WEEK 4 Flashcards

(72 cards)

1
Q

LYMPHATIC SYSTEM

A
  • Structurally→ lymph nodes are part of lymphatic system
  • Thousands of nodes are clustered around lymphatic veins→ collect interstitial fluid from tissues and transport it as a fluid (lymph) back into cardiovascular system near heart
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2
Q

RED BLOOD CELLS (ERYTHROCYTES) Structure

A
  • Anucleate, circular, biconcave discs
  • Diameter; 7-8μm
  • Nucleus shed before cell matures
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3
Q

RED BLOOD CELLS (ERYTHROCYTES) Relate structure of cell to function

A
  • Facilitates gaseous exchange across cell membrane by
  • Maximising surface area
  • Brining haemoglobin molecules closer to cell surface
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4
Q

RED BLOOD CELLS (ERYTHROCYTES) Function

A

Transport oxygen and carbon dioxide

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5
Q

BLOOD CELL COUNTS AND INDICES: RBCC

A
  • Red blood cell count→ Number of cells/ volume
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6
Q

BLOOD CELL COUNTS AND INDICES: Hb

A

Haemoglobin concentration→ Weight hb/ volume

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7
Q

BLOOD CELL COUNTS AND INDICES: HCT

A

Haematocrit→ % of rbc/ volume

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8
Q

BLOOD CELL COUNTS AND INDICES: RDW

A

Red cell distribution width→ variation in cell size

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9
Q

BLOOD CELL COUNTS AND INDICES: MCV

A

Mean cell volume→ Volume of each rbc

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10
Q

BLOOD CELL COUNTS AND INDICES: MCH

A

Mean cell haemoglobin→ amount of haemoglobin in each rbc

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11
Q

BLOOD CELL COUNTS AND INDICES: MCHC

A

Mean cell haemoglobin→ concentration of haemoglobin in each RBC

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12
Q

NORMAL VARIATIONS IN BLOOD

A

Blood composition may be influenced by;

  • Age (RBC and WBC is greater in infants than adults)
  • Race (RBC + Hb + Hct is greater in Caucasians than Africans)
  • Geography (RBC is greater living in mountains than sea level)
  • Activity of patient/food intake
  • Time of day
  • Total body fluid
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13
Q

ABNORMAL VARIATIONS IN BLOOD

A
  • May be due to disease processes
  • Hypoxia
  • Neoplasia
  • Infection
  • Haemolysis
  • Metabolic disorders
  • Trauma

2 common conditions affecting variations;

  • Anemia
  • Polycythaemia
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14
Q

ANEMIA: CAUSE

A
  • Any abnormality of/reduction in Haemoglobin leads to HYPOXIA as rbc cannot transport oxygen efficiently
  • Quality→ Abnormal Haemoglobin (Hb)
  • Quantity→ of RBC
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15
Q

ANEMIA: CLINICAL MANIFESTATIONS

A
  • Hypoxia and compensatory mechanisms
  • Movement of fluid from interstitium to blood to restore volume; less viscous blood
  • Increased cardiac output (increased stroke volume and heart rate)
  • Increased rate and depth of breathing
  • Redirection of blood from periphery to internal organs
  • Increased erythropoiesis (RBC production)
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16
Q

ANEMIA: SYMPTOMS

A
  • Pallor, fatigue, tachycardia, dyspnoea, lethargy, dizziness
  • FBC test results→ Low Hb
  • Jaundice (especially for haemolytic anemias)
  • The presence and severity of symptoms is related to the decrease in Hb level; however some people with severe anemia may be asymptomatic
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17
Q

ANEMIAS CAUSED BY REDUCED Hb: Disorders of iron metabolism: The Iron deficiency anaemias

A
  • Chronic blood loss: menorrhagia; or gastric or duodenal ulcers
  • Malnutrition/eating disorders
  • Increased demand: Infancy, adolescence, menstruating women, pregnancy, lactation
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18
Q

ANEMIAS CAUSED BY REDUCED Hb: Disorders of Haem Synthesis: The sideroblastic anaemias

A
  • Characterised by “ring sideroblasts” : granules of iron arranged in a ring around the nucleus found in the bone marrow
  • With defects in haem synthesis (such as the porphyrias) → Acquired causes in lead poisoning
  • Porphobilinogen (PBG) is one of the precursors to haem that is readily filtratable in the kidneys and thus is detectable in urine.
  • Testing for urinary PBG can be part of a screen for porphyria or acquired defects in haem synthesis
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19
Q

