questions Flashcards
(275 cards)
1
Q
What is mucositis in neutropenic patients?
A
Chemotherapy-induced damage to mucosal barrier causing ulceration and inflammation.
2
Q
How does mucositis present clinically?
A
Pain, swelling, difficulty eating, swallowing, diarrhoea, changes in mucus production.
3
Q
What are the additional risks of infection in neutropenic patients with mucositis?
A
Increased morbidity, complications, especially infections due to gut translocation.
4
Q
Explain the role of adaptive immunity in neutropenic patients.
A
Acts as the third line of defense involving both humoral and cellular mechanisms.
5
Q
What factors determine infections in immunocompromised hosts?
A
Type of immune deficit, severity, and duration of immune defect.
6
Q
List examples of immunocompromised hosts.
A
Extremes of ages, pregnant women, patients on immunosuppressive therapy, HIV/AIDS patients, stem cell transplant recipients.
7
Q
How does immunosuppression affect infection risk?
A
Increases susceptibility to severe, rapidly developing infections, reactivation of latent infections, and opportunistic pathogen infections.
8
Q
Define virulence and primary pathogen.
A
Virulence is microorganism’s disease-causing ability, primary pathogen causes disease regardless of host’s immune system.
9
Q
What is an opportunistic pathogen? Give examples.
A
Organism causing disease when host’s defenses are compromised. Examples include Pseudomonas, Mycobacteria, Herpes viruses.
10
Q
Describe the characteristics of Pseudomonas aeruginosa infections.
A
Nosocomial, severe, life-threatening infections, especially in neutropenic patients with persistence in hospital environments.
11
Q
Explain the significance of Mycobacteria in immunocompromised hosts.
A
Mycobacteria like M. tuberculosis can cause latent or reactivated disease, especially in those with reduced immunity.
12
Q
What are the key points about Aspergillus infections?
A
Opportunistic fungal disease from inhalation with a risk of pneumonia, especially in immunocompromised individuals.
13
Q
Discuss the impact of immunosuppression on herpes viruses.
A
Immunosuppression can lead to reactivation or acquisition of latent herpes virus infections.
14
Q
What is Pneumocystis jirovecii, and how is it transmitted?
A
It’s an airborne fungus with a poorly understood life cycle transmitted through exposure to infected individuals.
15
Q
Define necessary and sufficient causes in disease.
A
A necessary cause is required for a disease to occur; a sufficient cause alone can cause disease.
16
Q
Explain why most causes of non-communicable diseases are not necessary causes.
A
Non-communicable diseases often have multiple component causes that together are sufficient for the disease.
17
Q
List some factors at multiple levels that can be causes of certain effects.
A
Racism, genetic factors, violence, sex, social factors, and more are cited as influencing factors.
18
Q
Discuss the concept of evidence-based practice regarding pertussis vaccine and brain damage.
A
Evidence-based practice involves accessing and appraising the evidence, then applying it to the patient’s case.
19
Q
What are some key factors to consider in causal interference?
A
One must question if an association is real and critically appraise study methods before results.
20
Q
Explain the importance of bias and confounding in research studies.
A
Bias and confounding can skew results through selection bias, measurement bias, and unadjusted significant differences.
21
Q
Why is sample size important in research studies?
A
Sample size affects the ability to detect real associations and evaluate statistical significance.
22
Q
Discuss the Bradford Hill causal association criteria and its relevance in epidemiology.
A
The criteria include temporality, strength of effect, dose-response effect, biological plausibility, and consistency.
23
Q
Why is temporality considered an absolute requirement in causal inference?
A
Temporality ensures that the cause precedes the effect, essential for establishing causality.
24
Q
What are some key considerations in making clinical judgments based on evidence?
A
Factors include the best evidence available, disease epidemiology, and patient applicability and acceptance.
25
Define 'evidence' in the context of epidemiology and research.
Evidence refers to the best available data used to make informed clinical decisions.
26
What is the strong association of nodal enlargement with in endemic Burkitt lymphoma?
Strong association with EBV infection.
27
Describe the common sites of intestinal involvement in sporadic/non-endemic Burkitt lymphoma.
Most common in the ileum with mesenteric nodes.
28
What is the histological characteristic of Burkitt lymphoma with respect to cellular infiltration?
Diffuse infiltration of monomorphic, medium-sized cells.
29
Explain the 'starry sky' pattern seen in Burkitt lymphoma histology.
'Stars' are tingible body macrophages taking up apoptotic tumor cells.
30
What is the significance of a positive EBV stain (EBER) in Burkitt lymphoma?
Positive in endemic African cases and immunodeficiency cases.
