A. GLOMERULAR FILTRATION AND RENAL FUNCTION Flashcards
what are the 3 basic renal processes
- filtration from glomerular capillaries
- reabsorption from filtrate into peri-tubular capillaries
- secretion (excretion) from peritubular capillaries into filtrate
what is the primary property of a drug which determines whether it will be reabsorbed or not
polarity
- non-ionised have high tubule permeability and hence reabsorbed
what is excretion
filtration - reabsorption + secretion
what are the 3 barriers a substance must pass through to be filtered
- fenestrae
- basement membrane
- filtration slits of podocytes
- pores (fenestration) between the endothelial cells of glomerular capillary
- 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
what molecular weight can pass through pores of glomerular capillaries
- <70kDa
- +vely charged glycoproteins
(-vely charged glycoproteins repel anionic proteins)
- basement membrane (-vely charged)
- between glomerulus and Bowman’s capsule
- composed of -vely charged glycoproteins inc collagen (extracellular matrix proteins)
what does collagen do
provide structural strength
what do glycoproteins do
discourage filtration of small plasma proteins including smallest plasma protein albumin
how does the basement membrane act as an effective filter
-vely charged proteins repel -vely charged plasma proteins and hence plasma proteins are almost completely excluded from filtrate
- filtration slits between the foot process/pedicel of the podocyte cells
- 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
what is in the ultra-filtrate
- 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
what are mesangial cells
- 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
what is the glomerular filtration rate
volume of fluid entering Bowman’s capsule from blood flowing per unit time (mL/min)
what GFR influenced by
- filtration coefficient Kf
- net filtration pressure
what is GFR equation
GFR = Kf x net filtration pressure
*directly proportional
equation for filtration co-efficient, Kf
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
how does kidney disease reduce Kf
- reduces number of glomeruli and hence decreases SA
- increases thickness and hence decreases permeability of capillary membrane eg - hypertension, diabetes
what are the 4 forces which determine net filtration pressure
determined by physical forces (Starling forces - exist in all capillaries) which drive the movement of fluid between plasma and tubule
- Glomerular capillary hydrostatic pressure (PG)
- Plasma-colloid osmotic pressure (πG)
(sometimes called oncotic pressure) - Bowman’s capsule hydrostatic pressure (PB)
- Bowman’s capsule colloid osmotic pressure (πB)
what is the net filtration pressure
difference between forces favouring filtration and forces opposing filtration
(PG + πB) - (PB + πG)
glomerular capillary hydrostatic pressure (PG)
- 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
plasma-colloid osmotic pressure (πG)
- 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
Bowman’s capsule hydrostatic pressure (PB)
- this pressure pushes fluid out of the Bowman’s capsule into the glomerulus
Bowman’s capsule osmotic pressure (πB)
- has negligible influence on filtration
- would favour filtration but under normal conditions, it’s practically zero and ultrafiltrate is nearly protein free
what are the units of net filtration pressure
mmHg
how does the net filtration pressure act
forces large volumes of fluid from blood through the glomerular membrane due to the high net filtration pressure
why is there auto regulation of renal blood flow and GFR by the kidneys
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
what is renal function ‘protective’ against
- hypertensive irreversible renal damage (ie an increase in BP causing damage to nephrons’ capillaries)
- hypotensive ischaemia and necrosis of tubular segments (if too low)
why estimate GFR
- 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
what are the 3 methods used clinically to estimate GFR
- creatinine clearance
- Cockcroft and Gault formula for creatinine clearance
- eGFR: CKD-EPI formula or MDRD formula
what is clearance defined as
volume of plasma that is completely cleared of a substance by the kidneys per unit time
why is creatinine used to estimate GFR
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
what is creatinine produced from
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
does a person’s creatinine clearance change
no as long as their muscle mass doesn’t change it is relatively constant
what factors affect creatinine clearance
- skeletal muscle mass (more muscle more CC)
- age (less muscle as older and age >40, natural loss of 10% per 10 year)
signs of good kidney function with CrCl equation
- high urine creatinine
- low plasma creatinine
- high CrCl
what does the Cockcroft & Gault equation take into account
sex, age, weight of patient
signs of good kidney function with Cockcroft and Gault equation
- low serum creatinine
- high CrCl
when is Cockcroft & Gault equation the preferred method for estimating renal function
- elderly >75
- extremes of muscle mass: BMI <18 OR >40 (amputees, muscle builder)
what factors does Chronic kidney disease Epidemiology Collaboration (CKD-EPI) formula and Modification of diet in renal disease (MDRD) formula take into account
serum creatinine
sex
gender
ethnicity
units of eGFR
mL/min/1.73m2 (body SA of average sized person)
*not as accurate as people have gotten bigger in recent years
why is CKD-EPI used more
- more accurate for eGFR >
60ml/min/1.73m2 - MDRD overestimates eGFR for elderly
when should eGFR not be used
- children
- malnourished patients
- in pregnancy
- in oedema
- extremes of muscle mass (e.g. amputee, body builder, muscle-wasting disease)
- acute kidney injury
what is ACR
- urinary albumin:creatinine ratio
- with poor kidney function there is high urine albumin, low urine creatine and hence a high air
what GFR and ACR is associated with an increased risk of adverse outcomes like CV risks, stroke, ESKD
decreased GFR and increased ACR
issues with the formula regarding sex
- transgender person
- use ‘at birth’ sex assignment
uses with formula regarding race/ethnicity
- 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
