Glomerular diseases Flashcards
what are the major components of the glomerulus that can be damaged…leading to altered function?
podocytes, basement membrane, capillary endothelium, mesangium
What might lead to damage of any part of the glomerulus?
overwork, inflammation, mutations, depositions, infection
Explain nephrotic syndrome.
Damage to the glomerulus can cause fenestrations to be leaky. When this is mild, only albumin can leak through. Larger pores allow bigger proteins through like globin. The liver is able to compensate for this loss of proteins by creating more until the loss becomes greater than 3.5g/day. At that point you get nephrOtic syndrome characterized by high proteins in urine (proteinuria) low proteins in blood (proteinemia) and edema. Edema occurs because blood has lost so many proteins it no longer has enough osmotic pressure to pull fluid back in from the tissues. With increasing severity (bigger pores and more pores) allow additional even bigger proteins to come through like transferrin (results in anemia) and antithrombin III (results in hypercoagulation) and complement proteins (results in poor immune response). Liver tries to make as many proteins as possible to compensate. Unfortunately, liver cannot make protein without also making lipids. So you will see elevated plasma lipids and “fat oval bodies” of lipids in the urine.
Summarize the major findings associated with nephrotic syndrome.
1) Proteinurea
2) Proteinemia
3) Edema
4) fat oval bodies
5) anemia
6) frequent infection
7) hypercoagulability
Explain nephritic syndrome
Think of this as a worsening of nephrotic syndrome. Glomerular damage has gotten worse to a point where inflammation begins. Inflammation of the filters will actually stop many of the proteins from leaking through, so lab values will IMPROVE. You’ll have less protein in urine and more in the blood, so edema will improve. BUT the result of this will be LESS urine production (oligouria). With less urine being produced and a thick filter, you start to accumulate waste in the blood. Specifically creatinine and urea. This accumulation in the blood is called azotemia. When azotemia becomes severe enough to produce symptoms, it is called uremia. Accumulation of fluids leads to a bigger blood volume, resulting in hypertension. Now we have a higher blood pressure which will start forcing filtration at the inflammed glomerulus. This starts forcing RBC’s into the urine. The RBC’s will either be dysmorphic from being squeezed through inflamed passages, or it will be casts from having backed up in the nephron.
Summerize the major findings of nephrItic syndrome:
1) oligouria with azotemia
2) htn
3) hematuria (dysmorphic rbc’s and rbc casts)
4) lab values improve to “sub-nephrotic” values (meaning you loose <3.5g/protein daily)
How could acute kidney injuries like nephrotic or nephritic syndrome lead to chronic kidney problems?
Damage to epithelium signals the repair system. In this case that is fibrin. Fibrin comes in and stimulates epithelial growth. After this occurs collagen comes along and makes deposits that permanently thicken the membrane filters.
How do we treat nephritic and nephrotic syndromes?
control BP and fluid overload. Inflammation may require steroids. Dialysis in extreme cases
What mechanisms does the glomerulus employ to help keep proteins out of the urine
Filtration membrane:
1) Capillary epithelial cells are fenestrated (pores) each has a diameter around 70-100nm (nothing bigger can get through)
2) Filtration slits are the gaps between the interdigitations of the podocytes (bowman capsule side). These slits are 20-30nm.
3) Negative charge on the capillary endothelial cells, basement membrane, and podocytes. (Remember proteins like albumin are negatively charged, so they are repelled)
What is the mechanism of action of “minimal change disease”
Filtration membrane looses negative charge, so small proteins like albumin can leak through the fenestrations and the slits even though there is no actual change to the anatomy of the glomerulus. (Cytokines from infection, inflammation, etc will cause charge to neutralize)
How do you treat minimal change disease?
eliminate the cytokines/inflammation via steroids
What symptoms are present in minimal change disease?
similar to nephrOtic syndrome–>edema, proteinuria, proteinemia, hyperlipidemia, coagulation, anemia. Occurs frequently after acute illness.
