Formation of urine Flashcards
what is the force for filtration
- blood pressure
2. differing diameter of afferent and efferent arteriole
what is the glomerular filtration rate
= 125ml/min (normal plasma volume= 2-3l)
- rate at which glomerular filtrate is produced
- can be measured clinically and used as an indicator of renal function
what is glomerular filtration
the first stage of urine formation
what is ultrafiltration?
filtration on a molecular scale
what is filtered during glomerular filtration?
- all small molecules are filtered- electrolyte, amino acids, glucose, metabolic waste and some drugs and metabolites
- cells and large molecules remain in the blood- red blood cells, lipids, proteins, large size or protein bound drugs
what 2 factors is filtration dependent on
blood pressure and renal blood flow
describe the sequence that filtrate needs to pass through during glomerular filtration
- pores in glomerular capillary endothelium
- the basement membrane of Bowmans capsule (including contractile mesangial cells)
- epithelial cells of Bowmans capsule (podocytes) via filtration slits into capsular space
When does GFR remain constant
GFR generally remains constant even when systemic Blood pressure changes
- due to a process known as autoregulation of renal blood flow
what is auto regulation of renal blood flow
- renal blood flow subject to auto regulation over broad range of systemic blood pressures
- auto regulation persists in denervated kidneys and isolated perfused kidneys
- so it is not a neuronal or hormonal response but instead, an effect local to the kidneys
what are the 2 processes involved in auto regulation of renal blood flow
- myogenic- auto regulation is due to response of renal arteries to stretch
- eg. if blood pressure increases, renal arteries automatically constrict to maintain a constant renal blood flow - metabolic- renal metabolites modulate glomerular blood flow (eg. via action of endothelin on afferent and efferent arterioles) to maintain GFR
describe how major changes in blood pressure can alter systemic blood pressure
- a drop in filtration pressure (eg due to declining blood pressure) causes a drop in GFR
- lower GFR means less Na+ enters the proximal tubule
- the macula densa senses a change in tubular Na+ levels
- this stimulates juxtaglomerular cells to release renin into the blood
- renin release leads to generation of angiotensin II
- angiotensin II is a vasoconstrictor which causes blood pressure to increase
- increased blood pressure causes filtration pressure to increase and GFR returns to normal
describe how Na+K+ATPase drives reabsorption
- Na+K+ATPase pumps out na+ from cells into the blood against chemical an electrical gradients
- this process requires energy in the form of ATP
- accompanied by entry of K+ ions which rapidly diffuses out of the cell
- the ratio of transport is 3 na+ leaving cell: 2 k+ entering cell
describe sodium reabsorption from the proximal tubule
- pt cells have a low intracellular na+ conc due to action of the na+k+atpase
- pt cells have an overall negative charge due to presence of intracellular proteins
describe the process of water reabsorption from the proximal tubule
- water is reabsorbed by osmosis following solute reabsorption
- 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 osmolality of tubular fluid and increases osmolality of interstitial fluid
- a net flow of water from the tubule lumen to lateral spaces occurs by transcellular and paracellular routes
- there is no active water reabsorption along nephron
- it occurs by osmosis and follows sodium
describe the proximal tubules permeability to water
pt is highly permeable to water
- water flow from tubule lumen to lateral spaces occurs by paracellular and transcellular routes
what does the transcellular route of water reabsorption from the proximal tubule involve
transcellular routes involve aquaporins- specific water channels cell membranes
how many types of aquaporins have been identified
13 different types, 6 in the kidney
what are the 4 major renal aquaporins
- aquaporin 1- abundant distribution in proximal tubule and wide distribution (eg. lung, brain)
- aquaporin 2- present in collecting duct on apical surface AQP2 channel expression
- controlled by antidiuretic hormone - aquaporin 3 and 4- present on basolateral surface of collecting duct cells
describe the process of glucose reabsorption from the proximal tubule
glucose is co transported into the pt cell with sodium very efficiently so very little is excreted
what are SGLT2 inhibitors
new drugs for controlling type 2 diabetes
- idea is to make diabetic patients excrete more glucose leading to an overall hypoglycaemic effect
give examples of SGLT2 inhibitors
dapagliflozin, topogliflozin
describe the reabsorption of potassium in the proximal tubule
70% of filtered K+ is reabsorbed in the pt, mostly passively via tight junctions (paracellularly)
describe the reabsorption of urea in the proximal tubule
40-50% filtered urea is reabsorbed passively in the pt down its concentration gradient
describe the reabsorption of amino acids in the proximal tubule
7 independant transport processes for reabsorption of amino acids from the pt- depends on type of amino acid
- high Tm for transport so that as much as possible is reabsorbed from pt
how are proteins reabsorbed in the proximal tubule
