Kidney Disease: Understanding Your Lab Values

understanding-your-lab-values
Kidney Disease: Understanding Your Lab Values  

We'll talk about laboratory values for chronic kidney disease it is important that you track and understand your lab values we already talked about creatinine in the previous module creatinine is a waste product from the muscle which is normally removed by the kidneys the level in the blood rises when kidneys do not function well GFR or glomerular filtration rate is calculated based on your creatinine and it estimates the percent of normal kidney function blood urea nitrogen also known as BUN or some patients like to call it Bun it's a waste product from dietary protein which is removed by the kidneys BUN or bun is also used to estimate the level of kidney function but it is less reliable than creatinine it can be affected by how much fluid one drinks and some other variables.

We prefer to focus more on creatinine let's move on to electrolytes and acid-base balance in the blood most people know that too much sodium is not good for you, unfortunately, the level of sodium in the blood does not reflect how much sodium you're eating you might be eating three times as much as you should as an average American does yet your measured level will remain normal at the expense of drinking more fluid to dilute this extra sodium and possibly elevating your blood pressure and putting extra strain on your heart some people can, however, develop an abnormal level of sodium in the blood due to either poorly functioning heart or kidneys or liver or some hormonal disturbances normal level of sodium is between 135 and 145 potassium is a mineral in your blood.

That helps your heart and muscles work properly if the level is too high it can change your heartbeat and lead to potentially dangerous arrhythmia normal range is between three point five to five-point one if potassium level in your blood gets to be too high we'll educate you how to avoid foods which are high in potassium and use medications to help maintain healthy potassium level now bicarbonate is a measure of the acidity of your blood patients with chronic kidney disease often cannot excrete acid generated from the metabolism of foods that they ingest mainly it comes from protein and they develop metabolic acidosis so what metabolic acidosis big deal right well it is a big deal metabolic acidosis also known as too much acid or too little base can lead to muscle breakdown no one wants to have weak muscle right it can also lead to weak bones.

It can speed up the progression of chronic kidney disease normal value for bicarbonate is between 22 and 29 if your level is below that your nephrologist might prescribe baking soda or similar type of medication to correct it to neutralize extra acid in your body and thus protect your muscle protect your bones and slow down the progression of chronic kidney disease, the next three laboratory values have to do with bone health they can be are adversely affected by kidney disease and lead to weak bones calcium and phosphorus are important for strong bones abnormal levels of calcium and phosphorus besides leading to bone disease believe it or not they can get deposited in your blood vessels heart and other organs and cause damage as well normal levels for those minerals might slightly vary depending on the laboratory.

But usually our eight-point six to ten point five milligrams per deciliter for calcium and two-point seven to four point five for phosphorus we will help you maintain normal calcium and normal phosphorus levels with appropriate diet and if needed we use some medications now parathyroid hormone also known as PTH and not to be confused with thyroid hormone or TSH this is something different so PTH regulates the movement of calcium and phosphorus between your blood bones and also affects the excretion in the urine the acceptable level for PTH depends on the stage of kidney disease so you will have to check with your doctor what's the appropriate level for you if your PTH gets to be too high will prescribe a special type of vitamin D which will bring it down to more healthy levels we are moving on now to laboratory values for anaemia haemoglobin is part of red blood cells that carries oxygen from your lungs to all parts of the body haemoglobin is used to diagnose anaemia.

The target range for haemoglobin in patients with CKD is somewhere between nine points five to eleven and it's kind of a moving target but for now, this is what it is if your haemoglobin level is below this range your doctorate might prescribe special medication that will help you your body produce more blood we also periodically measure your iron stores are very important iron is a necessary building block for red blood cells should you be iron deficient your doctor will likely prescribe either iron pills or intravenous infusion to correct this deficiency let's talk about cholesterol for a moment everyone knows about cholesterol right cholesterol is a fat like substance that is found in all cells of the body your body certainly needs some cholesterol but if present in excess it can lead to heart disease normal cholesterol level is considered to be under 200 there are two basic types of cholesterol HDL also known as good cholesterol you get a smiley face for this it has protective properties to the heart so you want this number pretty high one of the ways to increase HDL is by exercise and we'll talk about this more LDL also known as bad cholesterol does not get a smiley face.

It can contribute to heart disease so you want this number on a lower side your doctor might ask you to take cholesterol medication even if your level of cholesterol is under 200 so normal right there is the reason is that patients with CKD are at high risk for heart disease regardless of cholesterol level as I mentioned in the previous module protecting your heart is our number-one priority yes we're kidney doctors yes we care about kidneys but heart comes first a triglyceride is another type of fat found in your blood and if elevated it might increase your risk of heart disease it's usually measured at the same time as measure cholesterol we are now down going over various blood tests and are ready to focus on testing of the urine in the normal state of kidney health there should be no blood no protein and no bacteria in the urine nothing like that presence of blood or protein cannot be detected with a naked eye.

That's why we asked you to submit a urine sample to the lab for more precise microscopic measurements if your kidneys are spilling protein in the urine we'll run an extra test to quantify how much protein is being wasted protein in the urine also known as proteinuria if you want to sound like a nephrologist can overtime cause damage to your kidneys whenever possible we use medications to decrease the amount of protein in the urine and to protect your kidneys besides checking blood and urine tests your nephrologist will likely want to have a picture of your kidneys this is done to make sure that you have two kidneys yes some people are born with just one kidney and they don't know about this it's an incidental finding and we also want to make sure that there is no obstruction or abnormal cysts in your kidneys depending on your situation.

Your you might be asked to do either a kidney ultrasound which is pretty simple or a little bit more sophisticated tests like cat scan or even MRI let's do two questions to test your understanding of this module question number one what blood tests do we use to estimate the level of kidney function or GFR is it a sodium or B potassium or C creatine or D phosphorus all right let's think about this for a second and the correct answer is C or creatinine is used to calculate GFR all right are you guys ready for question number two how much protein should be present in the urine option a none option B some but not too much and let's see option C the more the better all right which one is it okay and the correct answer is that there should be absolutely no protein in the urine protein in the urine is a risk factor for worsening kidney function over time we do everything we can to minimize the amount of protein in the urine congratulations you have completed the module on laboratory values for chronic kidney disease. 

Complete Blood Count / CBC Interpretation (Leukocytosis)

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Complete Blood Count / CBC Interpretation (Leukocytosis) 

The first in the series that we're going to talk about as we go through the CBC is the WBC and we'll talk about increased WBC here under the term leukocytosis okay so a couple of points regarding leukocytosis you know we're looking at a patient most typically in the hospital but this could also be seen as an outpatient as well you should know that the normal range is about 4.5 to 11 and then you'll have this term times 10 to the 9th which is like a billion divided into one litre so how many cells you see in one litre so obviously anything greater than 11 is going to define leukocytosis, okay but it can go as high as a hundred thousand you want to watch trends as we talked about in the first article so you know a 13 on a white blood cell count may be elevated but if the previous one was 20 and it's coming down to 13 then that's a process that's actually resolving and 13 is not to be worried about if on the other hand.

You've got a 5 and it's going to 13 that's something that obviously we need to worry about more okay so again as always watch the trends and then differential so the white count as you may know our white blood cells that are what the Leuco means that's white so these white blood cells are part of your immune system but these white blood cells are actually a collection of other cells there are bands there are segmented neutrophils we call those CEG's and these all sort of make up your neutrophils but then you also have lymphocytes you have monocytes you also have eosinophils, okay so they all have their own the function typically the bands and the neutrophils are seen elevated in pyogenic infections lymphocytes can also be elevated but they're usually more typical for viral okay so be aware of that.

You also may see this in tuberculosis same with monocytes you might see monocytes elevated in tuberculosis and also certain viral infections the one that you should know about though is eosinophils anytime you see elevated eosinophil you need to think about two things specifically one is either an allergy also think about parasites so think about drug allergies if you see high eosinophils think about parasites and there's also a third thing that you should think about is well I'll put it up here and this is just to keep in the back of your mind is Coxie coccidia mycosis which is a fungus that typically lives in the Southwest United States also in parts of South America Central America and that's a famous one that they like to use I bring it up.

Because that's where I live in this part of the world where we see coccidia mycosis and Yoson Affiliate is a nonspecific thing that you might see but think about Coxy think about allergies think about parasites if you see elevated eosinophil there are other things that can do it but that's one of the things that can do it but the one that you're probably going to see the most are these bands CEG's neutrophils and that will be elevated in pyogenic or bacterial infections and there's usually a range so typically what you would see in terms of percent is maybe about 60 percent will be bands and CEG's maybe about 22 or so percent and this won't add up to 100% but around 20 percent or so for lymphocytes about 5% for monocytes.

Maybe 2 to 4% for yo Sinha fills okay if you see a deviation from that then you know that there is a simple line that is increased so if this lymphocyte all of a sudden shoot up think about viruses if these segments go from 60 to 80 or 90 think about a pyogenic or bacterial infection if instead of 4% you're at 20% start thinking about what we talked about Coxy allergy or parasites so we talked about what's normal we talked about watching the trend we talked about the differential let's talk about causes and what to do if the white count starts going up on you on a patient in the hospital so in terms of causes the big four that I want you to know our infection steroids cancer/leukaemia or a catastrophic event and these are kind of listed in order of the most common.

Let's talk about infection first so typically with infection you're gonna see something called a left shift and what that means simply is that bands are basically released from the bone marrow and then it becomes segmented in neutrophils okay otherwise known as PM ends what happens is you see of very little bands and a lot of CEG's normally and when you have an infection the bands start to be released more and more and so you see the bands start to go up in circulation, they'll actually tell you how many bands there are if you start to see bands in circulation that's a very good indication that what you're dealing with an elevated white count is an infection the things that you want to look for clinically look for fever that will also tell you that that's what it is that's going on the look for signs of infection.

Okay, the other thing to do is ask the patient do they have pain that's usually a sign that there's an infection somewhere so look for corroborating evidence that there is an infection going on if you can't find it start to do diagnostic tests to confirm it so things that might be able to do it chest x-ray get a urinalysis you might even need to get a CT scan to look if the patient has a fever and is altered by all means get a lumbar puncture to rule out meningitis the biggest infections are pneumonia which you'll see on a chest x-ray a urinary tract infection which you'll see on a urinalysis look at their skin see if they've got cellulitis somewhere examine their belly see if they're tender think about cholecystitis think about diverticulitis all of these things are going to cause an elevation in the white blood cell count okay.