31
What is the characteristic feature of Anaplastic large cell lymphoma histology?
Large lymphoid cells with abundant amphophilic cytoplasm.
32
Explain the presence of ALK gene translocation in Anaplastic large cell lymphoma.
Lymphoma cells exhibit ALK gene translocation and expression of ALK protein.
33
Define Mycosis fungoides and Sezary syndrome in terms of presentation.
These are cutaneous lymphomas presenting on the skin.
34
What is the role of the spleen as a lymphoid organ?
Function as a lymphoid organ (white pulp).
35
Explain the function of the spleen in phagocytosing particulate matter and culling red cells.
Capacity for phagocytosing particulate matter and culling senescent red cells.
36
Describe the circulation pathways within the spleen.
Closed circulation via splenic artery and vein, open circulation through cords of Billroth.
37
What are the clinical implications of primary hypersplenism?
Marked massive splenomegaly and pancytopenia, usually requiring splenectomy.
38
Explain the term 'hypersplenism' and its association with pancytopenia.
Association between peripheral blood pancytopenia and splenic enlargement.
39
How is splenomegaly classified in terms of enlargement?
Grossly enlarged, moderately enlarged, mildly enlarged.
40
What are the causes of congestive splenomegaly?
Causes include chronic myeloid leukemia, myelofibrosis, amyloidosis, infections, autoimmune diseases.
41
Describe the characteristics of spleen in congestive splenomegaly.
Variably enlarged, thickened and fibrotic capsule, beefy-red color with firm brown nodules.
42
How is congenital asplenia or polysplenia characterized?
May present with accessory spleens or absence/multiple additional spleens.
43
Explain the relationship between splenic congestion and systemic infections.
Systemic infections cause moderate splenomegaly characterized by congestion.
44
What are the metabolic abnormalities required for Howard's definition of Laboratory TLS?
Hyperkalaemia, hyperuricaemia, hyperphosphataemia, hypocalcaemia
45
What defines the Modified Howard definition of Clinical TLS?
Same as laboratory TLS with elevated creatinine level, seizures, cardiac dysrhythmia, or death
46
How does cancer cell lysis lead to metabolic abnormalities in TLS?
Cells release potassium, phosphorus, uric acid overflow in blood
47
What can hyperuricaemia induce in TLS?
Acute kidney injury by crystallization and pro-inflammatory effects
48
Why is hyperkalaemia in TLS particularly dangerous?
It may cause serious and sometimes fatal cardiac dysrhythmias
49
How can hyperphosphataemia affect the body in TLS?
Can cause secondary hypocalcaemia, calcification in kidney and soft tissues
50
What complications can arise due to hypocalcaemia in TLS?
Neuromuscular irritability (tetany), dysrhythmia, seizures
51
What is a way to prevent TLS during treatment?
Adequate IV hydration to maintain high urine output
52
Which medications can be used to reduce uric acid load prophylactically in TLS?
Allopurinol, Rasburicase (recombinant urate oxidase)
53
What is the recommended course of treatment for TLS?
Watch renal function, hydration, uric acid reduction, electrolyte correction
54
What is the characteristic feature of gout in clinical presentation?
Acute painful arthritis in a single joint
55
What are gouty tophi and how do they impact the body?
Depositions of urate crystals causing local destruction, lack of function
56
How is gout diagnosed?
Clinical features, uric acid crystals in joint fluid, elevated serum uric acid levels
57
What is the treatment for gout?
Colchicine for pain, Allopurinol to reduce uric acid, Uricosurics
58
What is Multiple Myeloma characterized by?
Malignant proliferation of plasma cells in bone marrow
59
Which immunoglobulins do plasma cells produce in Multiple Myeloma?
Pairs of identical heavy and light chains; IgG, IgA, IgM, IgD, IgE
60
What is the significance of the extremely variable N-terminal end of each antibody?
Allows for millions of antibodies with different antigen binding sites.
61
Define polyclonal antibodies in the context of antibodies production.
Antibodies from different 'clones' of plasma cells, each with unique binding sites.
62
What does MM stand for in the context of antibody production?
Multiple Myeloma.
63
Explain the process leading to the production of a monoclonal antibody in Multiple Myeloma.
Uncontrolled proliferation leads to over-production of a single antibody.
64
What are some clinical presentations of Multiple Myeloma?
Includes bone pain, fatigue, pathological fractures, weight loss, and more.
65
What are the diagnostic criteria for Multiple Myeloma?
Clonal bone marrow plasma cells >10% or presence of CRAB or MDE features.
66
How are plasma proteins separated in protein electrophoresis?
