The Glomerulus Flashcards
Functions of the kidney
Removal of waste products
Removal of excess fluid
Balance salt, water and pH
Control of blood pressure
Red blood cell production
Maintenance of healthy bones
Removal of drugs from the body
What makes up the kidney?
Medulla
Cortex
Capsule- around the cortex
Nephron containing glomerulus and tube
Tubes come together to form medulla
The nephron
Consists of blood vessels that supply it, glomerulus, tubules
Contains 2 series of capillaries:
A capillary network that forms in the glomerulus
A capillary network that forms around the tubules and the vasa recta (this removes chemicals and moving water)
Nephron has a lot of diffusion and active processes
The nephron
Image
Kidney blood flow
Cardiac output is approx 5L/min
20% cardiac output passes through the kidneys
Renal blood flow is approx 1L/min
Large amount of cardiac output goes to kidneys as kidney processes are mistily active and so require a lot of energy
Urine flow is approx 1ml/min
Blood supply
1) abdominal aorta
2) renal artery
3) interlobar artery
4) arcuate artery
5) interlobular artery
6) afferent arteriole
7) glomerular capillary
8) efferent arteriole
9) peritubular capillaries
20) vasa recta
21) interlobular veins
22) arcuate veins
23) interlobar veins
24) renal vein
25) IVC
The glomerulus
Glomerulus is where all the exchange happens/ filtration
Afferent arteriole brings blood into glomerulus
Efferent arteriole takes blood out of glomerulus (exit)
Large surface area
Juxtagloerular apparatus
Located in the Hillum of every glomerulus
Juxtaglomerular cells and macula densa
Modified muscular layer of the afferent arteriole
Increased number of smooth muscle cells
Thicker cells
Less Actin/myosin but many granules containing renin (enzyme controls BP)
Cells act as barometers to change in BP
Low BP leads to less distended walls which leads to renin release
Auto regulation is intrinsic
maintains constant GFR and excretion of water and water products
If this system wasn’t in place, a drop or increase in GFR would lead to a change in filtration of chemicals- either filtering too much or too less out
This means if you take the kidney out of the body it would still be doing these functions
Two mechanisms
Tubuloglomerular feedback
Myogenic mechanism
Tubuloglomerular feedback
An increase in BP (can work in other way)
Causes an increase in blood flow to glomerulus and an increase in capillary pressure
This causes an increase in glomeular filtration rate (this means filtering more of these chemicals out
This results in more delivery of NaCl to macula densa
This triggers the afferent arterioles to constrict in order to balance this out
Renin- angiotensin- aldosterone system
Firstly, the kidney detects a fall in ECF volume because there’s a decrease in renal perfusion pressure
This acts on the juxtaglomerular apparatus causing the release of renin into the system
Renin now acts on a protein called angiotensinogen which is the precursor to angiotensin I. Renin cleaves angiotensinogen into angiotensin I
angiotensin I is now converted into angiotensin II by a protein called ACE (angiotensin converting enzyme). This conversion occurs in the lungs as that is where ACE is produced
Angiotensin II increases sympathetic activity in the sympathetic nervous system
Angiotensin II also causes arteriolar vasoconstriction so increase in BP
Adrenal gland detects the angiotensin II and secretes aldosterone
Aldosterone acts on the distal tubes of the kidneys and so it changes the re absorption of potassium and sodium and water retention (increase in water retention). Na and Cl reabsorption, K excretion and water reabsorption. This changes the effect in circulating volume
Aldosterone can also act in another way- ADH secretion again by the pituitary gland so there is more absorption of through the collecting ducts of the kidneys and there will also be a system wide arterial vasoconstriction which will increase the blood pressure as well. This changes circulating volume
Process repeats again
Myogenic reflex
An increase in BP causes a stretch in the blood vessel wall
This opens the stretch activated cation channels which causes membrane depolarisation