reabsorbed from the proximal tubule via receptor mediated endocytosis
describe the process of protein reabsorption 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 lysosomes and amino acids returned to blood - only limited transport capacity (low Tm)
what is proteinuria a sign of
sign of glomerular damage and impending renal failure
give examples of organic acids secreted into urine by the proximal tubule
endogenous acids: cAMP, bile salts, oxalate, prostaglandins, uric acid
drugs: acetozolimide, chlorothiazide, furosemide, penicillin
give examples of organic bases secreted into the urine by the pt
endogenous bases: creatinine, dopamine, adrenaline, noradrenaline, histamine, choline
drugs: atropine, cimetidine, morphine, amiloride
where does the remaining fluid from the proximal tubule enter
remaining fluid now enters the loop of henle
describe what occurs in the loop of henle
- tubular fluid is further modified in this part of the nephron
- the aim is to recover fluid and solutes from the glomerular filtrate
- the process can be divided into 2 stages
- extraction of water in the descending limb
- extraction of na+ and cl- in the ascending limb - this process is of more importance for juxtamedullary nephrons which have longer loops of henle
describe the process of extraction of water in the thin descending limb
- cells are flat, no active transport of salts
- but freely permeable to water via aquaporin 1 channels
- also some passive movement of water via tight junctions
describe the process of extraction of na+ and cl- in the thick ascending limb
- tubular wall is impermeable to water
- but has specialised Na+K+2Cl- co transporters
- na+, k+, cl- reabsorbed- but no water
describe how filtrate enters the loop of henle
- fluid entering loh from pt is isotonic
- water reabsorbed out of descending loh
- by the tip of the loh, the filtrate is hypertonic (very conc)
- solutes are then pumped out of the ascending loh
- by the end of the loh, the filtrate entering the distal tubule is hypotonic
what is countercurrent multiplication
- creates a 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
what is the role of urea in countercurrent multiplication
- active transport of NaCl contributes 600-1000mOsm, the remainder is due to urea
- urea is 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 conc gradient
- this adds to the osmolality of medullary interstitium
where does the remainder of the fluid enter following the loop of henle
remaining fluid now enters the distal tubule
describe what occurs in the distal tubule
- distal tubule performs further adjustments of urine
- active absorption and secretion of solutes takes place here
- sodium and chloride ions are actively reabsorbed from the tubular fluid
- this is in exchange for K+ or H+ ions which are secreted into the tubular fluid in late dt and early collecting duct
- this involves specialised cells called principal cells
- these cells are sensitive to aldosterone - this forms part of the renin angiotensin aldosterone system (RAAS)
what occurs in the renin angiotensin aldosterone system
- increases aldosterone release from adrenal glands
- increase na+ reabsorption from dt
- increases h2o reabsorption
- increase in blood pressure
what is the overall effect of the renal actions of aldosterone
more na+ reabsorbed so more water moves into plasma so blood pressure increases
what specialised cells does na+ exchanged for k+ in late dt and early collecting duct involve
principal cells
what specialised cells does na+ exchanged for h+ in entire dt and early collecting duct involve
intercalated cells
what is the role of intercalated cells
secrete acid (h+) into urine and reabsorb bicarbonate - this can lower urine ph to 6.5
describe the permeability of the collecting duct
relatively impermeable to movement of water and solutes
- however the permeability can be considerably increased by the action of the antidiuretic hormone
what is antidiuretic hormone and how does it act
- the most important hormone that regulates water balance
- also known as vasopressin
- plasma half life is 10-15 mins
- removed from the circulation by liver and kidneys - acts on V2 receptors on basal membranes of principal cells in dt and collecting duct cells, leading to activation of intracellular water channels (AQP2)
describe what occurs in maximal circulating ADH
- collecting duct becomes permeable to water so water reabsorption occurs
- therefore, water reabsorption increases
- delivery of fluid to the collecting duct is low
- urine volume can be reduced to 400ml/day
describe what occurs with no circulating ADH
- reabsorption of water occurs at various sites in the nephron
- collecting duct wall becomes impermeable to water
- volume of water excreted increases significantly
- ADH deficiency known as diabetes insipidus (can be treated using synthetic ADH)
where is ADH synthesised and stored
ADH is synthesised in the hypothalamus, then stored and released from posterior pituitary
what agents can increase ADH release
nicotine, ether, morphine and bariturates
- work by anti diuretic action (urine excretion decreases)
what agents inhibit ADH release
alcohol
- diuretic action (urine excretion increases)
what happens to the water and solutes reabsorbed from the tubule
it is all taken back into the peritubular vessels and vasa recta surrounding the tubule
