حسام أبو عوض- -Jaleel Sweis سليم خريشة-
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1 - حسام أبو عوض- -Jaleel Sweis سليم خريشة- 1 P a g e
2 Classification The white blood cells (also known as leukocytes) are divided into 5 groups: lymphocytes, monocytes, Neutrophils, basophils and eosinophils. WBCs are often classified into two classes: Granular: Neutrophils, eosinophils and basophils (granules) Agranular: Lymphocytes and monocytes (no granules) Old monocytes might have some fine granules. There is another classification that divides WBCs into 3 groups: Granulocytes, Lymphocytes and monocytes Count The normal total white blood cells count ranges from 5,000-10,000/mm³ (the doctor first said this) or 4,000-11,000/mm³ (the doctor then mentioned this number and said that he thinks that it is more accurate than the first) The second range was also mentioned in the lab (so I guess it is the correct one?). Healthy individuals might often have a count that is slightly out of the normal range (whether higher or lower) [Reminder: The RBC count is around 5 million/mm³ on average for the two genders]. A low WBC count is referred to as leukopenia while a high count is referred to as leucocytosis. Gender has no effect on the WBC count according to the doctor, but even in the same individual the count changes physiologically (e.g. it is highest in the evening and lowest in the morning, it increases after meals, exercises, excitement and during pregnancy). WBCs are nucleated and are larger in size than RBCs. WBCs move from capillaries to tissues to perform their functions. WBCs have short half-lives ranging from hours (6 hours for neutrophils) to a year (for some monocytes) according to the doctor. 2 P a g e
3 Average WBC count/mm³ : Neutrophils: 5,400 (60%) Eosinophils: 275 (3%) Basophils: 35 (0.5-1%) Lymphocytes: the doctor forgot to mention the value here, but from the internet: and by using the percentage it must be 3060 (34%) Monocytes: 540 (4%) Therefore, neutrophils are the most abundant followed by Lymphocytes then monocytes then eosinophils and finally basophils. According to the doctor, neutrophils are not always the most abundant WBCs, sometimes there can be more lymphocytes than neutrophils, but this is very rare. The lymphocytes we count make up only 50% of the total number of lymphocytes as the remainder adhere to the inner surfaces of the blood vessels. These adhering lymphocytes are referred to as the marginal pool and they are only released in some conditions like haemorrhage. Leukopoiesis Leukopoiesis: the production of white blood cells The duration required for the production of WBCs via leukopoiesis is 6 days, which is the same amount of time taken for the production of RBCs, but WBCs remain in the bone marrow for 6 more days after they are produced (the doctor said that that is so that they can be computerised, I guess that he meant that they get modified ) before being released to the circulation. All the WBCs are only produced in the bone marrow except the lymphocytes which are produced in both the bone marrow and the lymphoid tissues (e.g. lymph nodes, spleen, and thymus) The WBCs play a very important role in the immunity and therefore contain several enzymes and chemicals (e.g. hormones, heparin, histamine and serotonin). 75% of the cells in the bone marrow belong to the WBCs family, this is most likely due to their short half-lives. 3 P a g e
4 Leukopoiesis is the most complicated process in the body. A single type of stem cells produces many different cell types including RBCs and platelets. The process is very complicated because many factors affect each stage. Many chemicals (i.e. regulators) are involved in the production of WBCs such as IL-1 and Factor III. These chemicals affect many cell lineages. These chemicals are produced by many sources. In each stage there are many cells produced, and there is an overlap in the function of the regulating chemicals. The mother stem cell is affected by many factors to determine which pathway it follows. REFER TO DIAGRAM AT END OF THIS SHEET We ll see shortly that when there is a problem in the production of the WBCs, the RBCs and the platelets are also affected (e.g. in leukaemia). Granulocyte Macrophage Colony Stimulating Factor (GMCSF) affects several cells in the blood cells production lineages. We call it Colony stimulating factor because in the lab we use a single cell and that chemical and to produce many cells i.e. a colony. Diapedesis is the process by which WBCs move from the capillaries to the tissues in order to perform their functions. WBCs also move through tissues by their ability to use the Amoeboid Motion WBCs are repelled from the normal intact areas and are attracted to the infected/injured areas by a process called chemotaxis. Almost all of the WBCs have the ability to engulf, digest and kill bacteria. They can also engulf dead cells by the process called phagocytosis. 4 P a g e
5 So, all the WBCs have these 4 characteristics: Diapedesis, amoeboid motion, chemotaxis and phagocytosis. Disorders Black-skinned people tend to have leukopenia, even at the dead sea level. The the doctor talked about a study he previously carried, I don t know if the following info (in blue) is required: It is well known that hypoxia causes an increase in the RBC count, so the the doctor and his colleagues wanted to see how things go with hyperoxia (e.g. at the dead sea level), and they found that those who were living in areas with hyperoxia often had low RBC count. Then they decided to study the WBCs too, using samples from school students, they found that people living in those areas tend to have low WBC count too, but then, when they compared their results to the references, they figured out that it had to do more with the race (blackskinned people) than with the place/hyperoxia. The doctor said that in their study they noticed high number of monocytes in students with parasitic infections. Sometimes the low WBC count runs in families rather than whole races. The WBC count increases (for all the 5 types) in all types of infections, especially in bacterial infections. But, there are specific things to be noted for each cell type: Neutrophils: Increase mainly in bacterial infections. Lymphocytes: Increase drastically in viral infections Monocytes: Increase in parasitic infections Eosinophils: Increase in allergic reactions Basophil: Are not specific, but increase slightly in every condition. N.B: I think the info above about monocytes and basophils is actually wrong, for in the slides the doctor was using it was written that basophils had to do with parasitic infections not monocytes (and so we were told in other non physiology lectures too), but the doctor repeated the same thing over and over again 5 P a g e
