Renal - function, anatomy and blood flow

Question 1

Classify and summarise the function of the kidney

Answer 1

BLOOD COMPOSITION HOMEOSTASIS

1. Volume and osmolarity
2. Electrolyte balance
3. Acid-base
4. Removal of waste and drugs
5. Gluconeogenesis

ENDOCRINE

1. EPO
2. VIT D
3. Renin

Question 2

What kind of endothelium do the capillaries within the glomerulus have and why

Answer 2

Fenestrated endothelium to allow free filtration of fluid, solutes and small proteins. Albumin and blood cells are too large to be filtered.

Question 3

What makes up the basement membrane of the glomerulus

Answer 3

1. Type 4 collagen
2. Laminins
3. Heparan sulphate

Question 4

What are podocytes

Answer 4

Podocytes are negatively charged foot like processes that control the passage of certain substances into the bowman’s capsule

Question 5

Where are mesangial cells found and what is their function

Answer 5

In the glomerulus between the capillary loops

FUNCTION
(Cells of smooth muscle origin)
1. Contractile function —> role in regulation of filtration 
2. Structural support
3. Phagocytosis

Question 6

How is glomerular filtration pressure modified

Answer 6

By varying the relative resistance of the afferent and efferent arteriole of the glomerulus

Question 7

What are the vasa recta?

Answer 7

Additional set of arterioles that arise from the efferent arteriole. Their role is to supply blood to the renal medulla.

Special feature: The vasa recta descend with the ascending loop of Henle and ascend with the descending loop of Henle creating a counter-current arrangement,

The counter-current arrangement is required to generate the high solute concentration gradients of the renal medulla

Question 8

Why is the blood supply to the renal medulla relatively poor compared to the renal cortex

Answer 8

This is required to prevent washout of solutes from the medullary interstitium, which are required for water reabsorption

Question 9

What are the components of the juxtaglomerular apparatus. What is the basic function of each component

Answer 9

The DCT folds back to lie anatomically very close to its corresponding glomerulus. Its components include:

1. Granular cells –> located in wall of afferent arteriole –> secrete renin
2. Macula densa cells –> located at junction of DCT and thick ascending LOH –> sense tubular Na+ and CL- concentration
3. Extra-glomerular mesangial cells

The juxtaglomerular apparatus regulates RBF and the GFR.

Question 10

Describe renal blood flow in terms of % of CO and the relative flow to the cortex and the medulla

Answer 10

Kidneys make up 1% of body mass
Kidneys receive 20% cardiac output

Renal cortex: 500ml / 100g tissue per minute
Outer renal medulla: 100 ml / 100g tissue per minute
Inner renal medulla: 20 ml / 100g tissue per minute

Question 11

What happens if RBF is too high

Answer 11

End organ damage due to high pressure

Reduced time for reabsorption processes to occur –> pressure diuresis

Question 12

What happens when RBF is too low

Answer 12

Ischaemia, especially to:

1. Poorly vascularised medulla
2. Metabolically active PCTs
3. Toxic metabolite build up

Question 13

How is RBF maintained

Answer 13

Renal Autoregulation: RBF is kept constant over a range of ‘normal perfusion pressures: MAP 75 –> 165 mmHg

Question 14

What are the mechanisms of autoregulation

Answer 14

MYOGENIC
Increased afferent arteriole pressure –> increased afferent arteriole stretch –> mechanically gated non-specific cation channels open –> depolarization of arteriolar membrane –> smooth muscle contraction –> reduced vessel diameter –> increased resistance but constant flow.

TUBULOGLOMERULAR FEEDBACK
Increased RBF –> increased GFR –> increased filtration Na and Cl –> sensed by macula densa Na+/K+/2Cl- cotransporter –> Increased movement of Na, Cl- and H2O into macula densa cells –> swelling in proportion to GFR –> Adenosine based second messenger released in proportion to the swelling –> Adenosine 1 receptors JGA –>

1. Afferent arteriole vasoconstriction
2. Glomerular mesangial cell contraction (reduces surface area for filtration –> reduces GFR)
3. Granular cells inhibited from secreting renin.

