Hematology/Oncology (RBC related) Flashcards

Question

Explain B12 deficiency.

Answer 1

Eat. B12 is with animal protien. Pepsin from stomach will break the animal protien. the salivary gland ,the stomach and the billiary tract produces R protien that will attach to B12 to save it from the HCL in stomach. goes to duodenum where the Pancreastic enzyme called Protease will break the R protien cause it is not needed. Now Castle intrinsic factor (produced by stomach but travel through illeum) will join B12 and helps the absorption. after absorption Transcobalmine will bind to B12 to travel through blood. thats why pancreatic isufficiency, illeum destruction (chrons or tapeworm) , illeum resuction, stomch resection will cause deficiency of the B12 B12 either can go to liver to be store (for yearss) or to cells to be utilized in the dna synthesis

Answer 2

odd chain FA--->Propinyl CoA--------(B7 carbocylase)------> methylmalonyl CoA----(B12 mutase)-----> succinyl coa this succinyl coa will go to krebb cycle. now if there is a deficiency of B12 mutase cannot work leading to increase concentration of methylmalonyl and propynyl Coa these will replace acetyl Coa in neurons and myelin sheath leading to demyelination

Answer 3

``` pale tired Glossitis Peripheral Neuritis Lemon yellow skin subacute combined degenration od spinal cord Dementia ```

Answer 4

radioactive B12 is given and then it is noticed in urine to see if it is absorbed or not in the GIT.

Answer 5

If homocysteine ans Mathomalonyl acid increase = B12 if only homocysteine = folic see the pathways.

Answer 6

big oval ceels problem only with RBC . no other cells affected sometimes anaemia is not there. only MCV

Answer 7

size normal. low count rbc 1) acute blood loss (retculocytes < 2.5) any abdominal puncture. losing plasma and RBc at the same rate (start of trauma) plasma replaced after sometime so RBC count low as compared. 2) underproduction (retculocytes < 2.5) ``` anaemia of chronic disease and iron deficiency anaemia (usually ealy because later it becomes microcytic) renal failiure (EPO low) or aplastic (bone marrow problem) ``` 3) increased destruction (reticulocytes>2.5) (for compensation high reticulocytes are produced) intrinsic- Hb defect, membrane defect, G6PD deficiency Ectrinsic- antibpdies

Answer 8

yes but after some time. first we will see depletion of both plasma and RBC (hypovolemic shock) then plasma is compensated and RBC gets diluted we will see anaemia (normocytic) after that for compensation body will strat making more reticulocyte

Answer 9

Even though it is named anaemia, all blood cells are low in number. correctly it should be named Pancytopenia) Aplastic Anaemia= Pancytopenia + hypocellular BM ( MDS = Pancytopenia + Hypercellular BM ) ``` reason - Fanconi ANemia Radiation,drugs,toxin,viruses Intensive chemo therapy Tcells-->cytokines---> cytokines will destroy myeloid stem cells. ``` signs and symtoms will be those related to pancytopenia that includes of general anaemia, of thrombocytopenia and of leukocytopenia (Infections and diseases)

Answer 10

Classically, MDS has a hypercellular marrow – too many cells. In contrast, aplastic anemia has a hypocellular marrow, showing a very low number of cells Dx- hypocellularity (cells replaces by fat and Stroma)

Answer 11

Chronic kidney disease, also called chronic kidney failure, involves a gradual loss of kidney function. EPO deficiency is the cause of Anaemia related to CKD There are 5 stages on based on the GFR rate. Normal GFR is above 60 ``` 1st (normal ) 90-120 2nd (mild) 60-90 3rd (moderate) 30-60 4th (severe) 15-30 5th (end stage) 0-15 ``` the anaemia of CKD usually starts at Stage 3 and universally at stage 4

Answer 12

Nutrietional deficiency in cancer cachezia bowel bleeding due to treatment (radiation and chemo)

Answer 13

Pure absence/Low RBC is it diffrent from pancutopenia or aplastic anaemia as in this WBC and platelets ae normal problem only with RBC only one cell line is compromised from top to bottom (from proerythroblasts to Mature RBC) unlikely to progress to any other blood disease Main causes - Parvo 19 virus in Bone marrow biopsy-- Red cell Aplasia + giant pronormoblast (as they cannot progress to mature form) \ reticulocyte indiex will also be low

Answer 14

Hemolysis happening inside the Spleen (monocytes), liver (macrophages), Lymph nodes (histiocytes) too much destruction- High Unconjugated billirubin. High LDH due to RBC destruction high protophyrin

Answer 15

wheather it is due to over under production or due to blood loss. each type of anaemia is becaause of one of these causes

Answer 16

It is a Plasma protien produced by Liver When RBC's are destroyes EXtravascularly (by the rectoendohelial system) the Hb comes out. Haptoglobin is the protien that binds the Hb to form the Hapto-Hb complex In the case of hemolytic anaemias this complex is also phagotised by Macrophages leading to the decreased serum level of Haptoglobin.

Answer 17

deally, the macrophage is the umbrella term for any phagocytic agranulocyte. This can be divided into two major categories: 1) The histotiocyte is the macrophage of solid tissue. 2) The monocyte is the macrophage of blood.

Answer 18

hemolysis inside blood vessels. causes can be Macro or Microangiopathic Hemolytic Anaemia high unconjugates billirubin present high protophyrin since the destruction is taking place in the vessels some Hb will go as it is to the kidney which will give us hemoglobinuria /hemosudineria (only seen in intravascular) increase LDH less haptoglobin Hepatomegaly and splenomegaly both are seen in both intra and extravascular hemolysis

Answer 19

Hemolytic anaemia normal RBC= Biconcave, can expand through osmosis, canmaneuver/pass through sinusoidal spaces in spleen herediatry spherocytes- defect in the membrane (spectrin, ankyrin band3.1) microvesicles formed as membrane is not solid, h2o lost and cells become circular spherocytes can be seen with all types of hemolytic anaemia Hereditary spherocytosis can be autosomal recessive or dominant dark brown stone is seen as extravascular hemolysis taking place in spleen (cll stuck outside sinusioid due to their size and macrophage eats them) as too much CB is formed, goes to bile and with calcium forms stone)

Answer 20

Defect in spectrin band 4.1 Autosomal dominant many genes Family history this condition either can lead to hemolysis or not at all. this depends some person can live normally without any symtoms at all or some can have all the symtoms related to extravascular hemolysis

Answer 21

Autosomal Recssive subsaharan African Population Defect in Beta globin chain in the Hb (instead of Glutamine (hydrophillic), Valine (hydrophobic) is there) (point mutation) (non-conservative) This valine cause the RBC to change to Sickle shape when there is a deficiency of O2 no O2= sickle shape = destroyed present O2 = no sickle It is not the same as Beta thalessemia as in this no globin chain is formed. in sickle cell Beta chain is converted to a diffrent chain because a whole protien is replaced by another) Right oxygen curve is seen (oxygen not coming to cells/blood) In foetus cells will not sickle (upto 6 months) because they will have HbF (high affinity to O2) not HbS (no beta chain until 6 months)

Answer 22

all signs and symptoms of extravascular hemolysisi also signs and symtoms of vaso-occlusive crisis. Nephropathy

Answer 23

This occurs when the flow of blood is blocked to an area because the sickle-shaped cells have become stuck in the blood vessel. Pain can occur anywhere but most often occurs in the bones of the arms, legs, chest, and spine.

Answer 24

Acute chest syndrome is a term used to cover conditions characterized by chest pain, cough, fever, hypoxia (low oxygen level) and lung infiltrates. Acute chest syndrome may be the result of sickling in the small blood vessels in the lungs causing a pulmonary infarction/emboli or viral or bacterial pneumonia.

Answer 25

1) Autosplenectomy- Autosplenectomy can occur in cases of sickle-cell disease where the misshapen cells block blood flow to the spleen, causing scarring and eventual atrophy of the organ. (occlusion=ischemia=infarction) useless spleen= more prone to infection by encapsulated organisms like salmonella 2) sequestration = Sickle cell gets trapped in spleen=spleen enlarged and painful Hyposlenism can occur

Answer 26

1) Vaso-Occlusive crisis (pain,ischemia and infarction) 2) Aplastic crisis (when the body does not make enough new red blood cells to replace the ones that are already in the blood) 3) splenic sequestration crisis 4) Hemolytic crisis

Answer 27

having homozygous sickle cell trait. (being a carrier) (HbAHbS) sicle cell disease= HbSHbS

Answer 28

A Howell–Jolly body is a cytopathological finding of basophilic nuclear remnants (clusters of DNA) in circulating erythrocytes. During maturation in the bone marrow, late erythroblasts normally expel their nuclei; but, in some cases, a small portion of DNA remains. Jolly-Happy that the nuclear remains were somehow manage to survive :) usually these cells are destroyed by spleen but in case of splenectomy or Functional asplenia(seen in sickle cell vaso-occlusive crisis) these cells somehow manage to survive.

Answer 29

Free radicals like hydrogen peroxide (H2O2) damages cell by destroying DNA,protiens and cell membranes. Glutathione is the natural antioxidant that helps get rid of the free radicals When reacting with the H2O2 the glutathione becomes oxidised (inactive form) and h2o2 is converted to water and oxygen. H2O2------> H20 + O2 now NADPH comes and becomes NADP+ by reducing the glutathione and getting it back to it original form so now it is important that we have a surplus of NADPH so we can always get back the glutathione in its working state and to neutralize the free radicals. thats where G6Pd comes in place. G6PD reduces the NADP+ into NADPH. It does this by oxidising glucose-6-phosphate (already available through glucolysis) to 6 phosphogluconate. so heres the simple explanation. g6pd helps form NADPH that is needed to active the glutathione which will further help to neutralize free radical. Red blood cell is protected :) these free radicals converts the Fe+2 to Fe+3(ferric) state that causes the formation of met Hb

Answer 30

Most common enzymopathy worldwide. (10 percent of population) 2 variants- african and medeterranian X linked recessive. (affects male more) rare in females. males are either normal or affected (never carriers) females are either normal,carriers(heterozygous).affected(homozygous) signs syptoms- Related to intravascular haemolysis (RBC are damaged from inside in the vessels) Jaundice haemoglobinuria clinical signs- acute hemolytic anaemia not related to pherocyotis hemolytic episodes when stressors are removed full recovery can happen (fava beans or oxidative stresses)

Answer 31

Favism refers to the clinical syndrome of acute hemolytic anemia from the ingestion of fava beans as an oxidative challenge in patients with G6PD deficiency

Answer 32

