)

Front 27

How do you calculate renal blood flow?

Back 27

Renal plasma flow/(1-hematocrit)

Front 28

How do you measure GFR in patients?

Back 28

24 hour urine collection and plasma Cr level.

Front 29

What molecules does the filtration barrier allow to pass?

Back 29

1. Negatively charged molecules with a radius less than 30 Angstroms (plasma proteins)
2. Neutral molecules with a molecular radius of 35 Angstroms or greater
3. Positive molecules with a radius less than 40 Angstroms

Front 30

Describe the layers of the filtration barrier.

Back 30

1. Endothelial cell layer or the glomeral capillaries.
2. Negative basement membrane
3. podocytes

Front 31

Why is the hydrostatic pressure at the glomerulus so high?

Back 31

smooth muscle in the afferent arteriole can decrease the resistance in the afferent arteriole and reduce the pressure drop.

Front 32

How does the kidney produce filtration at the glomerulus?

Back 32

the hydrostatic pressure is much higher than the colloid oncotic pressure.

Front 33

How do you calculate GFR using the filtration coefficient?

Back 33

GFR = Kf x MFP

GFR (mL/min) = Filtration coefficient (ml/min/mmHg) x Mean filtration pressure (mmHg)

Front 34

How do you calculate MFP?

Back 34

MFP = (Pgc - Pbs) - Mean COPgc

Mean COPgc = (COP afferent + COP efferent)/2

Front 35

Factors that affect GFR

Back 35

1. Altered Pgc
2. Altered resistance of afferent or efferent arterioles change Pgc.
3. Altered COP (from hydration, loss of protein in urine, production of plasma proteins in liver)
4. Altered Kf of glomerular capillaries.

Front 36

How does inhibition of prostaglandins (by NSAIDs, ibuprofen) affect renal blood flow? Why is this bad for the kidney

Back 36

prostaglandins dilate afferent arterioles. inhibition of prostaglands decreases renal blood flow which is bad because kidneys need lots of blood for production of ATP.

Front 37

What gets reabsorbed in nephron?

Back 37

99% NaCl
99% Water
100% glucose, amino acids

Front 38

What gets secreted in nephron?

Back 38

metabolites, drugs

Front 39

How does water travel through nephron epithelium?

Back 39

Always travels along osmotic gradients through aquaporins. Transcellular.

Front 40

Which segments of the nephrons demonstrate leaky epithelia?

Back 40

proximal tubule and descending limb of henle's loop.

Front 41

Which segments of the nephrons demonstrate tight epithelia?

Back 41

ascending limb, distal tubule, collecting duct.

Front 42

Na+ reabsportion occurs in all segments but _______.

Back 42

descending limb of loop of Henle.

Front 43

What promotes sodium uptake at proximal convoluted tubule by stimulated Na+/H+ antiport?

Back 43

Angiotensin II

Front 44

Describe the transporters and epithelium found at the ascending limb of the loop of Henle.

Back 44

The Na+/K+/2Cl- transporter is found on the apical side of the epithelium and it pumps those from the filtrate into the epithelium.
The epithelium is tight, so no water can pass through.
The basal and apical sides both have K+ channels that allow it to travel down gradient out of the cell.
Basal side has Cl- channels for Cl- to exit.
Basal side has a Na+/K+ ATPase which keeps intracellular Na+ low and K+ high.

Front 45

How does furosemide (Lasix) work? Why is it called a loop diuretic? What is a danger of using loop diuretics?

Back 45

Blocks the NKCC transporter, raising the osmotic concentration of fluid in the distal tubule, resulting in less water reabsorptions.
Works on the "loop" of henle.
Side effect may be hypokalemia and dehydration.

Front 46

What is Bartter's syndrome?

Back 46

A mutation that targets the NKCC channels. It is as if a loop diuretic is always present.

Front 47

What is the mOsm/L of the cortex, outer medulla, and inner medulla?

Back 47

Cortex: 300
Outer: 300-600
Inner: 600-1200

Front 48

What is the goal of the vasa recta?

Back 48

To provide oxygen and nutrients to the cells in loop of henle WITHOUT ultimately changing the osmolarity of the blood.

Front 49

Why do people with sickle cell anemia/trait lose ability to concentrate urine?

Back 49

RBCs with this mutation sickle in low oxygen, high osmolarity environments with at the bottom of the vasa recta. When this happens, infarctions occur and loop of henle dies.

Front 50

What is the function of the early part of the distal convoluted tubule? What is reabsorbed here?

Back 50

NaCl reabsorption by the NCC (Na/Cl co-transporter) causes continued diluted of tubular fluid.

Front 51

What is the function of the late part of the distal convoluted tubule? What is reabsorbed here?

Back 51

Na+ reabsorption by the ENaC (epithelial sodium channel).
K+ secretion into the lumen by ROMK channels, Maxi K channels and K/Cl co transporters
H+ or HCO3+ secretion.
Variable water permeability.

Front 52

What type of epithelium is the early distal tubule?

Back 52

Tight

Front 53

What do thiazide diuretics do? What are some examples of thiazide diuretics?

Back 53

inhibit NCC at the early distal convoluted tubule.

Chlorthalidone, hydrochlorothiazide.

Front 54

What is Gitelman's syndrome

Back 54

loss of function of NCC. Na+ is lost in urine. like a constant thiazide.

Front 55

What is Gordon's syndrome?

Back 55

Gain of function of NCC at early distal tubule.
Uncontrolled Na+ retention.
Leads to hypertension because of hypervolemia.

Front 56

What does amiloride do?

Back 56

It is a diuretic inhibiting ENaC.

Front 57

What is Liddle' syndrome

Back 57

Gain of function of ENaC. Retain too much sodium.
Hypertension due to hypervolemia.
Hypokalemia

Front 58

Where is urea reabsorbed?

Back 58

50% of urea is reabsorbed at the Proximal tubule.
An additional 40% of urea is reabsorbed at the distal collecting duct IF ADH is present.

Front 59

How do you go from 600 mOsm/L to 1200 mOsm/L when ADH is present?

Back 59

1. Urea reabsorption at medullary collecting duct into medullary interstitium. Urea adds to sodiums effects.
2. A tubular flow rate slow enough for equilibration to occur.
3. Full activity of the NKCC transporter.

Front 60

Which parts of the nephron does ADH affect?

Back 60

Increases water reabsorption at the distal tubule/ cortical collecting duct, and the distal collecting duct.

Increases urea permeability at medullary collecting duct.

Front 61

What factors affect the magnitude of the longitudinal osmotic gradient set up by the loop of henle?

Back 61

1. length of loop of henle (desert animals have longer loops)
2. urea in medullary interstitium.
3. low protein= low urea= low concentration
4. flow rate. high rate decreases time for equilibrium.

Front 62

What are the systemic effects of ADH/vasopressin? Where is this hormone produced? Where is it released?

Back 62

Pressor effect. Increases blood pressure through V1/ADH receptor.
Decreases urine excretion through V2/ADH receptor.
Created in the cell body which is in the hypothalamus, goes down the axon and is released from the posterior pituitary.

Front 63

Does ADH change the amount of urinary solute excretion?

Back 63

No.

Front 64

Is ADH response more responsive to plasma osmolarity or blood volume.

Back 64

The normal plasma osmolarity is on a steep portion of the curve, whereas blood volume is not.

Front 65

How does the activation of V2 receptor lead to water reabsorption?

Back 65

ADH binds to basal adenylate cyclase (converts ATP to cAMP which stimulates PKA) PKA phosphorylates aquaporin 2 which inserts itself onto lumen side of epithelium. Water can flood in and exits through constitutively active aquaporins on interstitial side.

Front 66

Are the ADH levels in hyponatremia too high or low?

Back 66

too much ADH.

Front 67

Give a central cause and nephrogenic cause of diabetes insipidus.

Back 67

Central: problem with ADH synthesis. Genetic or acquired. Trauma, CNS tumor. Low ADH, high response.

Nephrogenic: ADH resistance. Acquired: lithium, kidney injury. High ADH, low response.

Front 68

What happens to colloid oncotic pressure of the peritubular capillaries when you increase glomerular filtration rate.

Back 68

it increases, because you filtere more protein free fluid.

Front 69

Why do you increase in weight when you eat salt?

Back 69

You increase the osmolarity of your extra cellular volume. water moves from ICV to ECV and your body makes you drink more.

Front 70

How does your body react immediately and long term to a 10% decrease in ECV and circulating volume?

Back 70

Immediate: Baroreceptors initiate reflex to maintain arterial pressure and ECV.
Long term: Sodium excretion reduced, water excretion reduced, ECV restored.

Front 71

What is glomerulotuberal balance

Back 71

the ability of the kidney to match increaes in filtered load of water and salt with increases in their reabsorption. The kidney reabsorbs a constant fraction of filtered sodium and water even when the absolute amounts filtered are changed.

Front 72

why does increased GFR lead to increased reabsorption?

Back 72

Because you filter a greater amount of protein free fluid, the oncotic pressure of the peritubular capillaries increases, drawing more water and sodium back in.

Front 73

What do cardiopulmonary volume receptors sense and what is their response?

Back 73

Senses change in circulating volume. Increase in ECV results in increase in firing and vice versa.

Front 74

What do baroreceptors sense and what is their response?

Back 74

Sense arterial pressur echanges. Increases in BP increase firing and vice versa.

Front 75

What do macula densa cells sense and what is their response?

Back 75

Detect NaCl delivery to distal tubule. An increase in NaCl leads to a decrease in renin. Vice verse.

Front 76

What do juxtoglomerular cells sense and what is their response?

Back 76

Reduced blood pressure means decreased venous pressure and hence a decreased peritubular capillary pressure. This causes a smaller capillary hydrostatic pressure which causes an increased absorption of sodium ions into the vasa recta at the proximal tubule. Because of this increased absorption, less NaCl is present at the distal tubule where the macula densa is located. The macula densa senses this drop in salt concentration and responds through two mechanisms: first, it triggers dilation of the renal afferent arteriole, decreasing afferent arteriole resistance and thus offsetting the decrease in glomerular hydrostatic pressure caused by the drop in blood pressure. Second, macula densa cells release prostaglandins, which triggers granular juxtaglomerular cells lining the afferent arterioles to release renin into the bloodstream.

Front 77

Where is renin secreted from?

Back 77

juxtoglomerular apparatus.

Front 78

What 3 triggers lead to release of renin?

Back 78

A decrease in arterial blood pressure (that could be related to a decrease in blood volume) as detected by baroreceptors (pressure-sensitive cells). This is the most direct causal link between blood pressure and renin secretion (the other two methods operate via longer pathways).

A decrease in sodium chloride levels in the ultra-filtrate of the nephron. This flow is measured by the macula densa of the juxtaglomerular apparatus.

Sympathetic nervous system activity, which also controls blood pressure, acting through the beta1 adrenergic receptors.

Front 79

What triggers the release of Atrial natriuretic peptide? What effect does it have?

Back 79

-Released during increased ECV. Inhibits sodium reabsorption by inhibiting ENaC in distal tubule and collecting duct and Na/K ATPase on basolateral membrane.
-Decreases renin secretion.
-Dilates afferent arteriole and increases GFR.

Front 80

What do the renal sympathetic efferent nerves do at decreased ECV (sweating while running from bears)?

Back 80

-Activity of renal sympathetics increases.
-Constrict afferent more than efferent and therefore decrease GFR.
-stimulate proximal tubule Na+/H+ antiporter, increasing proximal Na+ reabsportion.
-Increases renin secretion by stimulating JG cels.

Front 81

Angiotensin II effects.

Back 81

Stimulates proximal tubule Na/H antiporter.
Stimulates aldosterone secretion from zona glomerulosa in adrenal cortex.
Stimulates ADH secretion.
stimulates thirst.

Front 82

What does aldosterone do?

Back 82

-Rapid activation of ENaC
-Rapid activation of ENaC and increase Na+ reabsorption.
-Increased K secretion via ROMK (have to balance charges)

Front 83

What is the physiological pH range and what is normal?

Back 83

7.0-7.8. 7.4 is normal.

Front 84

What is the forgotten hero of intracellular buffering?

Back 84

protein takes on excess H+ ions.

Front 85

The kidney can secrete H+ ions at DCT and collecting duct. Is that enough? How does kidney excrete more H+ ions?

Back 85

No. glutamate can be broken down by glutaminase into ammonium and 2 bicarb ions. This is the main system.

Uses HPO4-2 in the filtrate to carry out H+.

Front 86

When the body takes on acid, HCO3- supply decreases. How do we "create" new bicarbonate?

Back 86

by secreting a proton onto something other than bicarbonate.

Front 87

What is normal intracellular potassium level? Extracellular?

Back 87

130-140 mM

3.5 - 5 mM

Front 88

How do we keep extracellular potassium so low despite it being high in our diet? Give short term and long term solutions.

Back 88

Short term: Skeletal muscle acts as a short-term reservoir for K+. Epinephrine and insulin stimulate Na+/K+ ATPase on skeletal muscle cells to increase their K+ uptake. K+ then slowly released so concentraiton doesn't increase too quickly.
Long term: kidneys

Front 89

What stimulates K+ secretion?

Back 89

1. Plasma K+: Stimulates Na/K ATPase on basolateral side.
2. Aldosterone: stimulates Na/K-ATPase and increases # of ROMK channels.
3. Dietary intake of K+: gut signals to kidney to increase ROMK.

Front 90

What are ROMK channels?

Back 90

renal outer medullary potassium channel. transports K+ out of cells into filtrate.

Front 91

Acidosis is often clinically correlated with ______.
Alkalosis is often clinically correlated with _____.
Hint: potassium

Back 91

hyperkalemia, hypokalemia.

Front 92

What is the connection between alkalosis and hypokalemia?

Back 92

As H+ ions decrease outside of cell, more H+ ions come out. To balance this charge, K+ goes in.

Front 93

How does angiotensin II affect GFR and afferent/efferent arterioles?

Back 93

it constricts glomerular arterioles, having a greater effect on efferent arterioles than afferent. As with most other capillary beds in the body, the constriction of afferent arterioles increases the arteriolar resistance, raising systemic arterial blood pressure and decreasing the blood flow. However, the kidneys must continue to filter enough blood despite this drop in blood flow, necessitating mechanisms to keep glomerular blood pressure up. To do this, angiotensin II constricts efferent arterioles, which forces blood to build up in the glomerulus, increasing glomerular pressure. The glomerular filtration rate (GFR) is thus maintained, and blood filtration can continue despite lowered overall kidney blood flow.

Front 94

What does Kf represent? What could a decrease in Kf represent?

Back 94

It reflexts the mls per minute per mm Hg filtered across the entire glomeruli of the two kidneys. It reflexts the hydraluic conductivity of the filtration barrier and the surface area of the functional glomerular capillaries. A decrease in Kf can reflext loss of functional glomeruli due to disease.

Front 95

What could account for a decline in GFR?

Back 95

A decline in Kf.

A decrease in MFP (due to decreased Pgc or increased COP.

Front 96

Why might protein appear in the urine?

Back 96

Due to a change in the charge of basement membrane.

Front 97

What are the transporters of sodium ions in 1. the proximal tubule, 2. the distal tubule/collecting duct, and 3. the ascending loop of henle. Where are they located? Basolateral or luminal.

Back 97

1. Apical: Na/H antiporter, Na/glucose cotransporter, Na/AA cotransporter.... Basolateral: Na/K ATPase.
2. Apical: NCC (early distal), ENaC... Basolateral: Na/K ATPase.
3. Apical: NKCC.... Basolateral: Na/K ATPase.

Front 98

What percentage of filtered load of NaCl and water enter the final urine in the presence of maximum or minimum ADH?

Back 98

(-ADH) NaCl: 0.6% H2O: 15%
(+ADH) NaCl: 0.6% H2O: 1%

Front 99

Why should people with hypertension avoid salty foods?

Back 99

It increases ECV, and increases blood pressure.