Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

RED - Kidney Pharmacology & Therapeutics > K2; Glomerular filtration & renal function > Flashcards

K2; Glomerular filtration & renal function Flashcards

1
Q

What stages of filtration does a substance pass through to be filtered from the blood?

A
  1. ) Fenestrations (pores) between the endothelial cells of the glomerular capillary wall
  2. ) Across the pavement membrane
  3. ) Through the slit pores (filtration slits) of the podocytes of the Bowman’s capsule to gain access to the lumen of the tule
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How is the glomerular capillary membrane organised?

A

1.) Capillary endothelium (wall); flattened cells with 1000s of fenestrations (little pores)
2.) Sits on basement membrane
(above two present in all endothelial cells)
3.) Podocytes (tubular cells); have foot-like processes (pedicels), with spaces between pedicels called slit pores

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the properties of the glomerular capillary wall/fenestrations that aid filtration?

A
  • Wall consists of a single layer of flattened endothelial cells
  • Wall perforated by fenestrae (pores) of 60-70 nm in diameter (limit size)
  • Negatively-charged glycoproteins of the endothelial wall repel anionic proteins (limit negatively charged proteins)
  • Fenestrae allow plasma components to cross vessel walls with exception of large plasma proteins, blood cells and platelets (large and many -vely charged)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What size particle do the fenestrae allow through?

A
  • Max MW of 70kDa
  • Sieving effect
  • Larger molecules retained in blood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the properties of the basement membrane that aid filtration?

A
  • Composed of negatively-charged glycoproteins (e.g. collagen and other extracellular-matrix proteins)
  • Collagen provides structural strength
  • Glycoproteins discourage filtration of small anionic plasma proteins inc. smallest one, albumin
  • Plasma proteins almost completely excluded from filtrate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the properties of the podocytes/fenestrae that aid filtration?

A
  • Podocytes (epithelial cells) encircle the glomerulus
  • Pedicels (long foot-like processes) are separated by slit pores through which the filtrate moves
  • Podocytes are negatively-charged, providing further restrictions to filtration of plasma proteins
  • All three layers of glomerular capillary wall provide a barrier to filtration of plasma proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are mesangial cells and what role do they play?

A
  • Sit between the glomerulus and the pedicels
  • Provide structural support for the capillaries ‘fill in the gaps’, allowing glomerulus to be more open
  • Possess phagocytic activity (taking up foreign substances)
  • Secrete extracellular matrix proteins
  • Secrete prostaglandins (vasodilatory ones; allowing good blood flow to the glomerular capillaries)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What factors determine if a molecule is filtered?

A
  • Molecular weight

- Electrical charge

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the largest particle allowed through the glomerular filter and what are some examples of those that freely pass through?

A
  • 70kDa

- Glucose, AAs, Na+, urea, K+, drugs/metabolites freely pass through

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is and isn’t found in the ultrafiltrate?

A
  • Inorganic ions (K+, Na+, Cl-, Ca2+, PO43-, H+, HCO3-)
  • Organic molecules such as glucose, AAs, urea

Not found (and thus present in efferent arteriole:

  • RBCs
  • WBCs
  • Platelets

> Ultrafiltrate has no protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is GFR?

A
  • Glomerular filtration rate

- The amount of filtrate produced from blood flowing through the glomerulus per unit time (mL/min)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the two factors that influence GFR; what is the formula?

A
  • Filtration coefficient, Kf
  • Net filtration pressure

GFR = Kf x net filtration pressure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What does the filtration coefficient, Kf entail?

A

Kf = glomerular surface area x glomerular capillary permeability

  • Kf is fairly constant in normal physiological conditions; there is no issue with the surface area or permeability of the glomerulus
  • Thus does not play a role in daily regulation of GFR
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What does a decrease in Kf mean for GFR and what could cause this?

A
  • Decrease of GFR
  • Kidney disease can reduce no. of glomeruli = decrease no. of functional nephrons thus decreasing glomerular surface area and thus GFR
  • Increased thickness of capillary membrane leads to decrease of capillary permeability (e.g. hypertension, diabetes)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the four Starling (physical) pressures that influence net filtration pressure (movement of fluid between plasma and tubule)?

A
  1. ) Glomerular capillary hydrostatic pressure (Pg); pressure exerted by a fluid (static/moving) on a membrane
  2. ) Plasma-colloid osmotic pressure (πg) AKA oncotic pressure; pressure exerted by proteins within the glomerulus
  3. ) Bowman’s capsule hydrostatic pressure (Pb); fluid within Bowman’s space exerting pressure on glomerular filter
  4. ) Bowman’s capsule colloid osmotic pressure (πb); protein (colloid) pressure on glomerular filter
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe the glomerular hydrostatic pressure, Pg.