``` Antimalarials Sulfa drugs ANtibiotics Analgesics Infections (No nadph) (WBC uses these h2o2 to fight infections) ``` Heinz bodies is seen (a signature of the cell being exposed to oxidative stress)

Answer 33

during acute episode the RBC with low G6PD are beinf hemolysized so the BM produces reticukocytes in high number (reticulocytosis) . now these reticulocytes wll have sufficient G6PD and will alter the test results. we should wait atleast 2-3 months before doing the test. management- blood transfusion folic acid supplements iron chelations

Answer 34

heinz bodies are the denatured or damaged inclusions of Hb in the cells (Heinz=Hb) ' they are the SIgnature that the rBC are exposed to Oxidative stress this part is usually removed by splenic macrophages leading to a half bitten cell called bite cell ``` ramanovsky stain- hemighost supravital stain- blue damaged Hb seen in - NADPH deficiency G6PD deficiency chronic liver disease asplenia/hyposplenia ```

Answer 35

Acquired Chronic hemolytic aaemia Defect in myeloid stem cells (PIGA gene) PIGA encodes the formation of GPI (anchor protiens for the inhibitory protiens of the myeloud lineage) No complementary inhibitory protiens - CD55 and CD59 RBC and other mylod lineage cell cannot protect themselves from the compement system (alternative pathway) they gets Intravascular hemolysis (inside vessels) So overall PNH is the Intrinsic, intravascular and acquired hemolytic anaemia hemolysis occurs throughout the day, in the night the urine have Hb (hemoglobinuria) most common death in PNH= Thrombosis. why? no one knows. maybe due to plastelets destruction (myelooid lineage) second cause is infection

Answer 36

group of 20 plasma protiens synthesized in liver mostly 11 protien involved three pathway 1) antigen antibody 20 bacterial endotoxin (alternative) (for pnh) 3)lectin pathway

Answer 37

Via regulatory protiens CD55 (DAF) and CD59 (MIRL) the rBC, Platetlets and WBC (only myeloid lineage) have anchor protiens GPI that have these inhibitory regulatory protien that prevents formation of convertase C3 and blocks binding of C9 and doesnt let form MAC. thus they prevent the complement to attack themselves.

Answer 38

Iron deficiency anaemmia and acute myeloid leukemia

Answer 39

Hemolytic anaemia Pancytopenia Thrombosis

Answer 40

yes. Reticukocytes are larger than RBC because they are one step immature. as they mature they become smaller in size

Answer 41

The Coombs' test is used to detect antibodies that act against the surface of your red blood cells. The presence of these antibodies indicates a condition known as hemolytic anemia, in which your blood does not contain enough red blood cells because they are destroyed prematurely.

