L9 - Haematological diseases Flashcards
Why do bacteria modulate their surface structures?
They modulate surfaces to adapt to different niches, respond to host factors, enhance colonization, and evade the immune response.
How does surface modulation benefit bacterial survival in hostile environments?
It allows bacteria to dynamically alter adhesin presentation and evade immune detection, thus increasing survival and transmission.
What is one ecological advantage of altering surface properties?
It enables bacteria to switch between adhesion and detachment, facilitating colonization of new sites within the host.
What is antigenic variation and how does it occur?
Antigenic variation involves genetic changes—often through recombination or slipped strand mispairing—that alter surface proteins.
How does phase variation differ from antigenic variation?
Phase variation refers to reversible on/off switching of gene expression, while antigenic variation results in structural changes in proteins.
What is antigenic drift?
Antigenic drift is the gradual accumulation of random mutations in surface antigens over time.
Which genetic mechanisms underlie these variations?
Mechanisms include homologous recombination, slipped strand mispairing, and RecA-dependent repair processes.
What is the key difference between Neisseria meningitidis and Neisseria gonorrhoeae?
N. meningitidis is encapsulated and primarily causes systemic infections like meningitis, whereas N. gonorrhoeae lacks a capsule and typically causes gonorrhea.
How do Neisserial adhesins contribute to colonization?
They mediate attachment by overcoming charge barriers using pili and outer membrane proteins such as Opa and Opc.
What is the significance of the capsule in N. meningitidis?
The capsule enhances immune evasion and is a major virulence factor in systemic disease.
Why is redundancy in adhesins advantageous for Neisseria?
Redundancy ensures that multiple adhesins can compensate if one is downregulated, ensuring persistent colonization.
How does homologous recombination contribute to pilin antigenic variation?
Recombination between multiple silent pilS copies and the expressed pilE locus generates diverse pilin variants.
What role does RecA play in Neisseria surface variation?
RecA facilitates homologous recombination, ensuring genetic diversity and repair that underpin both antigenic and phase variation.
Describe the mechanism of slipped strand mispairing (SSM).
SSM occurs during DNA replication when repetitive sequences misalign, resulting in the gain or loss of repeat units and altering gene expression.
How can changes in coding repeat numbers affect protein expression?
Variations may shift the reading frame, leading to truncated or non-functional proteins, thereby modulating the presence of surface antigens.
What is meant by genetic redundancy in the context of bacterial surface proteins?
It refers to multiple genes performing similar functions so that inactivation of one does not eliminate a critical phenotype.
How does redundancy in adhesins enhance virulence?
It allows bacteria to maintain attachment and colonization even if one adhesin is targeted by the immune system.
What additional strategies do Neisseria employ to evade host defenses?
They utilize surface sialylation, mimic host molecules, and shed excess outer membrane components to divert antibodies.
Why is continuous variation important for the long-term survival of pathogenic bacteria?
It enables rapid adaptation to changing host environments and immune pressures, ensuring persistent colonization and transmission.
What are the normal functions of lymph nodes?
Lymph nodes filter lymph, house immune cells, and facilitate antigen presentation.
What are some causes of non-malignant lymph node enlargement?
Causes include infections, autoimmune diseases, and reactive hyperplasia.
What is suppurative lymphadenitis?
Suppurative lymphadenitis is lymph node inflammation with pus formation due to bacterial infection.
What are the main bacterial causes of acute lymphadenitis?
Staphylococcus aureus and Streptococcus pyogenes.
What is tuberculosis?
A bacterial infection caused by Mycobacterium tuberculosis.
How is tuberculosis transmitted?
Via airborne droplets from infected individuals.
How does Mycobacterium tuberculosis evade the immune system?
By surviving inside macrophages and inhibiting phagosome-lysosome fusion.
What is the Ghon focus?
A primary lung lesion seen in tuberculosis.
What are the risk factors for tuberculosis?
Malnutrition, immunosuppression, overcrowding, and poor healthcare access.
What is the significance of lymphadenitis in tuberculosis?
