Week 2 Flashcards
1
Q
Which cell modulate hypersensitivity and destroys parasites
A
Eosinophils
2
Q
Which cell modulate immune response, phagocytic clearance and have regulatory functions
A
Monocytes –> Macrophages
3
Q
Which cells are involved in phagocytosis and acute inflammation
A
Neutrophils
4
Q
Lifespan of Neutrophils, Platelets and Red cels
A
Neutrophils - 7-8h
Platelets - 7-10days
Red cells - 120days
5
Q
What is a Myelocyte
A
Nucleated precursor between neutrophils and neutroblast
6
Q
What is the precursor of platelets
A
Megakaryocytes
7
Q
Define Differentiation
A
Descendent commits to one or more lineages
8
Q
Define Maturation
A
Descendants acquire functional properties and may stop proliferating
9
Q
What germ layer is the Hemopoietic stem cells derived from
A
The mesoderm
10
Q
When does the Bone marrow start being the site of hemopoiesis
A
Week 16 of development
11
Q
Major hemopoiesis site after 30
A
Vertebra, sternum and rib bone marrow
12
Q
Describe the -physises of a long bone
A
Epiphysis is at the very end.
Diaphysis is the long middle.
Metaphysis is between the Epi and the Dia.
The physis is the growth plate, between the Metaphysis and Epiphysis
13
Q
What is the interface between bone and bone marrow called
A
Endosteum
14
Q
Name a few regulators of hemopoeisis
A
C/EBPalpha, G-CSF, M-CSF, PU1 - Monocyte and Granulocyte
GATA1 and EPO - Erythroid
15
Q
Describe immunophenotyping
A
Antibodies with Fluorochromes are bound to CD proteins on cells. Different cells express different CD proteins.
Fluoresence study is done to determine what cell it is
16
Q
Where does T-cells and B-cells mature
A
T-cells - Thymus
B-cells - Bone marrow
17
Q
What are the Peripheral (secondary) lymphoid tissues
A
Lymph nodes
Spleen
Tonsils (Waldeyer’s ring)
Epithelio-lymphoid tissues
18
Q
What is Chylous Ascites
A
Accumulation of lipid-rich lymph in the peritoneal cavity, due to disruption of the lymphatic system secondary to trauma or obstruction
19
Q
How is lymph filtered in the lymph node
A
Enters through the capsule into the peripheral sinus
Filters through the node and exits through the efferent lymphatic vessel at the hilum
20
Q
Types of Lymphocytes
A
B cells
T cells (Helper and Cytotoxic)
NK cells
21
Q
What is a plasma cell
A
A fully differentiated B cell that only produces one type of antibodies
22
Q
What is red lines extending from a superficial inflamed lesion on the skin called
A
Lymphangitis
23
Q
Triad of Hyperslpenism
A
Spleomegaly
Fall in one or more cellular components of blood
Correction of cytopenias by splenectomy
24
Q
Features of Splenic enlargements
A
Dragging sensation in LUQ
Discomfort while eating
Pain if infarction
25
What is Niemann-Pick disease
Lipid storage disorder affecting Spleen, liver, brain, bone marrow and lungs.