Answer 42

eculizamab -- antibody against C5 to stop the formation of MAC

Answer 43

HAM test (ham=pig=piga gene)

Answer 44

In hemolytic anemia, red blood cells in the blood are destroyed earlier than normal. Immune hemolytic anemia occurs when antibodies form against the body's own red blood cells and destroy them. This happens because the immune system mistakenly recognizes these blood cells as foreign. if Mac formation- intravascular if IgG etc- intravascular as engulfed by macrophages in spleen

Answer 45

1) autoimmune 2) drug induced 3) alloimmune (non self such as transplant)

Answer 46

IgG is warm | IgM is cold

Answer 47

It is organ specific (RBC) can be warm (80% of the case) and cold (20%) dpending on th AB Usually all type of autoimmune diseases can be of two types- 1) organ specific (affecting only one type of organ) 2)Multisystem (Immune response against widespread target antigens) Warm - IgG - it is usually against the rhesus antigen - autoimmune hemolysis of RBC Cold- IgM - pentamer structure- binding of the antigen to the complement- cold Agglutination Disease. signs and symptoms are related to anaemia and extravascular hemolysis in case of warm. massive splenomegaly and jaundc is also seen It can be intravascular if the complemnt fixes itself completely if the complemmnt activation is weak its an extravascular hemolysis

Answer 48

Always lookout for other autoimmune diseases as one autoimmune disease is almost always acompanied by another one. sucl as SLE,CLL etc

Answer 49

Pyruvate kinase is the important enzyme in the last step of glycolysis. In glycolysis 4 ATP molecule are generated in which 2 is used by the pathway itself, the other two is used by the cell for energy after pyruvate is made it froms acetyl CoA and goes to mitochndria to participate in ETC however in RBC the glycolysis pathway ends at pyruvate (since RBC have no mitochondria) and this is the only way for the RBC to produce energy (2 ATP) PhosphoenolPyruvate------(pyruvate kinase)----->pyruvate 2ADP-->2ATP

Answer 50

Pyruvate kinase deficiency is a genetic blood disorder characterized by low levels of an enzyme called pyruvate kinase, which is used by red blood cells . Without pyruvate kinase, red blood cells break down too easily, resulting in low levels of these cells ( hemolytic anemia ). ``` Autosomal recessive Intracorpuscular defect (intrinsic)---extravascular hemolysis ``` No PK= No ATP = RBC dehydrated= Burr cells (echinocytes) (echino=sea urchin shaped)

Answer 51

The glycolysis will not complete. In theis pathway when 1,3 Bis-phosphoglutarate converts to 3 phosphoglutarate, this step will not occur and instead 2,3 bisphosphglutarte is formed 2,3BPG increase= right shift of curve= RBC gives O2 to tissues = symtoms of anaemia subsides :)

Answer 52

Drug-induced immune hemolytic anemia is a blood disorder that occurs when a medicine triggers the body's defense (immune) system to attack its own red blood cells. This causes red blood cells to break down earlier than normal, a process called hemolysis.

Answer 53

Cephalosporins Penicillin (BPO group of this drug adsorp on RBC and makes RBC susceptible to the macrophages) antimalarial drug like Quinine MethylDopa (change the structure of the Rh antigen on rbc) Nitrofurantoin Fludarapine

Answer 54

Patient takes penicillin-----> rash and hypotension ----> (this is allergic reaction type 1) Patient takes penicillin------> Jaundice and hemolysis---->DIIHA----> type 2 hypersen. Rxn (cytotoxic) patient takes pen.--->1-2 weeks later fever,urticaria arthalgia,------> serum sickness like rxn

Answer 55

Echinocytes (also called burr cells) have serrated edges over the entire surface of the cell and often appear crenated in a blood smear (small projections more number) These are also seen in Renal Failiure/uremia Spur cells appear to be the extreme form of acanthocytes and are seen in patients with severe liver disease (Large projections, less numbers)

Answer 56

Acantha == thorn Acanthocytes are found in 50-90% of cells on peripheral blood smear findings in abetalipoproteinemia, which is a rare autosomal recessive disorder with only about 100 cases described worldwide. Acanthocytes are also relatively common in severe liver dysfunction and malnutrition.

Answer 57

Any abnormally shaped cells are called poikilocytes phenomena of different size od RBC's are called anisocytosis Codocytes, also known as target cells, are red blood cells that have the appearance of a shooting target with a bullseye (from top view) and a mexican hat shape from side (basically a cup shape) High surface/volume ratio Cause- Liver disease, thalessemia, hemoglobinopathies

Answer 58

Except for acute blood loss and sequestraton the main causes of anaemia are hypoproliferaive or survavial causes