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renal > A. GLOMERULAR FILTRATION AND RENAL FUNCTION > Flashcards

A. GLOMERULAR FILTRATION AND RENAL FUNCTION Flashcards

1
Q

what are the 3 basic renal processes

A
  1. filtration from glomerular capillaries
  2. reabsorption from filtrate into peri-tubular capillaries
  3. secretion (excretion) from peritubular capillaries into filtrate
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2
Q

what is the primary property of a drug which determines whether it will be reabsorbed or not

A

polarity
- non-ionised have high tubule permeability and hence reabsorbed

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3
Q

what is excretion

A

filtration - reabsorption + secretion

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4
Q

what are the 3 barriers a substance must pass through to be filtered

A
  1. fenestrae
  2. basement membrane
  3. filtration slits of podocytes
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5
Q
  1. pores (fenestration) between the endothelial cells of glomerular capillary
A
  • glomerular capillary wa§ll consists of a single layer of flattened endothelial cells
  • capillary wall perforated by numerous pores (fenestrae), diameter 60-70nm
  • pores allow plasma components to cross vessel walls except large plasma proteins, blood cells and platelets
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6
Q

what molecular weight can pass through pores of glomerular capillaries

A
  • <70kDa
  • +vely charged glycoproteins
    (-vely charged glycoproteins repel anionic proteins)
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7
Q
  1. basement membrane (-vely charged)
A
  • between glomerulus and Bowman’s capsule
  • composed of -vely charged glycoproteins inc collagen (extracellular matrix proteins)
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8
Q

what does collagen do

A

provide structural strength

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9
Q

what do glycoproteins do

A

discourage filtration of small plasma proteins including smallest plasma protein albumin

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10
Q

how does the basement membrane act as an effective filter

A

-vely charged proteins repel -vely charged plasma proteins and hence plasma proteins are almost completely excluded from filtrate

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11
Q
  1. filtration slits between the foot process/pedicel of the podocyte cells
A
  • consists of a layer of epithelial/tubule cells (podocytes) that encircle the glomerulus
  • long foot-like processes separated by gaps (slit pores) through which filtrate moves
  • podocytes are -vely charged hence further restrictions to filtration of plasma proteins
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12
Q

what is in the ultra-filtrate

A
  • inorganic ions (K+, Na+, Cl-, Ca2+, PO43-, H+, HCO3-) as so small
  • fluids
  • glucose, amino acids, urea, creatinine
  • no RBCs, WBCs, platelets
  • virtually no protein but a small amount of albumin may be present
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13
Q

what are mesangial cells

A
  • surround glomerular capillaries
  • provide structural support for capillaries
  • secrete extracellular matrix
  • possess phagocytic activity
  • secrete prostaglandins which regulate blood flow through glomerular capillaries and the afferent and efferent capillaries
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14
Q

what is the glomerular filtration rate

A

volume of fluid entering Bowman’s capsule from blood flowing per unit time (mL/min)

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15
Q

what GFR influenced by

A
  • filtration coefficient Kf
  • net filtration pressure
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16
Q

what is GFR equation

A

GFR = Kf x net filtration pressure

*directly proportional

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17
Q

equation for filtration co-efficient, Kf

A

Kf = glomerular SA x glomerular capillary permeability

*SA of all glomerular capillaries
*under physiological conditions Kf is relatively constant as number of nephrons and hence SA and permeability doesn’t change and so doesn’t play a role in daily regulation of GFR

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18
Q

how does kidney disease reduce Kf

A
  • reduces number of glomeruli and hence decreases SA
  • increases thickness and hence decreases permeability of capillary membrane eg - hypertension, diabetes
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19
Q

what are the 4 forces which determine net filtration pressure

A

determined by physical forces (Starling forces - exist in all capillaries) which drive the movement of fluid between plasma and tubule

  1. Glomerular capillary hydrostatic pressure (PG)
  2. Plasma-colloid osmotic pressure (πG)
    (sometimes called oncotic pressure)
  3. Bowman’s capsule hydrostatic pressure (PB)
  4. Bowman’s capsule colloid osmotic pressure (πB)
20
Q

what is the net filtration pressure

A

difference between forces favouring filtration and forces opposing filtration

(PG + πB) - (PB + πG)

21
Q

glomerular capillary hydrostatic pressure (PG)

A
  • pressure exerted by blood within the glomerular capillaries
  • dependent on contraction of heart and blood flow resistance of afferent and efferent arterioles
  • high pressure pushes fluid out of glomerulus and into Bowman’s space
  • driving force of glomerular filtration
22
Q

plasma-colloid osmotic pressure (πG)

