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NSU AA Denver: Summer 2025 (2nd Semester) > Applied Physiology: Lecture 4 - Renal+Diuretics > Flashcards

Applied Physiology: Lecture 4 - Renal+Diuretics Flashcards

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1
Q

Where are the kidneys located in the body?

A

Around the level of T12-L3 in the retroperitoneal space, posterior to abdominal contents.

In the retroperitoneal space:
The space behind the peritoneum or the lining of the abdominal cavity

On both sides of the spine posterior to abdominal contents

Question? What surgical position is a patient usually in for a radical or partial nephrectomy?
Left lateral decubitus = jackknife

About 300grams

1100cc/min of blood flow to both kidneys. About 20% of CO (you would be out of blood in 10 minutes if clip the renal arteries????)

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2
Q

What is the average weight of a kidney?

A

About 300 grams.

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3
Q

What is the blood flow rate to both kidneys?

A

1100 cc/min, which is about 20% of cardiac output.

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4
Q

What is the pathway of blood flow from the renal artery to the glomerular capillaries?

A

Supplied by the Renal Artery which branch off laterally from the abdominal aorta around L1-L2

Renal artery > interlobar arteries > arcuate arteries > interlobular (radial) arteries > afferent arterioles > glomerular capillaries.

Renal vein takes filtered blood away from the kidneys back to IVC to the heart.

Question? Does filtered venous renal blood enter the hepatic circulation?
No it does not, goes straight back to heart

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5
Q

What does the renal vein do?

A

It takes filtered blood away from the kidneys back to the inferior vena cava (IVC) and then to the heart.

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6
Q

Glomerular Capillaries

A

Glomerular capillaries have 2 ends.

Afferent arteriole supplies blood to glomerulus.

Efferent arteriole. Which then lead to the peritubular capillaries

Glomerular capillaries are separated from the peritubular capillaries by the efferent arteriole.

A hydrostatic pressure gradient exists:

Glomerular capillaries hydrostatic pressure: 60mmHg (high pressure yields filtration)

Peritubular capillaries hydrostatic pressure: 13mmHg (low pressure yields reabsorption)

Kidneys can regulate afferent and efferent pressures to change filtration and tubular reabsorption to meet the bodies demands

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7
Q

What is the hydrostatic pressure in the glomerular capillaries?

A

60 mmHg, which is high pressure that yields filtration.

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8
Q

What is the hydrostatic pressure in the peritubular capillaries?

A

13 mmHg, which is low pressure that yields reabsorption.

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9
Q

What is the glomerular filtration rate (GFR)?

A

125 ml/min or around 180 L/day.

Glomerulrcapillaries into Bowmans capsule. No proteins, RBCs. (3 layer basement membrance)

Hydrostatic forces and a large surface area. 20% of plasma flowing through kidney is filtered. So the filtration fraction is .2

Membrane is vastly negative. Opposed proteins and prefers cations as opposed to anions.

Net filtration pressure: +10mmHg

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10
Q

What is the filtration fraction of plasma flowing through the kidney?

A

20%.

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11
Q

What is the net filtration pressure in the glomerulus?

A

+10 mmHg.

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12
Q

What is the capillary filtration coefficient (Kf) and how is it expressed?

A

Kf is expressed as permeability (hydraulic conductivity) X surface area and cannot be directly measured. (Highest point then anywhere else in the body)

But can be expressed:
Kf= GFR/Net filtration pressure. Normal is 12.5ml/min/mm

Much higher filtration coefficient in the glomerulus than any other capillary bed in the body. (400x)

What disease process last week did we talk about that may decrease Kf resulting in decreased GFR?
Diabetes (uncontrolled, makes the walls really thick)

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13
Q

How is Kf calculated?

A

Kf = GFR / Net filtration pressure; normal is 12.5 ml/min/mm.

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14
Q

How much higher is the filtration coefficient in the glomerulus compared to other capillary beds?

A

400 times higher.

