Las remesas familiares: ingresos, uso familiar

A. Neutrophils – when you have acute inflammation = ie appendicitis, neutrophilic leukocytosis, left shift, toxic granulation,

and leukamoid rxn. Leukamoid rxn means that it looks like leukemia but it isn’t and it’s benign. Usually involves any of cell lines. What causes leukamoid rxns? TB and sepsis. You see greater than 30-50,000 cells in the blood. Kids get these a lot (ie otitis media). Adult with otitis med = 12,000; kids with 30,000 (exaggerated). Example: Pertussus – whooping

cough – lymphocytosis (60,000) – pediatricians are worried about ALL leukemia, but kid doesn’t have anemia or

thrombocytopenia; kid comes in pale, coughing. Lymphocytes are mature and are totally normal. Lymphocytosis w/ viral infection or with pertussus.

In atypical lymphocytosis – this is a lymphocyte that is doing what it’s supposed to do when presented to and Ag. It’s responding to the Ag by dividing and getting bigger, so basically it’s an antigenic stimulated lymphocyte. When talking about atypical lymphocyte, the absolute first thing that pops into the mind is: mononucleolosis – EBV. Other dz that are seen with large, beautifully staining bluish cells: CMV, toxoplasmosis, any cause of viral hepatitis, phenytoin. EBV is called the kissing dz b/c the virus holds up in the salivary glands. EBV affects B cells and CD 21. Mono causes viremia, generalized painful lymphadenopathy, very commonly get exudative tonsillitis, jaundice (hardly ever seen), increased transaminases (off the chart), and spleen enlargement and can rupture. Therefore don’t play sports b/c can ruptured spleen can occur, so avoid contact sports usually for 6-8 weeks. Also causes macrocytic anemia via inhibiting intestinal conjugase).

Audio Day 3: Hematology File 5

Example: the boards will give you a classic hx of mono, and ask which tests you run, but monospot test is not on the choices b/c that’s the trade name, so pick heterophile antibodies (hetero = diff, phile = loving). Heterophile Ab’s are anti- horse RBC Ab’s (or anti-sheep); they are different, hence “hetero”phile Ab’s. Once you have mono, you always have it and will have 3-4 recurrences over your lifetime – ie reactivation consists of swollen glands, very tired, etc. EBV lives in B cells; the atypical lymphs in mono are T cells reacting against the infected B cells.

B. Monocyte = king of chronic inflammation, therefore expect monocytosis in pts with chronic infections – ie rheumatoid

arthritis, Crohn’s, ulcerative colitis, lupus, malignancy

Side Note: creatine gives energy b/c it binds to phosphate, and that is the phosphate you get from making ATP – so what serum

test is markedly elevated in someone taking creatine for their muscles? Creatinine! B/c the end product of creatine metabolism is Creatinine. The BUN is normal in this person. Worthy board question.

C. Eosinophilia

You would see eosinophilia in Hay fever, rash in pt with PCN, strongoloides

Protozoa infections DOES NOT produce eosinophilia, therefore it rules out amabiasis (pinworm), giardia, and malaria. Only invasive helminthes produces eosinophilia. Adult ascariasis does NOT cause eosinophilia b/c all they do is obstruct bowels, it’s when the invasive larvae form crosses into the lungs that causes eosinophilia. So anything that is Type I HPY causes eosinophilia; protozoa do not cause eosinophilia; ascariasis, and pinworms do NOT cause eosinophilia (all others – ie whipworms do b/c they invade).

Difference between serum Na and total body Na? yes. Serum Na is milliequavalents per liter of plasma; total body Na is milliliters per kg body wt (the total amount you have). Similarly: RBC mass = total # of RBC’s in entire body in mL/kg in body wt

RBC ct = # of RBC’s/microliter of blood , therefore its how many you have in a certain volume of blood. Why is this a big deal? Example: went running and vol depleted – RBC ct would be hemoconcentrated, therefore would look like more RBC’s per microliter of blood (b/c you depleted the plasma volume), but what would the RBC mass be? Normal (not actually synthesizing RBC’s). So, there are 2 types of RBC’s: relative and absolute. Relative = decrease in plasma vol causing an increase in RBC ct, but the RBC mass is normal. Absolute increase – is appropriate or inappropriate ?

When would it be appropriate? Syn of RBC’s – tissue hypoxia, so, any source of tissue hypoxia would be an appropriate response. Example: if you have lung dz, hypoxemia, COPD, high altitude – these are ie’s of appropriate polycythemias. What if we have normal blood gases, but didn’t have tissue hypoxia? This would be an inappropriate polycythemia. So, there are two things to think about with increased RBC mass: polycythemia rubivera, which is an ie of a stem cell proliferative dz of the BM, meaning that the stem cells are dictators, and nothing keeps them in check – a neoplastic dz; they can become leukemias. So, it would be inappropriate to have normal blood gases and no evidence of tissue hypoxia and have an increase in RBC mass. 2) Tumor or cyst with an excess production of EPO: renal adenocarcinoma making EPO, causing an increase in RBC mass – this is inappropriate b/c a tumor is inappropriately making it.