Proteins move based on charge towards anode or cathode in a buffer.
67
What can be determined by visually inspecting proteins separated by electrophoresis?
Concentrations and relative increases or decreases of proteins.
68
What lab features are associated with Multiple Myeloma?
Increased total protein, monoclonal antibodies, immunoparesis, and Bence Jones proteinuria.
69
List the human herpes viruses discussed in the notes.
Herpes simplex 1 & 2, Varicella-Zoster, Epstein Barr Virus, Human Cytomegalovirus, HHV 6 & 7, HHV 8.
70
Explain the characteristics of successful human parasites according to the notes.
High prevalence, minimal clinical disease, milder disease with early life infection.
71
Describe the virology of human herpes viruses discussed in the notes.
dsDNA, large, enveloped, complex genome, primary infection leads to latency and reactivation.
72
What are the characteristics of Herpes Simplex 1 and 2 infections?
Cause painful blisters at site of inoculation, can infect oral or genital sites.
73
Define Monoclonal Gammopathy of Undetermined Significance (MGUS).
Low level paraprotein (<30g/L), asymptomatic patient, without diagnostic features of plasma cell myeloma.
74
What is the progression rate of MGUS to overt disease per year?
1% per year.
75
List the CRAB criteria used for diagnosing symptomatic plasma cell myeloma.
Hypercalcaemia, Renal insufficiency, Anaemia, Bone lesions.
76
Explain the bone disease in plasma cell myeloma.
Osteoclast activation results in lytic lesions, osteoblast inhibition leads to bone resorption.
77
What are the common clinical problems associated with plasma cell myeloma?
Recurrent infections, abnormal antibody production, neutropenia, bleeding, amyloidosis, hyperviscosity.
78
How is plasma cell myeloma diagnosed?
M protein (>30g/L in serum), clonal plasma cells in BM, end organ damage, genetic changes.
79
Outline the management strategies for plasma cell myeloma.
Pain control, renal impairment management, hypercalcaemia treatment, bone disease care, anaemia treatment, infection control.
80
What are the specific aims of plasma cell myeloma management?
Control disease, improve quality of life, prolong survival.
81
Describe the management approach for patients eligible for stem cell transplant (SCT).
Combination chemotherapy cycles, stem cell collection, autograft; allograft has cure potential but high mortality risk.
82
What are the characteristics of aggressive B cell lymphomas?
Rapid progression, nodal/extra-nodal disease, risk of tumour lysis syndrome.
83
What are the common extranodal sites affected by aggressive B cell lymphomas?
Gastrointestinal tract (GIT), skin, CNS, other areas.
84
Describe the staging system utilized for Burkitt lymphoma.
Anne Arbour system.
85
What are common clinical presentations of T cell lymphoproliferative disorders?
Skin lesions (prominent pruritis), lymphadenopathy, hepatosplenomegaly, effusions, constitutional symptoms, bone lesions, and hypercalcaemia.
86
How is Chronic Myeloid Leukemia (CML) characterized at a genetic level?
Characterized by t(9:22), resulting in the BCR-ABL1 fusion gene on chromosome 22.
87
What are the symptoms associated with the cytokine clustering in myeloproliferative neoplasms?
Constitutional symptoms and fatigue.
88
What are the symptoms associated with hyperviscosity clustering in myeloproliferative neoplasms?
Headache, hypertension, visual disturbance, tinnitus, gout, vertigo, plethora, peripheral neuropathy.
89
What are the symptoms associated with splenomegaly clustering in myeloproliferative neoplasms?
Abdominal discomfort, early satiety.
90
What is the significance of JAK2 V617F mutation in myeloproliferative neoplasms?
Increases the risk of thrombosis.
91
How can Chronic Myeloid Leukemia (CML) be diagnosed?
Triade of splenomegaly, Philadelphia Chromosome BCR-ABL1, and ↑ granulocytes in peripheral blood and bone marrow.
92
What are the common morphological findings in the peripheral blood in Chronic Myeloid Leukemia (CML)?
Raised WCC, usually > 50 x 109/L, neutrophil predominance, basophilia, eosinophilia, normocytic normochromic anemia.
93
Describe the phases of Chronic Myeloid Leukaemia (CML).
Initial chronic stable phase, chronic phase with high-risk features, blast phase.
94
What are the defining features of the initial chronic stable phase in CML?
Granulocytic population expansion, retains ability to differentiate, <10% blasts, basophils <20%.
95
What differentiates the chronic phase with high-risk features in CML?
Increasing blast count 10-19%, basophil count ≥20%, platelet count extremes, spleen enlargement, additional cytogenetic abnormalities.