ANEMIAS CAUSED BY REDUCED Hb: Disorders of Globin Synthesis–> Review: Haemoglobin structure and genetics

A
  • A molecule of Hb consists of 4 polypeptide chains each containing a haem group
  • In the blood of a normal adult between 96-98% of the Hb is in the form of Hb A which consists of 2 a chains and 2 b chains
  • There is a seperate gene for each chain
  • The b chain gene is located on chromosome 11
  • The a chain gene is duplicated. Located on chromosome 16 both genes (a1 and a2) are active
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20
Q

ANEMIAS CAUSED BY REDUCED Hb: Disorders of Globin Synthesis–> The Thalassaemias

A
  • Inherited impaired rate of synthesis of either alpha or beta globin chains
  • When one or more of the genes for a chain are defective: thalassaemia minor/trait
  • When all genes for a chain are defective: thalassaemia major
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21
Q

ANEMIAS CAUSED BY REDUCED Hb: Disorders of Globin Synthesis–> Sickle Cell Anaemia

A
  • Inherited defect in beta globin→ a valine type amino acid is substituted for a glutamic acid-type amino acid
  • A decrease in pO2 causes the sickle cell- type beta chains to form aggregates leading RBC shape change
  • Modified RBC are trapped in organs (reticuloendothelial organs such as the spleen and liver) hence: an anaemic presentation
  • Person can experience an occlusive “sickling crisis” brought on by infection, acidosis, high altitudes, excessive physical activity, ischaemia
  • Heterozygotes (sickle cell trait) are commonly asymptomatic
  • The sickle cell gene has a high prevalence amongst people from or originating from West Africa
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22
Q

ANAEMIAS CAUSED BY REDUCED RBC NUMBERS: Defects in erythropoiesis: aplastic anaemia

A
  • Inherited disorder in DNA repair: Fanconi anaemia

- Secondary: caused by a number of drugs (e.g. some chemotherapeutic drugs, and the antibiotic chloramphenicol)

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23
Q

ANAEMIAS CAUSED BY REDUCED RBC NUMBERS: Increased/ Premature Erythrocyte destruction: Haemolytic Anaemias

A

Congenital defects; For example;

  • RBC membrane defects: Lead to shape changes
  • Glucose- 6- Phosphate dehydrogenase deficiency: G6PD is the only source of NADP in RBC and so these cells have a reduced capacity to regenerate reduced glutathione and thus the RBC become more sensitive to oxidative destruction. People with G6PD deficiency may manifest favism

Acquired Haemolytic Anaemias
- Autoimmune disease, Drug coated RBC, Haemolytic transfusion reaction, Haemolytic disease of the newborn, - A blood type incompatibility