It indicates systemic spread and involvement of lymph nodes.
How does tuberculosis appear histologically?
Tuberculous granulomas contain caseous necrosis, epithelioid cells, and Langhans giant cells.
What is the Ziehl-Neelsen stain used for?
Detects acid-fast bacilli, such as Mycobacterium tuberculosis.
What is sarcoidosis?
A granulomatous disease of unknown cause affecting multiple organs.
What are common radiologic findings in sarcoidosis?
Bilateral hilar lymphadenopathy and pulmonary infiltrates.
What is the characteristic histological feature of sarcoidosis?
Non-caseating granulomas with multinucleated giant cells.
What is toxoplasmosis?
A protozoan infection caused by Toxoplasma gondii.
How is toxoplasmosis transmitted?
Via ingestion of contaminated food, water, or cat feces.
What are symptoms of toxoplasmosis in immunocompromised individuals?
Severe neurological symptoms, chorioretinitis, and encephalitis.
What are the complications of congenital toxoplasmosis?
Hydrocephalus, intracranial calcifications, and chorioretinitis.
How is toxoplasmosis diagnosed?
Serology, PCR, and histopathology.
What is cat scratch disease?
A bacterial infection causing fever and lymphadenopathy.
What is the causative agent of cat scratch disease?
Bartonella henselae.
How is cat scratch disease diagnosed?
By serology, PCR, or histopathology.
How is cat scratch disease managed?
Usually self-limiting, but sometimes requires antibiotics.
What is Kikuchi disease?
A self-limiting necrotizing lymphadenitis of unknown cause.
What are the clinical features of Kikuchi disease?
Fever, lymphadenopathy, and fatigue.
Who is most commonly affected by Kikuchi disease?
Young women, particularly of Asian descent.
What is the histological hallmark of Kikuchi disease?
Necrotizing histiocytic lymphadenitis.
Why is Kikuchi disease sometimes mistaken for systemic lupus erythematosus (SLE)?
Both show lymphadenopathy and histiocytic inflammation.
What are the primary mechanisms bacteria use to adhere to host cells?
Pili, outer membrane proteins, and lipopolysaccharides.
How does antigenic variation help Neisseria evade immunity?
By altering its surface proteins to avoid recognition.
What is the role of pili in Neisseria infections?
Mediates adhesion to mucosal surfaces.
What is the significance of sialylation in Neisseria?
Prevents complement activation and immune recognition.
How does genetic recombination contribute to bacterial survival?
Promotes adaptation and immune evasion.
What is the role of outer membrane vesicles in immune evasion?
They bind host antibodies and divert immune attack.
What is the clinical significance of Neisseria gonorrhoeae’s lack of a capsule?
It makes it more susceptible to immune clearance.
How does Neisseria meningitidis cause systemic infections?
By crossing the blood-brain barrier and inducing inflammation.
What is the main mode of transmission for Neisseria species?
Through direct mucosal contact.
Why are Neisseria species restricted to human hosts?
They require human-specific nutrients and receptors.
What are the two main categories of bacterial variation mechanisms?
Recombinase-dependent and recombinase-independent mechanisms.
How does recombinase-dependent variation work?
By rearranging genes to create diversity.
How does recombinase-independent variation contribute to bacterial diversity?
Via mutation-based phase variation.
Why is rapid mutation rate an advantage for pathogenic bacteria?
It increases adaptability to host defenses.
What is the primary immune response to Neisseria infections?
Primarily antibody-mediated responses.
How does iron acquisition contribute to Neisseria virulence?
Iron is essential for bacterial growth and infection.
Why is Neisseria gonorrhoeae particularly difficult to vaccinate against?
Due to its high antigenic variability.
What are the two peaks of disease prevalence for N. meningitidis?
Neonates and adolescents.
How does Neisseria gonorrhoeae cause asymptomatic infections?
By modifying surface proteins to prevent detection.
What is the impact of antibiotic resistance in Neisseria species?
It complicates treatment and vaccine development.
What is the function of Opa proteins in Neisseria?
Mediates tight adherence to host cells.
