Today I'm gonna talk about nephrotic and nephritic syndrome, and how to differentiate between the two. To do that I will assume that we have five persons, but before that I think I should talk about the anatomy of the glomerulus (you should know that each kidney contains 1.2 million nephron, and the two kidneys combined can have up to 2 - 2.5 million nephron).
First the blood enters through the afferent arteriole and leaves through the efferent arteriole and the arteriole is surrounded by the bowman's capsule. Between the bowman's capsule and the arteriole we have the glomerular basement membrane (GBM). The arteriole wall got endothelial cells which are fenestrated (which means they have pores) and the bowman's capsule is lined with cells called podocytes, and these cells are lined in a fashion that they leave slits between them, now the pores size in the endothelial cells in the arteriole are about 70-100 nanometer, and the slits between the podocytes are about 20-30 nanometer, and if the molecules want to pass through these three layers first they have to be small (for example, the WBC, the RBC are large and can't pass through), the second thing is that negative charges can't pass through these membranes because the three membranes are themselves negatively charged (for example, albumin is small enough to pass through, but because its also negatively charged it can't pass through), is simple words any molecule which have to pass, it has to face the size barrier and the charge barrier.
Now lets move to the five persons I talked about, the first one is normal and all of these mechanisms and barriers are intact in him, so everything is working smoothly and clock wise , but in the second person there is a "tiny" damage to the glomerulus and only the small molecules will leak, like albumin, and because of this, this condition is called selective albuminuria (because albumin is the only thing leaked to urine), now if we move to the third person, the damage to the nephron is even more than the second one, so the membranes permeability is even more, so not only albumin is lost, but also globulins, for this reason this condition is called non selective proteinuria (because both albumin and globulins are leaked to urine), and an important thing to notice here is the lost is LESS that 3.5 g/day of protein , now if we move to the forth person, and he has even more damage that the third person, so he also loses albumin and globulins but at a higher extent and the loss is MORE than 3.5 g/day of protein, but why we emphasized on this cut point! because after the 3.5 g/day limit the liver wont be able to compensate for this loss, but the liver synthesis 10 - 12 g/day, so how come! I'm sure you must be wondering! well, let me tell you, it's because of the proximal convoluted tubule cells, these cells are phagocytic cells, and eats up (catabolize) all of proteins which are spilled into urine, so in fact this 3.5 grams which are present in the urine is just the amount of proteins which have escaped these cells, get it! and we have been talking about albumin all day long! so what is it function, why it's important!, well, albumin and other plasma proteins generate the oncotic pressure, now what's the function of oncotic pressure! well, normally the blood goes from the arterial to the venous end, in the arterial end the hydrostatic pressure is greater so fluids go from the the arterial end to the interstitium, and in the venous end the oncotic pressure is larger, so it sucks back (attract) the fluid to the vascular compartment, but when all of these proteins are lost, fluid will accumulate in the interstitium and edema will develop (at first will start as periorbital edema, then as generalized, and if it's sever enough it's called anasarca), also when this happens the volume of the blood will be decreases, so the renal perfusion will also be decreased and this will activate the renin angiotensin aldosterone system, this will end with the production of angiotensin II, and angiotensin II will constrict the blood vessels and in turn increase the hydrostatic pressure, which in turn will increase the fluid in the interstitium, which simply means more edema, and also the angiotensin II will go to the adrenal cortics, specifically to the zona glomerulosa and it will release aldosterone, and aldosterone will act on the principle cells of the nephron and they will reabsorb more sodium and water, and that will also lead to increased amount of fluid in the interstitium, so more edema will develop, and also during all of this the blood will become hemoconcentrated, so it will have high osmolality, and the patient will become hyperosmolar, this high osmolality will be detected by special cells in the hypothalamus and in turn this will lead to the release of antidiuretic hormone from posterior pituitary gland, the ADH will promote the nephron to reabsorb more water and this water will also be bushed to the interstitium and cause further edema, and during all of this the liver will try to compensate, but unfortunately at the same time it also synthesis lipoproteins and lipids, so the patient also develops hyperlipidemia (↑ LDL, ↑ IDL, ↑ VLDL, ↑ triglycerides), and the patient will also start loosing lipids through the urine (lipiduria), and once again the proximal convoluted tubule cells will also eat up these lipids and become filled with fat globules, and when these cells sheds in the urine we call them fat oval bodies, and also some other molecules may also leak, like transferrin (which is a protein responsible for moving iron in the blood) so the patient will become prone to iron deficiency anemia, another protein which also leaks is antithrombin III (this also another protein which inactivates several enzymes of the coagulation system) so the patient is more prone to thrombosis, and the story doesn't end here, because even some immunoglobulines are also lost, namely the proteins of the complement system, so the patient now is also prone to infections (especially the pneumococcal infections, because they are capsulated and we need the complement system to kill them, specifically we need the C3B as opsonin) and this whole clinical picture is called nephrotic syndrome.
Now lets move
to the fifth and last person, in this person the glomerulus is severely
injured and there is inflammation in it, so there is a lot of
macrophages, neutrophils, and even platelets sticking there, and also
there are even RBC's (dysmorphic or disfigured RBC's because they are
squeezed through the distributed membranes), so we will also see
hematuria, and if there is heavy RBC's leakage these RBC's will cause a
"traffic jam", so to speak, because they will stick together and
accumulate in the renal tubules, but when they come out they will have
this cylindrical shape and will mimic the tubules lumen, so when they
appear in urine we will call them RBC's cast, and because of these
inflammations and obstructions in the glomerulus, the glomerular
filtration rate will decrease, so there will be no urine production, and
if the urine is less that 400 ml/day then we say that the patient is
having oliguria, and also because GFR is less, then the waste product
like urea and creatinine will also accumulate in the blood, so azotemia
will develop, also the decrease in GFR will promote the release of
renin, and this will ultimately cause hypertension, and this whole
clinical picture is called nephritic syndrome.
I hope now you can differentiate between the two, and this post was easy to understand