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24
Q

MEGALOBLASTIC ANAEMIA: A MACROCYTIC ANAEMIA

A
  • Defects in erythropoiesis: development of the nucleus vs. the cytoplasm are not synchronised due to defects in DNA synthesis. The principal causes are;
  • B12 malabsorption (or deficiency)
  • Folate deficiency
  • Autoimmune gastritis
  • Incidence increases with age
  • Higher prevalence in Northern European races
  • As the disease mechanism is a defect in DNA synthesis, people with pernicious anaemia may also experience: gastrointestinal problems and loss of bone density
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25
MEGALOBLASTIC ANAEMIA: A MACROCYTIC ANAEMIA B12 deficiencies
- Vegans as there is no adequate plant supply of B12 - Gastric surgery - Congenital intrinsic factor deficiencies - Pernicious anemia: is an autoimmune disorder in which your body can’t make enough health RBC because it can’t absorb enough Vit B12
26
MEGALOBLASTIC ANAEMIA: A MACROCYTIC ANAEMIA | Folate deficiencies
- Nutritional deficiencies - Utilisation outstrips supply (e.g. pregnancy) - Malabsorption
27
HEMATINIC AGENTS
- Haematinic → An agent that improves the quality of blood, increasing the haemoglobin level and the number of RBC, e.g. iron, liver extract, B complex vitamins - EPO= erythropoietin, naturally occuring kidney hormone
28
POLYCYTHAEMIA→ TOO MANY RBC
- Erythrocytosis: elevated RBC - Neoplastic disorder: hyperproliferation of RBC→ largely affects elderly males - Secondary polycythaemia - Response to hypoxia - High altitude - EPO→ blood doping - Treatment→ phlebotomy
29
POLYCYTHAEMIA VERA→ TOO MANY RBC
- Too many RBC→ increased synthesis in overactive bone marrow - Circulatory problems relating to increased viscosity and volume: - Elevated BP - Congestive cardiac failure - Venous pooling - Thrombus formation - Pulmonary oedema
30
Summary→ RBC | Anaemia
- Microcytic hypochromic→ Fe deficiency and Thalassemia - Bone marrow → Sideroblastic and Aplastic - Sickle shape → Sickle cell - Macrocytic→ Folate/B12 deficiency/intrinsic factor - Normocytic normochromic, Poikilocytes→ Acute blood loss
31
Polycythemia
Increased RBC production
32
INCREASE IN LEUCOCYTE NUMBERS
- Leukocytosis - Increase in leukocyte cell number in response to infection or injury - Specific cell types may indicate the type of result → E.g. lymphocytes respond to viral infection
33
DECREASE IN LEUKOCYTE NUMBERS
- Leukopenia - Impaired cell production/maturation - E.g. inherited defect - Chemotherapy/radiotherapy - Cell destruction→ E.g. HIV infection
34
HAEMOPOIESIS
- Blood cell production (occurs in bone marrow) - Combines cell division and differentiation - Produces mature bone cells and platelets - Continuous→ can be accelerated on demand
35
MYELOPROLIFERATIVE DISORDERS
- Abnormally high levels of proliferation of a specific myeloid precursors 1) Polycythaemia rubra vera (PCV) RBC 2) Essential thrombocythemia (ET) platelets 3) Myelofibrosis → fibrosis of BM - A common underlying genetic mutation found in all 3 may see an affected person manifest a transition from PCV or ET to myelofibrosis
36
POLYCYTHAEMIA (PCV)
- Erythrocytosis: elevated RBC - Neoplastic disorder: - Hyperproliferation of RBC - Largely affects elderly males - Secondary polycythaemia - E.g. response to hypoxia - E.g. high altitude, also epo= blood doping - Treatment: Phlebotomy
37
ESSENTIAL THROMBOCYTHEMIA (ET)
- That is a megakaryocyte hyperplasia - Manifestations - Elevated platelet count , Splenomegaly is coming, Thrombosis and haemorrhage, Commonly also neutrophilia and erythrocytosis, Erythromelalgia: burning sensation in hand and feet, That is relieved by aspirin Treatment - Plateletpheresis to remove platelets from blood and aspirin to reduce thrombosis - Often disease is unchanged for 10-20 years or more - Some may convert to myelofibrosis - Progression to a malignancy is rare
38
MYELOFIBROSIS
- This represents a number of conditions where there is fibrosis of the bone marrow May present with - +/- extramedullary hematopoiesis: in the liver and spleen - Anaemia - Elevated WBC and platelet count but later: leukocytopenia with an increased myeloid precursor cells in the blood - Treatment→ manage the anaemia and use drugs that are anti-proliferative - Prognosis is worse for this disease than for PCv or ET→ 10-20% progress to leukaemia. Median survival age is 3.5 years
39
LEUKAEMIA- CAUSES
- A malignant proliferation of a haematopoietic cell type generally at the expense of normal hematopoietic cells - Hereditary factors→ ? fragile chromosomes - Chromosome abnormalities→ down syndrome - Other haematological disease - Viruses - Chemical carcinogens, Radiation
