formation of urine Flashcards
what are the 5 stages of urine formation?
- glomerulus- filtration of blood
- proximal tubule- reabsorption of filtrate, secretion into tubule
- loop of Henle- concentration of urine
- Distal tubule- modification of urine
- collecting duct- final modification of urine
what is the force of filtration?
- blood pressure
- differing diameter of afferent and efferent arterioles
what is glomerular filtration rate? 5
- 125ml/min
- rate at which glomerular filtrate is produced
- can be measured clinically as an indicator of renal function
- generally remains the same even when systemic BP changes
- this is due to a regulatory mechanisms known as auto-regulation of renal blood flow
what is glomerular filtration? 4
- the first stage of urine formation
- ultrafiltration= filtration on a molecular scale
- all small molecules are filtered
- cell and large molecules remain in the blood
what is glomerular filtration dependent on? 2
- blood pressure
- renal blood flow
what does glomerular filtrate have to pass through? 3
- pores in the glomerular capillary
- the basement membrane of Bowman’s capsule (includes contractile mesangial cells)
- epithelial cells of Bowman’s capsule (podocytes) via filtration slits into capsular space
describe auto-regulation of renal blood flow? 2
- renal blood flow is subject to auto regulation over a broad range of systemic BPs
- persists in denervated kidneys and isolated kidneys, so its not a neuronal or hormonal response but a local effect
what are the two hypotheses for auto regulation of renal blood flow?
Myogenic- autoregulation is due to response of renal arterioles to stretch (starlings’ law)
Is BP decreases, renal artery and efferent arterioles automatically constrict to maintain a constant renal blood flow
Metabolic- renal metabolites modulate afferent and efferent arteriolar contraction and dilation
describe reabsorption from the proximal tubule? 4
- glomerular filtrate enters the proximal tubule
- 60-70% of filtered water, Na+, HCO3-, Cl-, K+ and urea are reabsorbed
- almost all of glucose, amino acids and filtered proteins are reabsorbed
- the driving force for this reabsorption is Na+/K+ ATPase
describe hoe NA+/K+ ATPase can drive reabsorption? 4
- Na+/K+ ATPase pumps out Na+ from cells into the blood against the chemical and electrical gradients
- this requires ATP
- this is accompanied bu the entry of K+ ions which rapidly diffuse out of the cell
- 3Na+ in and 2K+ out
describe sodium reabsorption from the PT? 4
- against chemical gradients
- PT cells have a low intracellular Na+ concentration due to the action of the NA+/K+ ATPase
- PT cells have an overall negative charge due to the presence of intracellular proteins
- Cl- follows Na+ by facilitated diffusion, phosphate and sulphate are cotransported with Na+
describe water reabsorption from the PT? 6
- 60-70% of filtered water is reabsorbed in the PT, active transport of Na+ out of PT cells is the driving force
- movement of solutes reduces the osmolality of tubular fluid and increases osmolality or interstitial fluid
- a net flow of water from tubule lumen to lateral spaces occurs by transcellular and paracellular routes
- transcellular routs involve aquaporins channels located on apical and basolateral surfaces
- there is no active water reabsorption along the nephron- it occurs by osmosis and it follow sodium
- the PT is highly permeable to water. water flow from the tubule to lateral spaces occurs by paracellular and transcellular routes
describe how transcellular routes involve aquaporins? 5
- aquaporins are specific water channels located in the cell membranes
- there are 13 different types, 6 in the kidney
- Aquaporin-1 (AQP-1)
- Abundant distribution in proximal tubule. Also, other parts of the tubule where water is reabsorbed- descending limb of LOH
- Aquaporin-2 (AQP2)
- Present in collecting duct on apical surface. AQP-2 channel expression is controlled by antidiuretic hormone (ADH)
- Aquaporins-3 & 4 (AQP3 and AQP4)
- Present on basolateral surface of tubular cells involved in water reabsorption
describe glucose reabsorption from the PT? 2
- glucose is co-transported into the PT with Na+ very efficiently so very little is excreted
- urinary excretion of glucose indicates diabetes
describe SGLT2 inhibitors?