26
Common causes of Hyposplenism
```
Splenectomy
Celiac disease
Sickle Cell disease
Sarcoidosis
Iatorgenic
```
27
What is a Howell-Jolly Body
Small purple dot inside a red cell. Remnant of basophilic nuclear remnant. Usually a sign of damage or absent spleen
28
Glycophorin A is seen on
Red blood cells
29
What happens in Malignant Hemopoiesis
```
One or more of:
Increased proliferation
Lack of differentiation
Lack of maturation
Lack of apoptosis
```
30
Types of hemotological malignancies are based on three things
Speed of presentation (Actue or Chronic)
Site of malignancy (Medullary, Blood or Lymph-nodes)
Lineage (Myeloid, Lymphoid)
High grade or Low grade
31
What is blood and lymp-node malignancies called
Blood - Leukemia
| Lymph-node - Lymphoma
32
Plasma cell malignancy in marrow is called
Myeloma
33
What is Acute Leukemia
Rapidly progressive clonal malignancy of the marrow/blood with maturation defects
34
What is the definition of Acute Leukemia
20% or more blasts in either the peripheral blood or bone marrow
35
What are the types of Acute Leukemia
Acute Lymphoblastic Leukemia (ALL)
| Acute Myeloid Leukemia (AML)
36
Acute Lymphoblastic Leukemia is a malignant disease of
Lymphocytes
37
Most common childhood cancer
Acute Lymphoblastic Leukemia
38
Presentation of Acute Lymphoblastic Leukemia
Due to marrow failure (anemia, infections, bleeding)
Bone pain
Leukemic effects: High WCC and involvement of extra-medullary areas ie CNS, lymph nodes sometimes causing venus obstruction
39
Who gets Acute Myeloid Leukemia
Elderly
| Median age 70
40
Presentation of Acute Myeloid Leukemia
Similar to ALL
Marrow failure
Sub groups may present with DIC or gum infiltration
41
What is Disseminated Intravascular Coagulation
Widespread activation of the clotting cascade. This uses up all the platelets so bleeding may occur at other places.
May be caused by immature red blood cells in Acute Promyeloid Leukemia
42
Investigation for Acute Leukemia
Blood count and film
Coagultion screen
Bone marrow aspirate
43
What is seen on Blood film in acute leukemia
Reduction in normal
Presence of abnormal
Abnormal cells (Blasts) with a high nuclear:cytoplasmic ratio
Auer Rods
44
What is looked at on Bone marrow aspirate in Acute Leukemia
Morphology
Immunophenotype
Cytogenetics
45
How is AML and ALL bone marrow cells differentiated
By immuniphenotyping
46
What is Trephine
A surgical tool used to take a piece of bone out for investigation. Better assessment of cellularity achieved than marrow aspirate
47
Treatment of Acute Lympoblastic Leukemia
Multi-agent chemotherapy
Can last up to 2-3years
Varying phases and intensity of treatment
Target treatments depending on subset
48
Treatment of Acute Myeloid Leukemia
Multi-agent Chemotherapy
2-4 cycles of chemo (5-10 days of chemo followed by 2-4 weeks of recovery)
Prolonged hospitalisation
49
What is a Hickman-Line
Central venous catheter used for administration of chemotherapy.
Normally enter the jugular vein and the line travels under the body further down on the chest
50
What problems arise with chemotherapy in AML and ALL suppressing the bone marrow
Anemia
Neutropenia (infections more likely)
Thrombocytopenia (Bleeding, purpura or Petechiae)
51
How is Infection post chemotherapy dealt with
Give broad spectrum antibiotics as soon as neutropenic fever occur
(Particulary cover Gram negative organism)
52
What is Tumor lysis syndrome
```
Complication of Chemo
Elevated uric acid levels
Elevated serum potassium
Elevated serum phosphorous levels
Decreased Calcium
Potentially life-threatning
```
53
What is the cure rate in ALL and AML
Child ALL >85-90%
Adult ALL >30-40%
60y AML
54
Acute promyelocytic leukemia is associated with what
Specific chomosomal translocation t(15;17) and DIC coagulopathy
Treatable with VitA analogue and arsenic derivatives
55
What is the consistency of Lymphnodes in Lymphoma
Rubbery/soft
56
What is the surface of lymphnodes in Lymphoma vs Metastatic Carcinoma
Lymphoma - Smooth
| Metastatic carcinoma - Irregular
57
Are lymphnodes tethered in Lymphoma and Metastatic carcinoma
Lymphoma - No
| Metastatic carcinoma - Yes
58
What type of sample is needed if lymphoma or other malignancy is suspected
Not FNA or Core
| Need a big sample to assess architecture of the lesion
59
Can you diagnose Lymphoma with CT
No
60
Nodular sclerosing on histology is diagnostic of
Hodgkin's disease
61
How is Immunohistochemistry done in Lymphoma
Antibodies against surface proteins of lymphoma cells and enzyme reaction. Brown=positive
62
CD30 +ve Reed Sternberg cells is seen in
Hodgkin's disease
63
T(14:18) is seen in
Follicular Non-hodgkins lymphoma
64
T(11:14) is seen in
Mantle cell Non-hodgkins lymphoma
65
Lymphomas can be divided into three main categorize
Hodgkin's
T cell Non-Hodgkin's Lymphoma
B cell Non-Hodgkins lymphoma
66
What is Pancytopenia
A deficiency of blood cells of all lineages
67
Causes of Pancytopenia - reduced production
Bone Marrow Failure
| Can be inherited or aquired
68
What is Fanconi's anemia
Rare genetic disease damaging the DNA repair system. Causes Inherited marrow failure syndrome.
69
Signs of Fanconi's anemia
Short stature, Skeletal abnormalities, skin pigmentation such as Cafe au lait spots
70
When are the onset of Fanconi's anemia, what order to abnormalities occur
Median age: 7years
Macrocytosis -->Thrombocytopenia --> Neutropenia
Bone marrow failure - 20y
Lekuemia risk 52% by 40y
71
What is aplastic anemia
Autoimmune attack against hemopoietic stem cells
72
What is Myelodysplastic syndrome
Increased apopotosis of progenitor and mature cells (ineffective hemopoiesis)
73
Types of Acquired Primary Bone Marrow Failure
Aplastic anemia
Myelodysplastic syndromes
Acute Leukemia
74
How does histology of Aplastic anemia look
Very empty bone marrow
75
Causes of secondary bone marrow failure
Drug incuced (chemo, chloramphenicaul, alcohol)
B12/Folate deficiency
Malignancy
Others (HIV/storage disease)
76
Causes of increased destruction of blood componenets causing cytopenia
Hypersplenism
| Autoimmune
77
Causes of Hypersplenism
```
Splenic congestion (Portal hypertension or Congestive cardiac failure)
Systemic disease (RA)
Hematological disease (Myelofibrosis)
```
78
Rheumatoid Arthritis + Splenomegaly + Low WBC with recurrent infections. Diagnosis
Felty's
79
Is the Bone marrow hyper or hypo cellular in Pancytopenia
Can be either. Depends on the underlying cause
80
Treatment of Pancytopenia
Treat underlying cause
Give RBC, Platelet
Antibiotic treatment aggressively and prophylactic
81
Treatment of Idiopathic Aplastic Anemia
Immunosuppression
82
Ig variable element is generated from
V-D-J region recombination early in development
83
What happens to the B cell in the periphery
Travel to the follicle germinal centre of the lymph node
Identify the antigen and improve the fit by somatic mutation or be deleted
May return to the marrow as plasma cell or circulate as memory cell
84
Features of a Plasma cell
Clock face nucleus on histology
Open chromatin (Synthesizing mRNA)
Plentiful blue cytoplasm (Laden with protein)
Pale perinuclear area (Golgi apparatus)
85
What is a paraprotein
Monoclonal immunoglobin
Identical antibody all derived from clonal expansion of a single B-cell
Marker of underlying clonal B-cell disorder
86
Serum electrophoresis: What's in the Alpha-1 band
90% alpha-1 antitrypsin
87
What does alpha-1 antitrypsin indeficiency cause
Emphesema and COPD in young non smoking person
88
Serum electrophoresis: What's in the Alpha-2 band
Alpha-2 macroglobulin, caeruloplasmin, haptoglobin
89
Serum electrophoresis: What's in the Beta band
Transferrin, low density lipoprotein, C3
90
Serum electrophoresis: What's in the Gamma band
Immunoglobulins
91
What are Bence-Jones Protein
Immunoglobin light chains
92
How is Kappa light cahins and Lambada light chains present in the blood
Kappa - monomers
| Lambada - Dimers
93
What is MGUS
Monoclonal gammaopathy of undetermined significance
94
Causes of Paraproteinemia
MGUS
Myeloma
Amyloidosis
Lymphoma -- Asymptomatic myeloma -- Solitary or extramedullary plasmacytoma -- Chronic lymphocytic leukemia -- Waldenstrom's macroglobulinemia
95
How does Myeloma affect the body, 2 main groups
Direct tumor cell effects
| Paraprotein mediated effects
96
Myeloma: Direct tumor cell effects
Bone lesions
Increased calcium
Bone pain
Replace normal bone marrow --> Marrow failure
97
Myeloma: Paraprotein mediated effects
Renal failure
Immune suppression
Hyperviscosity
Amyloid
98
How is Myeloma classified
By the paraprotein (antibody) they produce
99
X-ray features of myeloma
Lytic Bone disease
Punched out lesions
