formation of urine Flashcards
what are the 5 stages of urine formation?
1) glomerulus: filtration of blood
2) proximal tubule: reabsorption of filtrate, secretion into tubule
3) loop of Henle: concentration of urine
4) distal tubule: modification of urine
5) collecting duct: final modification of urine
what is the force of filtration?
- blood pressure
- differing diameter of afferent and efferent arterioles
what is the glomerular filtration rate?
125mL/min
what is the normal plasma volume?
2-3L
what are the 2 factors filtration are dependent on?
1) blood pressure
2) renal blood flow
where does the filtrate have to pass through?
1) pores in the glomerular capillary endothelium
2) the basement membrane of the Bowman’s capsule
3) epithelial cells of Bowman’s capsule via filtration slits into capsular space
what are the characteristics of glomerular filtrate rate?
- this is the rate at which filtrate is produced in the kidneys
- it remains constant even when systemic BP changed
- this involved a regulatory mechanism known as auto regulation of renal blood blow
how is renal blood flow autoregulated?
- renal blood flow subject to auto regulation over broad range of systemic BPs
- autoregulation persists in denervated kidneys and isolated perfusion kidneys so it isn’t a neuronal, hormonal response but instead a local effect
what are the 2 hypothesis of auto regulation of renal blood flow?
1) myogenic: autoregulation is due to response of renal arterioles to stretch
2) metabolic: renal metabolites modulate afferent and efferent arteriolar contraction and dilation
how do changes in GFR alter the systemic blood pressure?
1) a drop in filtration pressure causes a drop in GFR
2) lower GFR means less Na+ enters the proximal tubule
3) the macula densa senses a change in tubular Na+ levels
4) this stimulates juxtaglomerular cells to release renin into the blood
5) renin release leads to generation of angiotensin II
6) Ang II is a vasoconstrictor which causes BP to increase
7) increased BP causes filtration pressure to increase and GFR returns to normal
what happens when glomerular filtrate enters the proximal tubule?
60-70% of filtered water, Na+, HCO3-, Cl-, K+ and urea are reabsorbed from the PT
what is almost completely reabsorbed in the proximal tubule?
- glucose
- amino acids
- small amounts of filtered proteins
how does Na+/K+/ATPase drive reabsorption?
- Na+/K+/ATPase pumps out Na_ from cells into the blood against chemical and electrical gradients
- this process requires energy in the form of ATP
- accompanied by entry of K+ ions which rapidly diffuses out of cell
- the ratio of transport is 3 Na+ leaving cell: 2 K+ entering cell
how is sodium reabsorbed from the proximal tubule?
- PT cells have a low intracellular Na+ concentration due to action of the Na+/K+/ATPase
- Cl- follows Na+ by facilitated diffusion
- phosphate and sulphate are also co-transported with Na+
- PT cells have an overall negative charge due to the presence of intracellular proteins
how is water reabsorbed from the proximal tubule?
- 60-70% filtered water reabsorbed in the PT: active transport of Na+ out of the PT cells is the driving force
- movement of solutes reduces osmolarity of tubular fluid and increases osmolarity of interstitial fluid
- a net flow of water from tubule lumen to lateral spaces occurs by transcellular and paracellular routes
- transcellular routes involve aquaporin channel locates on apical and basolateral surfaces
- there is no active water reabsorption along nephron: it occurs by osmosis and it follows sodium
- PT is highly permeable to water
- water flow from tubule to lateral spaces occurs by paracellular and transcqallular routes
- transcellular routes involve aquaporins: specific water channels located in cell membranes
how many aquaporins have been identified?
13 (6 in the kidney)
where is aquaporin 1 found?
abundant distribution in proximal tubule. also other parts of tubule where water is reabsorbed
where is aquaporin 2 found?
present in the collecting duct on apical surface
what controls the expression of aquaporin 2?
anti diuretic hormone (ADH)
where are aquaporins 3 and 4 found?
present in basolateral surface of tubular cells involved in water reabsorption
what 4 things are reabsorbed other than water in the proximal tubule?
- potassium
- urea
- amino acids
- proteins
how much of potassium is reabsorbed in the proximal tubule?
70% of filtered K+ is reabsorbed in the PT, mostly passively via tight junctions
how much of urea is reabsorbed in the proximal tubule?
40-50% filtered urea is reabsorbed passively in the PT down its concentration gradient
where are amino acids reabsorbed in the proximal tubule?
- 7 independent transport processes for reabsorption of AAs from the PT: depends on type of AA
- high Tm for transport so that as much as possible is reabsorbed from PT
where are proteins reabsorbed in the proximal tubule?
reabsorbed from the PT via receptor-mediated endocytosis
how is protein reabsorbed from the proximal tubule?
- small amounts of protein pass into filtrate via the glomerulus
- these are reabsorbed by pinocytosis
- vesicles transported into cell, degraded by lysosome and amino acids returned to blood
- only limited transport capacity (low Tm)
- proteinuria is a sign of glomerular damage and impending renal failure
how does secretion into the proximal tubule work?
- some endogenous substances and drugs cannot be filtered at the glomerulus which may be due to their size or protein binding
- specialised pumps in the PT can transport compounds from the plasma into the nephron
how is PAH secreted into the proximal tubule?
