eLFH - Renal Physiology Part 3

Question 1

Trigger for activation of Renin-Angiotensin-Aldosterone System (RAAS)

Answer 1

Fall in BP and thus fall in renal blood flow

Question 2

Overview of RAAS

Answer 2

Fall in BP detected by juxtaglomerular apparatus

Juxtaglomerular apparatus secretes renin

Renin stimulates conversion of angiotensinogen to angiotensin

Angiotensin causes vasoconstriction + Aldosterone secretion from adrenal cortex

Aldosterone causes Na+ and water reabsorption

Question 3

Juxtaglomerular apparatus structure and components

Answer 3

Macula Densa

Juxtaglomerular cells

Question 4

Macula Densa

Answer 4

Specialised epithelial cells

Increase renin release in response to low levels of delivered sodium due to fall in GFR or increase in proximal convoluted tubule reabsorption of Na+

Question 5

Location of Macula Densa

Answer 5

Wall of first part of distal convoluting tubule

Abuts the afferent and efferent arterioles

Question 6

Juxtaglomerular cells role

Answer 6

Secrete renin from granules

Question 7

Location of juxtaglomerular cells

Answer 7

Wall of afferent arteriole (in the media)

Just before arteriole enters the glomerulus

Question 8

Triggers for juxtaglomerular cells to secrete renin

Answer 8

Hypovolaemia

Increased sodium concentration in blood

Sympathetic stimulation

Question 9

Features of Renin

Answer 9

Glycoprotein hormone

Formed from pro-renin and pre-pro-renin

Question 10

Half life of renin

Answer 10

80 mins

Question 11

Control of renin secretion

Answer 11

Renal sympathetic nerves

Intrarenal baroreceptors

Angiotensin II

Question 12

Factors which increase renin secretion

Answer 12

Hypovolaemia
Cardiac failure
Cirrhosis
Renal artery stenosis
Catecholamines acting on beta 1 receptors

Question 13

Factors which decrease renin secretion

Answer 13

Angiotensin II
Vasopressin
Beta blockers

Question 14

Actions of renin

Answer 14

Cleaves Angiotensin I from Angiotensinogen

Angiotensin I converted to Angiotensin II by ACE in lungs / capillary endothelium

Angiotensin II converted to Angiotensin III in many tissues by aminopeptidase

Question 15

Actions of angiotensin II

Answer 15

Vasoconstrictor including afferent and efferent arterioles in kidney
Greater effect on efferent arteriole than afferent arteriole - increases GFR

Aldosterone release

Potentiates sympathetic activity

Release of ADH

Thirst by direct effect on hypothalamus

Stimulates Na+/H+ antiporters in proximal convoluting tubule to cause Na+ and water retention

Question 16

Triggers for aldosterone release from zona glomerulosa of adrenal cortex

Answer 16

Reduced renal blood flow via RAAS

Stress and trauma via ACTH release

Hyperkalaemia

Hyponatraemia

Question 17

Time of onset of aldosterone action and why

Answer 17

Hours

As works via protein synthesis

Question 18

Actions of aldosterone on distal convoluting tubules and collecting ducts

Answer 18

Increases sodium reabsorption and thus water reabsorption

Potassium and hydrogen ions are lost in exchange for Na+

Increases production of distal nephron transport mechanisms

Question 19

Site of ADH synthesis

Answer 19

Hypothalamus

Question 20

Site of ADH secretion

Answer 20

Posterior pituitary

Question 21

Factors which lead to ADH secretion

Answer 21

Baroreceptor and Osmoreceptor reflexes

Question 22

Inactivation site for ADH and half life

Answer 22

Inactivated in liver and kidney

Half life 18 mins

Question 23

Action of ADH on renal tubule

Answer 23

Inserts protein channels for water (aquaporins) into luminal membrane

Acts via cyclic AMP

Question 24

Action of ADH on arteriolar smooth muscle

Answer 24

At high concentrations of ADH, it causes arteriolar smooth muscle contraction

Reduces renal blood flow and GFR

Also increases MAP, hence use as second line vasopressor

Question 25

Role of ANP (atrial natriuretic peptide)

Answer 25

Secreted in response to atrial stretch Increases renal excretion of Na+ and water

Question 26

Mechanism of action of ANP

Answer 26

Afferent arteriolar dilatation and efferent arteriolar constriction - increases net filtration pressure and renal blood flow Inhibition of renin secretion and therefore inhibition of aldosterone release Direct action on collecting ducts to decrease sodium reabsorption

Question 27

Site of ANP release

Answer 27

Atrial myocytes

Question 28

Diagram with whole RAAS illustrated

Answer 28

Question 29

Glomerular filtration rate definition

Answer 29

Flow rate of filtered fluid through the kidneys

Question 30

Normal value for adult GFR

Answer 30

180 L/day aka 125 ml/min

Question 31

Renal Clearance definition

Answer 31

Volume of plasma completely cleared of that substance by the kidneys per unit time (ml/min)

Question 32

Use of clearance

Answer 32

Help quantify: - Excretory function of kidney - Rate of blood flow through kidneys - Basic functions of the kidneys Clearance of certain substances can be used to approximate GFR

Question 33

Clearance equation

Answer 33

Question 34

Substances used to measure GFR

Answer 34

Inulin Creatinine

Question 35

Features of Inulin including molecular weight

Answer 35

Polysaccharide Molecular weight 5200 Daltons

Question 36

Reasons Inulin is used to measure GFR

Answer 36

Freely filtered but not reabsorbed Not toxic, metabolised or protein bound - therefore rate of excretion is equal to filtration rate

Question 37

Issues with using inulin

Answer 37

Not endogenous and needs IV administration

Question 38

Features of creatinine

Answer 38

By product of muscle metabolism - therefore endogenous Almost entirely cleared by glomerular filtration Therefore creatinine clearance can estimate GFR

Question 39

Issues with using creatinine

Answer 39

Small amount is secreted Therefore amount of creatinine excreted slightly exceeds amount filtered Therefore overestimates GFR

Question 40

Renal plasma flow estimation

Answer 40

If a substance is completely cleared from the plasma, clearance of that substance should equal renal plasma flow GFR is only 20% of renal plasma flow

Question 41

Substance used to estimate renal plasma flow and why

Answer 41

Para-aminohippuric acid (PAH) It is 90% cleared by kidneys from plasma

Question 42

Renal plasma flow estimate equation

Answer 42

Question 43

Renal blood flow equation

Answer 43

Renal Blood flow = Renal Plasma flow / (1 - Haematocrit)