A
  • Pressure exerted by blood within glomerular capillaries
  • ‘Hydrostatic’; plasma or blood, moving or static
  • Dependent on contraction of the heart and blood flow resistance of afferent (larger bore) and efferent (smaller bore) arterioles
  • This high pressure pushes fluid out of the glomerulus and into the Bowman’s space
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Describe the plasma-colloid osmotic pressure, πg.

A
  • Opposing flow; water would move down its concentration gradient from low osmotic pressure (Bowman’s capsule) to high osmotic pressure (glomerulus)
  • Due to uneven distribution of plasma proteins across glomerular membrane
  • Plasma protein not filtered and retained in glomerular capillaries, absent in the Bowman’s capsule
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Describe the bowman’s capsule hydrostatic pressure, Pb.

A
  • Opposing flow

- Pressure exerted by fluid; pushing fluid out of the Bowman’s capsule into the glomerulus

19
Q

Describe the bowman’s capsule colloid osmotic pressure, πb.

A
  • Hypothetical pressure of proteins in the Bowman’s capsule
  • Would favour filtration and movement of water from capillaries to Bowman’s
  • But πb is practically zero under normal conditions; ultrafiltrate is protein-free
  • Not considered
20
Q

What is the net filtration pressure? (Hint: equation)

A
  • Difference between forces favouring filtration and forces opposing filtration
  • Forces favouring - Forces opposing
  • (Pg + πb) - (Pb + πg)
  • (60 + 0) - (18 + 32)
    = 10 mmHg

Thus forcing a large volume of fluid from blood through the glomerular membrane.

21
Q

What clinical factors affect the Starling forces that contribute to net filtration pressure?

A
  • Arterial blood pressure (BP); an increase results in an increase of Pg thus increasing GFR
  • Decrease/increase in plasma protein concentration; affecting πg (plasma-colloid osmotic pressure; a decrease in πg increases GFR and vice versa)
  • Effect on Pb (Bowman’s capsule hydrostatic pressure)
22
Q

Why does an increase in arterial blood pressure not result in an increase in GFR in a normal person?

A
  • Kidney can ‘autoregulate’ rapidly to changes in BP, maintaining constant blood flow/glomerular filtration
23
Q

What clinical circumstances see a decrease/increase in plasma protein and how would this affect net filtration pressure?

A

Decrease: severe burn with loss of protein-rich plasma, results in decrease in πg and thus increase in GFR.

Increase: dehydrating diarrhoea - loss of fluid results in concentrating protein in plasma thus increasing πg (an increase in the opposing pressure) which thus decreases net filtration pressure and GFR.

24
Q

What clinical circumstance see an increase in Pb (Bowman’s capsule hydrostatic pressure) and how does this affect GFR?

A
  • Urinary tract obstruction e.g. kidney stone, enlarged prostate
  • Results in a build-up of back pressure in the kidney tubules
  • Goes all the way back up thus increasing Pb and decreasing GFR (as Pb is an opposing force)
25
Q

What is autoregulation?

A

Maintaining a constant renal blood flow and glomerular filtration rate (GFR) over the physiological range of mean arterial pressure (MAP):

  • 80 - 180mmHg
  • Few % change in blood flow/GFR
26
Q

What does autoregulation protect the kidney against?

A
  • Hypertensive irreversible renal damage (fragile nephrons/glomeruli)
  • Hypotensive ischaemia (insufficient oxygen supply)
27
Q

How does autoregulation occur?

A

Rapid changes of diameter of the afferent arteriole depending on two factors:

  • myogenic (intrinsic; of the arteriole smooth muscle wall, resist stretch of vascular walls, contracting back to resist stretching, and dilating when there’s limited stretching)
  • tubuloglomerular feedback
28
Q

What does tubuloglomerular feedback entail?

A

Involves the juxtaglomerular apparatus:

  • juxtaglomerular/granular cells (mainly in afferent arteriole wall) secrete renin
  • macula densa cells (tubular cells at the top of the thick ascending limb of the LoH) detect changes in tubular fluid e.g. NaCl, secreting vasoactive chemicals which go through the interstitial fluid and affect the vasal tone of the afferent arteriole and some other capillaries too (constricting/dilating) - paracrine communication
29
Q

How does tubuloglomerular feedback respond to raised BP?

