Why does the GFR go down in nephritic syndrome?

Q. I have a question. Why do you see a decreased glomerular filtration rate in nephritic syndrome? I read on your blog and other places that it’s due to “hemodynamic changes”– from Robbins I’m assuming this is compensatory stuff- but wouldn’t that increase GFR?

A. It’s because of what’s going on in the glomerulus! In a normal glomerulus, the capillaries are all nice and open and patent. Blood flows through the capillaries like a little river, fluid gets filtered out into the urinary space, and the GFR is normal. But in nephritic syndrome, the glomeruli are stuffed full of cells, and blood flow slows way down.

Take a look at post-streptococcal glomerulonephritis, a common cause of nephritic syndrome. In that disorder, the glomeruli are huge and hypercellular, with tons of neutrophils in there (and probably some other proliferating glomerular cells as well). The poor capillaries are compressed by all that extra stuff, and you can imagine how hard it is for the poor blood to flow through there! If the blood can’t flow through at the same rate, then the filtration of fluid from blood into urine is decreased (and the GFR slows down to a sad little dribble).

Nice water drop: John “K”

What is an anti-antibody?

Q. I just had a quick question as I was going through some immunology notes and wondering if you could clarify what they mean when a person develops an anti antibody? (more…)

How is iron handled in the body?

Q. I’ve never been clear on the way iron is handled and was hoping you could clarify. Basically, I don’t understand the difference between serum iron and serum ferritin. (more…)

Antiphospholipid antibody syndrome

Q. Can you write a post about antiphospholipid syndrome? I could not find good source which explains its pathophysiology and laboratory results

A. First, before we get into the antiphospholipid syndrome, we need to talk about antiphospholipid antibodies. As you might expect from their name, antiphospholipid antibodies are autoantibodies in the patient’s plasma that are directed against various phospholipids (there are lots of phospholipid surfaces in the body – including the phospholipid surface upon which the coagulation factors interact). There are a bunch of different types of antiphospholipid antibodies, including anticardiolipin antibodies, anti-glycoprotein antibodies, and the so-called lupus anticoagulants (which were discovered in patients with lupus).

In addition to binding to various phospholipid surfaces in the body, these autoantibodies also just happen to bind to the phospholipid part of the PTT reagent (and sometimes, the PT reagent). Then there’s not enough usable reagent in the test tube, and the patient’s specimen doesn’t clot! The coagulation tests are therefore falsely prolonged.

Antiphospholipid antibodies are sometimes called “inhibitors” because they appear to inhibit coagulation in the test tube. But here’s a weird thing: in the body, they can be associated with thrombosis!

You may be asking yourself: how do you get these antiphospholipid antibodies? And are they dangerous?

It turns out there are different answers for different patients. Children, for example, sometimes develop antiphospholipid antibodies after an infection. In this setting, the risk of thrombosis is only slightly increased; it’s usually not a big deal clinically. Adults sometimes develop antiphospholipid antibodies as part of an autoimmune disorder like lupus (in fact, antiphospholipid antibodies – in whatever clinical setting – are often called “lupus inhibitors” because of this association). In these patients, the risk of thrombosis is moderately increased. Finally, elderly adults may develop antiphospholipid antibodies in association with drugs. This is virtually always a harmless event with no increased risk of thrombosis.

Okay, so here’s where we get to the antiphospholipid antibody syndrome part. This term is used when a patient with an antiphospholipid antibody has thromboses or pregnancy-related complications (like recurrent miscarriage, pre-term labor, or pre-eclampsia). This syndrome is a serious thing. In a small number of patients, the thromboses can be widespread, leading to multi-organ system damage and death. The term is reserved for patients who are symptomatic; you wouldn’t use the term in patients who have an antiphospholipid antibody but no symptoms.

So what would you do if you think your patient might have an antiphospholipid antibody? Well, you’d need to confirm this suspicion with laboratory tests. First, order a PTT (in fact, that’s how a lot of these patients get picked up – they present with an abnormally prolonged PTT in the face of clinical evidence of thrombosis).

Then, order up a mixing study. Remember what a mixing study is? You do this test when you have a patient with a prolonged PTT and you want to know why. It’s performed by taking the patient’s (probably abnormal) plasma and mixing it with some pooled (normal) plasma – then running the PTT on this new mixed sample.

If the new PTT value is within the normal range (if it “corrects”), then you know the pooled human plasma must have supplied something to the patient’s plasma to make it clot normally. The “something” is usually a coagulation factor that the patient is missing.

If the new PTT value is still abnormal (if it’s still prolonged, and doesn’t “correct”), then you know that even though you added a bunch of normal plasma to the mix, the patient’s plasma still couldn’t clot normally. There must be some other problem with the patient’s plasma. The “other problem” is usually an inhibitor.

One caveat: some antiphospholipid antibodies do not prolong the PTT. It all depends on the particular PTT reagent your lab is using (some reagents are just more easily swayed by the antiphospholipid antibodies). So if you really feel your patient may have an antiphospholipid antibody, you shouldn’t stop investigating that possibility just because the PTT comes back normal! There are plenty of fancy lab tests that can be done to detect antiphospholipid antibodies. Just call your friendly neighborhood pathologist and see what he/she has to offer.

What is array-based CGH?

Today’s post, authored by a very smart guest cytogeneticist, nicely describes array-based comparative genomic hybridization, a very cool DNA test that gives us a way to detect genetic abnormalities that are too small to be seen under the microscope. (more…)

Thyroid lab tests explained in under 150 words

Q. I have been trying to figure out the two basic thyroid lab tests, TSH and T4. If you have a high TSH and a low T4 does that mean that the pituitary gland is going crazy to reach homeostasis but the thyroid is not responding? And inversely, if the T4 is high and the TSH is low does that mean for some reason the thyroid is working overtime due to a disease like Graves disease, and the pituitary is trying to compensate by not producing TSH?

A. Yes! That’s exactly right. When the two (TSH and T4) are opposite of each other – high T4/low TSH or low T4/high TSH – that means that the problem is intrinsic to the thyroid gland (Graves disease or Hashimoto thyroiditis, for example) and the pituitary is trying to control the thyroid by producing more or less TSH. Those are the most common types of thyroid disease – those that are intrinsic, or primary to the thyroid gland itself.

On the other hand, if both TSH and T4 are either low or high – high T4/high TSH or low T4/low TSH – that means that the process is being driven by TSH. Either there’s a pituitary adenoma making a ton of TSH, or the pituitary is not working well for whatever reason (it’s been radiated, or has undergone necrosis) and it’s not making enough TSH.

Image credit: akay (http://www.flickr.com/photos/akay/245002004/), under cc license.