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what are the functions of the liver

• Filtration of blood
• Detoxification (incl drugs)
• Regulate blood pressure
• Regulation of blood pH
• Regulation of haematopoiesis
• Making vitamin D


are the kidneys peritoneal or retroperitoneal?



which kidney is higher up

left due to the liver on the right


how much of the cardiac output goes to the liver



what happens if you restrict afferent arteriole?

•Blood pressure in capillaries drops
•Filtration rate drops


what happens if you restrict efferent arteriole?

•Blood pressure in glomerular capillaries rises
•Filtration rate rises


what is the slit diaphragm?

the filter made of cells which get very close to one another and then connecting to each other with protein structures which leave a tiny gap
Only 3% is slit and the rest is diaphragm so this is a big resistance to fluid flow


why does the kidney need pressure from the heart?

to oppose osmosis (once the blood is filtered the water wants to dilute the unfiltered blood)


describe anticlogging in the kidney

• Pinocytosis of trapped proteins
o Vesicles which take proteins into the cell and either export them or break them down with lysosomes
o There is a LOT of this going on

• This only works for things small enough to pinocytose
o Big protein aggregates, bacteria, platelets can cause a problem
o For these there are fenestrae on the endothelial cells which let large proteins get to the basement membrane of the cell (the glomerular basement membrane)
o The GBM forms a finer filter but not as fine as the slit diaphragm

• The fenestrae are cleaned by blood flow and phagocytes

• The GBM is renewed by mesangial cells

• And the slit diaphragm is cleaned by pinocytosis by podocytes


describe plasma flow to the kidney

Blood flow to the kidneys is about 1.2L/min
Plasma flow to kidneys is about 0.66L/min
Rate of filtration through glomeruli = 0.13l/min
~20% of plasma is removed as filtrate


what structural properties does the proximal tubule have

tight junctions between cells are more leaky than other cells – some ions can get past them


what do nephron epithelia have to recover

• Na+
• K+
• Ca2+
• Mg2+
• Cl-
• HCO3-
• PO42-
• H2O
• Amino acids
• Glucose
• Proteins


what channels do we have to recover things

• Primary active transporter - Na/K ATPase, H ATPase
• Solute carrier family – SLC proteins – about 300 – many are co-transporters powered by established conc gradients (“secondary active transporters”)
• Aquaporins (water channels NOT pumps)
• Ion channels
• Protein endocytosis receptors


what is required to move things from the filtrate to the plasma

ATP – lots of mitochondria in the kidney cells


what are some channels involving sodium

Na/K ATPase sends 3 Na out for 2 K in which uses ATP.

There is an SLC which moves one proton out for one Na in – does NOT use ATP

Another SLC brings a Na and a Cl into the cell

Another co-transports one Na, one K and two Cl into the cell


how does K move out of the cell

There are regulatable K channels which can leak K out of the cells so they can be co-transported back in


how can amino acids be transported

Some channels bring in Na, 2 Cl and a particular type of amino acids – different channels for different amino acids


how is glucose transported

Glucose can be brought in along with Na - one channel needs one Na and another needs 2 but is better at bringing in Glucose from a low concentration


what happens to glucose in diabetes

there is excessive amount of glucose in the blood and therefore primary filtrate – the cells cannot reabsorb all of it and therefore it is excreted


describe OCTs

Organic Cation Transporters

can pump cations out of the cell in exchange for protons, pump them out at the cost of ATP (multiple drug resistance – chemotherapy agents being pumped out) or allow cations in

The cytoplasmic cation concentration should never exceed that of the plasma


describe OATs

Anions, on the other hand, push in and drift out
Alpha ketoglutarate moves in along with Na and then an OAT antiporter transports alpha ketoglutarate out in exchange for anions. Passive channels on the apical side to allow them out.
This is dangerous as if there is an organic anion which is toxic and does not have an efficient passive channel then there can be high concentrations in the cell. This is often the cause of drugs damaging kidney cells – methotrexate, furosemide and penicillin
Probenecid stops the OAT uptake, allowing penicillin to stay in circulation and not be excreted rapidly like normal


describe bicarbonate uptake

we have the SLC which pumps protons out for Na in. The proton can combine with any bicarbonate to make carbonic acid which can be hydrolysed by carbonic anhydrase to make water and CO2 which can cross the membrane. Once in the cell, carbonic anhydrase will turn it back into carbonic acid which will naturally dissociate into a proton and bicarbonate. Another SLC can then transport it back into the body from the cell along with a Na. this takes up bicarbonate without messing up body pH – no net loss of bicarbonate or H.


what happens to H in acidosis

If there are remaining protons but no bicarbonate (acidosis), the protons combine with hydrogen phosphate and leave the body as H2PO4. This DOES effect acid base balance as it results in a net loss of protons
Ammonia can also take up protons and be excreted as ammonium – net secretion of H. ammonia comes from the catabolism of glutamine. This not only leads to H excreted but also generates bicarbonate which can enter the body so very powerful at restoring acid base balance.


what are type A and B cells

The H ATPase expels H from the cell and there is also a transporter which takes up K and expels H from the cell – type A cell
Type B cell has the same H ATPase but on the basal side not the apical side. Bicarbonate goes out into the urine in exchange for Cl and H gets pumped into the body – corrects alkalosis


how can Ca move

The leaky tight junctions allow for Ca to move into the plasma if its concentration gets too high in the urine


how is water taken up

recovered passively through aquaporins


how can proteins be taken up

Proximal tubule cells take up proteins via receptors such as Megalin – endocytosis


how is phosphate taken up

recovered along with one Na and then actively exported from the cell into the basal side.


what is the primary filtrate like as it leaves the renal corpuscle

iso-osmotic to the plasma and has approximately the same concentration of small molecules


what happens in the proximal tubule

• A lot of sodium recovered. – through basal pump
• Glucose, amino acids etc are pulled through by sodium conc gradient
• Chloride, phosphate pulled through by sodium gradient
• Potassium pushed in at basal side by Na/K ATPase and can be pushed out or brought in at apical side
• HCO3 is recovered and H cycled, powered by the Na gradient
• All of this solute movement would lower the osmolarity of the tubule if water didn’t also flow passively from the tubule to counteract this
• Chloride also leaves passively to stop its conc increasing in the tubule