A
  • Increases Pg increasing GFR
  • Thus increasing flow rate of tubular fluid in the LoH
  • [NaCl] at macula densa is increased (less time for Na+ and Cl- reabsorption in LoH)
  • Vasoactive agents secreted e.g. endothelin, adenosine, ATP
  • Communicates with granular cells particularly around the afferent arteriole to cause vasoconstriction
  • This increases resistance to blood flow in the afferent arteriole, returning GFR toward the norm (decreases blood flow into the glomerulus, decreasing Pg and thus net filtration pressure)
30
Q

How does tubuloglomerular feedback respond to a fall in BP?

A
  • Decrease in Pg decreases GFR
  • Decreases flow rate in LoH
  • [NaCl] at macula densa is lowered (more time for Na+ and Cl- reabsorption in LoH)
  • Macula densa secretes vasoactive agents e.g. PGE1, E2, I2, bradykinin, NO (nitrous oxide)
  • Results in vasodilatation of afferent arteriole, bore increases (myogenic activity too)
  • Increases blood flow into glomerulus, increases Pg, increasing net filtration pressure and thus GFR
  • Decreased [NaCl] also leads to increase of renin release from granular cells of afferent/efferent arterioles
  • Activates RAAS, converting Ang I to Ang II; a vasoconstrictor, preferentially acting on the efferent arterioles (decreasing bore, increasing Pg) returning GFR toward norm
31
Q

Why is GFR estimated?

A
  • Provides estimate of how efficiently the kidney filters wastes from blood
  • Essential part of assessing patients with kidney disease providing information on:
    > severity and course of kidney disease
    > approximate percentage of kidney function (rise in GFR = partial recovery)
    > influences how much of a drug you can prescribe (dose adjustment etc)
32
Q

What 3 methods are used clinically to estimate GFR?

A
  • Creatinine clearance
  • Cockcroft & Gault formula
  • MDRD (Modification of Diet in Renal Disease ) formula
33
Q

Define: clearance.

A

Volume of plasma that is completely cleared of a substance by the kidneys per unit time.

34
Q

Why is creatinine used for eGFR?

A
  • It is almost completely cleared from the body by glomerular filtration; there is little secretion of reabsorption (thus only telling us about filtration)
  • Derived from breakdown of creatine phosphate (muscle)
35
Q

What factors need to be considered when working out Creatinine Clearance?

A
  • Skeletal muscle mass: men have more muscle muss thus greater creatine phosphate and more creatinine produced as a metabolite (CCr is greater)
  • Age; natural loss of kidney nephrons at 10% every decade; thus lower Cl
36
Q

What is measured to calculate creatinine clearance?

A
  • Plasma creatinine level: [P]cr (mmol/mL)

- Urine output collection (24hr): urine flow rate, V (mL/min) and a urine creatinine conc., [U]cr (mmol/mL).

37
Q

What is the formula for creatinine clearance and what does it mean?

A

[U]cr x V / [P]cr

  • Thus clearing more creatinine means having low levels in plasma [P]cr; a small denominator meaning good GFR/high creatinine clearance value = good kidney function
  • Poor kidney function = poor filtering = high [P}cr (accumulation in blood); greater denominator, creatinine clearance becomes a smaller value.
38
Q

What does the Cockcroft & Gault equation take into account and what is it known as?

A
  • Gender, age and weight
  • eCcr
  • Estimated as only account for serum creatinine: creatinine levels in the blood and not of the urine
  • High serum creatinine = poor clearance = poor filtration = large denominator = low estimated creatinine clearance
39
Q

What is the Cockcroft & Gault equation?

A

(140 - age [yrs]) x weight [kg] x constant/ serum creatinine (μmol/L)

40
Q

What is the Cockcroft & Gault constant in males and females respectively?

A

Males: 1.23
Females: 1.04

41
Q

What does the MDRD account for and what are its advantages?

A
  • Accounts for: serum creatinine levels, gender, age, ethnic origin, serum nitrogen urea and albumin
  • More reliable measure of renal function
  • Only accounts for serum creatinine levels; BUT gives eGFR and not just creatinine clearance
42
Q

What are the units for eGFR?

What does the extra factor not found in Ccr account for?

A
  • mL/min/1.73m^2

- m^2 refers to body surface area (estimated for average standard size person; 5ft 10 male of 70kg)

43
Q

When can MDRD (eGFR) not be used?

A

Individuals not of a ‘standard person’ size:

  • children
  • malnourished patients
  • pregnancy
  • oedema
  • extremes of muscle mass (e.g. amputees, body builders, muscle-wasting disease)

Not used in acute renal failure either.

RED - Kidney Pharmacology & Therapeutics (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions