Renal - function, anatomy and blood flow Flashcards
Classify and summarise the function of the kidney
BLOOD COMPOSITION HOMEOSTASIS
- Volume and osmolarity
- Electrolyte balance
- Acid-base
- Removal of waste and drugs
- Gluconeogenesis
ENDOCRINE
- EPO
- VIT D
- Renin
What kind of endothelium do the capillaries within the glomerulus have and why
Fenestrated endothelium to allow free filtration of fluid, solutes and small proteins. Albumin and blood cells are too large to be filtered.
What makes up the basement membrane of the glomerulus
- Type 4 collagen
- Laminins
- Heparan sulphate
What are podocytes
Podocytes are negatively charged foot like processes that control the passage of certain substances into the bowman’s capsule
Where are mesangial cells found and what is their function
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
How is glomerular filtration pressure modified
By varying the relative resistance of the afferent and efferent arteriole of the glomerulus
What are the vasa recta?
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
Why is the blood supply to the renal medulla relatively poor compared to the renal cortex
This is required to prevent washout of solutes from the medullary interstitium, which are required for water reabsorption
What are the components of the juxtaglomerular apparatus. What is the basic function of each component
The DCT folds back to lie anatomically very close to its corresponding glomerulus. Its components include:
- Granular cells –> located in wall of afferent arteriole –> secrete renin
- Macula densa cells –> located at junction of DCT and thick ascending LOH –> sense tubular Na+ and CL- concentration
- Extra-glomerular mesangial cells
The juxtaglomerular apparatus regulates RBF and the GFR.
Describe renal blood flow in terms of % of CO and the relative flow to the cortex and the medulla
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
What happens if RBF is too high
End organ damage due to high pressure
Reduced time for reabsorption processes to occur –> pressure diuresis
What happens when RBF is too low
Ischaemia, especially to:
- Poorly vascularised medulla
- Metabolically active PCTs
- Toxic metabolite build up
How is RBF maintained
Renal Autoregulation: RBF is kept constant over a range of ‘normal perfusion pressures: MAP 75 –> 165 mmHg
What are the mechanisms of autoregulation
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 –>
- Afferent arteriole vasoconstriction
- Glomerular mesangial cell contraction (reduces surface area for filtration –> reduces GFR)
- Granular cells inhibited from secreting renin.
Summarise the tubuloglomerular feedback and myogenic mechanisms of autoregulation
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 –>
- Afferent arteriolar vasoconstriction
- Glomerular mesangial cell contraction (reduced surface area for filtration)
- Granular cell inhibition and renin release inhibited
The opposite occurs if RBF decreases.
List the triggers for release of renin from granular cells
- Decreased tubular NaCl delivery –> adenosine based second messenger –> granular cell renin release
- Low afferent arteriolar pressure –> directly stimulates granular cells to release renin
- SNS stimulation via B1 receptors
Summary
- Reduced NaCl to macula densa
- Low afferent arteriolar pressure
- SNS B1
What is the effect of renin
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
What is the rate-determining step in the renin-angiotensin-aldosterone axis
The cleaving of angiotensinogen, by renin, into ANG 1
List the effects of angiotensin 2
- Kidney
- VC of efferent»_space; afferent (but VC of both) - Systemic vaculature
- Increased: vasoconstriction and venoconstriction - Adrenal gland
- Adrenal cortex - Zona glomerulosa –> increased aldosterone secretion –> volume expansion - Brain
- Increases thirst
- Increases ADH secretion - SNS
- Increases noradrenalin release at SNS neurons –> arteriolar vasoconstriction
How are eicosanoids involved in the regulation of renal blood flow?
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
Define acute kidney injury
Rapid (<48 hours) reduction in kidney function as determined by a rise in serum creatinine or a reduction in urine output
Classify and describe the causes of acute kidney injury
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
Classify the causes of intrinsic renal failure
- 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 - 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
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
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
How else can renal blood flow be calculated (apart from urinary clearance of PAH)
Renal artery and renal vein sampling for PAH –> apply the Fick principle
What is the basis of the Fick principle
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
