Understanding Hodgkin’s Lymphoma: Symptoms and Risk Factors

Hodgkin’s lymphoma is a type of cancer that affects the lymphocytes and is characterized by the presence of Reed-Sternberg cells. It is most commonly seen in people in their third and seventh decades of life. There are certain risk factors that increase the likelihood of developing Hodgkin’s lymphoma, such as HIV and the Epstein-Barr virus.

The most common symptom of Hodgkin’s lymphoma is lymphadenopathy, which is the enlargement of lymph nodes. This is usually painless, non-tender, and asymmetrical, and is most commonly seen in the neck, followed by the axillary and inguinal regions. In some cases, alcohol-induced lymph node pain may be present, but this is seen in less than 10% of patients. Other symptoms of Hodgkin’s lymphoma include weight loss, pruritus, night sweats, and fever (Pel-Ebstein). A mediastinal mass may also be present, which can cause symptoms such as coughing. In some cases, Hodgkin’s lymphoma may be found incidentally on a chest x-ray.

When investigating Hodgkin’s lymphoma, normocytic anaemia may be present, which can be caused by factors such as hypersplenism, bone marrow replacement by HL, or Coombs-positive haemolytic anaemia. Eosinophilia may also be present, which is caused by the production of cytokines such as IL-5. LDH levels may also be raised.

In summary, Hodgkin’s lymphoma is a type of cancer that affects the lymphocytes and is characterized by the presence of Reed-Sternberg cells. It is most commonly seen in people in their third and seventh decades of life and is associated with risk factors such as HIV and the Epstein-Barr virus. Symptoms of Hodgkin’s lymphoma include lymphadenopathy, weight loss, pruritus, night sweats, and fever. When investigating Hodgkin’s lymphoma, normocytic anaemia, eosinophilia, and raised LDH levels may be present.

Iron deficiency anaemia is characterized by microcytic and hypochromic cells, as well as pencil and target cells on a peripheral blood film. Schistocytes may be present due to mechanical heart valves, while rouleaux may be observed in cases of chronic liver disease and malignant lymphoma. Tear drop poikilocytes may be seen in myelofibrosis.

Pathological Red Cell Forms in Blood Films

Blood films are used to examine the morphology of red blood cells and identify any abnormalities. Pathological red cell forms are associated with various conditions and can provide important diagnostic information. Some of the common pathological red cell forms include target cells, tear-drop poikilocytes, spherocytes, basophilic stippling, Howell-Jolly bodies, Heinz bodies, schistocytes, pencil poikilocytes, burr cells (echinocytes), and acanthocytes.

Target cells are seen in conditions such as sickle-cell/thalassaemia, iron-deficiency anaemia, hyposplenism, and liver disease. Tear-drop poikilocytes are associated with myelofibrosis, while spherocytes are seen in hereditary spherocytosis and autoimmune hemolytic anaemia. Basophilic stippling is a characteristic feature of lead poisoning, thalassaemia, sideroblastic anaemia, and myelodysplasia. Howell-Jolly bodies are seen in hyposplenism, while Heinz bodies are associated with G6PD deficiency and alpha-thalassaemia. Schistocytes or ‘helmet cells’ are seen in conditions such as intravascular haemolysis, mechanical heart valve, and disseminated intravascular coagulation. Pencil poikilocytes are seen in iron deficiency anaemia, while burr cells (echinocytes) are associated with uraemia and pyruvate kinase deficiency. Acanthocytes are seen in abetalipoproteinemia.

In addition to these red cell forms, hypersegmented neutrophils are seen in megaloblastic anaemia. Identifying these pathological red cell forms in blood films can aid in the diagnosis and management of various conditions.

DIC is often associated with pregnancy complications such as placental abruption and shock, as well as bleeding from multiple sites and abnormal blood test results. Placenta praevia is characterized by painless vaginal bleeding, but when combined with other haematological results and occurring in a pregnant woman, it may indicate DIC rather than ITP. TTP typically presents with jaundice, low platelets, fever, renal complications, and CNS signs, which are not evident in this case, and clotting test results do not support this diagnosis. While von Willebrand’s disease can cause spontaneous bleeding, the platelet count is usually normal.

