renal blood flow and glomerular filtration Flashcards
what is the functional unit of kidney?
nephron
avg length of a nephron
4cm
what are the 2 elements of a nephron?
glomerulus and tubule
how many nephrons per kidney?
1 million
can the kidney regenerate new nephrons?
no
how do the tubules along the nephron connect with the blood supply?
peritubular capillaries
what are the diff types of capillaries a nephron has?
peritubular and glomerular
glomerular capillaries come into close contact with what?
the nephron in the Bowman’s capsule
name the 2 stages of urine formation
- glomeruli produce the liquid
2. tubules modifies its volume & composition
where does the majority of fluid that is forced out into the Bowman’s capsule go?
majority of fluid is reabsorbed when it comes into contact with peritubular capillaries again.
what is the consequence if you don’t reabsorb fluid?
you may become volume depleted
- hypovolaemia
as the blood flows into the nephron, where does it go?
it flows in via the afferent arteriole, down into the glomerular capillaries which are situated in the bowman’s capsule and then flowing out again through the efferent arteriole
why do we have such a huge filtration rate?
you need a big filtration rate in order to flush out the waste products (which then go into our urine) to keep levels in the blood low
how is glomerular fluid formed?
passive ultrafiltration of plasma across the glomerular membrane
what is the glomerular filtration rate (GFR) set by?
(i) autoregulation:
(ii) renal sympathetic vasomotor nerve activity
what does the glomerulus consist of?
a clump of capillaries & Bowman’s capsule
small solutes (NaCl, glucose, urea) - concentration in glomerular fluid
the concentration in glomerular fluid = the concentration in plasma
plasma proteins - concentration in glomerular fluid
almost zero
Proteinuria
protein in the urine
-sign of renal/urinary tract disease
the glomerular membrane sieves out solutes from plasma based on what?
their molecular size
what drives glomerular fluid formation?
an imbalance of Starling’s forces
what 2 pressures act in the opposite direction to the high capillary pressure?
- colloid osmotic pressure exerted by proteins in the blood
- pressure in the Bowman’s space
but net filtration force pushes fluid out
what happens to blood pressure and plasma concentration as the blood flows through the capillary from the afferent end to the efferent end?
- there is a slight drop in pressure
- plasma gets more concentrated due to fluid loss
what happens to the plasma COP (colloid osmotic pressure) as the blood flows from the afferent to efferent end?
COP rises because fluid is lost from capillaries, hence the protein is getting more concentrated thereby exerting a greater force driving fluid back from the tubule into the peritubular capillary
podocytes and pedicels
invaginated epithelial layer of the bowman’s capsule which coats the outer surface of the capillaries
-pedicels are the foot processes of the epithelial cell
what are the gaps in between the foot processes/pedicels?
filtration slits
what can travel through the fenestrations
Anything that’s dissolved in water can easily travel through fenestra and basal lamina (a matrix of various proteins) as long as there is a suitable channel through these proteins
how are the filtration slits subdivided?
subdivided into much smaller slits (4nm wide) created by a cytoskeletal arrangement of proteins nephrin and podocin
why can’t albumin pass through the filtration slits?
it would but the slits are further sub divided into a ladder of much smaller slits, and albumin gets trapped here
how far can ferritin travel?
travel freely through the fenestra, but pile up at the basal lamina and they don’t enter through the filtration slips because of their size
how far does myeloperoxidase (albumin-size protein) travel?
held up at the filtration slits, none penetrates into the urinary space
describe the structure of the glomerular membrane
slide 15 and 20 diagrams
3 sieves in series of increasing fineness
- fenestrated capillaries
- basement membrane
- filtration slits of podocytes
why does proteinuria occur?
if the BM or the filtration slits are damaged
nephrotic syndrome
albumin getting through the layers into the bowmans capsule
how can GFR be controlled?
intrinsic or extrinsic control
explain what is meant by intrinsic control
- GFR is held constant (120ml/min)
- Important for capacity of tubules to reabsorb filtrate not be overwhelmed by excessive GFR
- the mechanism holding GFR constant is an internal one called ‘autoregulation’
are changes in urine production usually due to changes in GFR?
no, usually due to changes in tubular reabsorption
explain “auto regulation” further
GFR & renal blood flow are held constant over a range of arterial pressure
This is important because blood pressure drives GFR, and blood pressure changes throughout the day, meaning the GFR would change and fluid would be forced out, causing dehydration
So, the whole system is regulated to make sure the GFR remains constant throughout your normal day-to-day fluctuations in blood pressure
if there was no auto regulation what would happen?
a relatively small increase in bp (from 100-125mmHg) would cause a similar 25% increase in GFR
and, if tubular reabsorption remained constant then urine flow would increase by 30-fold, depleting blood volume very quickly
this is why when things happen to alter your blood pressure (persistent hypotension) this will start being deterimental
what are the 2 mechanisms responsible for keeping GFR and renal plasma flow constant?