- possible new drug for controlling type 2 diabetes
- the idea is to make diabetic patients excrete more glucose leading to an overall hypoglycaemia effect
- dapagluflozin
- canagluflozin
- empagliflozin
describe further reabsorption in the PT? 4
- POTASSIUM- 70% of filtered K+ is reabsorbed in the PT, mostly passively via tight junctions
- UREA- 40-50% filtered urea is reabsorbed passively in the PT down its concentration gradient
- AMINO ACIDS- 7 independent transport processes for reabsorption of AAs from the PT- depends on the type of AA, type of AA, high Tm for transport so that as much as possible is reabsorbed from PT
- proteins- reabsorbed from PT via receptor- mediated endocytosis
describe protein reabsorption form the PT? 3
- small amounts of the protein pass into filtrate via the glomerulus
- these are reabsorbed by pinocytosis- vesicles are transported into the cell, degraded by lysosomes and amino acids returned to the blood
- only cited transport capacity (low Tm) proteinuria is a sign of glomerular damage and impending renal failure
describe secretion into the PT? 2
- some endogenous substances and drugs cannot be filtered at the glomerulus- this may be due to their size or protein binding
- specialised pumps in the PT can transport compounds fro the plasma into the nephron
describe secretion of PAH (para- hippurate) into the PT? 4
- PAH is secreted into the PH from the 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 the PT ells in exchange for another anion present in the PT lumen
describe the loop of Henle? 6
- Tubular fluid is further modified in this part of the nephron
- The aim here is to recover fluid and solutes from the glomerular filtrate
- The process can be divided into two 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 thin descending limb? 3
- Cells are flat, no active transport of salts
- But freely permeable to water via Aquaporin-1 channels
- Also, some movement of water via tight junctions
describe the thick ascending limb? 3
- Tubular wall is impermeable to water
- But has specialised Na+/K+/2Cl- co-transporters
- Transport Na+, K+, Cl- reabsorbed- but no water
describe the concentration of the fluid in the LOH at different points? 5
- Fluid entering LOH from proximal tubule is isotonic
- Water reabsorbed out of descending LOH
- By the tip of the LOH, the filtrate is hypertonic (very concentrated)
- Solutes are then pumped out of the ascending LOH
- By the end of the LOH, the filtrate entering the distal tubule is hypotonic
describe countercurrent multiplication? 9
- Creates large osmotic gradient within the medulla
- Facilitated by Na+/K+/2Cl- transport in ascending limb of the LOH
- Permits passive reabsorption of water from tubular fluid in descending LOH
- .
- Urea also plays a part
- Active transport of NaCl contributes- the remainder is due to urea
- Urea freely filtered at the glomerulus
- Some reabsorption in proximal tubule, but LOH and distal tubule relatively impermeable to urea
- Urea can diffuse out of the collecting duct into the medulla down its concentration gradient
- This adds to the osmolality of medullary interstitial
describe the distal tubule? 11
- The distal tubule performs further adjustment of urine
- Active absorption and secretion of solutes takes place here
- Sodium and chloride ions are actively reabsorbed from the tubular fluid
- This is an exchange for potassium or hydrogen ions which are secreted into the tubular fluid
- Na+ and Cl- exchanged for K+ throughout DT
- Na+ exchanged for K+ in late DT and early collecting duct
- This involves specialised cells called principal cells
- These cells are sensitive to aldosterone
- Na+ exchanged for H+ in DT and early collecting duct
- This involves specialised cells called intercalated cells
- Subtypes exist called alpha and beta intercalated cells
describe principal cells? 3
- Exchange Na+ for K+ in the late DT and early collecting duct
- This involves specialised cells called principal cells which are sensitive to aldosterone
- This exchange forms parts of the RAAS
what do alpha-intercalated cells do? 2
- Secretes acid via H+/Na+ or H+/K+ exchange involving ATPase or H+ATPase
- Reabsorbs bicarbonate
what do beta- intercalated cells do? 2
- Secrete bicarbonate via pendrin
- Reabsorbs acid
describe the collecting duct? 7
- The collecting duct is relatively impermeable to movement of water and solutes
- However, the permeability of the collecting duct can be considerably increased the action of ADH
- The most important hormone that regulates water balance, it is a nonapeptide
- Also known vasopressin or 8-arginine-vasopressin
- Release from the posterior pituitary subsequent to hypothalamic inputs
- Plasma half-life is 10-15 minutes
- ADH acts vasopressin receptors on basal membrane of principal cells in DT and collecting duct cells leading to activation of intracellular water channels
describe the modification of urine volume by maximal circulating ADH? 4
- 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
describe the modification of urine volume when there is no circulating ADH? 3
- Reabsorption of water occurs at various sites in the nephron
- 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- treated using synthetic ADH
describe diabetes insipidus? 10
- Nephrogenic:
- Due to the inability of kidney to respond normally to ADH
- Treatment:
- Chlortalidone (diuretic)
- Indomethacin (anti-inflammatory)
- .
- Neurogenic:
- Due to the lack of ADH production by the brain
- Treatment:
- Desmopressin (ADH analogue)
- Vasopressin
- Carbamazepine (anti-convulsive)
- .
- Dipsogenic
- Gestational
what is SIADH? 4
- syndrome of inappropriate ADH
- Excessive release of ADH due to head injury, unwanted effects of drugs
- SIADH can cause hyponatraemia and possibly fluid overload
- Treatment:
- V2 receptor blockers (ADH inhibitors)
where is ADH synthesised and released?
what increases release? 4
what inhibits release?
- ADH synthesised in the hypothalamus and then stored and released from the posterior pituitary
- Agents which increase ADH release:
- Nicotine
- Ether
- Morphine
- Barbiturates
- .
- .
- Agents which inhibit ADH release:
- Alcohol
what happens to the water and solutes that are reabsorbed from the tubule?
- It is all taken back into the peritubular vessels and vasa recta surrounding the tubule