Disseminated Intravascular Coagulation: A Condition of Simultaneous Coagulation and Haemorrhage

Disseminated intravascular coagulation (DIC) is a medical condition characterized by simultaneous coagulation and haemorrhage. It is caused by the initial formation of thrombi that consume clotting factors and platelets, ultimately leading to bleeding. DIC can be caused by various factors such as infection, malignancy, trauma, liver disease, and obstetric complications.

Clinically, bleeding is usually the dominant feature of DIC, accompanied by bruising, ischaemia, and organ failure. Blood tests can reveal prolonged clotting times, thrombocytopenia, decreased fibrinogen, and increased fibrinogen degradation products. The treatment of DIC involves addressing the underlying cause and providing supportive management.

In summary, DIC is a serious medical condition that requires prompt diagnosis and management. It is important to identify the underlying cause and provide appropriate treatment to prevent further complications. With proper care and management, patients with DIC can recover and regain their health.

Oxygen Transport and Factors Affecting Haemoglobin Saturation

Oxygen transport in the body is mainly carried out by erythrocytes, with only 1% of oxygen being transported as a solution due to its limited solubility. The amount of oxygen transported depends on the concentration of haemoglobin and its degree of saturation. Haemoglobin is a globular protein composed of four subunits, with two alpha and two beta subunits forming globin. Haem, which surrounds an iron atom in its ferrous state, can form two additional bonds with oxygen and a polypeptide chain. The oxygenation of haemoglobin is a reversible reaction, and the molecular shape of haemoglobin facilitates the binding of subsequent oxygen molecules.

The oxygen dissociation curve describes the relationship between the percentage of saturated haemoglobin and partial pressure of oxygen in the blood, and it is not affected by haemoglobin concentration. The curve can be shifted to the right or left by various factors. Chronic anaemia, for example, causes an increase in 2,3 DPG levels, which shifts the curve to the right, resulting in lower oxygen delivery. The Haldane effect causes a shift to the left, resulting in decreased oxygen delivery to tissues, while the Bohr effect causes a shift to the right, resulting in enhanced oxygen delivery to tissues. Factors that shift the curve to the left include low levels of H+, pCO2, 2,3-DPG, and temperature, as well as the presence of HbF, methaemoglobin, and carboxyhaemoglobin. Factors that shift the curve to the right include raised levels of H+, pCO2, and 2,3-DPG, as well as increased temperature.

Tranexamic acid prevents major haemorrhage by binding to plasminogen and preventing plasmin from breaking down fibrin clots. Its mechanism of action is not related to increasing the availability of vitamin K or inhibiting anticlotting factors protein C and S. Similarly, reducing the availability of vitamin K would not be the mechanism of action of tranexamic acid. While stimulating anticlotting factors protein C and S would maintain clots, it is not the mechanism of action of tranexamic acid.

Understanding Tranexamic Acid

Tranexamic acid is a synthetic derivative of lysine that acts as an antifibrinolytic. Its primary function is to bind to lysine receptor sites on plasminogen or plasmin, preventing plasmin from degrading fibrin. This medication is commonly prescribed to treat menorrhagia.

In addition to its use in treating menorrhagia, tranexamic acid has been investigated for its role in trauma. The CRASH 2 trial found that administering tranexamic acid within the first 3 hours of bleeding trauma can be beneficial. In cases of major haemorrhage, tranexamic acid is given as an IV bolus followed by an infusion.

Ongoing research is also exploring the potential of tranexamic acid in treating traumatic brain injury. Overall, tranexamic acid is a medication with important applications in managing bleeding disorders and trauma.

Angiosarcoma of the liver is a tumor that is not commonly found. However, it has been associated with exposure to vinyl chloride, as seen in this instance. While current factories have taken measures to reduce exposure to this substance, this was not always the case.

Occupational cancers are responsible for 5.3% of cancer deaths, with men being more affected than women. The most common types of cancer in men include mesothelioma, bladder cancer, non-melanoma skin cancer, lung cancer, and sino-nasal cancer. Occupations that have a high risk of developing tumors include those in the construction industry, coal tar and pitch workers, miners, metalworkers, asbestos workers, and those in the rubber industry. Shift work has also been linked to breast cancer in women.