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15
Q

Glomerular Hydrostatic Pressure:

A

Normal physiologic conditions: 60mmHg

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16
Q

What are the three ways glomerular hydrostatic pressure is manipulated to regulate GFR?

A
  • Changes in arterial blood pressure (systemic)
  • Afferent arteriolar resistance
  • Efferent arteriolar resistance

However, the kidneys are able to autoregulate:
GFR remains relatively constant despite fluctuations in systemic BP

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17
Q

What is renal autoregulation and its range?

A

Renal autoregulation maintains GFR and renal blood flow relatively constant between 75 mmHg and 160 mmHg despite changes in systemic blood pressure.

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18
Q

Factors that effect GFR

A
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19
Q

Formation of Urine

A

Renal autoregulation: 75mmHg-160mmHg

GFR and RBF remains relatively constant despite changes in systemic BP.

Main function of autoregulation in the kidneys is to allow for precise control of renal excretion of water and solutes

In general, RBF autoregulated in parallel with GFR

To mathematically show the importance:

Normal GFR is 180L/day and tubular reabsorption is 178L/day. So about 2 L of urine per day.

If BP increases from average of 100mmHg to 25mmHg: 25% increase in GFR to 225L/day and if tubular reabsorption remained constant, that is 46L of urine per day.

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20
Q

Formation of Urine Structures- Juxtaglomerular apparatus

A

Juxtaglomerular apparatus

Juxta meaning next to the glomerulus

Macula densa cells in the initial portion of the distal tubule.

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21
Q

What is the significance of the negative charge of the glomerular membrane?

A

It opposes proteins and prefers cations over anions.

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22
Q

What separates the glomerular capillaries from the peritubular capillaries?

A

The efferent arteriole.

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23
Q

What is the main way GFR is regulated?

A

Changes in glomerular hydrostatic pressure.

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24
Q

What is the role of the afferent arteriole in kidney function?

A

It supplies blood to the glomerulus.