What is the function of Opc proteins in Neisseria?
Facilitates invasion of endothelial cells.
How does Neisseria avoid complement-mediated killing?
By binding factor H to avoid complement deposition.
What is the importance of studying bacterial variation for public health?
It helps predict and prevent emerging infections.
How does tuberculosis differ in HIV-positive vs. HIV-negative individuals?
HIV-positive patients have a higher risk of disseminated TB.
What is the relationship between tuberculosis and socioeconomic factors?
Poverty, malnutrition, and inadequate healthcare access increase TB risk.
Why is tuberculosis considered a chronic granulomatous disease?
It leads to chronic granuloma formation.
How does tuberculosis cause delayed hypersensitivity?
By triggering a delayed-type hypersensitivity reaction.
What are the treatment challenges for tuberculosis?
Long treatment duration and resistance.
Why is tuberculosis more common in crowded conditions?
Close contact increases transmission risk.
What is the role of alveolar macrophages in tuberculosis pathogenesis?
They ingest bacteria but fail to kill them.
What is the significance of the Mantoux test?
A tuberculin skin test detecting immune response.
How does latent tuberculosis differ from active tuberculosis?
Latent TB is asymptomatic and non-infectious.
What role do cytokines play in tuberculosis?
Cytokines drive granuloma formation and immune response.
Why does tuberculosis require long-term antibiotic therapy?
Due to slow bacterial replication and persistence.
How do granulomas form in tuberculosis?
By macrophage aggregation and cytokine signaling.
What are the key diagnostic tests for tuberculosis?
Chest X-ray, sputum culture, and PCR.
How is toxoplasmosis treated?
With antiparasitic drugs such as pyrimethamine and sulfadiazine.
What is the role of the immune system in controlling toxoplasmosis?
Cell-mediated immunity controls infection.
How does Toxoplasma gondii manipulate host immunity?
By interfering with host cytokine responses.
What is the epidemiological significance of toxoplasmosis?
It is globally widespread with zoonotic potential.
Why is cat ownership associated with toxoplasmosis?
Cats excrete oocysts that infect humans.
What are the histopathological features of Kikuchi disease?
Histiocytic necrosis and paracortical hyperplasia.
How does Kikuchi disease typically resolve?
It is self-limiting over weeks to months.
What are the potential misdiagnoses for Kikuchi disease?
It can be mistaken for lymphoma or lupus.
How does sarcoidosis lead to granuloma formation?
By stimulating macrophages and T-cells.
What are the systemic manifestations of sarcoidosis?
Pulmonary, ocular, and neurological effects.
Why is sarcoidosis often an incidental finding?
It may be asymptomatic or diagnosed via biopsy.
What is the clinical significance of enlarged lymph nodes?
Lymphadenopathy can indicate infection, malignancy, or autoimmune disease.
How does the body’s immune system regulate lymph node size?
By regulating immune cell trafficking and proliferation.
What are the functions of erythrocytes?
Erythrocytes transport oxygen and carbon dioxide using hemoglobin.
What is the normal lifespan of a red blood cell?
A red blood cell typically lives for about 120 days.
How does erythropoietin regulate red blood cell production?
Erythropoietin, produced by the kidneys, stimulates the bone marrow to produce red blood cells in response to hypoxia.
What is anemia?
Anemia is a condition characterized by a reduced red blood cell count or hemoglobin concentration.
What are the common causes of anemia?
Common causes of anemia include blood loss, decreased red blood cell production, and increased red blood cell destruction.
How is anemia classified based on red blood cell size?
Anemia is classified as microcytic, normocytic, or macrocytic based on mean corpuscular volume (MCV).
What are the clinical symptoms of anemia?
Symptoms of anemia include fatigue, pallor, shortness of breath, and tachycardia.
What is iron-deficiency anemia?
Iron-deficiency anemia is caused by insufficient iron levels, leading to decreased hemoglobin synthesis.
What are the common causes of iron-deficiency anemia?
Common causes include chronic blood loss, dietary deficiency, and malabsorption.
