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A Physiology > 4.1. Circulation of the kidney. Glomerular-filtration. > Flashcards

4.1. Circulation of the kidney. Glomerular-filtration. Flashcards

1
Q

I. Kidneys
1. What is the location of kidneys?

A

Kidneys: Paired bean-shaped organs in the posterior abdominal cavity

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2
Q

I. Kidneys
2. What are the functions of kidneys?

A

1) Elimination of metabolites and waste products (filtration)
2) Contribute to homeostasis of various parameters (often sensors/effectors)
3) Hormone production + secretion (hormonal cascade)

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3
Q

I. Kidneys
2A. How can kidneys contribute to homeostasis of various parameters (often sensors/effectors)?

A
  1. Salt/water balance (influences EC-fluid volume + blood volume -> BP)
  2. Balance of electrolytes (K+, Ca2+, phosphate, Mg2+ etc.)
  3. Regulation of acid/base balance (pH)
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4
Q

I. Kidneys
2B. How can kidneys contribute to Hormone production + secretion (hormonal cascade)?

A
  1. Renin: not hormone by itself, but generates ANG1 to ANG2 (active form)
  2. Erythropoietin: produced in kidney cells in hypoxia (RBC↓) + responsible for RBC-production
  3. Calcitriol: active hormone, responsible for regulation in bone, tissue, intestinal region
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5
Q

I. Kidneys
3. What are the 2 regions of kidney?

A
  1. Outer cortex: Malpighi bodies and glomeruli only located here
  2. Inner medulla (divided into renal pyramids)
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6
Q

I. Kidneys
4. What is the ultrastructure of nephron?

A

Ultrastructure of nephron (functional unit)
- Renal corpuscle: glomerular capillaries enclosed within Bowman’s capsule
- Proximal tubule
- Loop of Henle: thick & thin ascending and thin descending
limbs
- Distal (convoluted) tubule: macula densa is the point where the distal tubule touches the glomerulus
- Collecting duct system: cortical and (inner & outer) medullary ducts

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7
Q

I. Kidneys
4A. Describe Renal corpuscle

A

Renal corpuscle: glomerular capillaries enclosed within Bowman’s capsule

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8
Q

I. Kidneys
4B. Describe Loop of Henle

A

thick & thin ascending and thin descending limbs

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9
Q

I. Kidneys
4C. Describe Distal (convoluted) tubule

A
  • Distal (convoluted) tubule: macula densa is the point where the distal tubule touches the glomerulus
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10
Q

I. Kidneys
4D. Describe Collecting duct system

A

cortical and (inner & outer) medullary ducts

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11
Q

I. Kidneys
5A. What are the 2 types of nephrone?

A
  1. Juxtamedullary nephrons
  2. Cortical nephrons
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12
Q

I. Kidneys
5B. What are the characteristics of Juxtamedullary nephrons?

A

Juxtamedullary nephrons: have their glomeruli near corticomedullary border
- Glomeruli are large in size
- Long loops of Henle (reaches deep into inner medulla + papilla)

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13
Q

I. Kidneys
5C. What are the characteristics of cortical nephrons?

A

Cortical nephrons: 90% of glomeruli are located here
- Their glomeruli are located in the (outer) cortex
- Short loops of Henle (reaches only into the outer medulla)

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14
Q

II. Renal circulation
1. What is the pathway of Renal circulation

A
  1. Renal artery
    -> Afferent arteriole
    -> Glomerular capillaries
    -> efferent arteriole
    -> Peritubular Capillaries (Cortical Nephrons) + Vasa Recta (Juxtamedullary Nephron)
    -> Venules
    -> Renal Veins
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15
Q

II. Renal circulation
2A. What is the value for renal blood flow?

A

Renal blood flow (RBF): 1200-1300 ml/min (20-25% of Cardiac output)

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16
Q

II. Renal circulation
2B. What is the value for Renal plasma flow (RPF)?

A

Renal plasma flow (RPF): 600-700 ml/min (about 1⁄2 of total renal flow)
-> High blood flow provides the blood plasma necessary for forming an ultrafiltrate in the glomeruli.