In summary: polycythemia is relative or absolute. Relative means that you just lost plasma vol (ie from running) with RBC ct increased, and mass is normal. Absolute increase: is it appropriate or inappropriate? Appropriate – anything that is a hypoxic stimulus for EPO release. If there isn’t a hypoxic condition causing the EPO production, then you are ectopically making EPO from a tumor or cyst or you have polycythemia rubivera (a myeloproliferative dz).

III. Myeloproliferative dz – neoplastic stem cell dz that has lost all regulation and nothing can inhibit it anymore. 4 dz’s that

fit under this definition: 1. Polycythemia rubivera

2. CML (only leukemia in this category)

3. Agnogenic myeloid metaplasia – BM is replaced by fibrous tissue

4. Essential thrombocythemia – where a stem cell that makes platelets goes crazy and make 1 million, 600 platelets for microliter,

5. Myelodysplastic syndrome

A. Polycythemia rubivera: 4 H’s:

1. Hyperviscosity (remember Pouseau’s law = TPR = viscosity/radius4_{). With polycythemia, it will have an increased} resistance and TPR will go up; it will predispose to thrombosis, which kills you – thrombosis of anything – ie dural sinuses; MCC Budd chiari = hepatic vein thrombosis; coronary artery, SMV, anything can be thrombosed b/c blood slugging around and this is why phlebotomy is done. Phlebotomy is performed to make you Fe def – they want to make you Fe def – why? If you make them Fe def, b/c then it will take longer to make RBC’s, so you purposefully slow down the process.

2. Hypovolemia – only polycythemia that has an increase in plasma volume that matches the increase in RBC mass; none

of the other causes have an increase in plasma vol (these are measured with radioactive techniques). So, it is very rare to see an increase in plasma vol with polycythemia, except for this case. Why? Myeloproliferative dz’s take years and years to develop therefore plasma vol is able to keep up; therefore both increase together over time.

3. Histaminemia – all cells are increased: RBC’s, WBC’s, platelets, including mast cells and basophils. Example: Classic

hx: pt takes a shower and gets itchy all over body – this is a tip off for polycythemia rubivera – why? Mast cells and basophils are located in the skin and temperature changes can degranulate mast cells, causing a release of histamine, leading to generalized itching (very few things cause generalized itching – bile salt deposition in the skin in pts with obstructive jaundice, and pts with mast cell degranulation), face is red looking, too b/c of histamine b/c vasodilatation, leading to migraine-like headaches.

4. Hyperuricema – b/c nucleated hematopoetic cells are elevated, they then die, and the nuclei have purines in them.

The purines will go into purine metabolism and become uric acid. Example: pt on chemotherapy must also be put on allupurinol to prevent urate nephropathy and prevent renal failure from uric acid. (allupurinol blocks xanthane oxidase). When killing cells you’re releasing millions of purines when the nucleated cells are killed and the tubules are filled with uric acid, leading to renal failure. Must put them on allupurinol. This called tumor lysis syndrome. The same thing occurs in polycythemia rubivera b/c there is an increase in number of cells that eventually die and you run the risk of hyperuricemia.

B. RBC mass/plasma vol/O2 sat/EPO

Polycythemia rubivera – h,h,N (inappropriate), low (have too much O2 b/c you have piles of RBCs and therefore suppress EPO (it’s a hormone). The hint was O2 content=1.34 * Hb * O2 sat +pO2

COPD, tetralogy of fallot, high alt – H, N, L, H (appropriate polycythemia b/c it’s responding to hypoxia)

Renal adenocarcinoma, hepatocellar carcinoma, any cyst (renal, esp. ie hydronephrosis, wilm’s tumor) – H, N, N, H (even with normal gas studies b/c ectopically produced)

Relative Polycythemia – N, L, N, N

IV. Leukemias

A. General characteristics of Leukemia; therefore, will always have:

1. Generalized lymphadenopathy, hepatosplenomegaly, etc…

2. Abnormal cells in the peripheral blood – BLASTS (myeloblasts, lymphoblasts, monoblasts, megakaryoblasts) – so some abnormal blasts are in the peripheral blood

3. B/c it is arising in the BM, will always crowd out the normal hematopoetic cells, and will ALWAYS have an anemia, usually normocytic

4. Thrombocytopenia b/c crowding out the normal megakaryocytes from making platelets 5. Usually an increase in WBCs ct with abnormal cells present

6. Acute vs. chronic – Do a bone marrow test and look at blasts – if blasts are <30%, this is chronic; if the % blasts is >30%, it is acute. Therefore the blast ct tells if its acute vs chronic

B. Age brackets: Know age brackets

0-14 = ALL

15-39 = AML – myeloblast with Auer rods in peripheral blood

40-59 AML, CML (separate with BM – AML with >30% and CML with <30%, 9, 22, Philly c’some) 60+ = CLL

MC overall leukemia regardless of age = CLL

MCC generalized nontender lymphadenopathy in pt 60+ = CLL; not b/c it’s a lymphoma, but b/c it mets to lymph nodes).

