Renal physiology Alfred Saturday Flashcards
Which part of the nephron is hugged by the afferent and efferent arterioles?
Thick ascending limb of Henle’s loop/Distal convoluted tubule
Which part of the kidney are the glomeruli in?
Cortex
(only 15-20% of the nephron is at juxtamedullary)
Filtration fracture
- Ratio of GFR to renal plasma flow
- Approximately 0.2
- How much plasma arrives into tubules
- RBF is 1L/min (cardiac output is 5L/min)
- Only plasma is filtered so 550ml/min (assume haematocrit is 0.45)
- GFR is 550 x 0.2 = 110 mL/min
How does the filtration fraction change with reduction in systemic pressure
Increases because because GFR is reduced less than RPF to maintain GFR
What are the factors that impact on the GFR?
- Glomerular hydrostatic pressure
- Tubular hydrostatic pressure
- Glomerular oncotic pressure
Where are the biggests drops in hydrostatic pressure in the nephron?
Afferent then efferent arterioles
What is the gold standard for measurement of GFR?
Isotopic GFR (nuclear study)
What factors causes afferent arterial dilatation or efferent arterial constriction
- Prostaglandins
- Kinins
- Dopamine (low dose)
- ANP
- NO
Of note, angio II causes afferent AND efferent arteriole constriction but greater effect on efferent than afferent
What factors causes constriction of the afferent arteriole
- Angio II (high dose)
- Adenosine
- Noradrenaline
- Endothelim
- Vasopressin
Of note, prostaglandin blockage (e.g. NSAIDs) will cause afferent constriction, dropping the GFR
What are the targets of angiotension and the MOA?
AT1
- Vasoconstriction
- Sympathetic activation
- Sodium and fluid retention
AT2
- Vasodilatation
- Inhibition of cell growth
- Apoptosis
AT1 has predominant action (target of ARBs)
What cells secrete renin?
Juxtaglomerular granular cells in the afferent (and less so efferent) arterioles
TGF feedback with sodium
- Volume expansion increases sodium and chloride in the macular densa
- That causes the nephron cells to release adenosine (through increased ATP production) and leads to vasoconstrivtion, renin suppression and increase in naturetic peptides
- Where is angiotensinogen produced?
- Where is angiotensin I converted to angiotensin II
- What stimulates production of renin?
- Liver
- Lung
- Hypotension
5 MOA of angiotensin II
- Increases sympathetic activity
- Increases Na+ reabsorption
- Increases aldosterone secretion
- Powerful vasoconstriction (except heart and brain)
- ADH secretion (posterior pituitary)
What are the 3 stimuli of aldosterone production?
- RAAS system
- ACTH
- Hyperkalaemia
Of note, anything that increases glucocorticoid production will increase aldosterone productionz
In tubular cells, which sides are the basolateral and apical membrane?
Apical membrane = urine side (brush side)
Basolateral = blood side
What are the differences between channels and transporters
Channels are always to facilitate diffusion, not ATP-driven. (E.g. aquaporin)
Transporters can be ATP dependent. The conformation of the protein changes to transport the materials. (e.g. Na+/K+ ATPase)
What are examples of primary active and secondary active transporters in the kidney?
Primary active = coupled directly to an energy source (e.g. Na+/K+ ATPase)
Secondary active = coupled indirectly to an energy source (e.g. Na+/glucose transporter that relies on the negative gradient intracellularly made by the Na+/K+ ATPase that drives Na+ through the basolateral membrane)
- Where is sodium not permeable in the nephron?
- Where is water not permeable in the nephron?
- Descending thin limb of the loop of Henle
- Ascending thin and thick limbs of loop of Henko; Distal convoluted tubules
What kind of receptors are ADH receptors and where are they located?
G-protein coupled receptor
Basolateral side of cell
Collecting duct
What are the transporters involved in sodium reabsorption in the nephron?
Proximal tubule
- Basolateral side
- 3Na+/2K+ATPase
- Apical side
- Na+/glucose (organics also including vitamins)
- Na+/K+
- Paracellular
Thick ascending limb
- Basolateral side
- 3Na+/2K+ ATPase
- Apical side
- Na+/2Cl-/K+ (Barter’s syndrome imacts on this channel, frusemide blocks this)
- These transports relies on K+ and Cl- channels
Distal tubule
- Basolateral
- 3Na+/2K+ ATPase
- 3Na+/Ca++
- Apical
- Na+/Cl- (blocked by Thiazide, which increases action of 2Na+/Ca++ to compensate and causes hypercalcaemia)
Convoluted tubule
- Basolateral
- 3Na+/2K+ ATPase
- HCO3-/Cl- (intercalated cell)
- Apical
- H+ ATPase (intercalated cell)
- H+/K+ ATPase (intercalated cell)
What is the main difference in function between the cortical collecting duct and medullary collecting duct?
Medullary collect duct is permeable to urea
Function of intercalated cells in the distal tubules
What part of the nephron has the greatest impact on the change in osmality of the luminal urine?
Ascending limb of Henle (because it is not permeable to water)
Where is potassium regulated in the kidney?
Mainly freely filtered in the glomerulus
Site of regulation is cortical collecting duct by aldosterone (where K+ is secreted)
How does the acid base state affect ionization of calcium
There is increased protein binding of calcium in alkalotic states because the amino acids are anions (neg charged) in alkalosis and binds to the positively charged calcium.
This also affects the reabsorption of calcium
Where is the site of action of PTH for reabsorption of calcium?