96
How does tyrosine kinase inhibitors (TKIs) prevent progression in CML?
Displace ATP from BCR ABL1 kinase pocket. Imatinib is first line in stable phase.
97
What molecular testing is used in CML to monitor treatment efficacy?
Quantitative PCR for BCR ABL1 on peripheral blood.
98
Name the three types of Philadelphia-negative MPN disorders.
Essential Thrombocythaemia (ET), Polycythaemia Vera (PV), Primary Myelofibrosis (PMF).
99
What are the main causes of morbidity and mortality in Philadelphia-negative MPNs?
Arterial and venous thrombosis.
100
What is the key characteristic of Essential Thrombocythaemia (ET) on a molecular level?
Clonal haematopoietic stem cell disorder with active Jak-Stat signalling.
101
How is clonality assessed in Essential Thrombocythaemia?
Via mutation analysis: JAK2 V617F, CALR, MPL mutations or triple negative status.
102
What is the main pathological finding in Polycythaemia Vera (PV)?
Increase in red blood cell production independent of regulatory mechanisms.
103
What are the serum markers used to diagnose Polycythaemia Vera (PV)?
Elevated hemoglobin or hematocrit, often with increased white cell and platelet counts.
104
In ET, how is thrombosis managed based on platelet count?
Low dose aspirin unless count >1500 x 10^9/L or actively bleeding.
105
Why does EBV transform naive B cells during primary infection?
To evade immune recognition and persist since naive B cells are not normally long-lived.
106
Which latency gene of EBV is expressed after the specific immune response develops during primary infection?
EBNA 1 is expressed as the other 9 latency genes are driven down.
107
What percentage of B cells in a healthy seropositive person are infected with EBV?
Approximately 1 in 10,000 B cells in a healthy seropositive person are infected.
108
What is the treatment approach for EBV-associated diseases?
Reduction in immunosuppression, rituximab (CD20 monoclonal antibody), and no benefit from antivirals.
109
What are the key oncogenes associated with EBV lymphoproliferative diseases?
LMP-1 and LMP-2A are key oncogenes associated with EBV lymphoproliferative diseases.
110
What is the primary disease associated with HHV6 in babies?
Primary infection in babies presents as roseola Infantum with febrile illness, rash, and febrile convulsions.
111
What percentage of humans have germline HHV6 with high blood viral load and DNA in all body cells?
About 0.8-1.5% of humans have germline HHV6 with high blood viral load and DNA in all body cells.
112
What are the possible ways HHV8 can be transmitted?
High prevalence: mother to child, close contact in families. Low prevalence: sexual transmission in adulthood.
113
Which diseases are associated with HHV8 due to poor immune control of virus-infected cells?
Kaposi sarcoma, Multicentric Castleman’s disease, Primary effusion lymphoma, Plasmablastic lymphoma.
114
What are the key diseases caused by HHV8 with oncogenes derived from altered cellular genes?
Diseases include Kaposi sarcoma, Multicentric Castleman’s disease, Primary effusion lymphoma, Plasmablastic lymphoma.
115
What is the main route of excretion for uric acid?
Mainly excreted by the kidney (75%) and rest via the intestine.
116
Why do humans have higher blood uric acid levels compared to other animals?
Humans lack uricase which degrades uric acid to non-toxic allantoin.
117
Explain the uric acid paradox in humans.
Humans evolved strategies to retain uric acid due to its antioxidant and immune enhancing properties.
118
What base pairs with thymine in DNA?
Adenine (A) pairs with thymine (T) in DNA.
119
What are the characteristics of purine nucleotides metabolism?
Managed by de novo synthesis, catabolism, salvage, and eventually degradation to uric acid.
120
What are the causes of hyperuricaemia related to overproduction?
Include malignancy, myeloproliferative disorders, and increased de novo synthesis.
121
How is Tumour Lysis Syndrome characterized?
Characterized by hyperkalaemia, hyperuricaemia, hyperphosphataemia, and hypocalcaemia.
122
What are common tumours associated with Tumour Lysis Syndrome?
Hematological malignancies such as ALL, AML, and NHL.
123
When can Tumour Lysis Syndrome occur?
Usually 48-72 hours after the start of chemotherapy, radiotherapy, or steroid treatment.
124
Why is Tumour Lysis Syndrome considered a life-threatening emergency?
Due to high morbidity and risk of mortality associated with metabolic complications.
125
What is the gold standard for detecting HSV in cerebrospinal fluid?
PCR
126
What is the primary cause of chickenpox in children?
Varicella
127
What is the main reason for the adult manifestation of chickenpox known as shingles?