C. Different Types of Leukemia:

Example: peripheral smear of 49 y/o, 150,000 WBC ct, 1% myeloblast in peripheral blood and BM, generalized nontender lymphadenopathy, hepatosplenomegaly, thrombocytopenia, and normal anemia – dx? CML (look at age bracket and % blasts). To prove, get 9, 22 study (abl protooncogene with nonreactor tyrosine kinase activity and goes from 9 to 22 and fuses with the cluster fusion gene). LAP – leukocyte alkaline phosphatase stain can also be used. Look at which neutrophils take it up – mature neutrophils all have LAP in them; neoplastic neutrophils do not – why? B/c they are neoplastic. So, if no stain, know its neoplastic (normal cells take up stain). Called a LAP score – always low in CML. So, the two tests: Philly c’some and LAP score, which is always low.

Example: tear drop cell b/c there was a dictator in BM, and cells have to move to the spleen, so there is a migration of hematopoetic cells from the BM to the spleen. When you take up hematopoesis anywhere other than the bone marrow, this is called extramedullary hematopoesis. So, the spleen in huge – esp. in atherogenic myeloid metaplasia. Some of the megakaryocytes go back to the marrow to lay down collagen; and megakaryocytes go back. Fibrosis of the BM occurs (used to be called myelofibrosis metaplasia). So, not everyone left the BM, and stay in the fibrotic marrow. For them to get to the spleen, they have to work their way through strands of fibrotic tissue, often times damaging their membrane, leading to tear drop cells (so, it gets passed the ‘barbed wire’ – fibrous tissue – and getting into the sinusoids, they are tear drop cells in the peripheral blood). So, pt with huge spleen, with tear drop cells – atherogenic myeloid metaplasia.

Example: too many platelets – essential thrombocythemia (makes too many platelets)

Example: 4 y/o pt that presents with sternal tenderness, fever, generalized nontender lymphadenopathy, hepatosplenomegaly, normocytic anemia, 50,000 WBC count many of which had an abnormal appearance cells. What is the dx? ALL (acute lymphoblastic leukemia. MC cancer in kids; the most common type is: common ALL Ag B cell leukemia . CD10+; calla+ Ag B-cell ALL, associated with down’s syndrome

Example: 65 y/o, normal criteria, smudge cells and normocytic anemia. They also have hypogammaglobinemia b/c they are neoplastic B cells and cannot change to plasma cells to make Igs. Therefore, MCC death in CLL = infection related to hypogammaglobinemia. What is the Dx? CLL

Example: 62 y/o, normal criteria, special stain of TRAP (tartrate resistant acid phosphatase stain) – hairy cell leukemia (know the TRAP stain)

Example: 35 y/o pt, with normal criteria, with 50,000 abnormal WBCs and Auer rods (abnormal lysosomes), 70% blast cells in the BM. What is the Dx? AML. Know what Auer rods look like, know the leukemia that infiltrates gums (acute monocytic anemia – M5), and acute progranulocytic anemia (M3) – they always have DIC, has a translocation 15,17. Rx = retinoic acid (vit A – causes blasts to mature into b9 cells).

V. Lymph nodes

A. General Characteristics:

1. Painful vs painless: lymphadenopathy that is painful is not malignant; mean that you have inflammation causing it (does not always mean infection) – you are stretching the capsule, it’s an inflammatory condition (lupus), and that produces pain. When you have non-tender, think malignant, either (1) mets or 2) primary lymphoma originating from it. Always tell if painful/less.

2. Localized vs. generalized lymphadenopathy: Localized (ie exudative tonsillitis goes to local nodes; breast cancer goes to local nodes. Generalized (systemic dz – ie HIV, EBV, Lupus).

3. Examples:

(a) Bruton’s agammaglobinemia – germinal follicle absent: B-cell (b) DiGeorge syndrome– paratrabeculae messed up: T-cell country

(c) Histiocytes (Han shculler Christian/letterman sieve dz) – involves sinuses

(d) SCID (adenine deaminase def) – B and T cell deficiency, therefore no germinal follicle and no paratrabeculae but will have sinuses.

(e) Reactive lymphadenopathy: Macrophage takes Ag, and presents to germinal follicles and they spit out a plasma cell, making Ab’s

B. Non-Hodgkin’s lymphoma

Follicular lymphoma = MC Non-Hodgkin’s Lymphoma: B-cell; translocation 14,18; and apoptosis gene knocked off, so the cells are immortal.