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25
What is the role of the efferent arteriole in kidney function?
It carries blood away from the glomerulus to the peritubular capillaries.
26
Macula Densa
Major function in the tubuloglomerular feedback system Links changes in Sodium concentration at Macula Densa with renal arteriolar resistance. Both efferent and afferent. Macula Densa senses decreased Sodium concentration: 2 things happen: 1: Dilation of afferent arterioles thereby increasing glomerular hydrostatic pressure thereby increasing GFR. 2: Increases release of renin by JG cells: Renin increase formation of AG1. AG1 converted to AG2. AG2 constricts efferent arteriole causing increase in glomerular hydrostatic pressure thereby increasing GFR.
27
What happens to GFR during fluctuations in systemic blood pressure?
GFR remains relatively constant due to autoregulation.
28
Why do we need to urinate more after a high protein mean and after a high sugar intake?
Eat a high protein meal> increase amino acid and urea formation>sodium reabsorbed along with Aas> Macula densa senses less sodium in the tubule> leads to increased GFR by afferent arteriole dilation> increased urine production. Same with high glucose meal except instead of Aas, we have glucose being reabsorbed in the distal tubule. Same feedback system.
29
Tubular Reabsorption and Secretion
Tubular reabsorption and secretion: Highly selective unlike glomerular filtration. GFR and tubular reabsorption are closely liked to prevent major fluctuations in urinary excretion. Active and passive transport system promoting reabsorption and excretion.
30
What is the clinical significance of the filtration coefficient (Kf) in kidney diseases?
A decrease in Kf can result in decreased GFR.
31
What is the main function of autoregulation in the kidneys?
To allow for precise control of renal excretion of water and solutes.
32
How is renal blood flow (RBF) autoregulated in relation to glomerular filtration rate (GFR)?
RBF is autoregulated in parallel with GFR.
33
What is the normal GFR and how much urine is typically produced per day?
Normal GFR is 180L/day with tubular reabsorption of 178L/day, resulting in about 2L of urine per day.
34
What happens to GFR and urine production if blood pressure decreases from 100mmHg to 25mmHg?
GFR increases by 25% to 225L/day, leading to 46L of urine per day if tubular reabsorption remains constant.
35
What is the juxtaglomerular apparatus?
It is a structure next to the glomerulus that plays a key role in regulating kidney function.
36
What are macula densa cells and where are they located?
Macula densa cells are located in the initial portion of the distal tubule and are involved in the tubuloglomerular feedback system.
37
What is the major function of the macula densa in the kidneys?
It links changes in sodium concentration at the macula densa with renal arteriolar resistance.
38
What occurs when the macula densa senses decreased sodium concentration?
* Dilation of afferent arterioles increases glomerular hydrostatic pressure and GFR * Increased release of renin by JG cells, leading to the formation of angiotensin II (AG2) which constricts the efferent arteriole, also increasing GFR
39
Why do we urinate more after a high protein meal?
Increased amino acid and urea formation leads to sodium reabsorption, which the macula densa senses as less sodium, resulting in increased GFR and urine production.
40
How does a high glucose meal affect urine production?
Similar to a high protein meal, glucose is reabsorbed in the distal tubule, leading to the same feedback system that increases GFR and urine production.
41
What is the difference between glomerular filtration and tubular reabsorption/secretion?
Tubular reabsorption and secretion are highly selective processes, unlike glomerular filtration.
42
What percentage of sodium is reabsorbed in the proximal convoluted tubule (PCT)?
65% of sodium is reabsorbed in the PCT.
43
What substances are reabsorbed in the proximal convoluted tubule?
* NaCl * HCO3 * H2O * K * Glucose
44
What is secreted in the proximal convoluted tubule?
* H+ * NH3 (ammonia) * Organic acids * Salts * By-products of penicillins and salicylates
45
What are the characteristics of the proximal convoluted tubule cells? (will be questions from slide 17)
They are highly metabolic with many mitochondria, a large surface area due to brush borders, and significant Na+/K+ ATPase activity. As well as a lot of membrane surface area,(brush border) loaded with protein channels that aid in co transport As well as counter transport. Sodium reabsorbed in exchange for Hydrogen ions.
46
What are the three functionally distinct segments of the Loop of Henle?
* Thin descending limb * Thin ascending segment * Thick ascending segment Thin segments have thin epithelial walls, few mitochondria and no brush border
47
What is the permeability of the thin descending segment of the Loop of Henle?