This opens up voltage dependant calcium channels which causes an increase in intracellular calcium
This leads to smooth muscle contraction and so an increase in vascular resistance and minimises changes in GFR
A decrease in BP causes opposite to occur
This only affects the pre-glomerular resistance vessels
So post-glomerular resistance vessels do not have these voltage gated channels
The filtration barrier
This is the passage of fluid from the blood into the Bowman’s space to form filtrate
Distal part of the nephron (tubule) responsible for secretion and reabsorption, allowing chemicals to go back and forth
3 components of filtration barrier
Podocytes (visceral epithelium)
These have filtration slits between them
Have slit diaphragm between them
Glomerular basement membrane
Fenestrated capillary endothelium
Factors determining filtration
Pressure
Size of molecule
Charge
Rate of blood flow
Protein binding
1) Pressure
Favours filtration:
Glomerular capillary blood pressure
Opposes filtration:
Fluid pressure in bowmnan’s space
Osmotic forces due to protein in plasma
2) Size
Small molecules and ions up to 10kDa can pass freely
E.g. glucose, Uric acid, potassium, creatinine
Larger molecules increasingly restricted
E.g. plasma proteins (albumin)
3) Charge
Fixed negative charge in GBM (glycoproteins) repels negatively charged anions
4) Rate of blood flow
In the afferent the GFR, filtration rate, is higher when theres a lower flow.
This is because theres less blood being taken away before getting to the glomerulus- if its going really fast theres not enough time for molecules to diffuse across the barrier
The efferent is similar but in the reverse
So if theres a really fast flow in the efferent, which is pulling substances away, there isn’t enough time for everything to reach here
5) Protein binding
Albumin has a molecular weight of around 66kDa but is negatively charged therefore cannot easily pass into the tubule
Filtered fluid is essentially protein-free
Tamm Horsfall protein in urine produced by tubule
Affects drugs that can bind to proteins, calcium, thyroxine etc.
Glomerular filtration rate
Glomerular filtration rate= filtration volume per unit time (minutes)
Equation on slide
Kf is the filtration coefficient
Net filtration is normally always positive
GFR determined by
1) Net filtration pressure
2) Permeability of the filtration barrier
3) Surface area available for filtration (approx 1.2-1.5 m2 total)
Regulation of GFR
1) Sympathetic nervous system
2) Hormones/Autocoids (hormones working on a local level)
Sympathetic nervous system
Afferents (and efferent) arterioles receive sympathetic innervation
Strong sympathetic stimulus causes constriction of afferent arteriole which reduces the renal blood flow and so reduces GFR
Important in bleeding, shock, ischaemia and periods of illness
Hormones affecting GFR
Table on image
Increased GFR
Constrict efferent arteriole
Or dilate afferent arteriole
Decrease GFR
Constrict afferent arteriole
Dilate efferent arteriole
Renal clearance
GFR NOT MEASURED DIRECTLY
Calculated by measuring excretion of marker (M)
Equation on image
EGFR is estimated GFR
Creatinine is the marker used in EGFR
Properties of a good marker
Freely filtered (not instructed by the membrane)
Not secreted or absorbed
Not metabolised
Therefore all the Marker that is filtered will end up in the urine, no more (as it is not secreted) and no less (as it is not reabsorbed)
Normal GFR
125ml/min
Creatinine usually used
This is a muscle metabolite
Constant production
Freely filtered and not metabolised
However it is secreted- tubular secretion
Things affecting creatinine
Age/ gender/ ethnicity/ height/ weight
Renal tubular handling
Creatinine supplements
Medications
Dietary protein intake
Other marker that can be used: endogenous (found in body)- Cystatin C
Non glycosylated protein produced by all cells
Freely filtered but is reabsorbed and is metabolised
Influenced by thyroid disease, corticosteroids, age, sex and adipose tissue
Other marker that can be used: exogenous (found outside body)- Inulin
Gold standard- filtered freely, not absorbed or secreted and secreted
If really concerned then this is used