How is iron-deficiency anemia diagnosed?
Diagnosis involves low serum iron, low ferritin, increased total iron-binding capacity (TIBC), and microcytic hypochromic red cells on blood smear.
What is pernicious anemia?
Pernicious anemia is an autoimmune condition causing vitamin B12 deficiency.
What causes pernicious anemia?
It results from autoimmune destruction of gastric parietal cells that produce intrinsic factor.
What is the role of intrinsic factor in vitamin B12 absorption?
Intrinsic factor is necessary for vitamin B12 absorption in the ileum.
What is megaloblastic anemia?
Megaloblastic anemia is characterized by large, immature red blood cells due to impaired DNA synthesis.
How does folate deficiency cause megaloblastic anemia?
Folate is required for DNA synthesis; its deficiency leads to ineffective erythropoiesis.
What are the main laboratory findings in megaloblastic anemia?
Findings include macrocytic red blood cells, hypersegmented neutrophils, and low serum B12 or folate levels.
What is hemolytic anemia?
Hemolytic anemia is caused by the destruction of red blood cells before their normal lifespan.
What are some causes of hemolytic anemia?
Causes include autoimmune diseases, infections, hereditary defects, and mechanical trauma.
What is the difference between intravascular and extravascular hemolysis?
Intravascular hemolysis occurs within blood vessels, while extravascular hemolysis occurs in the spleen or liver.
What are the key laboratory findings in hemolysis?
Laboratory findings include elevated lactate dehydrogenase (LDH), decreased haptoglobin, and increased reticulocyte count.
What is sickle cell disease?
Sickle cell disease is a genetic disorder causing abnormal hemoglobin S production.
What genetic mutation causes sickle cell disease?
It is caused by a point mutation in the β-globin gene, leading to hemoglobin polymerization and sickling.
How does sickle cell disease affect red blood cell function?
Sickled red blood cells are rigid and can block blood vessels, causing pain and organ damage.
What is the clinical presentation of sickle cell disease?
Symptoms include vaso-occlusive crises, anemia, jaundice, and increased infection risk.
What are common complications of sickle cell disease?
Complications include stroke, acute chest syndrome, and avascular necrosis.
What is thalassemia?
Thalassemia is a genetic disorder causing decreased or absent production of globin chains in hemoglobin.
What are the types of thalassemia?
Types include alpha-thalassemia and beta-thalassemia.
How does thalassemia affect hemoglobin production?
Thalassemia leads to ineffective erythropoiesis, hemolysis, and anemia.
What are the laboratory findings in thalassemia?
Findings include microcytic anemia, target cells on blood smear, and hemoglobin electrophoresis abnormalities.
What is hereditary spherocytosis?
Hereditary spherocytosis is a disorder causing defects in red blood cell membrane proteins.
How does hereditary spherocytosis affect red blood cell shape?
It leads to spherical red blood cells that are prone to destruction in the spleen.
What is glucose-6-phosphate dehydrogenase (G6PD) deficiency?
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder affecting red blood cell metabolism.
How does G6PD deficiency lead to hemolysis?
G6PD deficiency reduces the ability to handle oxidative stress, leading to hemolysis.
What triggers hemolysis in G6PD deficiency?
Triggers include infections, certain medications (e.g., sulfa drugs), and fava beans.
What are Heinz bodies?
Heinz bodies are aggregates of denatured hemoglobin seen in G6PD deficiency.
What is aplastic anemia?
Aplastic anemia is a failure of bone marrow to produce blood cells.
What are the causes of aplastic anemia?
Causes include radiation, chemicals, infections, and autoimmune diseases.
How is aplastic anemia diagnosed?
Diagnosis involves pancytopenia, hypocellular bone marrow, and low reticulocyte count.
What is polycythemia?
Polycythemia is an increased red blood cell mass.
What are the types of polycythemia?
Types include polycythemia vera (a myeloproliferative disorder) and secondary polycythemia (due to hypoxia or EPO-secreting tumors).
What are the clinical features of polycythemia?
