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