40
Acute leukaemia
- Malignant proliferation of immature precursor cell - Rapid onset and progression - Commonly short survival time
41
Chronic leukaemia
- Malignant proliferation of more differentiated cell - Gradual onset, slow progression - Relatively longer survival time
42
Morphology
- Leukaemias can be classified by type of cell - Myeloid or myelocytic - Lymphoblastic or lymphocytic
43
LEUKAEMIA: CLINICAL
- General loss of haematological functions; as in the ‘leukemic hiatus’ of acute leukaemias - Loss of specific functions of lineage from which the malignant cell is derived - E.g. chronic lymphocytic leukaemia of B lymphocytes: failure to synthesis antibodies leads to increased susceptibility to infection - Also symptoms can be related to infiltration of normal tissue→ e.g. neurological problems of acute leukaemia
44
LEUKAEMIA: DIAGNOSIS
- Blood tests: → FBC, blood film - Bone marrow biopsy - Genetic tests
45
LEUKAEMIA: TREATMENT
- Chemotherapy and radiotherapy - Treatment of complications - Stem cell/bone marrow transplant
46
MULTIPLE MYELOMA: DESCRIPTION
- Malignancy involving plasma cells in Bone Marrow - The cancerous cell is a malignant form of a B lymphocyte - The malignant cells have the appearance of the mature plasma cell - Malignant precursors in the bone marrow continue to develop in the circulation and the lymphoid tissue - Malignant cells infiltrate marrow and invade calcified tissue - Highest incidence in African Americans (amongst top 10 causes of death) and Pacific Islanders
47
MULTIPLE MYELOMA: CAUSES
- Oncogene→ mutation on C14 - Higher risk in petrol industry and metal workers - Higher numbers of plasma cells→ huge pressure on bones→ holes→ high Ca++ - Blood becomes very viscous due to high concentrations of antibodies→ together with high Ca++ → renal damage
48
MULTIPLE MYELOMA: CLINICAL
- Bone pain (commonly first sign) - Osteolysis leads to hypercalcaemia - Bone marrow infiltration leads to impaired hematopoiesis - Increased susceptibility to infections: myeloma cells synthesis large amounts of ineffective immunoglobulin diagnosed from - M proteins→ high concentration of IgM protein detectable in the blood OR - Bence-Jones proteins: Small Ig molecules that are excreted in the urine
49
MULTIPLE MYELOMA: TREATMENT
- High dose chemotherapy with autologous stem cell transplantation - Allogeneic transplantation offers prolonged disease free outcomes and potential cure, but at a high cost of treatment related mortality - Autologous: prior to chemotherapy some of patients own bone marrow stem cells are removed and stored. The chemo takes out the cancerous cells and the stem cells are returned to repopulate the marrow - Allogeneic: bone marrow provided by a tissue matched donor
50
LYMPHOMA: DESCRIPTION
- Malignant proliferation of lymphocytes or phagocytic cells or their precursor cells in lymphoid tissue 2 types - Hodgkin’s - Non- Hodgkins
51
LYMPHOMA: CLINICAL
- Enlarged painless mass due to expansion of the lymphoid tissue - Other manifestations can be explained by the production of cytokines by the malignant cells - Fever, weight loss, night sweats, thrombocytosis, leukocytosis
52
LYMPHOMA: DIAGNOSIS
- X-ray, lymphangiography, biopsy - Hodgkin’s lymphoma (HL) Reed- Sternberg cells in the affected tissue. Otherwise Non-Hodgkin’s lymphoma - The distinction between the 2 types is associated with different patterns of growth - HL spread from site of origin is generally a predictable spread to adjacent lymph nodes
53
LYMPHOMA: TREATMENT
- Chemotherapy and radiotherapy - Prognosis is good and without significant systemic spread the person can expect cure or a prolonged survival - Generally well managed by radiation or combination chemotherapy (85% survival)
54
NON-HODGKIN’S LYMPHOMA
- Massive lymphadenopathy→ Generally affects older men - Different subtypes depending on rate of growth of malignant cells - Incidence is increasing rapidly - Commonly associated with weakened immune system - Incidence also linked to exposure to pesticides and solvents - Staging dictates treatment and prognosis, commonly CHOP therapy
55
BLOOD GROUPS