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17
Q

II. Renal circulation
3. Why is large blood flow necessary for appropriate filtration in glomerulus?

A
  • Large blood flow is necessary for appropriate filtration in glomerulus
    -> If fluid is filtered out of glomerular capillaries, without large molecules (albumin + proteins), the colloid osmotic concentration increases in the vessels
    +) Will counteract against the filtration
    +) In order to get enough filtration, we need this huge blood supply
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18
Q

III. Regulation of Renal circulation
1A. What is the role of regulation of renal circulation? (5)

A
  1. Protects glomerular capillaries from excessively high BP, and prevents high blood flow and high Glomerular filtration rate (GFR)
  2. Provides balanced blood supply for the individual nephrons
  3. In case of Na+-deficiency it promotes Na+-conservation
  4. In severe emergency situations it reduces RBF, thereby contributing to the blood supply of vital organs
  5. In case of sodium overload/volume expansion, hemodynamic changes in the kidney contribute to natriuresis
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19
Q

III. Regulation of Renal circulation
1B. What are the 3 types of regulation of renal circulation? (5)

A
  1. Autoregulation
  2. Sympathetic nerves
  3. Atrial natriuretic peptide (ANP)
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20
Q

III. Regulation of Renal circulation
2A. How does auto regulation participate in regulation of renal circulation?

A

Autoregulation: maintain constant blood flow despite changes in pressure
- Afferent and efferent arterioles are the major resistance vessels in the kidney, and thereby determine the renal vascular resistance
- The kidneys control their blood flow by adjusting vascular resistance in response to changes in the arterial pressure

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21
Q

III. Regulation of Renal circulation
2B. Autoregulation of renal circulation occurs due to 2 reason. What are they?

A
  1. Protect glomerular capillaries from excessively high BP
  2. Prevent high blood flow and high GFR
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22
Q

III. Regulation of Renal circulation
2C. How can Autoregulation of renal circulation protect glomerular capillaries from excessively high BP?

A

Because if BP is high in glomerular capillaries, filtration will increase proportionally
=> Is a problem: if we filter 1,5 times as much NaCl and glucose, 1,5 times as much has to be reabsorbed as well

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23
Q

III. Regulation of Renal circulation
2D. What are the mechanism responsible for autoregulation of RBF and GFR?

A

1) Myogenic mechanism (Bayliss effect
2) Tubule-glomerular feedback: [NaCl] dependent

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24
Q

III. Regulation of Renal circulation
2D1. How can Myogenic mechanism (Bayliss effect) be responsible for autoregulation of RBF and GFR?

A

Myogenic mechanism (Bayliss effect) only in afferent arteriole, would ↑ pressure in capillaries if also in efferent arteriole
- Tendency of VSMs to contract when stretched
+) Stretch induces opening of stretch-activated, non-selective cation channels in the VSM
+) Resultant depolarization leads to an influx of Ca2+ that stimulates contraction
=> Bayliss effect provides constant blood flow and GFR in a wide range (90 – 180mmHg)

25
Q

III. Regulation of Renal circulation
2D2. What are the 2 cases of Tubule-glomerular feedback which is responsible for autoregulation of RBF and GFR?

A

Tubule-glomerular feedback: [NaCl] dependent
1. In case of increased GFR (↑BP) or Na+-surplus
2. In case of reduced GFR (BP↓) or Na+-deficiency = [NaCl]↓

26
Q

III. Regulation of Renal circulation
2D2a) How does Tubule-glomerular feedback: [NaCl] dependent work In case of increased GFR (↑BP) or Na+-surplus?

A
  1. GFR increases and causes a rise in [NaCl] in the loop of Henle
  2. More NaCl enters the macula densa cells
  3. The increase in [NaCl]IC induces an increase in formation and release of ATP and adenosine
  4. Adenosine binds on A1-receptors (Gi) on SMC, causing vasoconstriction of AFFERENT arteriole (adenosine= vasodilator in skeletal muscle + heart, constrictor here)
    => NaCl- detection effects neighboring (secretory) granular cells = renin-containing
27
Q

III. Regulation of Renal circulation
2D2b) What does it mean when there is an increase in [NaCl]

A
  • Secretion of adenosine
  • SMC tone ↑
  • cAMP ↓ - is a SM relaxant, so a decrease means constriction - cAMP↓ also in granular cells (renin secretion ↓)
28
Q

III. Regulation of Renal circulation
2D2c) How does Tubule-glomerular feedback: [NaCl] dependent work In case of reduced GFR (BP↓) or Na+-deficiency = [NaCl]↓?