Bayliss myogenic response
-direct vasoconstriction of afferent arteriole with increase in perfusion pressure
Tubuloglomerular feedback (TGF) -flow-dependent signal detected in macula densa that alters tone of afferent arteriole
which mechanisms responds to slower BP fluctuations, over intervals of 20 seconds or great?
tubuloglomerular feedback
Bayliss myogenic response
increase in perfusion pressure leads to an immediate increase in vessel radius (few seconds only), so blood flow goes up briefly
Bayliss observed that this resulting stretch of smooth muscle in the afferent arteriole quickly results in contraction and a reduction in diameter & increase in resistance - readjustment to an intermediate value within about 30s
explain the relevance of the bayliss myogenic response on kidney function
if we increase the pressure in the artery the afferent arteriole constricts and becomes very narrow, reducing the flow going into the glomerular capillaries and maintaining that pressure. If the pressure is maintained, the GFR will not change
what detect the stretch in the afferent arteriole?
myogenic stretch receptors in the wall of the afferent arteriole
when does auto regulation fail, and what happens as a result?
when you go below a certain pressure, e.g. in hypotension, shock and haemorrhage
results in olguria, which is failed urine output.
Myogenic
contraction that originatesfrom the cell itself and not from an external source
How does contraction of afferent arteriole regulate glomerular capillary pressure ?
the afferent arteriole drops pressure by constricting and therefore increasing the resistance, reducing the flow into the capillaries and maintaining the pressure in the capillaries so GFR doesn’t change
afferent arterioles are resistance vessels - what does this mean?
they alter resistance to maintain GFR in the capillaries
what comes back into contact with the afferent and efferent arterioles?
the distal convoluted tubule
what are juxtaglomerular cells?
modified smooth muscle cells in walls of afferent arteriole proximal to glomerulus – store inactive pro-renin
the areas is known as the macula dense
Tubulo-glomerular feedback (TGF)
- GFR increases
- flow through tubule increases, and flow past macula dense increases
- increase in [NaCl] and osmolarity in DCT, which is sensed by the macula densa
- paracrine/vasoactive agents diffuse from the macula dense to the afferent arteriole
- afferent arteriole constricts, increasing resistance
- hydrostatic pressure in the glomerulus decreases
- GFR decreases (restored)
- superimposed on this is the RAAS system
what can renal sympathetic nerves do?
reduce GFR by resetting autoregulation to a lower level (from 120 to 100)
in which 3 situations does resetting of autoregulation to a lower level via renal sympathetic nerves occur? why does this occur?
- standing upright (orthostasis)
- heavy exercise
- haemorrhage
- the role is to conserve body fluid volume during physical stress
- conserve blood loss and cardiac output (haemorrhage)
what can these sympathetic actions by aided by? (during shock)
circulating vasoconstrictor hormones such as adrenaline, angiotensin and vasopressin
Two major clinical disorders of the GFR
- Glomeruli too leaky to plasma protein: nephrotic syndrome (eg. Filtration slit disordered by nephrin deficiency)
- Proteinuria (because the glomerular basement membranes become damaged and more leaky. basement membranes becomes thicker, maybe due to deposition of immunoglobulins)
- Hypoproteinaemia
- Oedema
- GFR too low (more common)
chronic glomerulonephritis (infection) nonfunctioning glomeruli
When GFR < 30 ml/min, this is chronic renal failure.
why does nephrotic syndrome cause oedema?
loss of proteins from the plasma means oncotic pressure isn’t as high anymore, so fluid isn’t absorbed at the venous end of the capillaries
what usually happens to fluid at the venous end?
usually fluid is reabsorbed at the venous end because the oncotic pressure at this point is higher than the capillary pressure
what happens to any fluid left that isn’t reabsorbed at the venous end?
any fluid left enters the lymphatic system as tissue fluid
chronic glomerulonephritis appearance
fibrosed glomeruli, virtually no blood flow or red blood cells, so no glomerular filtrate produced
treatment for patient with chronic glomerulonephritis
- dietary restriction, renal dialysis
- or a renal transplant if match available