It is highly permeable to water, with 20% of water absorption occurring here, almost all of which happens in the thin descending segment
48
What is the permeability of the ascending segments of the Loop of Henle?
They are virtually impermeable to water and are important for concentrating urine.
49
What are the characteristics of the thick ascending segment of the Loop of Henle?
It has thick epithelial cell walls, high metabolic activity, and is virtually impermeable to water.
50
What ions are actively reabsorbed in the nephron?
* Sodium (Na) * Chloride (Cl) * Potassium (K)
51
What percentage of filtered sodium, chloride, and potassium is reabsorbed in the Loop of Henle (LOH)?
25% of filtered load of the above are reabsorbed in LOH. Mostly all in Thick ascending segment. Ca, Bicarb and Mg as well. ATPKasepump maintains low intracellular Na concentration. Creates favorable movement of sodium into the cell from the tubular fluid In the thick ascending loop, movement of sodium across the luminal membrane is mediated primarily by a 1-sodium, 2-chloride, 1-potassium co-transporter This co-transport protein carrier in the luminal membrane uses the potential energy released by downhill diffusion of sodium into the cell to drive the reabsorption of potassium into the cell against a concentration gradient.
52
Which segment of the Loop of Henle is primarily responsible for the reabsorption of sodium?
The thick ascending segment.
53
What mechanism maintains low intracellular sodium concentration in renal cells?
The ATPKase pump.
54
How is sodium movement across the luminal membrane in the thick ascending loop primarily mediated?
By a 1-sodium, 2-chloride, 1-potassium co-transporter.
55
What role does the sodium-potassium ATPase pump play in potassium secretion in the distal tubule?
It maintains a high intracellular potassium concentration, allowing potassium to diffuse into the tubular lumen.
56
What is the primary function of the distal convoluted tubule?
To reabsorb most ions while being virtually impermeable to water and urea, resulting in dilute tubular fluid. First portion of distal tubule forms Macula Densa 5% of sodium reabsorption here. Sodium Chloride co transporter Thiazide diuretics work here.
57
What type of diuretics work in the distal convoluted tubule?
Thiazide diuretics.
58
Late Portion of Distal Tubule and Cortical Collecting Tubule
Site for sodium reabsorption and potassium secretion. Largely controlled by hormones. Aldosterone How does potassium get secreted? Energy and diffusion. The secretion of potassium by these cells from the blood into the tubular lumen involves two steps: (1) Potassium enters the cell because of the sodium-potassium ATPase pump, which maintains a high intracellular potassium concentration, and then (2) once in the cell, potassium diffuses down its concentration gradient across the luminal membrane into the tubular fluid. This is where Spironolactone works. Potassium sparing diuretic. Amiloride and triamterene are sodium channel blockers that work here. Also considered K sparing diuretics.
59
Late Distal Tubule and Cortical Collecting Tubule
Where ADH exerts its affect. ADH otherwise known as vasopressin. ADH: Anti-diuretic hormone. A hormone that increase water reabsorption. High levels of ADH in this segemtof nephron: highly permeable to water, leading to water reabsorption. Absent levels of ADH: virtually impermeable to water leading to water excretion in urine. Important hormonal mechanism involved in dilution or concentration of urine.
60
What hormones control sodium reabsorption and potassium secretion in the late distal tubule and cortical collecting tubule?
Aldosterone.
61
How does potassium get secreted into the tubular lumen?
Potassium enters the cell via the sodium-potassium ATPase pump and then diffuses down its concentration gradient into the tubular fluid.
62
What is the effect of aldosterone on the collecting duct?
It increases the expression of apical epithelial sodium channels (ENAC) to enhance sodium reabsorption.
63
What is the role of ADH (vasopressin) in the nephron?
ADH increases water reabsorption in the late distal tubule and collecting duct.
64
What happens to water permeability in the nephron in the presence of high levels of ADH?
The nephron becomes highly permeable to water, leading to increased water reabsorption.
65
What occurs in the absence of ADH in the nephron?
The nephron becomes virtually impermeable to water, leading to water excretion in urine.
66
What is the final site for processing urine in the nephron?
The medullary collecting duct. Reabsorb less than 10% of filtered water and sodium. Final site for processing urine Permeability of water controlled by ADH High levels of ADH water is reabsorbed, thereby decreasing urine volume and increasing urine solute concentration. Medullary collecting duct a large site of Hydrogen ion secretion against a gradient. Plays a key role in acid base regulation.
67
Hormone and Site of Action
68
Filtration, Reabsorption and Excretion Rates of Different Substances by the Kidneys