- An individual's blood group is determined by the combination of antigens on their red blood cells - The difference between any 2 antigens can sometimes represent allelic differences (same gene but differences in sequence of DNA) this is where there are different groups within one blood group system - E.g. ABO system comprises of 4 blood groups: A, B, AB and O - In other cases, one can distinguish between 2 different blood group systems where each is based on a different gene locus - E.g. The ABO system vs. Rh(esus) or D system - While there are a number of clinically important blood group systems it is incompatibilities within either the ABO or Rh systems that are the most common cause of clinical problems
56
ABO GROUP
- The distinction relates to the presence/absence of an enzyme that adds sugar groups to a RBC membrane protein - A variation in which sugar groups are added distinguishes between A-type and B-type RBC - When these sugar additions don’t occur because the enzyme is inactive that results in O type RBC - If someone has both the A allele and B allele- this will result in AB type RBC
57
PRACTICE OF BLOOD TRANSFUSIONS
- Blood donation is performed aseptically, the blood is collected into a sterile plastic bag containing an anticoagulant - The blood is initially separated into 3 components by centrifugation Red cells Buffy coat (White Blood Cells) Plasma (and Platelets) - The RBC concentrate is the most commonly used for blood transfusion - Platelets can be isolated from the plasma fraction and the buffy coat combined and used as an acute treatment for thrombocytopenia (e.g. aplastic anaemia) - The plasma can be used as source of; albumin, antibodies and clotting factors - If blood from the wrong group is donated to someone, they will experience a transfusion reaction associated with immune targeting of the donor RBC that is: haemolytic anaemia and immune complex mediated damage
58
Rh SYSTEM- ANTIGEN
- Another important classification of RBC is the Rh system where there are genes for the C/c; D; E/e antigens - The RhD gene product is the most antigeni. The impact upon blood transfusions - Most people will know if they: - Possess at least one functional RhD gene and so are Rh+ (abbreviated to positive) - E.g. Mr X is B positive and his rbc express the B antigen and the D antigen - Do not possess a functional RhD gene, and so are Rh- (abbreviated to negative) - E.g. Someone could be AB negative, and their rbc do not express the D antigen
59
Rh system- Antibodies
- People are born with AB (or none) antibodies - People develop Rh antibodies after exposure - Pregnancy OR Blood transfusions
60
HAEMOLYTIC DISEASE OF THE NEWBORN- CLINICAL | DESCRIPTION
- Not always caused by Rh - Other blood groups can have different effects - Most reported cases of HDN result in minor consequences for the neonate: principally jaundice - Commonly ABO incompatibility - E.g. when a type O mother carries an A- or B- blood type fetus
61
HAEMOLYTIC DISEASE OF THE NEWBORN- CLINICAL CLINICAL
- Haemolysis can trigger a compensatory increase in the size of hematopoietic organs (liver and spleen) - Impaired liver function can lead to impaired albumin synthesis in turn leading to potentially fatal oedema - High levels of unconjugated bilirubin can lead to severe brain damage- kernicterus
62
HAEMOLYTIC DISEASE OF THE NEWBORN- CLINICAL TREATMENT
- Repeated intrauterine transfusions of blood cells (these have to be Rh-) - Mother can undergo plasmapheresis: her blood is channeled through a machine which removes anti-Rh antibodies - In less severe cases, postpartum the baby is exposed to UV light to treat haemolysis induced jaundice
63
UNIVERSAL DONOR
O-
64
UNIVERSAL RECIPIENT
AB+
65
Blood Type O-
Antigen - No antigen Antibodies - A and B, Can develop Rh+ Can give blood to - O+, O-, A+, A-, B-, B+, AB+, AB- (Universal donor) Can receive blood from - O-
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Blood Type O+
Antigen - Rh Antibodies - A and B Can give blood to - O+, A+, B+, AB+ Can receive blood from - O+, O-
67
Blood Type A-
Antigen - A Antibodies - B, Can develop Rh+ Can give blood to - A+, A-, AB+, AB- Can receive blood from - A-, O-
68
Blood Type A+
Antigen - A and Rh Antibodies - B Can give blood to - A+, AB+ Can receive blood from - A+, A-, O-, O+
69
Blood Type B-
Antigen - B Antibodies - A, Can develop Rh+ Can give blood to - B+, B-, AB+, AB- Can receive blood from - B-, O-
70
Blood Type B+
Antigen - B, Rh Antibodies - A Can give blood to - B+, AB+ Can receive blood from - B-, B+, O+, O-
71
Blood Type AB-
Antigen - A, B Antibodies - Nil Can develop Rh+ Can give blood to - AB-, AB+ Can receive blood from - O-, A-. B-, AB-
72
Blood Type AB+
Antigen - A, B, Rh Antibodies - Nil Can give blood to - AB+ Can receive blood from - AB+, AB-, O-, O+, A+, A-, B+, B- (Universal recipient)