The latency period between exposure to carcinogens and the development of cancer is typically 15 years for solid tumors and 20 years for leukemia. Many occupational cancers are rare, such as sino-nasal cancer, which is linked to wood dust exposure and is not strongly associated with smoking. Another rare occupational tumor is angiosarcoma of the liver, which is linked to working with vinyl chloride. In non-occupational contexts, these tumors are extremely rare.

GVHD is a condition where T cells from the donor tissue (the graft) attack healthy cells in the recipient (the host). This can occur after a haematopoietic cell transplantation and is diagnosed based on symptoms such as fever, rash, and gastrointestinal issues. Antigen-presenting cells activate the donor T cells, but do not attack host cells. B cells, host T cells, and mast cells do not contribute to the attack on host tissue in GVHD.

Understanding Graft Versus Host Disease

Graft versus host disease (GVHD) is a complication that can occur after bone marrow or solid organ transplantation. It happens when the T cells in the donor tissue attack the recipient’s cells. This is different from transplant rejection, where the recipient’s immune cells attack the donor tissue. GVHD is diagnosed using the Billingham criteria, which require that the transplanted tissue contains functioning immune cells, the donor and recipient are immunologically different, and the recipient is immunocompromised.

The incidence of GVHD varies, but it can occur in up to 50% of patients who receive allogeneic bone marrow transplants. Risk factors include poorly matched donor and recipient, the type of conditioning used before transplantation, gender disparity between donor and recipient, and the source of the graft.

Acute and chronic GVHD are considered separate syndromes. Acute GVHD typically occurs within 100 days of transplantation and affects the skin, liver, and gastrointestinal tract. Chronic GVHD may occur after acute disease or arise de novo and has a more varied clinical picture.

Diagnosis of GVHD is largely clinical and based on the exclusion of other pathology. Signs and symptoms of acute GVHD include a painful rash, jaundice, diarrhea, nausea, vomiting, and fever. Chronic GVHD can affect the skin, eyes, gastrointestinal tract, and lungs.

Treatment of GVHD involves immunosuppression and supportive measures. Intravenous steroids are the mainstay of treatment for severe cases of acute GVHD, while extended courses of steroid therapy are often needed in chronic GVHD. Second-line therapies include anti-TNF, mTOR inhibitors, and extracorporeal photopheresis. Topical steroid therapy may be sufficient in mild disease with limited cutaneous involvement. However, excessive immunosuppression may increase the risk of infection and limit the beneficial graft-versus-tumor effect of the transplant.

Ulcerative colitis, a type of inflammatory bowel disease characterized by bloody diarrhea, can be treated with various medications such as sulfasalazine, infliximab, 6-mercaptopurine, and in severe cases, a colectomy. 6-mercaptopurine is a purine analogue that is activated by HGPRTase, leading to decreased purine synthesis and reduced DNA synthesis. It is commonly used to treat non-malignant conditions like systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease. On the other hand, 5-fluorouracil is a pyrimidine analogue that acts as an antimetabolite, interfering with DNA synthesis, and is used to treat colorectal and pancreatic cancer. Methotrexate, an antimetabolite that acts as a folic acid analogue, is widely used in many malignancies and non-malignant conditions such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Bleomycin, doxorubicin, and daunorubicin cause free radical formation, leading to breaks in the DNA strand, while busulfan is an alkylating agent that causes cross-links in the DNA and is typically used to ablate a patient’s bone marrow before a bone marrow transplant.

Cytotoxic agents are drugs that are used to kill cancer cells. There are several types of cytotoxic agents, each with their own mechanism of action and potential adverse effects. Alkylating agents, such as cyclophosphamide, work by causing cross-linking in DNA. However, they can also cause haemorrhagic cystitis, myelosuppression, and transitional cell carcinoma. Cytotoxic antibiotics, like bleomycin and anthracyclines, degrade preformed DNA and stabilize DNA-topoisomerase II complex, respectively. However, they can also cause lung fibrosis and cardiomyopathy. Antimetabolites, such as methotrexate and fluorouracil, inhibit dihydrofolate reductase and thymidylate synthesis, respectively. However, they can also cause myelosuppression, mucositis, and liver or lung fibrosis. Drugs that act on microtubules, like vincristine and docetaxel, inhibit the formation of microtubules and prevent microtubule depolymerisation & disassembly, respectively. However, they can also cause peripheral neuropathy, myelosuppression, and paralytic ileus. Topoisomerase inhibitors, like irinotecan, inhibit topoisomerase I, which prevents relaxation of supercoiled DNA. However, they can also cause myelosuppression. Other cytotoxic drugs, such as cisplatin and hydroxyurea, cause cross-linking in DNA and inhibit ribonucleotide reductase, respectively. However, they can also cause ototoxicity, peripheral neuropathy, hypomagnesaemia, and myelosuppression.

