Lecture 7 Flashcards
What is vasculogenesis? In which stage of life does it primarily occur?
Vasculogenesis is the de novo formation of blood vessels, primarily occurring during embryogenesis.
What is angiogenesis, and what triggers it?
Angiogenesis is the formation of new blood vessels from pre-existing vessels. It is triggered by ischemia, which causes hypoxia and stimulates the release of pro-angiogenic factors like VEGF.
What are two modes of angiogenesis, and how do they differ?
- Sprouting angiogenesis: Endothelial cells migrate and proliferate to form new capillary branches. 2. Intussusceptive angiogenesis: An existing capillary splits into two through endothelial growth along its length.
What role does hypoxia-inducible factor (HIF) play in angiogenesis?
HIF activates transcription of pro-angiogenic genes like VEGF in response to hypoxia. HIF is degraded in the presence of oxygen, so its expression is hypoxia-dependent.
What is the function of VEGF in angiogenesis, and which cells express its receptor?
VEGF is the main pro-angiogenic factor that stimulates endothelial cell proliferation. Its receptor is expressed specifically on endothelial cells (ECs).
How does ischemia lead to angiogenesis? What is the role of oxygen availability?
Ischemia reduces oxygen supply, leading to hypoxia. Under hypoxia, HIF stimulates VEGF production, driving angiogenesis to restore blood flow. In oxygen-rich environments, this process is suppressed.
What is arteriogenesis, and how does it differ from angiogenesis?
Arteriogenesis is the development of collateral arteries from pre-existing arterioles. Unlike angiogenesis, it is triggered mechanically by increased shear stress, not ischemia.
How does shear stress stimulate arteriogenesis?
Shear stress stretches the endothelial cell plasma membrane, activating intracellular signaling pathways through the cytoskeleton to upregulate growth factors.
Which types of molecules drive arteriogenesis, and how do they affect endothelial cells and smooth muscle cells?
Growth factors like CSFs, FGFs, and TGF, along with adhesion molecules, are upregulated. These promote endothelial cell proliferation and smooth muscle cell growth in the vessel wall (tunica media).
What is an anastomosis, and what role does it play in arteriogenesis?
An anastomosis is a small channel connecting two larger vessels. During arteriogenesis, blood flow is diverted through anastomoses, which then enlarge to form collateral arteries.
Define anaemia. How does it affect oxygen transport?
Anaemia is a reduction in red blood cell count or functionality, leading to decreased oxygen-carrying capacity of the blood.
What are three symptoms of anaemia, and why do they occur?
- Pallor (reduced hemoglobin), 2. Fatigue (low oxygen delivery), 3. Icterus (if RBC destruction occurs, leading to bilirubin buildup).
What are the main causes of anaemia? List one example for each.
- Bleeding (e.g., trauma), 2. Hemoglobin defects (e.g., thalassaemia), 3. RBC destruction (e.g., hemolysis), 4. Bone marrow failure (e.g., leukaemia).
Why does thalassaemia cause microcytic anaemia?
Thalassaemia is caused by defective hemoglobin synthesis, leading to small (microcytic), poorly functional red blood cells.
How does leukaemia cause anaemia?
In leukaemia, malignant cells displace erythroid precursors in the bone marrow, impairing erythropoiesis and causing anaemia.
What are cytopenias? Provide definitions for neutropenia and thrombocytopenia.
Cytopenias are reductions in specific blood cell types. Neutropenia: Low neutrophil count; increases infection risk. Thrombocytopenia: Low platelet count; increases bleeding risk.
A patient on chemotherapy presents with fever and neutropenia. What is the likely diagnosis and treatment?
Infection secondary to chemotherapy-induced neutropenia. Treatment: Broad-spectrum antibiotics and G-CSF prophylaxis.
What are the three alleles of the ABO system, and how do they interact?
The alleles are A, B, and O (recessive). A and B are co-dominant. Genotypes like AO result in blood group A, while OO results in blood group O.
What enzymes do the A and B alleles encode, and how do they modify the H antigen?
A allele: Encodes an enzyme that adds N-acetylgalactosamine. B allele: Adds galactose. O allele produces no functional enzyme, leaving the H antigen unmodified.
Why do individuals with blood group O have both anti-A and anti-B antibodies?
Blood group O individuals lack A and B antigens, so their immune system produces anti-A and anti-B antibodies during early development.
What is the Bombay phenotype, and why can it cause transfusion problems?
The Bombay phenotype (hh) lacks the H antigen required for ABO antigen expression. These individuals produce anti-H antibodies and are incompatible with all blood types except their own.
Why is blood group O negative considered the universal donor?
O negative blood lacks A, B, and Rh antigens, preventing immune reactions in recipients of any blood group.
Explain how paternity was disproven in the case of Charlie Chaplin using the ABO system.
Chaplin (blood group O) could not be the father of a child with blood group B, as B antigen requires at least one B allele.
What determines whether someone is rhesus positive or negative?
Rhesus positivity is determined by the presence of the RHD gene, which encodes the RhD antigen on red blood cells. A deletion or nonfunctional RHD gene results in rhesus negativity.
Why is rhesus incompatibility a concern during pregnancy?
An Rh-negative mother carrying an Rh-positive fetus can generate anti-Rh antibodies, which may attack fetal red blood cells in subsequent pregnancies, causing hemolytic disease of the newborn.
How is rhesus incompatibility managed during and after pregnancy?
Anti-D immunoglobulin is administered to Rh-negative mothers to prevent sensitization. If hemolytic disease occurs, fetal blood transfusion or postnatal transfusions are performed.
What are the three main types of haematological neoplasias?
- Leukaemia (arises in bone marrow), 2. Lymphoma (originates in lymph nodes), 3. Myeloma (cancer of plasma cells).
How does leukaemia disrupt normal blood cell production?
Malignant cells occupy bone marrow niches, displacing normal haematopoietic progenitors and causing bone marrow failure.
How does Hodgkin’s lymphoma differ morphologically from non-Hodgkin’s lymphoma?
Hodgkin’s lymphoma is characterized by Reed-Sternberg cells, which are large, multinucleated abnormal B cells.
Describe a case presentation of Hodgkin’s lymphoma. What features suggest the diagnosis?
Symptoms: Fatigue, night sweats, enlarged lymph nodes. Diagnosis: Biopsy showing Reed-Sternberg cells against a reactive leukocyte background.
What is myeloma, and how does it affect the bone marrow and blood?
Myeloma is a plasma cell malignancy that causes abnormal immunoglobulin production, bone lesions, and reduced normal blood cell production.
