GFR And Filtration

Question 1

Functions of the kidney

Answer 1

Regulation - controls concentrations of key substances in ECf

Excretion

Endocrine - synthesis: renin, erythropoietin, prostaglandins

Metabolism - active form of VD, catabolism of insulin, PTH calcitonin

Question 2

How much fluid is filtered per day and what do the kidneys recover and how much fluid do they excrete?

Answer 2

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

Question 3

Breakdown of fluid contributions in 70kg man

Answer 3

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)

Question 4

Electrolyte compositions of intra and extra cellular fluids

Answer 4

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

Question 5

Difference between osmolaLity and osmolaRity

Answer 5

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

Question 6

Normal GFR

Answer 6

Unique to everybody but roughly 140-180 L/ day

Question 7

What is filtration fraction and how do you calculate it?

Answer 7

Proportion of fluid reaching the kidneys that passes into the renal tubules (20%)

GFR/ RPF (renal plasma flow- normally 800mL/ min)

Question 8

Which nephrons take part in autoregulation?

Answer 8

Cortical

Are up 90% of nephrons, shorter LOH just into medulla near cortex -> peritubular capillary, high renin conc

Question 9

Differences in relative concentrations between plasma and ultra-filtrate?

Answer 9

Same concentrations but ultra-filtrate has no RbCs, WBCs or plasma proteins

Question 10

Location of macula densa cells

Answer 10

Side of DCT closer to glomerulus, cells with bigger nuclei, afferent and efferent arterioles fork over so can communicate (part of juxta-glomerular apparatus)

Question 11

What makes up the filtration barrier of the nephron?

Answer 11

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

Question 12

What’s the biggest molecule that can get through the filtration barrier, how big is it?

Answer 12

Inulin- 5200 Mr

Hb and serum albumin are too big

Question 13

What’s the affect of charge on permeability to the barrier? what happens if this fails?

Answer 13

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

Question 14

What pressures act between the glomerulus and the bowman’s capsule? What’s the net filtration pressure?

Answer 14

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

Question 15

What are the four types of autoregulation of GFR?

Answer 15

1st line: Myogenic

1st line: Tubular glomerular feedback

Neural regulation

Glomerulotubular balance

Question 16

Myogenic autoregulation of GFR

Answer 16

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)

Question 17

Tubuloglomerular feedback if GFR increases

Answer 17

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

Question 18

Tubuloglomerular feedback if GFR decreases. What can impair this mechanism?

Answer 18

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

Question 19

What can happen if the tubuloglomerular feedback fails to maintain GFR? What medication do you have to be cautious of prescribing in these cases?

Answer 19

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

Question 20

Neural regulation of GFR

Answer 20

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

Question 21

What’s the last line of defence for maintenance of GFR?

Answer 21

Glomerulotubular balance

The PCTwill always reabsorbed 67% of filtered substances - prevents GFR changing too much

Can regulate GFR if Bp fluctuates