The other thing that you'll see is steroids so a lot of time people will come in and they'll need steroids for either a COPD exacerbation or they'll need steroids for an asthma exacerbation and you'll put patients on stage for whatever reason what you'll notice almost invariably is the WBC count is going to go up now why does the WBC count go up it goes up for three reasons and this will help us decide and distinguish between why it might be an infection, okay the first reason is something called D margination what does this mean here's your vessel with the white blood cells the middle of it what you don't realize is that their white blood cells have already adhered to the wall and so what happens is the steroids cause these cells to come into the centre of the blood vessel so when you draw the blood.

You're gonna get more of those white blood cells in your sample that's de margination about 60% of the effect that we see with an elevated white count is from D margination now the other thing that might cause this is delayed migration so everybody knows that these white cells go out of the blood vessel and into the tissue that's where they fight infections in the tissue well if you delay that migration of cells of white blood cells into the tissue they're going to be more likely to be in the blood vessel when you draw the blood and get the leukocytosis and we see that about 30% of that effect is due to that the last one that we see here is about 10% of the effect and that is bands released from the bone marrow but this is such a small proportion of the reason.



Why the white blood cells go up so small that in fact, we can actually look at this situation and say that if you see the bands going up significantly it's probably not from steroids it's probably an infection and that if we see all of the different white blood cells going out, for instance, we see the lymphocytes and the neutrophils and the monocytes and they're all going up proportionately that's usually a result of D margination and that's typically what we're gonna see in steroid use so if you've got a patient has pneumonia and you put them on steroids because they're having a COPD exacerbation because of pneumonia and the white cells go up but you don't see a left shift you don't see band Emia then you can probably chalk that up to steroids within reason right steroids are only gonna make the white blood cell go up you know maybe from 12 to 20 at most.

Okay if you start to see 30 40 50 then there's gonna be a problem speaking of which if we go back to infection on number one there is a very famous infection that I would be remiss in mentioning that we see in patients especially in the hospital and that the corollary is c-diff okay I don't want you to miss that if you start to see white counts in the 30 to 40 to 50 and higher range okay so these incredibly high white blood cells something you have to think about is Clostridium difficile colitis and in this situation, you typically do imaging like a CT scan to look at the bowel wall and you'll see thickening of the colonic wall in that situation typically the treatment includes Pio vancomycin, not IV vancomycin but Pio vancomycin and either Pio or IV Flagyl there are other treatments there are even surgical treatments so earlier.

You catch this the better so think about seed if you have a very very high white count, okay so we talked about certain types of infection we talked about steroids causing elevated white-blood-cell the other thing that can do this is if there is leukaemia, of course, remember with leukaemia and lymphomas there's a problem with the production or their survival of these white blood cells so, in other words, there is some sort of gene that gets turned on and these white blood cells start dividing rapidly and so you're making a lot of these and another potential reason why you could have leukaemia or lymphoma is if the cell doesn't die and doesn't involute and just hangs around so there are different variations on this, of course, you know that there is acute lymphocytic leukaemia there is chronic lymphocytic leukaemia there is acute myelogenous leukaemia which is a really bad player and then there's chronic myelogenous leukaemia.

That's the one with the Philadelphia chromosome etc so all of these can do it the thing that you must remember or one of the things that you should remember is something called lap or leukocyte alkaline phosphatase and this is the stuff inside the cells that are responsible for breaking down and killing bacteria well in cancer cells each cell has a lower amount of this leukocyte alkaline phosphatase so in the old days before we had flow cytometry and more genetic ways of figuring out whether or not there was leukaemia or lymphoma what they would do is check score okay and if there was a high leukocytosis but a low lap the score that was indicative of cancer leukaemia if the lab score was elevated that means that there was an appropriate amount of leukocyte alkaline phosphatase in these cells and that probably wasn't it so what should we look for again.

If it's lymphocytic leukaemia obviously we're gonna see elevated amounts of lymphocytes and so if you see a high white count and they're almost all lymphocytes think about this as a diagnosis if, on the other hand, you see various different types of myelogenous type of cells myelogenous meaning segmented neutrophils or eosinophils or monocytes things of that nature then that would be something along the lines of AML or even CML depending so these are divided okay what you really need is a peripheral smear and you need a pathologist to review the cells to see if they look atypical then you need to get even deeper and you might even need a bone marrow biopsy done to evaluate for that okay.

Then the last thing that we're going to talk about is a catastrophic event so a catastrophic event like myocardial infarction or a cardiac arrest or a massive pulmonary embolism is such a stress on the system or even surgery could be a stress on the system that this would cause a transient increase in the white count so what you would see is a bump up very quickly and then the white count would come back down again as you were to track it, okay there are many other things that can cause leukocytosis that I have not included here even a cold shower can make your white count go up so think about these things as you look at your WBC on your CBC thanks for joining us.

Wrist Ultrasound Exam

Wrist-Ultrasound-Exam
Wrist Ultrasound Exam

We are going to examine the wrist today, and the best transducer for this examination is the L25, the small footprint. We will check that the exam type is correct. We are doing an MSK type of exam. For orientation, there is a marker here, which corresponds to the turquoise dot on the screen. Keep this marker proximal when I am examining longitudinally and medial when I am examining transversally. We will start the wrist on the dorsal surface and examine transversally first. There are six compartments, beginning with the first compartment at the base of the thumb, and the sixth compartment near the ulnar styloid.

When we look at the wrist structures, we are looking at not only tendons and bones, but we are also looking at a multitude of joints. If I come over here to a middle portion, we are looking at carpal bones here. With the presence of synovitis, we would have hyperechoic or anechoic fluid and thickening of synovium at these recesses, which are the joints. None of that is present here. We will move over to the extensor tendons of the thumb, where you can sometimes see de Quervain's tenosynovitis, and here is a nice view of one of the long tendons of the thumb.

These extensor Digitorum tendons here are normal in an appearance on the cross-section. You see right over the distal end of the radius, which is right here these two thumb tendons. This then can be traced distally out toward the thumb, and these tendons and their Peritendinous tissue can be examined carefully. On the other side of the wrist toward the ulna, we have a very nice view of the extensor carpi Ulnaris tendon, which is one of the largest extensor tendons in the wrist and easiest to see. It also is frequently surrounded, in a patient with an inflammatory process, with fluid or synovium, and that can be seen as either anechoic or hyperechoic shadow around the distinct oval-shaped tendon, which is hyperechoic, and you can see the fibrillar nature within it. If we look longitudinally, keeping this dot proximal, and find that extensor carpi Ulnaris tendon, you can see these parallel lines, which are going from left to right.

There are areas that are hyper echo alternating with hypoechoic. This is a normal appearance of the tendon and visualizes Peritendonous tissue. The retinaculum, which is up here, in deep to this, this, is the distal part of the ulna. The first part of carpal bones and the triangular ligament is in here. Next, we look at the volar, or palmer surface of the wrist. Most of the time, we are going to be looking at the median nerve in this area. Again, the transducer marker is placed medially. This structure here is the median nerve. We can go toward the radial side and see the artery, the hyperechoic or anechoic area that has a small pulsation.

Sometimes checking colour Doppler signal or Doppler signal is helpful, and the median nerve, then, is seen right here in the middle. On the lunar surface, going in this direction is the ulnar artery, and we can freeze the image and take a measurement of the median nerve if it is desired to see whether this is enlarged using the direct correlation between this measurement and the presence of carpal tunnel syndrome. So I have placed my callipers on both sides of the median nerve, just inside the perineurium, and then I'm going to hit this ellipse button. Then I can actually take an approximate surface area. She has a .08 centimetre squared area, which is normal, and so by ultrasound criteria does not have carpal tunnel syndrome.

Scanning Technique - Ultrasound Foot Exam

Ultrasound-Foot-Exam
Scanning Technique - Ultrasound Foot Exam

We are going to exam the ankle. She is lying down on her back with her knee flexed and ankle in approximately this position. I have selected an L25 transducer because it has a small footprint. It is easy to get around the curves in the ankle. On the SonoSite M-Turbo, I have set for its factory preset for Msk. For orientation, this mark on the transducer corresponds to the turquoise dot on the upper left portion of the screen. And I'll examine the anterior portion of the true ankle joint first. And on the left side of the screen is the tibia. And in this view, you see the tibiotalar joint.

There is a hypoechoic, or anechoic, stripe over the talus, which is cartilage. And there are vessels and tendons superficially. This would be one of the best views for a rheumatologist to find an ankle effusion. And that can be seen as an anechoic area in that V between the two bones. The lateral aspect of the ankle joint can also be examined. The fibula is the bony structure underneath the marker. And the talus is to the right. You can see an effusion again, between those bones as well. Transverse images are very good for looking at extensor tendons, and for tendon abnormalities. You might see anechoic fluid around the tendon or synovitis. And also see in the middle of the screen, the Dorsalis Pedis artery pulsating.

It is very important to identify the position of the arteries so that when you do injections, so you'll be able to avoid them. Next, I am going to examine the medial aspect of the ankle. The medial tendons, three of them, run just inside, or just posterior, to that medial malleolus. It is best to examine these initially in the transverse plane. And we can see two of those tendons very clearly, right superficial to the tibial bone. As a rheumatologist, you can see Peritendinous processes with fluid and synovial proliferation. You can also find large tears or tendinopathy. A longitudinal image of those tendons is also very easy to obtain because they're so superficial. We can look at the lateral aspect of the ankle.

The peroneus tendons are present here. And just posterior to the lateral malleolus are the peroneus tendons. You can see them on the screen just to the right of the bone. There are two tendons there. For examination of the Achilles tendon, it's best to have the patient in the prone position and have the Achilles tendon lined up. The image that you see on the screen, the bony structure is the calcaneus. The Achilles tendon is inserting into the calcaneus distally. This is a frequent zone of calcification. And then going proximally, you can get a very nice view both medially and laterally of this Achilles tendon. The structures deeper to the tendon include a bursa and some fatty tissue. This is the area where many tendon tears occur.