Symptoms include headache, dizziness, hypertension, and thrombotic complications.
What is leukemia?
Leukemia is a malignancy of white blood cells.
What are the types of leukemia?
Types include acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML).
How does acute leukemia differ from chronic leukemia?
Acute leukemia is characterized by rapid progression and immature cells, while chronic leukemia progresses slowly with mature cells.
What are the common symptoms of leukemia?
Symptoms include fatigue, recurrent infections, bleeding, and hepatosplenomegaly.
What is the Philadelphia chromosome?
The Philadelphia chromosome is a translocation between chromosomes 9 and 22, leading to BCR-ABL fusion.
How does the Philadelphia chromosome relate to leukemia?
It is associated with chronic myeloid leukemia (CML).
What is lymphoma?
Lymphoma is a malignancy of lymphocytes affecting lymphoid tissue.
What are the main types of lymphoma?
Main types include Hodgkin lymphoma and non-Hodgkin lymphoma.
How does Hodgkin lymphoma differ from non-Hodgkin lymphoma?
Hodgkin lymphoma is characterized by Reed-Sternberg cells, while non-Hodgkin lymphoma has diverse subtypes.
What are Reed-Sternberg cells?
Reed-Sternberg cells are large, binucleated cells seen in Hodgkin lymphoma.
What are the symptoms of lymphoma?
Symptoms of lymphoma include painless lymphadenopathy, fever, night sweats, and weight loss.
What is multiple myeloma?
Multiple myeloma is a plasma cell malignancy affecting the bone marrow.
How does multiple myeloma affect the bone marrow?
It leads to excessive monoclonal antibody production, bone destruction, and renal dysfunction.
What are the common symptoms of multiple myeloma?
Symptoms include bone pain, fractures, anemia, hypercalcemia, and renal failure.
What laboratory findings suggest multiple myeloma?
Findings include monoclonal (M) spike on electrophoresis, lytic bone lesions, and Bence Jones proteins in urine.
What are Bence Jones proteins?
Bence Jones proteins are free light chains excreted in urine, associated with multiple myeloma.
What is hemophilia?
Hemophilia is a bleeding disorder caused by clotting factor deficiencies.
What are the types of hemophilia?
Types include hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency).
What is the inheritance pattern of hemophilia?
It follows an X-linked recessive inheritance pattern.
What clotting factors are deficient in hemophilia A and B?
Hemophilia A is due to factor VIII deficiency, while hemophilia B is due to factor IX deficiency.
What are the clinical features of hemophilia?
Symptoms include prolonged bleeding, hemarthrosis, and easy bruising.
What is von Willebrand disease?
Von Willebrand disease is a disorder of platelet adhesion due to von Willebrand factor deficiency.
How does von Willebrand disease affect coagulation?
It impairs clot formation and leads to mucosal and skin bleeding.
What is disseminated intravascular coagulation (DIC)?
Disseminated intravascular coagulation (DIC) is a pathological activation of coagulation leading to widespread clotting and bleeding.
What are the causes of disseminated intravascular coagulation?
Causes include sepsis, trauma, malignancy, and obstetric complications.
How is disseminated intravascular coagulation diagnosed?
Diagnosis involves elevated D-dimer, prolonged PT and aPTT, and thrombocytopenia.
What is immune thrombocytopenic purpura (ITP)?
Immune thrombocytopenic purpura (ITP) is an autoimmune disorder causing platelet destruction.
What causes immune thrombocytopenic purpura?
ITP is caused by autoantibodies against platelets.
How does immune thrombocytopenic purpura present clinically?
Symptoms include petechiae, purpura, and increased bleeding.
What is thrombotic thrombocytopenic purpura (TTP)?
Thrombotic thrombocytopenic purpura (TTP) is a microangiopathic hemolytic anemia with thrombocytopenia.
What is the pathophysiology of thrombotic thrombocytopenic purpura?
It is caused by ADAMTS13 deficiency, leading to platelet aggregation and vessel occlusion.
What are the symptoms of thrombotic thrombocytopenic purpura?
