Structure and function of the renal tubule Flashcards
What is the difference between the glomerular filtrate and plasma composition?
No cells and very little protein in glomerular filtrate
Why is the composition of the plasma not the same as the urine?
Selective modification of filtrate as it passes through tubule
What is reabsorption equal to?
Reabsorption = tubular lumen → peritubular plasma
What is secretion equal to?
Secretion = peritubular plasma → tubular lumen
Where do substances move through to be reabsorbed/ secreted?
Through epithelial cell of the tubular lumen
Thriugh peritubular fluid
Through peritubular capillary
Vice versa for secretion into the tubular lumen
What 2 physiological processes are involved with secretion and reabsorption?
Active and passive transfer
Describe the premise of Active Transfer/Primary Active Transport
- Moving molecule/ion against conc gradient (low→high)
- Operates against an electrochemical gradient
- Requires energy - driven by ATP
Describe the premise of Passive Transfer
- Passive movement down a concentration gradient (requires suitable route)
- Active removal of one component concentrates other components
Describe the premise of Co-transport/Secondary Active Transport
- Movement of one substance down its concentration gradient generates energy Allows transport of another substance against its concentration gradient
- Requires carrier protein
- 2 types: symport and anti-port
What is symport and antiport transfer?
Symport = transported species move in the same direction e.g. Na+-glucose
Antiport = transported species move in opposite directions e.g Na+-H- antiport
Describe the combination of active and passive mechanisms for transcellular transport over luminal and basolateral membranes
- There is a high concentration os Na+ in tubule lumen (140mM) - this moves into the epithelial cells down a concentration gradient, aided by the electrochemical gradient.
- This generates energy so glucose can be transported against its concentration gradient into the epithelial cell, using a symport protein (SGLT2)
- Glucose is the transported down its concentration gradient from the epithelial cell into the PT capillary by a GLUT-2 transporter
- Sodium in the epithelial cell is actively pumped by a Na+/K+ pump int PT capillary - keeps Na+ low in epithelial cell
This is the transcellular mode of transport
Familial Renal Glycosuria is caused when you cannot produce SGLT2
SO SGLT2 inhibitors to treat diabetes – - Dapagliflozin (Europe) & Canagliflozin (USA)
- A symport also transports sodium and AA into epithelium via a symport protein, and an antiport transports sodium into epithelial cell and hydrogen ions out into tubule
- These sodium are actively transported into the capillary by a Na+/ K+ ATPase
What techniques investigate tubular function?
- Clearance studies
- Micropuncture & Isolated Perfused Tubule
- Electrophysiological Analysis
- Potential measurement
- Patch clamping
1 = applied to man
2 & 3 = applied to lab animals
What happens during a micropuncture? (how is it performed?)
- Puncture
- Inject viscous oil
- Inject fluid for study
- Sample and analyse
What happens during an electric potential measurement ( potential measurement)? (how is it performed?)
- Combine with microperfusion to alter potential difference (PD)
- Measure whether ion moving with or against an electrochemical gradient
- Actively transported?
What happens during patch clamping (how is it performed)?
- Current flow through individual ion channel measured
- Measure electrical resistance
- Across patch of cell membrane
- Changes when channels open/close - Types of channels & response to drugs & hormones
Describe the structure of the nephron (done previously)
On image
What are the 2 types of nephrons and how are they different?
The major anatomic difference between the Cortical nephrons & Juxtamedullary nephrons is the length of the loops of Henle.
Cortical neprhons have short-reach loops that just penetrate the boundary between the inner and outer zones of the medulla. These loops do not extend into the medulla.
Juxtamedullary nephrons have long-reach loops that penetrate deep into the medulla. (better at concentrating urine) In humans about 15 per cent of nephrons are juxtamedullary and 85 per cent are cortical.
Vascular system is also different.
Cortical nephrons – entire tubular system is surrounded by and extensive network of capillaries
Juxtamedullary nephrons – long efferent arterioles extend from glomeruli to outer medulla and divided into specialised capillaries (vasa recta) that extend downward into medulla and lie side by side with loops of Henle
The kangaroo rat is a rodent, but it is unlike any other rodent on Earth: it is able to survive in the desert with virtually no drinking water. But how is it possible to live with virtually no drinking water? The answer lies mainly in the rat’s kidneys. Research has shown that the kangaroo rat produces the most concentrated urine of all mammals, and only passes a few drops per day. The kangaroo rat’s Loop of Henle is much longer than that of other rodents.
How does the PCT have a high capacity for reabsorption and special cellular characteristics?
Highly metabolic, numerous mitochondria for active transport
Extensive brush border on luminal side large surface area for rapid exchange
What is the function of the PCT?
Major site of reabsorption
~65-70% of filtered load reabsorbed here
On image
`What are the 3 segments of the loop of henle?
Thin Descending
Thin Ascending
- thin epithelial cells, no brush border, few mitochondria & low metabolic activity
Thick Ascending
- thick epithelial cells, extensive lateral intercellular folding, few microvilli, many mitochondria high metabolic activity
What is the role of the Loop of Henle?