EDTA is known to induce pseudothrombocytopenia, which is a condition where platelet counts are falsely reported as low due to EDTA-dependent platelet aggregation. On the other hand, sodium fluoride inhibits glycolysis and prevents enzymes from functioning, leading to the depletion of substrates like glucose during storage. While sodium citrate, sodium oxalate, and lithium heparin are all anticoagulants commonly found in vacutainers, they are not linked to thrombocytopenia.

Causes of Thrombocytopenia

Thrombocytopenia is a medical condition characterized by a low platelet count in the blood. The severity of thrombocytopenia can vary, with some cases being more severe than others. Severe thrombocytopenia can be caused by conditions such as immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), and haematological malignancy. On the other hand, moderate thrombocytopenia can be caused by heparin-induced thrombocytopenia (HIT), drug-induced factors such as quinine, diuretics, sulphonamides, aspirin, and thiazides, alcohol, liver disease, hypersplenism, viral infections such as EBV, HIV, and hepatitis, pregnancy, SLE/antiphospholipid syndrome, and vitamin B12 deficiency. It is important to note that pseudothrombocytopenia can also occur as a result of using EDTA as an anticoagulant.

The Factor V Leiden mutation causes activated protein C resistance, resulting in excess clotting due to inefficient inactivation of factor V. This is the correct answer.

Antiphospholipid antibodies binding to plasma membranes is not the correct answer as it is a mechanism of blood clot formation in antiphospholipid syndrome (APS).

High levels of platelets in the blood is also not the correct answer as it is not implicated in Factor V Leiden. Thrombocytosis, or high levels of platelets, can lead to clots but is not related to this mutation.

Low levels of factor V in the blood is also not the correct answer as factor V deficiency is a rare inherited bleeding disorder, not a clotting disorder. It is a form of haemophilia.

Understanding Factor V Leiden

Factor V Leiden is a common inherited thrombophilia, affecting around 5% of the UK population. It is caused by a mutation in the Factor V Leiden protein, resulting in activated factor V being inactivated 10 times more slowly by activated protein C than normal. This leads to activated protein C resistance, which increases the risk of venous thrombosis. Heterozygotes have a 4-5 fold risk of venous thrombosis, while homozygotes have a 10 fold risk, although the prevalence of homozygotes is much lower at 0.05%.

Despite its prevalence, screening for Factor V Leiden is not recommended, even after a venous thromboembolism. This is because a previous thromboembolism itself is a risk factor for further events, and specific management should be based on this rather than the particular thrombophilia identified.

Other inherited thrombophilias include Prothrombin gene mutation, Protein C deficiency, Protein S deficiency, and Antithrombin III deficiency. The table below shows the prevalence and relative risk of venous thromboembolism for each of these conditions.

Overall, understanding Factor V Leiden and other inherited thrombophilias can help healthcare professionals identify individuals at higher risk of venous thrombosis and provide appropriate management to prevent future events.

Condition | Prevalence | Relative risk of VTE
— | — | —
Factor V Leiden (heterozygous) | 5% | 4
Factor V Leiden (homozygous) | 0.05% | 10
Prothrombin gene mutation (heterozygous) | 1.5% | 3
Protein C deficiency | 0.3% | 10
Protein S deficiency | 0.1% | 5-10
Antithrombin III deficiency | 0.02% | 10-20

Cholestatic jaundice and prolonged antibiotic therapy can lead to a deficiency in vitamin K.

Abnormal coagulation can be caused by various factors such as heparin, warfarin, disseminated intravascular coagulation (DIC), and liver disease. Heparin prevents the activation of factors 2, 9, 10, and 11, while warfarin affects the synthesis of factors 2, 7, 9, and 10. DIC affects factors 1, 2, 5, 8, and 11, and liver disease affects factors 1, 2, 5, 7, 9, 10, and 11.

When interpreting blood clotting test results, different disorders can be identified based on the levels of activated partial thromboplastin time (APTT), prothrombin time (PT), and bleeding time. Haemophilia is characterized by increased APTT levels, normal PT levels, and normal bleeding time. On the other hand, von Willebrand’s disease is characterized by increased APTT levels, normal PT levels, and increased bleeding time. Lastly, vitamin K deficiency is characterized by increased APTT and PT levels, and normal bleeding time. Proper interpretation of these results is crucial in diagnosing and treating coagulation disorders.

The chemotherapy regime R-CHOP, which is likely being used to manage the patient’s non-Hodgkin’s lymphoma, includes cyclophosphamide, a drug that functions as an alkylating agent and promotes cross-linking of DNA. This can lead to haemorrhagic cystitis, which is likely the cause of the patient’s haematuria. Other drugs in the regime have different mechanisms of action, such as inhibition of microtubule formation with vincristine, inhibition of topoisomerase II and DNA/RNA synthesis with doxorubicin, and monoclonal antibody targeting of CD20 with rituximab. Pyrimidine analogues like 5-fluorouracil, which block thymidylate synthase and induce cell cycle arrest and apoptosis, are not commonly used in the management of non-Hodgkin’s lymphoma.

Cytotoxic agents are drugs that are used to kill cancer cells. There are several types of cytotoxic agents, each with their own mechanism of action and potential adverse effects. Alkylating agents, such as cyclophosphamide, work by causing cross-linking in DNA. However, they can also cause haemorrhagic cystitis, myelosuppression, and transitional cell carcinoma. Cytotoxic antibiotics, like bleomycin and anthracyclines, degrade preformed DNA and stabilize DNA-topoisomerase II complex, respectively. However, they can also cause lung fibrosis and cardiomyopathy. Antimetabolites, such as methotrexate and fluorouracil, inhibit dihydrofolate reductase and thymidylate synthesis, respectively. However, they can also cause myelosuppression, mucositis, and liver or lung fibrosis. Drugs that act on microtubules, like vincristine and docetaxel, inhibit the formation of microtubules and prevent microtubule depolymerisation & disassembly, respectively. However, they can also cause peripheral neuropathy, myelosuppression, and paralytic ileus. Topoisomerase inhibitors, like irinotecan, inhibit topoisomerase I, which prevents relaxation of supercoiled DNA. However, they can also cause myelosuppression. Other cytotoxic drugs, such as cisplatin and hydroxyurea, cause cross-linking in DNA and inhibit ribonucleotide reductase, respectively. However, they can also cause ototoxicity, peripheral neuropathy, hypomagnesaemia, and myelosuppression.

The risk of venous thromboembolism is elevated in individuals with polycythaemia due to the abnormal overproduction of red blood cells, which leads to increased blood viscosity and slower flow rate, increasing the likelihood of clot formation. Conversely, low BMI does not increase the risk of VTE, while obesity is a known risk factor. Additionally, thrombophilia, not haemophilia, is a risk factor for VTE.

Risk Factors for Venous Thromboembolism

Venous thromboembolism (VTE) is a condition where blood clots form in the veins, which can lead to serious complications such as pulmonary embolism (PE). While some common predisposing factors include malignancy, pregnancy, and the period following an operation, there are many other factors that can increase the risk of VTE. These include underlying conditions such as heart failure, thrombophilia, and nephrotic syndrome, as well as medication use such as the combined oral contraceptive pill and antipsychotics. It is important to note that around 40% of patients diagnosed with a PE have no major risk factors. Therefore, it is crucial to be aware of all potential risk factors and take appropriate measures to prevent VTE.

Aprotinin, which decreases bleeding by inhibiting fibrinolysis, was taken off the market in 2007 due to its link to higher mortality rates. Vitamin K-dependent protein C may actually increase the risk of thrombosis in the initial stages of warfarin treatment.

The Coagulation Cascade: Two Pathways to Fibrin Formation

The coagulation cascade is a complex process that leads to the formation of a blood clot. There are two pathways that can lead to fibrin formation: the intrinsic pathway and the extrinsic pathway. The intrinsic pathway involves components that are already present in the blood and has a minor role in clotting. It is initiated by subendothelial damage, such as collagen, which leads to the formation of the primary complex on collagen by high-molecular-weight kininogen (HMWK), prekallikrein, and Factor 12. This complex activates Factor 11, which in turn activates Factor 9. Factor 9, along with its co-factor Factor 8a, forms the tenase complex, which activates Factor 10.

The extrinsic pathway, on the other hand, requires tissue factor released by damaged tissue. This pathway is initiated by tissue damage, which leads to the binding of Factor 7 to tissue factor. This complex activates Factor 9, which works with Factor 8 to activate Factor 10. Both pathways converge at the common pathway, where activated Factor 10 causes the conversion of prothrombin to thrombin. Thrombin hydrolyses fibrinogen peptide bonds to form fibrin and also activates factor 8 to form links between fibrin molecules.

Finally, fibrinolysis occurs, which is the process of clot resorption. Plasminogen is converted to plasmin to facilitate this process. It is important to note that certain factors are involved in both pathways, such as Factor 10, and that some factors are vitamin K dependent, such as Factors 2, 7, 9, and 10. The intrinsic pathway can be assessed by measuring the activated partial thromboplastin time (APTT), while the extrinsic pathway can be assessed by measuring the prothrombin time (PT).

Platelets, also known as thrombocytes, are derived from myeloid stem cells, similar to red blood cells. The process involves the development of a megakaryocyte from a common myeloid progenitor cell. Megakaryocytes are large cells with multilobulated nuclei that grow to become massive before breaking up to form platelets.

The primary signal responsible for megakaryocyte and platelet production is thrombopoietin.

Erythropoietin initiates the signal for red blood cell production, while granulocyte-colony stimulating factor stimulates the bone marrow to produce granulocytes. Interleukin-5 is a cytokine that stimulates the proliferation and activation of eosinophils.

Haematopoiesis: The Generation of Immune Cells

Haematopoiesis is the process by which immune cells are produced from haematopoietic stem cells in the bone marrow. These stem cells give rise to two main types of progenitor cells: myeloid and lymphoid progenitor cells. All immune cells are derived from these progenitor cells.

The myeloid progenitor cells generate cells such as macrophages/monocytes, dendritic cells, neutrophils, eosinophils, basophils, and mast cells. On the other hand, lymphoid progenitor cells give rise to T cells, NK cells, B cells, and dendritic cells.

This process is essential for the proper functioning of the immune system. Without haematopoiesis, the body would not be able to produce the necessary immune cells to fight off infections and diseases. Understanding haematopoiesis is crucial in developing treatments for diseases that affect the immune system.

The lymphatic system of the breast is responsible for draining excess fluid and waste products. Lymph from the upper outer quadrant of the breast drains to the axillary lymph nodes, while lymph from the inner quadrants drains to the parasternal lymph nodes. Additionally, some lymph from the lower quadrants drains to the inferior phrenic lymph nodes.

Lymphatic drainage is the process by which lymphatic vessels carry lymph, a clear fluid containing white blood cells, away from tissues and organs and towards lymph nodes. The lymphatic vessels that drain the skin and follow venous drainage are called superficial lymphatic vessels, while those that drain internal organs and structures follow the arteries and are called deep lymphatic vessels. These vessels eventually lead to lymph nodes, which filter and remove harmful substances from the lymph before it is returned to the bloodstream.

The lymphatic system is divided into two main ducts: the right lymphatic duct and the thoracic duct. The right lymphatic duct drains the right side of the head and right arm, while the thoracic duct drains everything else. Both ducts eventually drain into the venous system.

Different areas of the body have specific primary lymph node drainage sites. For example, the superficial inguinal lymph nodes drain the anal canal below the pectinate line, perineum, skin of the thigh, penis, scrotum, and vagina. The deep inguinal lymph nodes drain the glans penis, while the para-aortic lymph nodes drain the testes, ovaries, kidney, and adrenal gland. The axillary lymph nodes drain the lateral breast and upper limb, while the internal iliac lymph nodes drain the anal canal above the pectinate line, lower part of the rectum, and pelvic structures including the cervix and inferior part of the uterus. The superior mesenteric lymph nodes drain the duodenum and jejunum, while the inferior mesenteric lymph nodes drain the descending colon, sigmoid colon, and upper part of the rectum. Finally, the coeliac lymph nodes drain the stomach.