Symptoms include fever, anemia, thrombocytopenia, renal failure, and neurological symptoms.
What is heparin-induced thrombocytopenia (HIT)?
Heparin-induced thrombocytopenia (HIT) is an immune-mediated reaction to heparin.
What causes heparin-induced thrombocytopenia?
It occurs when antibodies form against heparin-platelet factor 4 complexes.
How is heparin-induced thrombocytopenia diagnosed?
Diagnosis involves thrombocytopenia, thrombosis, and positive HIT antibody testing.
What is factor V Leiden mutation?
Factor V Leiden mutation increases the risk of venous thrombosis.
How does factor V Leiden mutation increase the risk of thrombosis?
It causes resistance to activated protein C, reducing anticoagulation.
What is antiphospholipid syndrome?
Antiphospholipid syndrome is an autoimmune disorder leading to thrombosis.
What are the clinical features of antiphospholipid syndrome?
Symptoms include recurrent thrombosis, pregnancy complications, and livedo reticularis.
What laboratory findings suggest antiphospholipid syndrome?
Findings include lupus anticoagulant, anticardiolipin antibodies, and anti-β2 glycoprotein antibodies.
What is the role of plasmin in fibrinolysis?
Plasmin degrades fibrin clots in fibrinolysis.
How does fibrinolysis contribute to hemostasis?
Fibrinolysis prevents excessive clot formation and aids in clot resolution.
What is the function of protein C and protein S in coagulation?
Protein C and protein S inhibit clotting by inactivating factors Va and VIIIa.
What is the function of antithrombin III?
Antithrombin III inhibits thrombin and factor Xa to regulate coagulation.
What is warfarin and how does it affect coagulation?
Warfarin inhibits vitamin K-dependent clotting factors (II, VII, IX, X).
What is the mechanism of action of heparin?
Heparin activates antithrombin III, accelerating clot breakdown.
How do direct oral anticoagulants (DOACs) work?
Direct oral anticoagulants (DOACs) inhibit thrombin or factor Xa.
What is the role of vitamin K in coagulation?
Vitamin K is essential for the synthesis of clotting factors II, VII, IX, and X.
What is the function of platelets in hemostasis?
Platelets form a temporary plug in hemostasis.
How is platelet aggregation regulated?
Platelet aggregation is regulated by ADP, thromboxane A2, and fibrinogen.
What are the stages of primary hemostasis?
Primary hemostasis includes platelet adhesion, activation, and aggregation.
What is the role of thromboxane A2 in platelet function?
Thromboxane A2 promotes platelet aggregation and vasoconstriction.
What are the laboratory tests used to assess coagulation?
Coagulation tests include PT, aPTT, fibrinogen, and D-dimer.
What is the significance of an elevated D-dimer level?
Elevated D-dimer indicates active clot formation and breakdown.
What is the role of tissue factor in coagulation?
Tissue factor initiates the extrinsic coagulation pathway.
How does endothelial injury promote thrombosis?
Endothelial injury triggers clot formation via the coagulation cascade.
What is Virchow’s triad?
Virchow’s triad includes endothelial injury, stasis, and hypercoagulability.
How does deep vein thrombosis (DVT) develop?
Deep vein thrombosis (DVT) occurs due to blood stasis and hypercoagulability.
What are the risk factors for deep vein thrombosis?
Risk factors include immobility, surgery, and thrombophilia.
What are the clinical symptoms of deep vein thrombosis?
Symptoms include leg swelling, pain, and redness.
What is the treatment for deep vein thrombosis?
Treatment includes anticoagulation (heparin, warfarin, DOACs).
What is the significance of a pulmonary embolism?
Pulmonary embolism occurs when a clot dislodges and blocks lung arteries.
How is pulmonary embolism diagnosed?
Diagnosis involves D-dimer, CT angiography, and ultrasound.
What are the common causes of acquired thrombophilia?
Acquired thrombophilias include antiphospholipid syndrome and cancer.
How do inherited and acquired thrombophilias differ?
Inherited thrombophilias are genetic conditions increasing clot risk.
