Renal Macromolecules Flashcards
What does the glomerular ultrafiltrate consist of?
Glucose AA Hormones vitamins Salts Water Urea
What part of the kidney receives the most blood flow?
Cortex
What does the Proximal tubule reabsorb?
100% of glucose and AA
80% of electrolytes, phosphate
60% urea
How are filtered proteins reabsorbed?
endocytosis via receptors (megalin & cubulin)
The kidney is the prime location for removal of water or lipid soluble toxins
Lipid-soluble toxins are hard to get rid of.
Liver may convert them to water soluble toxins.
Kidney is therefore prime site for removal of water-soluble toxins
When do the glucose transporters get saturated?
Approx 2x normal blood glucose
What is glucose reabsorption coupled to?
Na
What breeds of dog are predisposed to nephrotic syndrome?
Dobermann, Rottweiler
What are the clinical sigs and diagnosis of nephrotic syndrome?
Weight loss, oedema, ascites, hypoalbuminaemia
Diagnosis: Loss of protein in urine (proteinuria)
What is the salt composition of ECF and ICF?
ECF is nearly all sodium
ICF is nearly all potassium
What is Hypernatraemia and what does it induce?
Hypernatraemia is high ECF Na and induces a natriuresis to cause a net loss of Na ions
How does Na cause aldosterone release?
Hyponatraemia stimulates aldosterone and Hypernatremia inhibits aldosterone
How does aldosterone act with regard to Na?
It acts via the distal tubule (by basolateral Na, K and ATPase) and the collecting duct (by apical ENaC) to resorb Na, this increases the ECF volume and subsequently BP increases.
The concentration of Na doesn’t change markedly but this is because as the quantity of Na increases the volume of ECF also increases.
What is ENaC and what does its activation in the collecting duct result in?
Epithelial sodium channel
Number of functional ENaC channels open
Plasma membrane targeting of functional ENaC channels (longevity in the membrane)
ENaC are sensitive to which loop diuretic?
Amiloride - a powerful loop diuretic that inhibits ENaC and prevent Na+ reabsorption
What is the effect of potassium on aldosterone?
Potassium concentration will affect aldosterone: a meal high in K will cause a transient increase in ECF K and this will stimulate aldosterone.
What is the effect of Addison’s on K and Na?
In Addison’s where no aldosterone is secreted K and Na levels rise (potentially too high potassium)
Where is ADH made?
In the hypothalamus and secreted from the posterior pituitary
What increases the ADH levels?
Hypovolaemia Hypotension Dehydration Angiotensin II sympathetic activation
How does ADH function?
ADH acts to conserve water via receptors in cortical and distal collecting duct, it activates aquaporins in apical membrane of principal cells
What is ANP and what causes its release?
Atrial Naturetic peptide
Caused by atria distention and increased venous return
An increase in ANP will cause…
renal vasodilatation Increased GFR Decreased Renin (opposes the RAAS) Decreased aldosterone Decreased resorption of Na Decreased ADH secretion
Where is ANP stored?
Right atrium
Where are other Natriuretic peptides stored?
Brain, but still activated by atrial stretch
What causes and inhibits the release of renin?
Increased ECF (from increased salt), Increases BP, Increases blood flow to kidneys which inhibits release renin
Release caused by a decrease in blood flow
What does angiotensin induce?
Insertion of Na+/H+ exchanger via (AT1 receptor) on the PT and thick ascending limb
Insertion of ENaC on the collecting duct
How does Na leave the Loop of Henle?
The thin ascending limb is permeable to Na and some leaves here by passive diffusion
Thick ascending limb pumps K+ in and Na out
Why does the DT have a positive charge in the lumen?
This net positive charge helps drive paracellular uptake of any remaining positively charged ions in tubule (e.g. Na, K, Ca, Mg)
What do type B intercalated cells have in the DT?
Type B intercalated cells; have an H+ATPase that establishes a H+ gradient which is used to drive the secretion of HCO3- coupled to resorption of Cl-
How is Na reabsorbed in the PT?
65% via basolateral Na/K ATPase
What causes hyperkalaemia?
If internal redistribution impaired: Insulin resistance/ Beta-blockers
If increased potassium leak (muscle cells): Cell destruction and acidaemia
Structural or functional abnormalities in the kidney: Decreased GFR, decreased filtration
Where is most of the potassium reabsorbed?
Actively in the proximal tubule