Which part of the loop of henle is permeable to water and impermeable
LoH critical role in concentrating/diluting urine
»adjusting rate of water secretion/absorption
Descending thin LoH = permeable
Ascending LoH = impermeable
Describe the medullary osmotic gradient?
LoH creates an osmolality gradient in medullary intersitium
Collecting Duct traverses medulla: urine concentrated as water moves out by osmosis
Describe multiplication by LoH
Why is it called a countercurrent system?
On image
The descending and ascending loop of Henle is parallel and is therefore called a countercurrent system - flow in opposite direction
When fluid enters the loop is has the same osmolarity as plasma
On ascending limb there is lots of sodium-potassium transporters - pumping NaCl out - this enters the tissue space around LoH - this creates an osmotic gradient
This gradient pulls fluid out of the descending limb by osmosis - as it flows down the descending limb osmolarity increases as water is removed
In the ascending limb, salts are being pumped out so osmolarity decreases - hypo-osmotic
Describe the absorption and excretion of ions in the thick ascending LoH
On image
What maintains the medullary osmotic gradient?
Why is vaso recta blood flow low?
Why blood flow low?
What can an altered blood flow do?
Vaso recta is a countercurrent system
As it descends into medulla H20 diffuses out and salts diffuse in
Reverse occurs as it ascends
Blood flow in VR is low ~5% of renal blood flow » minimizes solute loss from interstitium & maintains medullary interstitial gradient
Alteration of blood flow in VR can change gradient
What is the DCT connected to and form?
1st part (macula densa) linked to juxtaglomerular complex
Provides feedback control of GFR & tubular fluid flow in the same nephron
2nd part very convoluted
What does the Connecting Tubule connect to and form?
What is its function?
Connects end of DCT to collecting duct – mainly in outer cortex
Overlap in functional characteristics with 2nd part of DCT
What are the functions of the DCT?
- Solute reabsorption continues, w/out H2O reabsorption
- High Na+,K+-ATPase activity in basolateral membrane
- Very low H2O permeability
- Further dilution of tubular fluid
- Anti-diuretic hormone (ADH) can exert actions
- Role to play in acid-base balance via secretion of NH3
What are the collecting ducts joined by and by what type of cells?
Collecting ducts formed by joining of collecting tubules
- cuboidal epithelia, very few mitochondria
2 types of cells:
- Intercalated cells
- Involved in acidification of urine and acid-base balance - Principal cells
- Role to play in Na balance & ECF volume regulation
What detects changes in osmolarity?
What does an increase in plasma osmolarity cause the release of and where does it travel and cause?
Describe the mechanism of action of ADH
What does this also stimulate?
osmoreceptors
ADH from posterior pituitary to the kidney to the collecting ducts and increase water permeability and causes an increase in permeability, the hormone is re-uptaken here
ADH bind to a V2 receptor on a principle cell, this activates the G-alpha-S pathway to produce PKA and inserts aquaportin- 2 into collecting duct
Production of new aquaporins
How is urea excreted?
How can urea levels be monitored?
The collecting ducts are also permeable to urea, this will collect around the loop of Henle and contribute to the osmotic gradient
Urea levels monitored using BUN (blood urea nitrogen) test
What happens during water deprivation and excess water intake?
Water deprivation
Hypo-osmotic fluid enters the collecting ducts, and AP are inserted, sodium, chloride and urea are removed, water is removed - small water volume with a high osmolarity
Water excess
No ADH, no water absorption, sodium and chloride absorption - a large volume of water produced with low osmolarity
What are the major factors contributing to build-up of solute concentration in the renal medulla?
- Active transport of Na+ and co-transport of K+ & Cl- out of thick ascending limb into medullary interstitium
- Active transport of ions from collecting ducts into medullary interstitium
- Facilitated diffusion of large amounts of urea from collecting ducts into medullary interstitium
- Very little diffusion of water from ascending limbs of tubules into medullary interstitium
What is Polycystic Kidney Disease (PKD)?
Describe diseases of the glomerulus
Diseases of the tubules
Polycystic Kidney Disease (PKD)
Genetic disorder characterised by growth of numerous cysts in kidney
Diseases of the glomerulus
- Usually called glomerulonephritis (GN)
- Inflammation of glomeruli of some or all of million nephrons in kidney
- Can be primary or secondary to systemic disease like diabetes mellitus
- Inherited diseases of the glomerular basement membrane
Diseases of the tubules
- obstruction (reducing glomerular filtration)
- Impairment of transport functions (reducing water & solute reabsorption) eg. Fanconi’s syndrome
Describe acquired kidney diseases?
Hypertension
- Kidneys regulate ECF volume and hence influence blood pressure⇒compensatory mechanisms in response to high BP can lead to chronic kidney damage
Congestive Cardiac Failure
- Fall in cardiac output⇒renal hypoperfusion⇒registered as hypovolaemia, compensation results in pulmonary oedema
Diabetic nephropathy
- As a consequence of diabetes, filtering system of kidneys gets destroyed over time
Lithium treatment results in acquired nephrogenic diabetes insipidus
- Due to reduction of AQP2 expression