A
  • caused by unequal distribution of plasma proteins across glomerular membrane
  • plasma proteins aren’t filtered so are present in glomerular capillaries and absent in bowman’s capsule
  • due to osmosis, water moves down its concentration gradient from Bowman’s capsule to glomerular capillaries
23
Q

Bowman’s capsule hydrostatic pressure (PB)

A
  • this pressure pushes fluid out of the Bowman’s capsule into the glomerulus
24
Q

Bowman’s capsule osmotic pressure (πB)

A
  • has negligible influence on filtration
  • would favour filtration but under normal conditions, it’s practically zero and ultrafiltrate is nearly protein free
25
Q

what are the units of net filtration pressure

A

mmHg

26
Q

how does the net filtration pressure act

A

forces large volumes of fluid from blood through the glomerular membrane due to the high net filtration pressure

27
Q

why is there auto regulation of renal blood flow and GFR by the kidneys

A

to maintain a constant renal blood flow and GFR over the physiological range of mean arterial pressure

MAP 80-180mmHg - a few % change in blood flow and GFR

28
Q

what is renal function ‘protective’ against

A
  • hypertensive irreversible renal damage (ie an increase in BP causing damage to nephrons’ capillaries)
  • hypotensive ischaemia and necrosis of tubular segments (if too low)
29
Q

why estimate GFR

A
  • estimates how efficiently the kidney filters wastes from blood
  • provides info on:
    severity and course of the kidney disease, approximate % of kidney function (fall in GFR = disease is progressing, rise in GFR = partial recovery), influences how much of a drug you can prescribe
30
Q

what are the 3 methods used clinically to estimate GFR

A
  1. creatinine clearance
  2. Cockcroft and Gault formula for creatinine clearance
  3. eGFR: CKD-EPI formula or MDRD formula
31
Q

what is clearance defined as

A

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

32
Q

why is creatinine used to estimate GFR

A

it is cleared from the body almost completely by glomerular filtration

*excretion = filtration -reabsorption + secretion
*0 is reabsorbed and a small amount by secretion so hence it is filtration

33
Q

what is creatinine produced from

A

breakdown of creatine and creatine phosphate in energy production in muscle

*if you add creatine to diet or eat more meat you will get more in the urine

34
Q

does a person’s creatinine clearance change

A

no as long as their muscle mass doesn’t change it is relatively constant

35
Q

what factors affect creatinine clearance

A
  • skeletal muscle mass (more muscle more CC)
  • age (less muscle as older and age >40, natural loss of 10% per 10 year)
36
Q

signs of good kidney function with CrCl equation

A
  • high urine creatinine
  • low plasma creatinine
  • high CrCl
37
Q

what does the Cockcroft & Gault equation take into account

A

sex, age, weight of patient

38
Q

signs of good kidney function with Cockcroft and Gault equation

A
  • low serum creatinine
  • high CrCl
39
Q

when is Cockcroft & Gault equation the preferred method for estimating renal function

A
  • elderly >75
  • extremes of muscle mass: BMI <18 OR >40 (amputees, muscle builder)
40
Q

what factors does Chronic kidney disease Epidemiology Collaboration (CKD-EPI) formula and Modification of diet in renal disease (MDRD) formula take into account

A

serum creatinine
sex
gender
ethnicity

41
Q

units of eGFR

A

mL/min/1.73m2 (body SA of average sized person)

*not as accurate as people have gotten bigger in recent years

42
Q

why is CKD-EPI used more

A
  • more accurate for eGFR >
    60ml/min/1.73m2
  • MDRD overestimates eGFR for elderly
43
Q

when should eGFR not be used

A
  • children
  • malnourished patients
  • in pregnancy
  • in oedema
  • extremes of muscle mass (e.g. amputee, body builder, muscle-wasting disease)
  • acute kidney injury
44
Q

what is ACR

A
  • urinary albumin:creatinine ratio
  • with poor kidney function there is high urine albumin, low urine creatine and hence a high air
45
Q

what GFR and ACR is associated with an increased risk of adverse outcomes like CV risks, stroke, ESKD

A

decreased GFR and increased ACR

46
Q

issues with the formula regarding sex

A
  • transgender person
  • use ‘at birth’ sex assignment
47
Q

uses with formula regarding race/ethnicity

A
  • black or not, diversity/mixed race in populations
  • many US labs use CKI-EPD creatinine equation to estimate GFR (serum cystitis C, serum creatinine, age, sex, no race)
    = more consistent method of estimating kidney function
  • not yet adapted globally

renal (13 decks)

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