69
What is the effect of high levels of ADH in the medullary collecting duct?
Water is reabsorbed, decreasing urine volume and increasing urine solute concentration.
70
What triggers the release of renin from the juxtaglomerular apparatus (JGA)?
* Decreased sodium delivery to the distal convoluted tubule * Reduced perfusion pressure at the afferent arteriole * Sympathetic response to B adrenergic stimulation of JGA * Inhibited by ANP (atrial stretch due to increased volume/pressure)
71
What is angiotensinogen converted to with the help of renin?
Angiotensin I (AG1).
72
What converts angiotensin I to angiotensin II (AG2)?
Angiotensin-converting enzyme (ACE), primarily in the lungs.
73
What are the effects of angiotensin II (AG2) binding to AT I and AT2 receptors?
* Vasoconstriction * Sodium reabsorption in the proximal convoluted tubule * Increased release of norepinephrine * Stimulation of aldosterone * Increased thirst (hypothalamus) * Increased ADH release
74
AG2 stimulated release of Aldosterone from the adrenal cortex
Aldosterone increases expression of apical epithelial in collecting duct to reabsorb Na At ENAC pump. Causes decrease in plasma serum K
75
What are osmotic diuretics?
Work by increasing osmotic pressure of tubular fluid by being non-reabsorbable.
76
What is mannitol?
A substance that cannot be reabsorbed in the nephron, attracting water into the tubule system. Mannitol cant be reabsorbed so it attracts water into the tubule system by increased osmotic pressure and promotes excretion of water into the urine. Promotes free water diuresis. Increases RBF Works in the proximal convoluted tubule.
77
What is free water diuresis?
The promotion of water excretion into urine.
78
Use for Mannitol
Free radical scavenging Renal protection during transplantation Rhabdo Diuretic widely used in brain surgery to promote dry field, decrease ICP, decrease IOP, Onset: 20-30 min Dose: 0.5-1 g/kg (DOUBLE CHECK!!!)
79
Problems with Mannitol
Cardiac decompensation in setting of cardiac pathology Pulmonary edema Give mannitol, wait 20-30 minutes and check a blood gas. What do you expect to see? It is going to look funky (LOOK INTO MORE!!) Have to watch Potassium, could go low (Hyperventilation, Mannitol and Lasix)
80
What does RBF stand for?
Renal Blood Flow, which is increased by osmotic diuretics.
81
What part of the nephron do osmotic diuretics work?
Proximal convoluted tubule.
82
What are the uses of osmotic diuretics?
* Free radical scavenging * Renal protection during transplantation * Treatment of rhabdomyolysis
83
What are loop diuretics?
Include Lasix, Bumex, Ethacrynic acid, and Torsemide. Decrease active sodium and potassium reabsorption in Thick Ascending Loop of Henle Uses: Decompensated HF Fluid overload states Need for Serum K decrease Commonly given to liver transplant patient
84
What is the site where loop diuretics decrease active sodium and potassium reabsorption?
Thick Ascending Loop of Henle.
85
What are the uses of loop diuretics?
* Used for decompensated heart failure * Fluid overload states * To decrease serum potassium
86
What are potential problems with loop diuretics?
* Can cause hypokalemia * Metabolic alkalosis * Potentially hearing loss * All except Ethacrynic Acid are sulfa drugs
87
What do thiazide diuretics do?
Act at the distal tubule and inhibit sodium reabsorption.
88
By how much do thiazide diuretics increase sodium excretion when given alone?
Only increase sodium excretion by 3%-5%. Work much better when combined with Loop Diuretics (Lasix) Considered to be K wasting
89
What do potassium-sparing diuretics do?
Inhibit sodium reabsorption in the collecting tubule.
90
What is the maximal sodium excretion with potassium-sparing diuretics?
Can only maximally excrete 2% of the filtered sodium load. Many times used with Lasix or thiazide (DOUBLE CHECK!!) to help (LOOK UP!!!)
91
What are aldosterone antagonists?
Include Spironolactone and Eplerenone, which work in the collecting tubule. Direct aldosterone receptor antagonists work in the collecting tubule Inhibit Na reabsorption and K excretion Uses: liver dz, heart failure,
92
What are problems associated with spironolactone?
* Can cause hyperkalemia * Metabolic acidosis * Gynecomastia in men. Eplerenone lacks this effect
93
What do triamterene and amiloride do?
Sodium channel blockers at the collecting tubule. K Sparing Combined with other more potent diuretics to minimize risk of Hypo K Can cause hyper K and metabolic acidosis
94
What are carbonic anhydrase inhibitors?
Include Diamox (Acetazolamide) and work in the proximal tubule.
95
What are the uses of carbonic anhydrase inhibitors?
* Used to correct metabolic alkalosis * Reduce intraocular pressure * Treat altitude sickness
96
What are potential problems with carbonic anhydrase inhibitors?
Can cause mild hyperchloremic metabolic acidosis.

NSU AA Denver: Summer 2025 (2nd Semester) (28 decks)

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