A

In case of reduced GFR (BP↓) or Na+-deficiency = [NaCl]↓
1. GFR decreases and [NaCl] in the tubular fluid
2. Less NaCl enters the macula densa cells
3. ATP and adenosine production and release declines

  1. Decrease in adenosine results in activation of granular cells and SMCs due to an increase in [cAMP] and [PGE2], which in turn increases renin secretion of granular cells
    => Renin ↑ = ANG1↑ = ANG2↑ => Na+-conservation in body (BP↑)
  2. Renin angiotensin cascade ultimately results in vasoconstriction of EFFERNT arterioles

Additional effects: (vascular, aldosterone) -> hormone that conserves Na+ (↑ Na+- reabsorption)

29
Q

III. Regulation of Renal circulation
3A. How can sympathetic nerves affect the renal circulation?

A
  • Afferent and efferent arterioles are innervated by the sympathetic system
  • In case of a severe drop in BP (ex: due to hemorrhage), sympathetic nerves affect the blood flow in following mechanisms:
    1) Afferent arteriole vasoconstriction
    2) Efferent arteriole vasoconstriction
30
Q

III. Regulation of Renal circulation
3B. How does Afferent arteriole vasoconstriction regulate renal circulation?

A
  • Catecholamine (NE, E) binds on α1-
    receptors (Gq) located on afferent arterioles
  • Gq -> IP3 + DAG ↑ -> [Ca2+]↑ -> constriction
31
Q

III. Regulation of Renal circulation
3C. How does efferent arteriole vasoconstriction regulate renal circulation?

A
  • Catecholamines (NE, E) binds on β1-receptors (Gs) on the granular cells
  • Renin-angiotensin cascade is activated, which ultimately leads to production of ANG2
  • Efferent arteriole is more sensitive to ANG2 than afferent arteriole
  • Granular cells release renin due to:
    1. Direct sensing of low BP
    2. Sympathetic activation
    3. Macula densa signaling
    => These processes occur to redistribute blood flow to vital organs, in case of severe drop in BP
    => RBF↓, GFR↓ (due to excessive sympathetic activity)
32
Q

III. Regulation of Renal circulation
4A. How does Atrial natriuretic peptide (ANP) regulate renal circulation?

A
  • In case of Na+-overload or (blood) volume expansion, the volume receptors (low pressure receptors) in the atria and large veins detects this change and increases the secretion of ANP.
  • 2 mechanism: atrial natriuretic peptide (ANP) will produce vasodilation of afferent arterioles and vasoconstriction of efferent arterioles.
33
Q

III. Regulation of Renal circulation
4C. Atrial natriuretic peptide (ANP) will produce vasoconstriction of arterioles.
=> What are the 3 consequences

A
  1. Afferent arteriole constriction: decreases blood flowing into renal corpuscle
  2. Efferent arteriole constriction: makes it more difficult for blood to leave glom. capillaries
  3. Aff. art. dilation + eff. art. constriction.
34
Q

III. Regulation of Renal circulation
4A. How does Atrial natriuretic peptide (ANP) regulate renal circulation?

A
  • In case of Na+-overload or (blood) volume expansion, the volume receptors (low pressure receptors) in the atria and large veins detects this change and increases the secretion of ANP.
  • 2 mechanism: atrial natriuretic peptide (ANP) will produce vasodilation of afferent arterioles and vasoconstriction of efferent arterioles.
35
Q

III. Regulation of Renal circulation
4B. atrial natriuretic peptide (ANP) will produce vasodilation of afferent arterioles. How does it affect renal circulation?

A

ANP dilates afferent arteriole (cGMP-mediated)
-> pressure increase in glomerular capillaries
-> filtration increases
-> excretion of Na+ + Cl- increases = renal filtration and urine secretion ↑

36
Q

III. Regulation of Renal circulation
4C. Atrial natriuretic peptide (ANP) will produce vasoconstriction of arterioles.
=> What are the 3 consequences

A
  1. Afferent arteriole constriction: decreases blood flowing into renal corpuscle
  2. Efferent arteriole constriction: makes it more difficult for blood to leave glom. capillaries
  3. Aff. art. dilation + eff. art. constriction.
37
Q

III. Regulation of Renal circulation
4C1. Atrial natriuretic peptide (ANP) will produce vasoconstriction of arterioles.
=> What are the effects of Afferent arteriole constriction?

A

Afferent arteriole constriction: decreases blood flowing into renal corpuscle
1. Decreases hydrostatic pressure in glom. capillaries
2. Decreases GFR
3. Decreases blood flow

38
Q

III. Regulation of Renal circulation
4C2. Atrial natriuretic peptide (ANP) will produce vasoconstriction of arterioles.
=> What are the effects of Efferent arteriole constriction?

A

Efferent arteriole constriction: makes it more difficult for blood to leave glom. capillaries
1. Increases hydrostatic and oncotic pressure in glom. capillaries
2. Increases GFR
3. Decreases blood flow

39
Q

III. Regulation of Renal circulation
4C3. Atrial natriuretic peptide (ANP) will produce vasoconstriction of arterioles.
=> What are the effects of Aff. art. dilation + eff. art. constriction?