Major cause of bone pain
100
Most common types of Myeloma
IgG myeloma - 59%
IgA myeloma - 21%
Bence Jones myeloma - 15%
101
How does Myeloma cause Lytic bone lesions
Myeloma cells act on stromal cells and release IL-6
| IL-6 activates Osteoclasts
102
How does Myeloma cause Hypercalcemia
Due to the increased activation of osteoclasts the bone matrix is broken down and release Ca2+
103
What does Hypercalcemia cause
```
Stones
Bones
Abdominal groans
Psychiatric moans
Thirst -- Dehydration -- Renal impairment
```
104
How does Myeloma affect the kidney
```
Tubular cell damage by light chains
Ligh chain deposition - Cast nephropathy
Sepsis
Hypercalcemia and dehydration
Drugs: NSAIDs
Amyloids
Hyperuricemia
```
105
How does Cast injury occur in Myeloma
Light chains is filtered through the Glomerulus. Normally it is reabsorbed in the proximal tubules but if there's too much it continous to the loop of Henle
In the Thick ascending limb it bounds with the native protein Tamm-Horsfall proteins and this produce insoluble casts which blocks the nephron
106
Onset and survival of Myeloma
Median age at diagnosis 65
| Survival 5-8years
107
Treatment of Myeloma
```
Corticosteroids (dexamethasone or prednisolone)
Alkylating agents (Cyclophosphamid, melphalan)
Novel agents (Thalidomide, bortezomib, Lanalidomide)
High dose chemo/autologous stem cell transplants in fit patients
```
108
Symptom control of Myeloma
```
Opiates (avoid NSAIDs)
Local radiotherapy (Pain relief or spinal cord compression)
Bisphosphonates (corrects hypercalcemia and bone pain
Vertebroplasty - inject sterile cement into fractured bone to stabilize
```
109
Features of MGUS
Paraprotein
110
What is AL Amyloidosis
Amyloid Light-chain Amyloidosis
Small plasma cell clone
Mutation in the light chain -->altered structures
Precipitates in tissue as an insoluble beta pleated sheet
111
Organ damage in AL amyloid
```
Kidney (nephrotic syndrome)
Heart (Cardiomyopathy)
Liver (Organomegaly and deranged LFTs)
Neuropathy (Autonomic and Peripheral)
GI tract (Malabsorption)
```
112
How is AL Amyloidosis diagnosed
Organ biopsy and Congo red stain to confirm deposits
113
IgM paraprotein is linked to
Waldenstrom's Macroglobulinemia
114
Tumor effects of Waldenstrom's macroglobulinemia
Lymphadenopathy
Splenomegaly
Marrow failure
115
Paraprotein effects of Waldenstrom's Macroglobulinemia
Hyperviscosity
| Neuropathy
116
What does Waldenstrom's macroglobulinemia Hyperviscosity syndrome present as
Faitgue, visual disturbance, confusion, coma
Bleeding
Cardiac failure
Also, night sweats and weight loss
117
Treatment of Waldenstroms Macroglobulinemia
```
Chemo
Plasmapheresis (removes paraprotein from the circulation)
```
118
What are Myeloproliferative disorders
Clonal hemopoietic stem cell disorders with an increased production of one or more types of hemopoietic cells
Maturation is relatively preserved
119
Two subtypes of Myeloproliferative disorders
BCR-ABL1 Negative
| BCR-ABL1 Positive
120
What Myeloproliferative disorders are BCR-ABL1 Negative
Idiopathic myelofibrosis
Polychyhemia Rubra Vera
Essential Throbocytemia
121
What Myeloproliferative disorders are BCR-ABL1 Positive
Chronic Myeloid Leukemia
122
What is the BCR-ABL1 Gene associated chromosome
Philadelphia chromosome
| Reciprocal translocation between chromosome 22 and 9
123
When should Myeloproliferative disorders be considered
When there's no other explanation to a high blood count (of any or more type) Splenomegaly or Thrombosis in an unusual place