Ascending limb of loop of Henle and distal tubules
The reabsorption of calcium in the proximal tubule is passive (60-70% is reabsorbed there)
MOA of FGF23
Fibroblast growth factor 23 - role in phosphate and vit D metabolism
Secreted in response to elevated calcitriol
Increase in FGF 23:
- decreases the reabsorption and increases excretion of phosphate (proximal tubule)
- suppress 1-alpha-hydroxylase, reducing its ability to activate vitamin D and subsequently impairing calcium absorption
Assoc with mortality in CVS disease
Where is magnesium mainly reabsorbed?
Distally/loop
Why does hypomag lead to hypokalaemia
low Mg stimulates ROMK (renal outer medullary potassium channel) leading to increased K+ excretion
Bartter’s syndrome
- transported affected
- what drug overdose does it mimic
- what is the clinical outcome
- Either directly or indirectly affected K+/2Cl-/Na+ on apical side
- Type 3 most common in adults actually inhibits the basolateral Cl channel
- Type 5 is Gain of function in CaSR, inhibiting the entry of positive changes at the apical side through the ROMK channel and therefore reduces the NKCCT activity
- Frusemide overdose
- Hypokalaemia, hypercalciuria (or normal), metabolic alkalosis
Of note, the differentiating factor between Bartter and Gittelman is that Gittelman has hypocalciuria
Bartter’s is caused by aminoglycosides
What is the treatment of Bartter and Gitelman?
- NSAIDs to inhibit prostaglandins
- Spironolactine or amiloride to block Na/K distal tubule exchange
- ACE inhibitors
- K+, Mg supplements
Liddle’s:
- Inheritance
- Clinical features
- Treatment
- Autosomal domninant
- EnaC function increased, similar findings as in mineralcorticoid excess
- hypertension, hypokalaemia, metabolic alkalosis
- Ameliroride (spironolactone wont work due to aldosterone resistance)
What substances affect osmolality but not tonicity
Urea and ethanol
what inhibits release of antidiuretic hormone?
Alcohol
What is the urine osmolality in suppressed ADH?
Should be <100 mosmol/kg
how is urine osmolality affected in advanced CKD
eGFR <15 mL/min
the minimal urine osmol rises to 200-250mosm/kg
However, the serum osmolality may stay norma due to high urea, which does not have tonicity and the patient is still susceptible to fluid shifts
How does thiazides cause hyponatraemia
Inhibits Na+/Cl- transported on apical membrane in the distal convoluted tubule
Causes decreased Na+ reabsorption but not water
Can mimic SIADH
MOA of cerebral salt wasting
Due to dehydration through inappropriate Na wasting in the urine (following neurosurgery/SAH etc)
ADH is increased in compensation -> hyponatraemia
Fluid state is main differentiator with SIADH
Treatment is to treat the dehydration - N/Saline or 3% HSaline
What is the pH range of urine?
4.5 - 8
Where is bicarbonate mainly reabsorbed?
Proximal tubules
Where is H+ mainly secreted?
Distal convoluted tubule
(requires the production of ammonia to buffer the tubular fluid ammonia)
What is the strong ion difference
Strong ions are cations and anions which are disassociated completely
strong cations are: Na+, K+, Ca2+, Mg2+
strong anions are: Cl- and SO42-
The difference is ~40 and is predominantly made up by HCO3-
What is the mechanism of hyperchloraemic acidosis with N/Saline administration?
The normaly extracellular Na+:Cl- is 140:100
With increase in Cl-, HCO3- is reduced to maintain electrical neutrality and results in a metabolic hyperchloraemic acidosis
How does albumin affect the anion gap?
Albumin is an anion
so an fall in albumin will underestimate the anion gap and mask the presence of an exogenous acid
Fall of 10g/L of albumin from baseline of 40 will reduce the calculated anion gap by 2.5
Causes of normal anion gap acidosis
- Normal saline infusion - strong ion explanation see previous flashcard
- Through hyperchloraemia and compensation with decrease in HCO3-
- GI loss
- Diarrhoea, small bowel fistulae/drainage, ileal conduits
- Through loss of electrolytes
- Renal causes
- RTA
- Through impaired renal HCO3- and impaired renal acid secretion
Diarrhoea can cause acidosis OR alkalosis depending on the ratio of electrolyte loss
Types of RTA and causes
- Proximal RTA (Type 2)
- Defect in HCO3 reabsorption
- Causes
- Congenital (Fanconi, Wilson’s disease)
- Carbonic anhydrase inhibitor)
- Paraprotinaemia)
- Distal RTA (Type 1)
- H+ secretion issue
- Cannot acidify the urine, urine pH always >5.5
- Can lead to nephrocalcinosis and other complications of hypocalcaemia
- Causes
- Hyperglobulinaemia
- SLE
- Lithium, amphotericin
- Hyperkalaemic distal RTA (Type 4)
- Hyperkalaemia is main issue. This suppresses production of ammonia and suppresses secretion of H+
- Norallly ilk acidosis
- Causes
- Hypoaldosteronism (most common cause is diabetes)
- Renal transplant rejection
- ACEI
- Heparin (toxic effect on zona glomerulosa)
- Primary adrenal insufficiency
- Gordon’s syndrome
- Aldosterone resistance
Treatment of metabolic alkalosis in vomiting
- Give normal saline
- This is because alkalosis is driven by hypovolaemia
- INcreases proximal Ha+/HCO3- reabsorption
- INcreases aldosterone leading to more H+ excretion
Why does urine sodium fluctuate in hypovolaemia metabolic alkalosis due to vomiting/NG drainage?
The loss of HCO3- in urine can also increase the Na+ in the urine
This is only in extreme cases
In the cases of alkalotic urine, the urine chloride can be used