Latency in ganglia
128
How is EBV primarily transmitted in adults?
Saliva
129
What is the % of lymphocytes in adults with infectious mononucleosis?
90-100%
130
What is the gold standard for diagnosing CMV in immunocompromised individuals?
PCR
131
What is the typical presentation of CMV in adult patients?
IM-like illness, fever, sore throat, lymphadenopathy
132
How is HHV8 mainly transmitted?
Early life - cell transform, proliferation, angiogenesis
133
What is the characteristic feature of the transmission of HHV8 in adults?
Sexual transmission less common
134
What is the primary defense mechanism in the body that prevents entry of pathogens?
Physical and biochemical barriers
135
What type of response does adaptive immunity provide against pathogens?
Specific response to particular pathogen with memory
136
What component of innate immunity is responsible for damaging the cell walls of Gram+ bacteria?
Lysozyme in tears, nasal secretions
137
What is the mechanism through which neutrophils kill bacteria?
Phagocytosis and killing bacteria
138
What are the cells responsible for phagocytosis in innate immunity?
Neutrophils and macrophages
139
What is the primary risk associated with neutropenia?
Increased risk of infection, dissemination, severe sepsis
140
Which bacteria is commonly associated with infections in neutropenic patients?
Pseudomonas aeruginosa
141
Name a gram-positive cocci commonly causing infection in neutropenic patients.
Viridans Streptococci
142
What are some fungi species that can cause infections in immunocompromised individuals?
Candida albicans and Aspergillus fumigatus
143
Which virus is associated with infections in HIV/AIDS patients?
Herpes simplex
144
What pathogen causes diseases normally controlled by T cell immunity in immunocompromised individuals?
Mycobacterium tuberculosis
145
How does diabetes mellitus affect neutrophils' immune response?
Decreases chemotaxis, adherence, phagocytosis, opsonisation, increases apoptosis.
146
What vascular complication in diabetes promotes anaerobic organism growth?
Local tissue ischaemia
147
Which organisms commonly colonize the skin and mucosa of diabetics?
S. aureus and Candida species
148
What increases adhesion of Candida to epithelium in diabetics?
High glucose levels
149
What is the epidemiological definition of a determinant?
Any factor that brings about change in a health condition.
150
Define a necessary cause in epidemiology.
A factor that must be present before a disease occurs.
151
What are component causes in epidemiology?
Individual factors working with necessary causes to produce disease.
152
Explain a sufficient cause in epidemiology.
A combination of factors sufficient to produce disease in some cases.
153
What are the common sites of involvement for mature lymphoid neoplasms?
Lymph nodes, organs, skin, other soft tissue, and bone.
154
What are the two primary growth patterns of mature lymphoid neoplasms?
Lymphomatous (growing in tissues) and leukaemic/lymphoproliferative (circulating in blood).
155
Which are the key types of mature lymphoid neoplasms with leukaemic tendencies mentioned?
Chronic Lymphocytic Leukaemia (CLL), Follicular Lymphoma, Diffuse Large B-cell Lymphoma (DLBCL), Mantle Cell Lymphoma, Splenic Marginal Zone Lymphoma.
156
What are some of the basic lab tests mentioned for investigating mature lymphoid neoplasms?
Complete Blood Count (CBC), white cell differential count, blood film, ESR, LDH, CMP, uric acid, liver function, renal function, HIV testing.
157
What are the possible causes of lymphocytosis mentioned in the course notes?
Infection (viral, certain bacteria), stress, smoking, drug allergies, post-splenectomy changes, endocrine disorders, lymphoid neoplasms.
158
What are some special investigations used in the diagnosis of lymphoid neoplasms?
Biopsy/histology, bone marrow biopsy, flow cytometry, immunohistochemistry, cytogenetics.
159
What are the presenting symptoms of Chronic Lymphocytic Leukaemia (CLL) as per the course notes?
Fatigue, infections, autoimmune conditions like AIHA, ITP, cytopenias, lymphocytosis, organ involvement.
160
What are some adverse prognostic factors mentioned in the course notes for CLL?
Unmutated biological factors, ZAP-70 and CD38 expression, cytogenetic abnormalities like del11q, del17p, etc.
161
What are some indications for treatment of CLL according to the course notes?
Constitutional symptoms, bone marrow failure, AIHA/ITP not responsive to steroids, progressive lymphadenopathy, splenomegaly.
162
What are the possible management options for CLL discussed in the course notes?
Observation, palliation with alkylator e.g., chlorambucil, aggressive combination chemotherapy, new biological treatments.
163
Describe the histological spectrum of early stage Kaposi's sarcoma.
