GFR And Filtration Flashcards
Functions of the kidney
Regulation - controls concentrations of key substances in ECf
Excretion
Endocrine - synthesis: renin, erythropoietin, prostaglandins
Metabolism - active form of VD, catabolism of insulin, PTH calcitonin
How much fluid is filtered per day and what do the kidneys recover and how much fluid do they excrete?
180L/ day (filtered over ten times)
-> 99% reabsorbed (water, Na, Cl)
100% reabsorbed (bicarbonate, glucose, amino acids)
- > waste excreted (H+ lose more)
1. 5 L/ day of urine
Breakdown of fluid contributions in 70kg man
70kg man -> 60% is fluid -> 1/3rd is ECF -> 3.5 litres is intravascular plasma (+ ICF 2L RBCs makes 5.5L circulating volume) And 10.5L (75% is interstitial water)
Electrolyte compositions of intra and extra cellular fluids
Salty banana (intra cellular high K+ and low Na+, extracellular has high Na+ and low K+)
ICF- many large organic anions
ECF- main anion CL- and HCO3
Maintained by active transport, important for transport and electrical functions
Difference between osmolaLity and osmolaRity
OsmolaLity - Solute per kilogram of solvent
OsmomlaRity- osmoles of solute per litRe
Drives move to of water, all ions and many organic molecules
Measured in milli-osmoles
Normal GFR
Unique to everybody but roughly 140-180 L/ day
What is filtration fraction and how do you calculate it?
Proportion of fluid reaching the kidneys that passes into the renal tubules (20%)
GFR/ RPF (renal plasma flow- normally 800mL/ min)
Which nephrons take part in autoregulation?
Cortical
Are up 90% of nephrons, shorter LOH just into medulla near cortex -> peritubular capillary, high renin conc
Differences in relative concentrations between plasma and ultra-filtrate?
Same concentrations but ultra-filtrate has no RbCs, WBCs or plasma proteins
Location of macula densa cells
Side of DCT closer to glomerulus, cells with bigger nuclei, afferent and efferent arterioles fork over so can communicate (part of juxta-glomerular apparatus)
What makes up the filtration barrier of the nephron?
Capillary glomerulus
fenestrated capillary endothelium
Bowman’s space
Acellular gelatinous glycoprotein layer (negatively charged) ‘basement membrane’ space
Podocytes with feet which wrap around loop of capillary (and basement membrane) with filtration splits between feet
What’s the biggest molecule that can get through the filtration barrier, how big is it?
Inulin- 5200 Mr
Hb and serum albumin are too big
What’s the affect of charge on permeability to the barrier? what happens if this fails?
Glycoproteins in basement membrane are negatively charged so repel other negative molecules (mostly proteins) so if positively charge can be a bit bigger and still get through
Some disease processes of nephrotoxic nephritis the negative charge on the filtration barrier is lost -> proteinuria
What pressures act between the glomerulus and the bowman’s capsule? What’s the net filtration pressure?
Hydrostatic pressure in the glomerular capillary (PGC) pushes water into BC (NET force)
Opposing:
- Oncotic pressure from oncotic proteins in capillaries pulls water into capillary
- hydrostatic pressure in bowman’s capsule pushes water into capillary
What are the four types of autoregulation of GFR?
1st line: Myogenic
1st line: Tubular glomerular feedback
Neural regulation
Glomerulotubular balance
Myogenic autoregulation of GFR
PGC and renal blood flow are directly proportional and have a linear relationship, able to maintain GFR when Bp between normal limits (80-180mmHg)
As renal arterial pressure increases: afferent arterioles constrict (allows less blood through) and efferent arterioles dilate (to make exiting the glomerulus the easier route)
Opposite if BP has decreased
Property of predominately preglomerular resistance vessels (arcuate, interlobular, afferent arterioles)
Tubuloglomerular feedback if GFR increases
Acts in response to acute perturbations in the delivery of fluid and solutes to the fixation-glomerular apparatus (granular cells)
Afferent arteriole resistance:
If GFR increase->
Macula densa cells have an increase of NaCl through NaKCC transporter (throughout DCT) ->
Increased production of ATP->
Move into interstitium (between MD and mesangial cells) through exit channels ->
ATP catabolised to AMP then adenosine by adenylate cyclase ->
Moves into (extraglomerular cells in afferent arteriole) mesangial cells through adenosine-1 receptor (GPCR) ->
Gi inhibits AC and Go increases intracellular Ca->
Ca moves through gap junctions yo smooth muscles cells of AA->
Vasoconstriction ->
Reduces PGC/ GFR/ conc of NaCl
Tubuloglomerular feedback if GFR decreases. What can impair this mechanism?
Efferent arteriole feedback (hormonal)
Prostaglandins released from macula densa cells -> vasodilation of afferent arteriole -> increased plasma entering -> increase GFR
NSAIDS inhibit prostaglandins so always check kidney function before prescribing/ check meds if suspect kidney problem
What can happen if the tubuloglomerular feedback fails to maintain GFR? What medication do you have to be cautious of prescribing in these cases?
Maintenance of GFR when Renal perfusion is low (e.g. bilateral renal artery stenosis, volume depletion and elderly patients with chronic heart failure)
Angiotensin 2 causes vasoconstriction of efferent arteriole
Can block effects with ACE- inhibitors and ARBs which will lead to acute renal failure in these cases
Neural regulation of GFR
Sympathetic nerve fibres innervation afferent and efferent arterioles
Normally innervation is low but during fight or flight/ ischaemia or severe haemorrhage Renal vessels are stimulated
Vasoconstriction of AA occurs to preserve blood volume and can decrease GFR
Parasympathetic innervation leads to release of NO for endothelial cells and causes vasodilation
What’s the last line of defence for maintenance of GFR?
Glomerulotubular balance
The PCTwill always reabsorbed 67% of filtered substances - prevents GFR changing too much
Can regulate GFR if Bp fluctuates