124
What is Chronic Myeloid Leukemia (CML)
Proliferation of myeloid cells (Granulocytes and their precursors, Other lineages, platelets)
Chronic phase followed by Accelerated phase followed by Blast crisis
125
Clinic features of Chronic myeloid Leukemia
```
Asymptomatic
Splenomegaly
Hypermetabolic symptoms
Gout
Priapism (not common)
```
126
Lab features of Chronic Myeloid Leukemia
Normal/redued Hb
Leucocytosis w/ neutrophilia and myeloid precursors, eosinophilia, basophilia
Thrombocytosis
Bone Marrow - Increase in myelocytes and eosinophils
127
What is the hall mark of Chronic Myeloid Leukemia
Philadelphia chromosome
A philadelphia chromosome is the BCR and ABL gene are next to each other on chromosome 22. (ABL normally on chromosome 9)
128
What is Imatinib
Tyrosine kinase inhibitor drug. Used in ie Chronic Myeloid Leukemia
129
Features common to MPD
Asymptomaic -- Increased cellular turnover (Gout, fatigue, weight loss, sweats)
Splenomegaly
Marrow failure
Thrombosis (TIA, MI, Abdominal vessel thrombosis, claudication, erythromelalgia)
130
What is Polycythemia rubra vera
High hemoglobing/hematocrit accompanied by erythrocytosis (a true increase in red cell mass) but can have exessive production of other lineages
131
Polycythemia rubra vera needs to be distinguished from two other conditions
```
Secondary polycythemia (Chronic hypoxia, smoking, erythropoietin-secreting tumor etc)
Pseudopolycythemia (Dehydration, diuretic, therapy, obestiy)
```
132
Clinical features of Polycythemia Rubra vera
Headaches, fatigue (Blood viscosity is up but not plasma viscosity)
Itch (aquagenic puritis)
133
What is aquagenic puritis
Intense Itching sensation without any visible lesions and is made worse by water
134
What is the mutations in Polycythemia Rubra vera that is most common
JAK2 mutation
| 95% of patients has the mutation
135
Investigations for polycythemia
CXR
O2 saturation and ABGs
Others
136
Treatment of Polycythemia Rubra Vera
Venesect (Hematocrit
137
What is Essential Thrombocytopenia
Type of Myeloproliferative disorder
| Uncontroled production of Abnormal platelets
138
What can Essential Thrombocytopenia lead to
Thrombosis
| Bleeding due to acquired von Willebrand disease
139
What needs to be excluded when Essential Thrombocytopenia is suspected
Reactive Thrombocytosis
| CML
140
Which mutations are seen in Essential Thrombocytopenia
JAK2 mutation (50%)
CALR (Carlreticulin)
MPL mutation
141
Treatment of Essential Thrombocytopenia
None in low risk cases
Anti-platelet agents (Aspirin)
Cytoreductive therapy to control proliferation
142
Dacrocytes (Teardrop-shaped RBCs) in peripheral blood is linked with
Beta Thalassemia major Idiopathic myelofibrosis
143
Features of Idiopathic myelofibrosis
Leukoerythroblastosis
Marrow failure
Bone marrow fibrosis
Extramedullary hematopoiesis (liver and spleen)
144
What is Leukoerythroblastosis
Anemia caused by a space occupying lesion in the bone marrow
145
Typical blood film for Myelofibrosis
Tear-drop shaped RBC and Leycoerythrocytoblastosis
146
Lab featrues of Myelofibrosis
Dry bone marrow aspirate
Fibrosis on trephine biopsy
JAK2 or CALR mutation
Typical blood film (tear drop and leuoerythroblastic)
147
What causes Leucoerythroblastic blood film
Reactive (sepsis)
Marrow infiltration
Myelofibrosis
148
Treatment of Myelofibrosis
```
Supportive care (blood transfusions, platelets, antibiotics)
Ruxolitib (JAK 2 inhibitor)
```
149
Cytotoxic drugs: Antimetabolites act by
Impair nucleotide synthesis/incorporation