A

1.Blood flow remains the same
2. Increases hydrostatic pressure
in glom. capillaries
3. Increases GFR

40
Q

III. Glomerular filtration
1. What is the value for Glomerular filtration rate GFR?

A

120 ml/min or 180 L/day

41
Q

III. Glomerular filtration
2A. What is the value for Filtrated fraction (FF)?

A

Filtrated fraction (FF): 20%

42
Q

III. Glomerular filtration
2B. What is the definition for Filtrated fraction (FF)?

A

refers to ratio of plasma filtered to total plasma flowing through the glomerulus

43
Q

III. Glomerular filtration
3. What is the relationship between Glomerular filtration rate (GFR) and Renal plasma flow (RPF)?

A

FF = GFR/ RPF = 120/600 = 0.2 = 20%

44
Q

III. Glomerular filtration
4. Are GFR and FF higher or lower than normal capillary filtration rates? Why?

A

GFR and FF are higher than normal capillary filtration rates because:
- Glomerular capillary pressure is ~2x systemic capillary pressure
- Filtration coefficient (CF) determined by permeability + filtration surface area is 100x higher than in systemic capillaries

45
Q

III. Glomerular filtration
5A. What is the role of Filtration barrier?

A

Filtration structure of the renal corpuscle

46
Q

III. Glomerular filtration
5B. What are the 3 layers of Filtration barrier?

A
  1. Fenestrated endothelium
  2. Basement membrane
  3. Podocyte processes
47
Q

III. Glomerular filtration - Filtration barrier
5B1. What is the role of Fenestrated endothelium

A
  1. A negatively charged surface
    -> repels anionic proteins
  2. Permeable to water, small solutes (Na+, urea, glucose)
48
Q

III. Glomerular filtration - Filtration barrier
5B2. What is the feature of Basement membrane?

A

Lies beneath the endothelium
-> thick + negatively charged

49
Q

III. Glomerular filtration - Filtration barrier
5B3. What is the feature of Podocyte processes?

A

Interdigitating finger-like processes of podocytes are connected by porous slit diaphragms (also repels negatively charged molecules)

50
Q

III. Glomerular filtration
6. What is the General glomerular filtration rule?

A
  • The larger or more negatively charged a molecule, the less likely it will pass the filtration barrier (due to the restrictive actions of small pores and negative charges of
    the filtration barrier components)
  • Because of these restrictions on filtered substances, water and all the smaller solutes of blood are filtered, whereas proteins and blood cells are not
51
Q

III. Glomerular filtration
7. Renal clearance:

A
  • The volume of plasma per unit time from which all of a given substance passes through the filtrate and is excreted in the urine (ml/min)
  • Indicated by Cx (x is the substance being cleared)
52
Q

IV. Glomerular filtration of various substances
1. What are the input and output sources of kidney?

A
  • Renal artery is the only input source to the kidney
  • Renal vein and ureter are 2 major output routes
    => Arterial input = venous output + urine output
53
Q

IV. Glomerular filtration of various substances
1. What are the input and output sources of kidney?

A
  • Renal artery is the only input source to the kidney
  • Renal vein and ureter are 2 major output routes
    => Arterial input = venous output + urine output
54
Q

IV. Glomerular filtration of various substances
3. How is Albumin filtered?

A
  • Not filtered at all due to size and negative charge
  • remains in the capillar
55
Q

IV. Glomerular filtration of various substances
4. How is glucose filtered?

A
  • filtered, but completely reabsorbed into peritubular capillaries
  • (glucose reabsorption transporters can be saturated when blood [glucose] is too high and leads to glycosuria, as seen in diabetes mellitus)
56
Q

IV. Glomerular filtration of various substances
5. How is PAH (para-aminohippurate) filtered?

A

Filtrated, and completely secreted by the peritubular capillaries
- PAH is cleared from all plasma filtrated through the glomerulus AND all plasma which continues past the glomerulus without being filtrated

57
Q

IV. Glomerular filtration of various substances
6. How is Inulin filtered?

A
  • Renal artery is the only input source to the kidney
  • Renal vein and ureter are 2 major output routes
    => Arterial input = venous output + urine output
58
Q

IV. Glomerular filtration of various substances
7. How is creatine be filtered?

A
  • Filtered, and NOT reabsorbed, secreted or metabolized by kidney cells
  • byproduct of skeletal muscle creatinine metabolism (breakdown product of
    creatinine phosphate)
  • do not need to inject like inulin, because it is infused naturally into the plasma via a
    normal physiological process
  • GFR can be estimated from plasma concentration of creatinine
  • So, GFR can be estimated from plasma concentration of creatinine
  • If GFR decreases, plasma concentration of creatinine increases
    +) 2x normal Pcreatinine = 1⁄2 normal GFR

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