We also should then examine the Achilles tendon transversely. And this can be done all the way distal, to the point where this Achilles tendon gets smaller and smaller, and inserts on the bone. Or as we move proximally, you might be able to see areas of tendinosis, or tendonitis, or rupture here. There are a number of appropriate measurements that are frequently taken for the size, accessing the size of the Achilles tendon. These can be done both in the transverse and longitudinal plane. And usually, we go just to the border where the calcaneus ends and freeze the image.

Then using the callipers, and place one on this side and one on this site for getting a measurement from medial to lateral. You can then get another measurement of thickness from the superficial to the deep. You can also measure an area. Probably the best way to do it is manual. And so then this gives us an area of the tendon, in a cross-section, and that area is .85 centimetres squared. You can also take measurements of the Achilles tendon in the longitudinal plane. And measure the thickness at the edge of the calcaneus.

Acute Myeloid & Lymphoblastic Leukemia - Causes, Symptoms & Pathology

Acute-Myeloid-&-Lymphoblastic-Leukemia
Acute Myeloid & Lymphoblastic Leukemia
Learning medicine is hard work! Osmosis makes it easy. It takes your lectures and notes to create a personalized study plan with the exclusive article, practice questions and flashcards, and so much more. Try it free today! With acute leukaemia, Leuk- refers to white blood cells, and -anaemia refers to the blood, so in acute leukaemia, there’s an uncontrolled proliferation of partially developed white blood cells, also called blast cells, which build up in the blood over a short period of time. Although leukaemia means cancer white blood cells, it can also be used to refer to cancer of any of the blood cells, including red blood cells and platelets. Acute leukaemia can be broadly classified into acute myeloid leukaemia or AML; and acute lymphoblastic leukaemia, ALL. AML is more common in old age, whereas ALL is more common in children. 

In both cases, the accumulation of blast cells interferes with the development and function of healthy white blood cells, platelets, and red blood cells. Now, every blood cell starts its life in the bone marrow as a hematopoietic stem cell. Hematopoietic stem cells are multipotent -- meaning that they can give rise to both myeloblasts, which are precursors of myeloid blood cells, and lymphoblasts, which are precursors of lymphoid blood cells. These lymphoblasts can be pre-B cells, which develop into B lymphocytes; or pre-T cells, which develop into T lymphocytes. If a hematopoietic stem cell develops into a myeloid cell, it’ll mature into an erythrocyte -- or a red blood cell, a thrombocyte -- or a platelet, or a leukocyte -- or a white blood cell, like a monocyte of granulocyte. Granulocytes are cells with tiny granules inside of them -- they include neutrophils, basophils, and eosinophils. If a hematopoietic stem cell develops into a lymphoid cell, on the other hand, it’ll mature into some other kind of leukocyte: a T cell, a B cell, or a natural killer cell, which are referred to as lymphocytes. 

Once the various blood cells form, they leave the bone marrow, and travel around the blood, or settle down in tissues and organs like the lymph nodes and spleen. Acute leukaemia is caused by a mutation in the precursor of blood cells in the bone marrow. In the case of ALL, it’s usually due to a chromosomal translocation or due to an abnormal chromosome number. Common chromosomal translocations include translocation of chromosome 12 and 21 and translocation of chromosome 9 and 22, also called the Philadelphia chromosome. These result in the production of abnormal intracellular proteins, which affect the cell’s function and cell division. ALL can further be classified into T-cell ALL, where there’s the proliferation of T-cell precursors, and B-cell ALL, where there’s a proliferation of B-cell precursors. AML is caused by a wide variety of abnormalities like chromosomal translocations, which are used to subclassify AML into a few different types. 

AML can also be classified based on the morphology of the myeloblast into AML without maturation; AML with minimal maturation, AML with maturation; acute promyelocytic leukaemia; acute myelomonocytic leukaemia, acute monocytic leukaemia, acute erythroid leukaemia, and acute megakaryoblastic leukaemia. Of these, acute promyelocytic leukaemia is an important subtype. It is characterized by translocation of chromosome 15 and 17 which disrupts the retinoic acid receptor alpha gene, which is required for normal cell division. Now, there are also certain conditions that can actually lead to AML, like myelodysplastic syndrome, which is characterized by defective maturation of myeloid cells and buildup of blasts in the bone marrow. 

Usually, the buildup is initially less than 20% blasts. But that’s enough to cause a decrease in the function of red blood cells, granulocytes, and platelets. As the disease progresses, the blast percentage may go over 20%, resulting in AML with a background of myelodysplasia. Another condition often associated with both AML and ALL is Down syndrome, which is caused by an extra 21st chromosome - so that there’s a trisomy 21. Finally, there are also some risk factors for acute leukaemia like exposure to radiation, and alkylating chemotherapy, which may have been used as a treatment of some other type of cancer. Alright, now regardless of the type of mutation, acute leukaemias share similar pathogenesis. The mutation does two things. First, it causes these precursor blood cells to lose their ability to differentiate into mature blood cells. 

