formation of urine Flashcards
1
Q
what are the 5 stages of urine formation?
A
- 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
2
Q
what is the force of filtration?
A
- blood pressure
- differing diameter of afferent and efferent arterioles
3
Q
what is glomerular filtration rate? 5
A
- 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
4
Q
what is glomerular filtration? 4
A
- 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
5
Q
what is glomerular filtration dependent on? 2
A
- blood pressure
- renal blood flow
6
Q
what does glomerular filtrate have to pass through? 3
A
- 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
7
Q
describe auto-regulation of renal blood flow? 2
A
- 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
8
Q
what are the two hypotheses for auto regulation of renal blood flow?
A
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
9
Q
describe reabsorption from the proximal tubule? 4
A
- 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
10
Q
describe hoe NA+/K+ ATPase can drive reabsorption? 4
A
- 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
11
Q
describe sodium reabsorption from the PT? 4
A
- 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+
12
Q
describe water reabsorption from the PT? 6
A
- 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
13
Q
describe how transcellular routes involve aquaporins? 5
A
- 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
14
Q
describe glucose reabsorption from the PT? 2
A
- glucose is co-transported into the PT with Na+ very efficiently so very little is excreted
- urinary excretion of glucose indicates diabetes
15
Q
describe SGLT2 inhibitors?
A
- 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
16
Q
describe further reabsorption in the PT? 4
A
- 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
17
Q
describe protein reabsorption form the PT? 3
A
- 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
18
Q
describe secretion into the PT? 2
A
- 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
19
Q
describe secretion of PAH (para- hippurate) into the PT? 4
A
- 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
20
Q
describe the loop of Henle? 6
A
- 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
21
Q
describe the thin descending limb? 3
A
- 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
22
Q
describe the thick ascending limb? 3
A
- Tubular wall is impermeable to water
- But has specialised Na+/K+/2Cl- co-transporters
- Transport Na+, K+, Cl- reabsorbed- but no water
23
Q
describe the concentration of the fluid in the LOH at different points? 5
A
- 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
24
Q
describe countercurrent multiplication? 9
A
- 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
25
Q
describe the distal tubule? 11
A
- 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
26
Q
describe principal cells? 3
A
- 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
27
Q
what do alpha-intercalated cells do? 2
A
- Secretes acid via H+/Na+ or H+/K+ exchange involving ATPase or H+ATPase
- Reabsorbs bicarbonate
28
Q
what do beta- intercalated cells do? 2
A
- Secrete bicarbonate via pendrin
- Reabsorbs acid
29
Q
describe the collecting duct? 7
A
- 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
30
Q
describe the modification of urine volume by maximal circulating ADH? 4
A
- 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
31
Q
describe the modification of urine volume when there is no circulating ADH? 3
A
- 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
32
Q
describe diabetes insipidus? 10
A
- 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
33
Q
what is SIADH? 4
A
- 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)
34
Q
where is ADH synthesised and released?
what increases release? 4
what inhibits release?
A
- 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
35
Q
what happens to the water and solutes that are reabsorbed from the tubule?
A
- It is all taken back into the peritubular vessels and vasa recta surrounding the tubule