Question 15

Summarise the tubuloglomerular feedback and myogenic mechanisms of autoregulation

Answer 15

Myogenic
afferent arteriolar stretch –> smooth muscle contraction –> afferent arteriolar vasoconstriction

Tubuloglomerular feedback
Increased RBF –> increased NaCl delivery to macula densa –> adenosine-based second messenger released –>

1. Afferent arteriolar vasoconstriction
2. Glomerular mesangial cell contraction (reduced surface area for filtration)
3. Granular cell inhibition and renin release inhibited

The opposite occurs if RBF decreases.

Question 16

List the triggers for release of renin from granular cells

Answer 16

1. Decreased tubular NaCl delivery –> adenosine based second messenger –> granular cell renin release
2. Low afferent arteriolar pressure –> directly stimulates granular cells to release renin
3. SNS stimulation via B1 receptors

Summary

1. Reduced NaCl to macula densa
2. Low afferent arteriolar pressure
3. SNS B1

Question 17

What is the effect of renin

Answer 17

It cleaves angiotensinogen (made in the liver) into Angiotensin 1. ANG 1 is converted in the lungs by ACE into ANG 2 –> ANG 2 has multiple affects

Question 18

What is the rate-determining step in the renin-angiotensin-aldosterone axis

Answer 18

The cleaving of angiotensinogen, by renin, into ANG 1

Question 19

List the effects of angiotensin 2

Answer 19

1. Kidney
   - VC of efferent»_space; afferent (but VC of both)
2. Systemic vaculature
   - Increased: vasoconstriction and venoconstriction
3. Adrenal gland
   - Adrenal cortex - Zona glomerulosa –> increased aldosterone secretion –> volume expansion
4. Brain
   - Increases thirst
   - Increases ADH secretion
5. SNS
   - Increases noradrenalin release at SNS neurons –> arteriolar vasoconstriction

Question 20

How are eicosanoids involved in the regulation of renal blood flow?

Answer 20

In situations where concentrations of circulating vasopressors noradrenalin and angiotensin II are persistently high (including haemorrhage and sepsis), prolonged afferent and efferent arteriolar vasoconstriction causes a significant reduction in RBF.

Vasodilatory prostaglandins: PGE2 and PGI2 –> oppose the effects of circulating vasoconstrictors are produced locally within the kidney in an attempt to increase GFR and RBF and GFR.

Patients who take NSAIDS are less able to utilize this safety mechanism as COX is inhibited by NSAIDS which inhibits the synthesis of these protective prostaglandins

Question 21

Define acute kidney injury

Answer 21

Rapid (<48 hours) reduction in kidney function as determined by a rise in serum creatinine or a reduction in urine output

Question 22

Classify and describe the causes of acute kidney injury

Answer 22

PRE-RENAL

• hypovolaemia/hypotension–> fall in GFR
• Reversible as glomerular and tubular function remain intact

INTRINSIC RENAL
- Prolonged pre-renal iscahemia / cytotoxic / inflammatory insults –> structural damage to glomerulus/tubules (not immediately reversible once causative factors removed)

POST-RENAL
- Obstruction to the flow of urine –> raised tubular pressure –> decreases glomerular filtration pressure –> reduced GFR

Question 23

Classify the causes of intrinsic renal failure

Answer 23

1. Acute tubular necrosis
   - most common cause intrinsic renal disease
   - high BMR plus relatively poor blood supply (vs. glomerulus) –> vulnerable to ischaemia
   - Prolonged hypoperfusion / tubular toxins: myoglobin, aminoglycosides
2. Glomerular inflammation of the:
   - podocytes = minimal change disease
   - basement membrane = goodpasture’s disease
   - mesangial cells = IgA nephropathy
   - glomerular capillaries = Ag-Ab complex deposition in SLE and RA

Question 24

What should be the characteristics of the substance used to calculate renal blood flow. What is this substance and how is renal blood flow calculated

Answer 24

Substance should be 100% filtered and secreted into the tubule so that all the substance entering the renal arteries passes into the urine.

Para-amino hippuric acid (PAH)

Renal plasma flow = Clearance of PAH

Clearance of PAH and therefore RPF

= Volume urine per minute x [PAH]urine
______________________________
[PAH]plasma

And

RBF = RPF
________________
1 - haematocrit

Question 25

How else can renal blood flow be calculated (apart from urinary clearance of PAH)

Answer 25

Renal artery and renal vein sampling for PAH --> apply the Fick principle

Question 26

What is the basis of the Fick principle

Answer 26

That the consumption of a substance from blood should equal the difference between the arterial and venous contents for this substance CO = oxygen consumption / A - V content O2