This means that they’re stuck in the blast stage of development, and the blast cells don’t function effectively. Second, it makes the blast cells divide uncontrollably, and in the process take up a lot of space and nutrition in the bone marrow. This means that the other normal blood cells growing in the bone marrow get “crowded out”, and it’s tough for them to survive with the extra competition for nutrients. This causes cytopenias, or a reduction in the number of healthy blood cells, like anaemia, which is a reduction of healthy red blood cells, thrombocytopenia, a reduction of healthy platelets, and leukopenia, or a reduction of healthy leukocytes. As the number of blast cells in the bone marrow keeps increasing, they spill out into the blood. 

Now some of these guys, especially lymphoblasts, settle down in organs and tissues across the body, like the liver and spleen. Sometimes, pre- T cells, in T- cell ALL migrate to the thymus or lymph nodes like normal T-cells do and settle down there, causing these structures to enlarge. Also, in acute promyelocytic leukaemia, the promyelocytes activate the clotting process, and this combined with the already decreased platelets, results in disseminated intravascular coagulation. Symptoms of both AML and ALL include fatigue, because of the anaemia, easier bleeding, because of the thrombocytopenia, and more frequent infections, because of the leukopenia. Pain and tenderness in the bones can occur when there’s increased cell production which causes the bone marrow to expand. Hepatosplenomegaly often causes a feeling of abdominal fullness, while the lymphadenopathy often causes mild, but localized pain in the lymph nodes. However, hepatosplenomegaly and lymphadenopathy are both seen more prominent in ALL than in AML. In addition, monocytic variety of AML causes swelling of gums because of monocytic infiltration. 


Thymus enlargement in T-ALL may present as a mass, or growth in the mediastinum. The diagnosis of AML and ALL usually starts with a peripheral blood smear, which shows a lot of blast cells, myeloblasts in case of AML, and lymphoblasts in case of ALL. This is usually followed up by a bone marrow biopsy, which also shows an increase in blast cells. In acute leukaemia, the percentage of blast cells in the bone marrow goes up from their normal value of 1-2% to greater than 20%! An important step in the diagnosis is to differentiate AML from ALL. This can be done by identifying the blast cells as either myeloblast or lymphoblasts in a specially stained smear. Myeloblasts are usually large cells with nuclei containing fine chromatin and prominent nucleoli. A classic feature of myeloblasts in AML, especially acute promyelocytic leukaemia, is the presence of Auer rods in the cytoplasm, which are crystallized aggregates of the myeloperoxidase enzyme. 


On the other hand, lymphoblasts are relatively smaller cells with coarse chromatin, which are clumped together and have small nucleoli. Lymphoblasts have very little cytoplasm, which has glycogen granules. In addition, immunophenotyping is done to detect certain markers, for example, TdT, which is a DNA polymerase that’s present only in the nucleus of the lymphoblast, is a marker for lymphoblasts, and CD10 is a surface marker for pre-B cells. Treatment of acute leukaemia is mainly aimed at reducing the number of blast cells, to allow the other blood cells to develop normally. Treatment of AML and ALL is based on the type and stage of cancer, but in general involves chemotherapy, biological therapy, stem cell transplants, or bone marrow transplants. Acute promyelocytic leukaemia can be treated with all-trans-retinoic acid, or ATRA, which is a derivative of vitamin A. ATRA binds to the disrupted retinoic acid receptor and causes the blasts to mature into neutrophils, which eventually go on to die, thereby clearing out a lot of the blasts from the blood. All right, as a quick recap. Acute leukaemia is a cancer of the blood cells and is classified into AML and ALL. AML can be further subdivided into different types based on cytogenetic abnormalities or based on blast cells morphology. 


ALL, on the other hand, is classified into T-cell ALL and B-cell ALL. Both AML and ALL lead to accumulation of blast cells in the bone marrow, which interferes with the development and function of healthy white blood cells, platelets, and red blood cells. Major symptoms include fatigue, easy bleeding, fever, bone pain, hepatosplenomegaly, gum swelling in monocytic type, and mediastinal mass in T-ALL. 

How Coronavirus Test Kits Work

How-Coronavirus-Test-Kits-Work
How Coronavirus Test Kits Work

Researchers around the world are hustling to create this test kit. The rapidly-spreading new coronavirus has put test kits at the centre of how infected patients are diagnosed, so they can get treatment quickly. But there's one issue with these nose and throat-swabbing tests. The results aren't always accurate. At the centre of the epidemic in Wuhan, some people tested negative, only later to find out that they actually have the disease. In the U.S., the CDC sent out test kits to public health labs that gave inconclusive results in the verification process.

The unreliability of these tests even forced Chinese health officials to expand how they classify patients, which resulted in a surge of more than 14,000 cases in one day. They are now including results from test kits and other diagnostic methods like chest scans. So how do these test kits exactly work, and why are there so many problems? This government lab in Singapore has produced test kits for the country's public hospitals. It's also shipped about 10,000 tests to China. Dr Sidney Yee leads the team that developed them.

