Introduction to Renal Flashcards
What are the functions of the kidney?
- Filtration of blood
- Detoxification (incl metabolic processing drugs)
- Regulation of blood pressure
- Regulation of blood pH
- Regulation of haematopoiesis
- Making active form of vitamin D
What are the problems the kidneys are meant to solve?
- The blood fills up with waste products and toxins that need to be cleared from the body (deamination of amino acids= urea and creatine from muscle)
- The blood is full of small molecules about the same size as waste products and toxins (or smaller, in the case of water) that are precious and must not be lost from the body- amino acids, glucose
Describe the functional solution of the kidneys
- Non-specific filter (high pressure blood filtered)
- Selective recovery- small and good molecules through, keep the right amount of good molecules
- Impermeability to waste
- Control/feedback systems to operate
What do we need in the kidneys?
- Pump to push liquid through= heart, blood pressure from heart
- Filter
What are the ‘design’ problems with the filter?
-We need to make a very fine filter (cut off c. 4nm = 40Å, free flow below 18Å )
=small molecules get through, large molecules do not (like proteins)
-We need the filter not to clog= cannot be replaced
-We need to be able to filter a lot of fluid in a small-ish space
How is the fine filter made?
-Cells get very close together, connect to each other with protein structures with very fine holes
-Cells with long finger like processes= podocytes, wrap around blood capillaries
=Processes interdigitating
-Slit diaphragm= line of protein between foot processes of adjacent podocytes with holes
=proteins called nephrins (integral membrane proteins that stick out and together so nephrins of cells make adhesive structure in middle)
=pores are the spaces through which glucose and salts and albumin can fit through
=3% total area is actually slit so major source of resistance to fluid flow
Why do we need high pressure in the kidney?
-Push fluid through filter
-Overcome fluids tendency to want to push back
=second law of thermodynamics
=water from dilute solution into more concentrated solution (filter to blood as no proteins in filtrated side) therefore osmotic pressure needs to be overcome
What is the effect of restricting afferent arterioles?
- Blood pressure downstream in capillaries drops
* Filtration rate drops
What is the effect of restricting efferent arterioles?
- Blood pressure in glomerular capillaries rises
* Filtration rate rises
How do we prevent the filter from clogging?
-Clogged by proteins being trapped in pores
-Pinocytosis= little vesicles of membranes with receptors for proteins that take them in- export or degrade in lysosomes
-Only works for proteins small enough to pinocytose
=If big protein aggregates like antibody-antigen complexes- bigger problem if bacteria and platelets got jammed against the slit membrane
What is the additional filter that prevents big proteins from clogging the filter?
-2 layers
-Endothelial cell wall
=fenestrae (windows), allow large proteins through cell
=cleaned by blood flow and phagocytes
-Basement membrane surrounds endothelial cells= glomerular basement membrane (embedded in glomerulus)= forms finer filter to remove larger proteins
=constantly renewed by mesangial cells (patrol and degrade existing membrane and make new membrane)
How is the kidneys able to filter a lot of fluid in a small space?
-Bundle lots of capillaries coated with podocytes
=renal corpuscle
=contains tight knot of capillaries
=afferent arteriole in, efferent arteriole out
=covered in Bowman’s capsule which captures the filtrate and routes it into tube
-Many renal corpuscles in kidneys so many glomeruli
What are the typical values associated with filtration?
- Blood flow to kidneys - 1.2L / min
- Plasma flow to kidneys – 0.66L /min (assuming normal haematocrit of 0.45)
- Rate of filtration through glomeruli (summed across all) = 0.13L /min
- > 20% of plasma is removed as filtrate.
- declines in renal problems
How can we measure glomerular filtration rate?
-Averaged over all glomeruli
-Creatinine filtered into urine but is not recovered
-Measure flow rate of urine
-Divide by minutes in hours taken
Glomerular filtration rate x plasma concentration= urine flow rate x urine concentration
Describe dialysis
-Work same way as filtration in real kidneys
-Membrane= fine filter
=Blood on one side returning to patient, other side= dialysate (liquid identical to plasma in good molecules with no toxins) so net flow of toxins to dialysate
-Every 2/3 days
-Not great long-term solution