150
Cytotoxic drugs: Examples of Antimetaboltites
Methotrexate
6-Mercaptopurine/Cytosine arabinoside/ Fludarabine
Hydroxyurea
151
How does Methotrexate act
Inhibits dihyrofolate reductase
Blocks nucleoside synthesis (Thymidine specific)
Also blocks purine and pyridine side ring synthesis
152
Cytotoxic drugs: Mitotic spindle inhibitors
```
Vinca Alkaloids (Vincristine/Vinblastine)
Taxotere (Taxol)
```
153
Cytotoxic drugs: Non-cell cycle specific agents
Alkalating agents
Platinum derivatives
Cytotoxic antibiotics
154
What is the negative about Non-cell cycle specific agents
Damage healthy cells as well as tumor cells
155
Immediate side effects of Cytotoxic drugs
Bone marrow suppression
Gut mucosal damage
Hair loss (Alopecia)
156
Side effects of Vinca alkaloids, Anthracyclines and Cis-platinum
Vinca alkaloids - neuropathy
Anthracyclines - cardiotoxicity
Cis-platinum - Nephrotoxicity
157
Long term side effects of Alkylating agents
Infertility
| Secondary malignancy
158
Long term side effects of Anthracyclines
Cardiomyopathy
159
How can some types of tumors escape systemic chemotherapy
Evade into the CNS. drugs do not cross the blood brain barrier
160
Where are stem cells taken from for a transplantation
Mainly blood
161
High vs Low dose of chemo kills cells by what mechanism
Low dose - Apoptosis
| High Dose - Necrosis
162
What is Neutropenic Sepsis
Sepsis + Neutrophil count
163
Whai is given to treat fungal infections in chemo patiets
Prophylactic antifungal drugs
| Itraconazole OR Posaconazole
164
What is found in Hodgkin's lymphoma on microscopy
Reed-Sternberg cells
165
Rituximab is what type of drug, binds to what
Monoclonal antibody
Binds specifically to CD20 B cells.
IgG Fc domain works in synergy with human immunesystem
166
What hematological cancers is Rituximab used for
High grade B cell NHL
Chronic Lymphocytic Leukemia
Low grade and Mantle cell NHL
167
Anti-B cell antiboidies
Rituximab
Ofatumunab
Obinutumab
168
What drug is used in Hodgkin's disease and what is the target
Brentuximab Vedotin
| CD30
169
What hematological cancer is Biological treatments used in
Multiple Myeloma
170
What is Bortezomib
Protesome inhibitors
| Blocks breakdown of old proteins, therefore build up of toxins occur
171
What are IMIDs
Immunomodulatory drugs
Derivatives of Thalidomide (Lenalidomide)
Used in Low grade NHL and CLL when chemo doesn't work anymore
Used in combo with chemo in mantle cell NHL
172
Treatment of Chronic Myeloid Leukemia
Tyrosine kinase inhibitor
Imatinib
Nilotinib -- Dasatinib -- Ponatinib
173
What are Ibrutinib and Idelalisib
Drugs affecting B cell signaling pathway
| Effective in low grade NHL and B cell CLL that don't respond to Rituximab and chemotherapy
174
What is Nivolumab
Binds to tumor cells "evasion" protein. Normally this allows the tumor to evade the immune system but this drug block the evasion and the immune system attacks the tumor
175
What happens if you give Amoxycillin to EBV tonsillar lymphadenopathy
Induced rash
| Diagnostic of EBV
176
How are the lymphnodes in viral infection
Painful/tender
Hard and regular
Not tethered
177
Hodgkin's disease vs NHL
Suspect in young patient esp female
Disease above diaphragm more common
B symptoms and itch, alcohol induced pain more common than with NHL
Node biopsy is the real way to differentiate
178
What is seen on biopsy of lymphnode in Hodgkins disease
Nodular sclerosing
| Reed Sternberg cells
179
How is Hodgkin's Disease staged
CT and PET scan
180
Done week 2 lectures
Yes