She says most doctors use a type of lab test called RT PCR, which can be used to detect small amounts of pathogens including viruses like HIV. So this is the gold standard that's being used. What it does is, it actually directly detects the presence of the pathogen. It's pretty easy to use. A doctor collects samples from a patient by swabbing the nose or throat for mucus. Those swabs are then sent to a lab for a test that detects the genetic material of a pathogen. The sample is first mixed with reagents in a tube, then put into a machine that duplicates the genetic material. (machine whirring) So if the virus exists, these copies will amplify its presence, confirming that a patient has tested positive for the coronavirus.

Dr Yee says the first place for error could be at the swabbing stage. Most of the time, the sampling for COVID-19 comes from a throat swab. COVID-19 is actually a lung infection disease, so doing the throat swab really depends on how much of the pathogen you're able to capture. Another place for error is the time it takes for the sample to reach the lab. The pathogen on the swab is not going to last for many, many hours, so that transportation, the logistics, is also important. 

Transportation is a huge hurdle in Wuhan, where the city has been on lockdown since mid-January. When the sample gets to the lab, what is the infrastructure of the lab that is able to deal with running tests, as well as the expertise and the experience of the lab technicians that are running these tests? -  Dr Yee says the most critical moment for human error is when doctors decide to use the test kit. For instance, many people have been showing mild symptoms, but that doesn't mean they don't have the pathogen.


It's very hard to make the direct correlation between what our test kit can be used, on which stage of the disease progression, with respect to how much the pathogen is present in the patients. - Just how accurately these test kits are being used is on trial in Wuhan. Here, hospitals have been overstretched with limited resources. There are not enough staff to swab patients, and labs are inundated with the backlog of samples that wait to be tested. - There are many, many different steps, and different processes involved in just running a test. It's not just with respect to the test kit itself. 

COVID-19 (Coronavirus Disease 19) Causes, Symptoms, Diagnosis, Treatment, Pathology

COVID-19
COVID-19 (Coronavirus Disease 19)

By now, you've probably heard of COVID-19, or coronavirus disease discovered in 2019, which is responsible for a global pandemic. COVID-19 is caused by SARS-CoV-2, or Severely Acute Respiratory Syndrome Coronavirus 2, because it's genetically similar to the SARS Coronavirus, which was responsible for the SARS outbreak in 2002 (2003). Now, coronaviruses that circulate among humans are typically benign, and they cause about 1/4 of all common cold illnesses. In COVID-19, what happened is that there was a coronavirus circulating among bats, which are a natural animal reservoir, and it mutated just enough to start infecting an intermediate host the Pangolin, an animal that looks like a cross between an anteater and an armadillo, In late 2019, the coronavirus mutated again and started causing disease in humans. 


The outbreak began in China but has since spread around the world. As of March 9th, 2020, or roughly 3 months into the outbreak there have been 109,578 confirmed cases of COVID-19 and 3,809 deaths, resulting in a fatality rate of 3.5%, but that represents an average across different countries and timeframes. Based on a large study in China, digging deeper reveals that the fatality rate in China was actually 16% for cases between January 1st and January 10th, but then, it fell steadily over time until it was only 0.8% for patients with symptom onset after February 1st. There are two main reasons for this: first, the hospitals and clinics were initially overwhelmed and couldn't manage the disease, so both patients and healthcare providers were getting severely ill and dying, but within a few weeks with better equipment, testing, and processes in place, the healthcare system responded and brought down the fatality rate dramatically.

Now as a point of comparison, the flu typically causes a fatality rate of 0.1%, so even based on this data, COVID-19 is still 8 to 35 times more deadly than the flu. It's also worth pointing out that for COVID-19, the mortality rates differ by group, so for example, if you split things out by age, you can see from this table that fatality rate is relatively low if you're below 60, with no deaths seen in children at 9 and younger, but then it starts to really climb up for the elderly, so they're really the ones at highest risk. Similarly, the fatality rate is higher for folks with hypertension, diabetes, cardiovascular disease, chronic respiratory disease, and cancer, relative to folks without any of these conditions. and of course, a lot of the elderly typically have one or more of these conditions, so it's not surprising that they go hand in hand. Now, although the COVID-19 pandemic is still ongoing, the good news is that in China and also in South Korea, the number of new cases per day has dropped off largely due to the aggressive public health measures like quarantining, aggressive testing, and ensuring hospitals have the right equipment and staffing. Based on the current data, over 80% of the patients with COVID-19 have a mild infection and some people won't develop any symptoms at all. 


For others, they can develop symptoms that can range from pretty mild like fever, cough, and shortness of breath, all the way to serious problems like pneumonia. Severe lung damage can cause Acute Respiratory Distress Syndrome or ARDS, which occurs when the lung inflammation is so severe that fluid builds up around and within the lungs, the severe infection can cause septic shock which happens when the blood pressure falls dramatically and the body's organs are starved for oxygen. ARDS and shock are the main causes of death for people with the infection and again this is most likely to occur in those over the age of 60, smokers and people with other medical conditions like heart disease. In addition to causing disease, coronaviruses can spread quickly, usually, the virus spreads when people cough or sneeze, and tiny droplets containing the virus are released. These droplets can land on another person's mouth, nose, or eyes, and that allows the virus to enter a new person. 

