The Glomerulus Flashcards

1
Q

Functions of the kidney

A

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

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2
Q

What makes up the kidney?

A

Medulla

Cortex

Capsule- around the cortex

Nephron containing glomerulus and tube

Tubes come together to form medulla

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3
Q

The nephron

A

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

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4
Q

The nephron

A

Image

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5
Q

Kidney blood flow

A

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

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6
Q

Blood supply

A

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

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7
Q

The glomerulus

A

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

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8
Q

Juxtagloerular apparatus

A

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

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9
Q

Auto regulation is intrinsic

A

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

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10
Q

Two mechanisms

A

Tubuloglomerular feedback

Myogenic mechanism

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11
Q

Tubuloglomerular feedback

A

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

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12
Q

Renin- angiotensin- aldosterone system

A

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

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13
Q

Myogenic reflex

A

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

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14
Q

The filtration barrier

A

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

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15
Q

3 components of filtration barrier

A

Podocytes (visceral epithelium)
These have filtration slits between them
Have slit diaphragm between them

Glomerular basement membrane

Fenestrated capillary endothelium

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16
Q

Factors determining filtration

A

Pressure

Size of molecule

Charge

Rate of blood flow

Protein binding

17
Q

1) Pressure

A

Favours filtration:
Glomerular capillary blood pressure

Opposes filtration:
Fluid pressure in bowmnan’s space
Osmotic forces due to protein in plasma

18
Q

2) Size

A

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)

19
Q

3) Charge

A

Fixed negative charge in GBM (glycoproteins) repels negatively charged anions

20
Q

4) Rate of blood flow

A

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

21
Q

5) Protein binding

A

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.

22
Q

Glomerular filtration rate

A

Glomerular filtration rate= filtration volume per unit time (minutes)
Equation on slide

Kf is the filtration coefficient

Net filtration is normally always positive

23
Q

GFR determined by

A

1) Net filtration pressure

2) Permeability of the filtration barrier

3) Surface area available for filtration (approx 1.2-1.5 m2 total)

24
Q

Regulation of GFR

A

1) Sympathetic nervous system

2) Hormones/Autocoids (hormones working on a local level)

25
Q

Sympathetic nervous system

A

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

26
Q

Hormones affecting GFR

A

Table on image

27
Q

Increased GFR

A

Constrict efferent arteriole

Or dilate afferent arteriole

28
Q

Decrease GFR

A

Constrict afferent arteriole

Dilate efferent arteriole

29
Q

Renal clearance

A

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

30
Q

Properties of a good marker

A

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)

31
Q

Normal GFR

A

125ml/min

Creatinine usually used
This is a muscle metabolite
Constant production

Freely filtered and not metabolised
However it is secreted- tubular secretion

32
Q

Things affecting creatinine

A

Age/ gender/ ethnicity/ height/ weight

Renal tubular handling

Creatinine supplements

Medications

Dietary protein intake

33
Q

Other marker that can be used: endogenous (found in body)- Cystatin C

A

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

34
Q

Other marker that can be used: exogenous (found outside body)- Inulin

A

Gold standard- filtered freely, not absorbed or secreted and secreted

If really concerned then this is used