6 If a patient comes with a suspected allergy the doctor is supposed to ask for an eosinophil count test. Low white blood cell count In contrast with high white blood cell count, there are some cases in which specific kinds of leukocytes decrease in number leading to a low white blood cell count. Neutrophils decrease in number in : a- Prolonged exposure to radiations b- Drug toxicity c- Vitamin B12 deficiency d- Systemic lupus erythematous(sle) Lymphocytes decrease in prolonged illness, immunosuppression, and treatment with cortisol Monocytes decrease in : a- Bone marrow failure b- Cortisol treatment Eosinophils decrease in : a- Drug toxicity b- Prolonged stress Basophils decrease in : a- Pregnancy b- Hyperthyroidism c- ovulation and stress When leucocytosis (increase in the WBC count) occurs and the cause is identified and then removed, the count is supposed to return back to normal, if it doesn t return to the normal range then this condition is called Leukaemia (an uncontrolled production of the WBCs), the number increases drastically, it is a tumour condition. 6 P a g e
7 The causes of leukaemia include chronic exposure to radiations, chemicals or viruses and genetic factors. Leukaemia occurs either acutely (occurs suddenly, usually in children) or chronically. Leukaemia symptoms: feeling cold, bone pain, paleness, tendency to bleed, frequent infections and anaemia The chronic form is the most common form in adults as it develops slowly with time (so it has enough time in adults compared to children) and sometimes the leukaemia may take years to be detected. The WBCs originate either from the lymphoid lineage or the myeloid lineage, leukaemia can occur in one of the two pathways so we have myelocytic leukaemia (e.g. in neutrophils, basophils or eosinophils only) and lymphocytic leukaemia (e.g. in lymphocytes or monocytes only), other times leukaemia affects all the WBC types. The leukaemia cells are bizarre, highly undifferentiated and appear very different from other normal WBCs, usually the more undifferentiated the cells are the more acute is the leukaemia, but in chronic conditions that span a very long duration (e.g years) the leukaemia cells are highly differentiated. Leukaemia cells, especially those that are highly undifferentiated, are usually non-functional, which is why the patients get easily infected. The effects of leukaemia on the body: metastatic growth of leukaemia cells in abnormal areas as the leukaemia cells in the bone marrow invade the neighbouring tissues (leukaemia often metastasizes to spleen, lymph nodes, liver and vascular regions) (leukaemia is curable before widespread metastasis), development of infections, severe anaemia (remember that when we discussed leukopoiesis we said that diseases affecting the production of WBCs also affect the production of RBCs and platelets), bleeding tendency (thrombocytopenia, low platelet count). The most important effect of leukaemia is the continuous use of the nutrients, vitamins and substrates by the growing cancerous cells leading to weakness in the patient as often proteins need to be broken down to provide the cancerous cells with required amino acids. 7 P a g e
8 Obviously, after metabolic starvation has continued long enough, this alone is sufficient to cause death. For no reason, the doctor suddenly talked about the histological differences between the duodenum, the jejunum and the ileum and he said that the duodenum doesn t have a mesentery (which is wrong as only the first and last inches of the duodenum are not covered by a mesentery, but the rest is covered ). [Note: most of the body s iron supply absorption occurs in the jejunum due to the presence of the tools enabling the process to occur and due to the length of the jejunum (the same iron absorbing proteins are present in the duodenum, but the duodenum is not long enough to absorb large amounts of iron)]. The doctor also said that most of the digestion and absorption (in general, not just iron) occurs in the duodenum and the jejunum Platelets Platelets (also known as thrombocytes) develop from giant cells called megakaryocytes. In physiology, we say that a single megakaryocyte produces 4000 platelets (in histology the known number is different.). Platelets have no nuclei. The differentiation time from stem cells to platelets (thrombopoiesis) is 10 days (6 days for WBCs and 6 days for RBCs). The platelets survival time is also 10 days. The production of platelets is controlled by the hormone thrombopoietin which is produced by the liver. The normal platelet count is 200, ,000. Low platelet count is referred to as thrombocytopenia while the high count is referred to as thrombocytosis. Platelets play an important role in haemostasis because they contain many different substances. Haemostasis (haemo from blood) is not the same as homeostasis, but the doctor never said what haemostasis is (From Wikipedia: haemostasis is the process that causes the bleeding to stop by keeping the blood within the damaged blood vessel). 8 P a g e
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