Florid reactive hyperplasia with invagination of mantle zone lymphocytes, follicular lysis, moth-eaten appearance.
164
What are the histopathological findings in late-stage HIV lymphadenitis?
Lymphocyte depletion, fibrosis, vascular proliferation; not specific but often characteristic.
165
Which viral capsid is shown on staining with p24 antigen in HIV lymphadenitis?
Viral capsid of HIV.
166
What occurs in the later stages of HIV lymphadenitis?
Profound loss of B-cells in germinal centers, depletion of T-cells, presence of other opportunistic infections/malignancies.
167
List neoplastic causes of lymphadenopathy.
Primary neoplasms (Hodgkin lymphoma, Non-Hodgkin lymphoma), Secondary neoplasms (Metastases).
168
What is the distinguishing feature of Hodgkin Lymphoma?
Presence of large neoplastic Reed-Sternberg cells in a background of reactive cells.
169
Differentiate between Nodular lymphocyte predominant HL and Classical HL.
NLPHL: B-cell neoplasm, good prognosis; Classical HL: Large Reed-Sternberg cells, reactive cell background.
170
Identify the variants of Classical Hodgkin lymphoma based on histology.
Nodular lymphocyte predominant, Lymphocyte rich, Nodular sclerosis, Mixed cellularity.
171
What determines blood viscosity?
Blood viscosity is determined by water content, protein, and blood cells.
172
What can cause hyperviscosity?
Hyperviscosity can be caused by decreased water content, increased protein (e.g., paraprotein), and an increase in blood cells (WBC, RBC, platelets).
173
What classification criteria are used for acute leukemia?
Acute leukemia classification is based on morphology and staining, immunophenotyping, cytogenetics, and molecular genetics.
174
What is the aim of acute leukemia treatment?
The aim of treatment is to destroy the leukemic clone without harming the residual stem cell compartment.
175
What supportive care is provided in leukemia management?
Supportive care includes transfusions, treating infections aggressively, and managing metabolic complications.
176
What is neutropenic fever?
Neutropenic fever is a serious complication of chemotherapy characterized by fever and low neutrophil count.
177
How should neutropenic fever be managed?
Management includes taking cultures, starting broad-spectrum antibiotics promptly, and avoiding rectal examination in neutropenic patients.
178
What is the prognosis of acute leukemia without treatment?
Without treatment, acute leukemia has a median survival of around 5 weeks.
179
What factors contribute to the etiology of hematological malignancies?
Factors include genetic and environmental influences with some cases linked to inherited factors and environmental exposures.
180
How do hematopoietic growth factors regulate cell differentiation?
Hematopoietic growth factors interact at different levels in the marrow, regulating proliferation and differentiation of progenitors.
181
What are the main stages of the interphase in the cell cycle?
The interphase consists of G1 phase, S phase (DNA replication), and G2 phase (organelle duplication).
182
What are the functions of cell cycle checkpoints?
Checkpoints control cell cycle, coordinate divisions, and check the integrity of DNA for repair before proceeding.
183
What is the commonest viral cause of congenital abnormalities?
Cytomegalovirus (CMV)
184
What are the delayed onset symptoms of congenital CMV infection?
Mental retardation and deafness
185
What is the main clinical feature of CMV disease in immunosuppressed patients?
Persistent virus controlled by cell mediated immunity
186
Which organs can be affected by end organ disease in CMV infection?
Lung, eye, GIT, and brain
187
What is the significance of IgG in CMV serology?
Indicates past exposure
188
What is the drug of choice for life-threatening CMV infection?
Ganciclovir/valganciclovir (GCV)
189
How do Foscarnet and cidofovir compare to Ganciclovir in treating CMV?
They have modest anti-CMV activity and significant toxicity
190
What is the transmission route for Epstein Barr Virus (EBV)?
Saliva, kissing
191
What antibodies are detected in the Monospot test for EBV?
Antibodies that bind and agglutinate sheep RBCs
192
What viral component do patients make antibodies to during primary EBV infection?
Viral capsid antigen (VCA)
193
What test results confirm acute infectious mononucleosis?
Positive VCA IgM and IgG; negative EBNA IgG
194
What percentage of adults have antibodies to HSV1/2?
Almost 100% of adults.
195
What percentage of children have antibodies to HSV1/2?
20-40% of children.
196
Where does HSV establish latent infection in the host?
In sensory ganglion cells.
197
Which nerve innervates the skin for orofacial herpes?
Trigeminal ganglion.
198
Which nerve innervates the skin for genital herpes?
Sacral ganglia.
199
What triggers can cause reactivation of HSV1 and 2 from latent state?
Sunlight, stress, febrile illness, menstruation, immuno-suppression.
200
What is the characteristic appearance of dendritic ulcers in corneal HSV infection?
Branching appearance.
201
What can cause aseptic meningitis during primary genital herpes infection?
HSV2.
202
In what part of the body does HSV switch to a lytic cycle during reactivation?
In the cell body of the neuron.
203
Where do the virus particles travel during reactivation of HSV?
Down the axon to reinfect the skin or mucous membrane at the original site.
204
What are some triggers that can cause recurrent reactivation of HSV?
Sunlight, stress, febrile illness, menstruation, immuno-suppression.
205
What is a rare life-threatening complication of HSV infection in neonates?
Neonatal HSV.
206
What is the gold standard for diagnosing lymphadenopathy?
Excision of lymph node
207
What type of response is associated with Paracortical Lymphoid Hyperplasia?
Predominantly T-cell response
208
What is a common cause of granulomatous lymphadenitis?
TB and atypical mycobacteria
209
In which type of lymphadenitis is a neutrophilic infiltrate seen with pyogenic organisms?
Acute nonspecific lymphadenitis
210
What can cause granulomatous lymphadenitis besides infections?
Foreign bodies or secondary response to malignancy
211
What triad is seen in histology of Toxoplasmosis-related lymphadenopathy?
Follicular hyperplasia, adjacent granulomas, marginal zone B-cell hyperplasia
212
What stain is used to detect acid-fast bacilli in TB lymphadenitis?
Ziehl-Neelsen stain
213
What features are found in sarcoidosis histology resembling tuberculosis?
Giant cells at the periphery and asteroid bodies
214
What is noted in ~60% of sarcoidosis cases histology?
Schaumann bodies
215
What surrounds histiocytes in sarcoidosis histology, compared with tuberculosis?
Inconspicuous cuff of lymphocytes
216
What does IgG HSV1/2 antibodies indicate?
Exposure (past infection)
217
What is the preferred method for testing HSV1 and 2?
PCR Assays
218
How is Varicella transmitted?
Highly infectious, droplet spread
219
What are the symptoms of Varicella primary infection?
Mild febrile illness, generalised vesicular rash
220
What is Varicella zoster virus reactivation known as?
Zoster
221
What is the incubation period of Varicella?
21 days
222
What is the main cause of stroke in children associated with Varicella?
Vasculitis (due to replication in CNS blood vessels)
223
What is the recommended treatment for severe HSV and VZV infections?
Aciclovir
224
How is Varicella post-exposure prophylaxis managed for a healthy adult?
Varicella vaccine (or acyclovir)
225
What is the primary mode of transmission of human cytomegalovirus?
Close contact
226
Define acute leukaemia.
Acute leukaemia implies rapid cell proliferation at an early stage, leading to death within weeks or months.
227
How does chronic leukaemia differ from acute leukaemia?
Chronic leukaemia involves cells that are able to mature and may not require intensive chemotherapy, with slower onset and death in months to years.
228
What are the clinical effects of leukaemia?
Infiltration and disruption of normal tissue function, leading to bone marrow failure, bleeding, infections, anaemia, and bone pain.
229
List the diagnostic classification systems for leukaemia.
French American British (old), WHO classification (2001-present), based on morphology, cell surface markers, cytogenetics, and molecular genetics.
230
What are the clinical characteristics of mature lymphoid neoplasms?
May present as low or high grade, with growing lumps, destructive lesions, cytopenias, infections, constitutional symptoms, lymphadenopathy, hepatosplenomegaly, and B symptoms.
231
Explain Burkitt lymphoma, Myeloma, and Chronic lymphocytic leukaemia.
They are important types of mature B cell neoplasms.
232
What are the typical presentation syndromes of lymphoma?
B symptoms, significant lymphadenopathy, cytopenias, lymphocytosis, and growth of tumor masses in body cavities causing disturbance of function.
233
What is the primary cause of mediastinal mass in the young and an important differential diagnosis of lung cancer?
Lymphoma.
234
What are myeloproliferative neoplasms characterized by?
Proliferation of granulocytic, megakaryocytic, and/or erythroid lineages.
235
What is seen in chronic myeloid leukemia (CML)?
Philadelphia chromosome (BCR-ABL1 fusion on Chromosome 22).
236
What are the driver mutations implicated in Ph-negative myeloproliferative neoplasms?
Mutations resulting in increased JAK-STAT signaling.
237
What organs are considered primary lymphoid organs?
Bone marrow and thymus.
238
What is the purpose of lymph nodes in the body?
Detect and inactivate foreign antigens present in lymph fluid.
239
What is the function of germinal centers in lymph nodes?
To generate immune responses with a predominance of B cells.
240
Why are tingible body macrophages important in germinal centers?
They process antigen to pass to lymphocytes for immune responses.
241
What clinical features are common in myeloproliferative neoplasms?
Increased risk of thrombosis and bleeding.
242
What are the causes of lymph node enlargement?
Infection, autoimmune disorders, neoplasms (primary or metastatic).
243
When is allogeneic hematopoietic stem cell transplant considered in PMF?
Used in intermediate or high-risk PMF to reduce spleen size.
244
What are cytokines and their role in the immune system?
Cytokines are small proteins important in cell signaling, mediating immunity, inflammation, and hematopoiesis.
245
How do growth factors regulate cells in the hematopoietic system?
Growth factors regulate growth, differentiation, and function of hematopoietic and immune cells.
246
Explain the production and function of Erythropoietin.
Erythropoietin stimulates red blood cell production, especially when oxygen levels are low.
247
What are the characteristics of acute leukemia?
Acute leukemia involves uncontrolled proliferation of primitive hematopoietic blasts primarily in the bone marrow.
248
Describe chronic leukemias and their characteristics.
Chronic leukemias involve the proliferation of mature/differentiated cells with a low growth fraction.
249
List signs of acute leukemia pathogenesis through infiltration of blasts.
Signs include lymphadenopathy, hepatosplenomegaly, gum hypertrophy, and less commonly hyperviscosity among others.
250
What are the key classes of molecules controlling cell cycle checkpoints?
Cyclins and Cdk (cyclin dependent kinases)
251
Which molecule plays a central role in the G1-S checkpoint?
p53
252
Describe the role of p53 when damaged DNA is sensed.
p53 prevents activation of Cyclins, allowing time for potential repair.
253
Explain the role of apoptosis in maintaining tissue homeostasis.
Apoptosis ensures disposal of defective cells, preventing transmission of faulty DNA.
254
What genetic change leads to reduced apoptosis in Follicular Lymphoma?
t(14;18) translocation of the BCL2 gene.
255
How do BAX proteins contribute to apoptosis?
BAX increases mitochondrial membrane permeability, leading to cytochrome C release.
256
What determines a cell's susceptibility to apoptosis?
The ratio of BAX to Bcl-2 proteins.
257
What is the role of oncogenes in cancer development?
Oncogenes result from gain of function mutations in proto-oncogenes.
258
Explain the mechanism of action for tumour suppressor genes.
Tumour suppressor genes protect against malignancy by regulating the cell cycle.
259
What genetic alterations are visible at a microscopic level?
Translocations leading to abnormal karyotypes.
260
Why are neoplastic cells genetically unstable?
Genetic instability allows for further mutations in neoplastic cells.
261
What is clonal evolution in the context of genetic mutations?
Mutations in progeny cells provide a survival advantage, leading to clonal evolution.
262
What are the two types of bone marrow mentioned in the notes?
Red bone marrow and yellow bone marrow.
263
Which cells are made in the bone marrow according to the notes?
Erythrocytes, neutrophils, and platelets.
264
What forms an open network of trabeculae in bone marrow?
The matrix.
265
What are the components of blood mentioned in the notes?
Plasma, erythrocytes, neutrophils, platelets, and lymphocytes.
266
What cell can ultimately reconstitute the entire bone marrow according to the notes?
Haematopoietic stem cell.
267
How do megakaryocytes contribute to blood production?
They break into small fragments (platelets) that enter the blood.
268
What is the function of stem cells in the bone marrow?
To differentiate into various functional mature cells.
269
What is the role of red bone marrow in blood cell production?
Supplies nutrients to cells, forms erythrocytes, leukocytes, platelets.
270
What are clues to the diagnosis of Hodgkin lymphoma?
Eosinophilic or basophilic nuclei, and focal necrosis or granulomas.
271
What is characteristic of Hodgkin lymphoma (HL)?
Up to 40% of cases are associated with the Epstein-Barr virus (EBV).
272
Describe the spread of Hodgkin lymphoma.
Begins in lymph nodes, then spreads to other groups or extra nodal sites.
273
What are complications associated with Hodgkin lymphoma?
Infection, cachexia, organ infiltration, and treatment-related complications.
274
What are the risk factors for non-Hodgkin lymphoma?
Factors include viruses (EBV, HTLV-1, HIV, HHV-8) and immunodeficiency.
275
What are the types of Burkitt lymphoma?
Endemic, sporadic, and immunodeficiency-associated types.