- para-amino hippurate (PAH) is secreted into PT from blood
- not an endogenous compound so PAH can be used as a tool to measure tubular secretion
- transported into PT cells from blood with alpha-ketoglutarate or other di/tri carboxylates
- transported out of PT cells in exchange for another anion present in the PT lumen
what happens in the loop of Henle?
- tubular fluid is further modified
- the aim here is to recover fluid and solutes from the glomerular
what are the 2 stages that occur in the loop of Henle?
1) extraction of water in the descending limb
2) extraction of Na+ and Cl- in the ascending limp
which type of nephrons is the processes that occur in the loop of Henle more important in?
juxtamedullary nephrons because the loop of Henle is longer
what are the cells like in the thin descending limb of the loop of Henle?
cells are flat, no active transport of salts
what happens in the thin descending limb of the loop of Henle?
- freely permeable to water via aquaporin-1 channels
- some passive movement of water via tight junctions
what happens in the thick ascending limb of the loop of Henle?
- tubular wall is impermeable to water
- has specialised Na+/K+/2Cl- as co-transport
- transport: Na+, K+, Cl- reabsorbed but no water
what happens in the loop of Henle?
- fluid entering LOH from the proximal tube is isotonic
- water reabsorbed out of descending LOH
- by the tip of the LOH, the filtrate is hypertonic
- solutes are then pumped out of the ascending LOH
- by the end of the LOH, the filtrate entering the distal tubule is hypotonic
how can the concentration of the filtrate vary from isotonic to hypertonic over a short distance in the medulla?
countercurrent multiplication
what happens with the countercurrent multiplication?
- creates large osmotic gradient within medulla
- facilitated by Na+/K+/2Cl- transport in ascending limb of LOH
- permits passive reabsorption of water from tubular fluid in descending LOH
how does urea play a part in the countercurrent multiplication?
- active transport of NaCl contributes 600-1000mOsm…the remainder is due to urea
- urea freely filtered at glomerulus
- some reabsorption in proximal tubule, but LOH and distal tubule relatively impermeable to urea
- urea can diffuse out of collecting duct into medulla down its concentration gradient
- this adds to the osmolarity of medullary interstitium
how does the distal tubule further adjust the urine?
- active reabsorption and secretion of solutes takes place here
- sodium and chloride ions are actively reabsorbed from the tubular fluid
- this is in exchange for potassium or hydrogen ions which are secreted into the tubular fluid
how is the distal tubule involved in urine formation?
- the distal tubule performs further adjustment of urine
- Na+ and Cl- exchanged for K+ throughout the DT
- Na+ exchanged for K+ in the late DT and early collecting duct
- Na+ exchanged for H+ in DT and early collecting duct
what cells help the exchange of Na+ for K+ in the late distal tubule and early collecting duct?
principle cells
what are principle cells sensitive to?
aldosterone
what cells help the exchange of Na+ for H+ in the distal tubule and early collecting duct?
intercalated cells
what type of intercalated cells are there?
alpha and beta intercalated cells
what type of exchange forms part of the renin-angiotensin aldosterone system (RAAS)?
exchange of Na+ for K+ in the late DT and early collecting duct using principle cells
how does the collecting duct help in the formation of urine?
- the collecting duct is relatively impermeable to movement of water and solutes
- however, the permeability of the collecting duct can be considerable increased the action of ADH
what is the most important hormone that regulates water balance?
ADH
what is the molecular weight of ADH?
just over 1000
what is another name of ADH
vasopressin of 8-arginine-vasopressin
what is the plasma half life of ADH?
10-15 mins
where does ADH act?
acts on vasopressin V2 receptors on basal membrane of principle cells in DT and collecting duct cells leading to activation of intracellular water channels
what are the 2 types of ADH?
- maximal circulating ADH
- no circulating ADH
what is the function of maximal circulating ADH?
- collecting duct becomes permeable to water due to maximal AQP2 insertion so water reabsorption occurs
- reabsorbs up to 66% of the water entering the collecting duct
- delivery of fluid to the collecting duct is low
- urine volume can be reduced to 300mL/day
what is the function of no circulating ADH?
- reabsorption of water occurs at various sites in the nephron as described previously
- however the collecting duct wall becomes impermeable to water due to no AQP2 so a large volume of water is excreted
- lack of ADH: diabetes insipidus
how do you treat diabetes insipidus?
synthetic ADH
what are the 2 main types of diabetes insipidus?
nephrogenic and neurogenic
what is nephorgenic diabetes insipidus?
due to inability of kidney to response normally to AHD
what is neurogenic diabetes insipidus?
due to lack of ADH production by the brain
what is the treatment for nephrogenic diabetes insipidus?
chlortalidone, indomethacin
what is the treatment of neurogenic diabetes insipidus?
desmopressin, vasopressin, carbamazepine
what is SIADH?
syndrome of inappropriate ADH
- excessive ADH
what can SIADH lead to?
hypomatraeia and possibly fluid overload
what is the treatment for SIADH?
V2 receptor blockers
where is ADH synthesised
in the hypothalamus
where is ADH stored and released?
posterior pituitary gland
what agents increased ADH release?
- nicotine
- ether
- morphine
- barbiturates
(anti-diuretic action)
which agent inhibits ADH release?
- alcohol
diuretic action
what happens to all the water and solutes reabsorbed from the tubule?
it is all taken back into the peritubular vessels and vasa recta surrounding the tubule