When a person with COVID-19 travels to a non-affected area, this is called an imported case. If they start spreading the disease to household contacts and those around them, it's called local transmission, since it's usually isolated to a small area and can be easily traced back to the original person. However, when people begin to contract the disease without a clear source, it's called community transmission. To prevent or contain community transmission, some schools and businesses have shut down; and some conferences, sporting events, and other large gatherings have been postponed or cancelled. Once a person is infected, symptoms develop about five days later, this is called the incubation period. Now there's debate about how much asymptomatic or pre-symptomatic people, which is to say folks that are in the incubation period are spreading the disease, and it may be much more than what we originally thought. Viruses are given a reproductive number or R-naught, based on how quickly they spread and person-to-person transmission has been confirmed both in and outside of China an R-naught of 1 means that an infected person passes it on to one new person, an R-naught of 2 means that one person spreads it to two new people. 

If the R-naught is below 1, the infection peters out, if it's at one, it stays steady; and if it's above one, then it continues to spread, the current estimate for COVID-19 is an R-naught of 2.2. As a point of comparison, the R-naught of the flu virus is about 1.3, so COVID-19 spreads quite a bit more easily. To confirm the diagnosis, a reverse transcription-polymerase chain reaction or RT PCR test can be done which can detect very small amounts of viral RNA. It's worth mentioning, however, that early in the disease, the RT-PCR can often miss the infection altogether, meaning that it's not very sensitive, so if the severe pulmonary disease is suspected, a chest CT should also be done to help detect the presence of viral pneumonia. It's also important to look for other causes of similar symptoms by doing things for example like a quick flu test, or a respiratory viral panel to look for alternative causes of the symptoms. Treatment is focused on supportive care, such as providing fluids, oxygen, and ventilatory support for really ill people. There are also early data showing that Remdesivir, an antiviral drug previously used against Ebola can be helpful, and it's being tested in large-scale clinical trials in the US and China. 


Unfortunately, there's no vaccine currently available to protect against COVID-19, having said that, there are some being researched including one that is in clinical trials and will likely be ready by 2021. So, the main goal is to avoid person-to-person transmission, in areas with community transmission, anyone with mild symptoms regardless of whether they have been diagnosed as having COVID-19 or not should wear a mask and they should self-quarantine within their home, if those symptoms worsen, they should call their clinic or use telemedicine to talk to a clinician. For people with symptoms that live with others or even with pets, they should self-quarantine in a separate room and use a separate bathroom if possible and they should avoid sharing household items like bedding or eating utensils. In fact, there has been a confirmed case of human-to-dog transmission, where COVID-19 went from a person to their pet dog. however the dog didn't get sick, and there's no evidence that pets can spread this disease or become sick, so it's not necessary to take measures against companion animals. 

Finally, anyone with symptoms including children and younger adults should not attend school, work, or any other in-person gathering, and should avoid travel. Now for individuals that don't have symptoms but are at higher risk like those over age 60, and people with a chronic disease, the recommendation is that they also self-quarantine to avoid the chance of getting sick. Self-quarantining requires keeping a few weeks supply of your medications, groceries, & household items as well as having an emergency contact person. Coronaviruses don't usually spread over long distances in the air, but they can get flung from one person to another on tiny droplets of saliva when someone's coughing or sneezing. In addition, some strains of coronavirus can survive on surfaces for over a day. With that in mind, if you're a healthy person living in a non-outbreak area, the recommendation is to avoid travel to disease outbreak areas, generally, stay away from crowded places and stay at least 6 feet or 2 meters away from anyone with symptoms. Wearing a surgical mask is not recommended because they're meant to catch droplets from a cough or sneeze going out rather than preventing you from breathing in the virus. Similarly, wearing an N95 mask is not recommended because they're only meant to be worn by healthcare workers. In addition, cleaning and sterilizing frequently-touched surfaces like toilet seats, door handles, phones, and keyboards are also a good idea. As always, careful hand-washing is key, and it should be done with soap or alcohol-based hand sanitizers and scrubbing for 20 seconds. 



Also, avoid touching your eyes, nose, and mouth, this is the area known as your T-zone, it's a common entry point for viruses into the body. For healthcare workers who are around people with COVID-19, the recommendation is to apply droplet and contact precautions, that includes wearing personal protective equipment like a clean dry surgical mask, gloves, long-sleeved gowns, and eye protection like goggles, or a face shield, when performing a procedure that generates aerosol like tracheal intubation, bronchoscopy, CPR, or non-invasive ventilation, it's important to wear an N95 respirator. This prevents 95% of the small particles like respiratory droplets from passing through. Alright, as a quick recap, the SARS-CoV-2 virus causes COVID-19. The virus travels in respiratory droplets and enters the body via the mouth, nose, or eyes, it can cause symptoms like fever, cough, and shortness of breath. And in some people, it can progress to more dangerous complications like pneumonia, ARDS, and shock. 

The highest risk is among the elderly and those with other serious health conditions. Treatments are focused on supportive care, but medications like Remdesivir are in clinical trials, and there's a vaccine in clinical trials as well that will likely be ready by 2021. In the meantime, the best strategy is prevention, this includes careful hand-washing, avoiding travelling to disease outbreak areas, and crowded places when possible, avoiding touching your T-zone, and if you're a healthcare worker, using personal protective equipment.