The standard chemotherapy regimen for non-Hodgkin lymphoma is R-CHOP, which includes Rituximab (in certain patients), cyclophosphamide, hydroxydaunorubicin, Oncovin (vincristine), and prednisolone. However, one of the significant side effects of vincristine is chemotherapy-induced peripheral neuropathy, which can cause tingling or numbness starting from the extremities. It can also lead to severe neuropathic pain and distal weakness, such as foot drop.

While Rituximab can cause adverse effects such as cardiotoxicity and infections, it is not commonly associated with neurological effects. Cyclophosphamide, on the other hand, can cause chemotherapy-induced nausea and vomiting, bone marrow suppression, and haemorrhagic cystitis due to its toxicity to the bladder epithelium.

Hydroxydaunorubicin is known to cause dilated cardiomyopathy, which can lead to heart failure and has a high mortality rate.

Cytotoxic agents are drugs that are used to kill cancer cells. There are several types of cytotoxic agents, each with their own mechanism of action and potential adverse effects. Alkylating agents, such as cyclophosphamide, work by causing cross-linking in DNA. However, they can also cause haemorrhagic cystitis, myelosuppression, and transitional cell carcinoma. Cytotoxic antibiotics, like bleomycin and anthracyclines, degrade preformed DNA and stabilize DNA-topoisomerase II complex, respectively. However, they can also cause lung fibrosis and cardiomyopathy. Antimetabolites, such as methotrexate and fluorouracil, inhibit dihydrofolate reductase and thymidylate synthesis, respectively. However, they can also cause myelosuppression, mucositis, and liver or lung fibrosis. Drugs that act on microtubules, like vincristine and docetaxel, inhibit the formation of microtubules and prevent microtubule depolymerisation & disassembly, respectively. However, they can also cause peripheral neuropathy, myelosuppression, and paralytic ileus. Topoisomerase inhibitors, like irinotecan, inhibit topoisomerase I, which prevents relaxation of supercoiled DNA. However, they can also cause myelosuppression. Other cytotoxic drugs, such as cisplatin and hydroxyurea, cause cross-linking in DNA and inhibit ribonucleotide reductase, respectively. However, they can also cause ototoxicity, peripheral neuropathy, hypomagnesaemia, and myelosuppression.

GVHD occurs when T cells from the donor tissue attack the recipient’s cells. This often manifests as skin and gastrointestinal symptoms in a host who lacks T cells, following a bone marrow or stem cell transplant. The immune response is initiated by donor CD4+ T cells recognizing the recipient’s MHC II as foreign, while donor CD8+ T cells cause tissue damage.

Understanding Graft Versus Host Disease

Graft versus host disease (GVHD) is a complication that can occur after bone marrow or solid organ transplantation. It happens when the T cells in the donor tissue attack the recipient’s cells. This is different from transplant rejection, where the recipient’s immune cells attack the donor tissue. GVHD is diagnosed using the Billingham criteria, which require that the transplanted tissue contains functioning immune cells, the donor and recipient are immunologically different, and the recipient is immunocompromised.

The incidence of GVHD varies, but it can occur in up to 50% of patients who receive allogeneic bone marrow transplants. Risk factors include poorly matched donor and recipient, the type of conditioning used before transplantation, gender disparity between donor and recipient, and the source of the graft.

Acute and chronic GVHD are considered separate syndromes. Acute GVHD typically occurs within 100 days of transplantation and affects the skin, liver, and gastrointestinal tract. Chronic GVHD may occur after acute disease or arise de novo and has a more varied clinical picture.

Diagnosis of GVHD is largely clinical and based on the exclusion of other pathology. Signs and symptoms of acute GVHD include a painful rash, jaundice, diarrhea, nausea, vomiting, and fever. Chronic GVHD can affect the skin, eyes, gastrointestinal tract, and lungs.

Treatment of GVHD involves immunosuppression and supportive measures. Intravenous steroids are the mainstay of treatment for severe cases of acute GVHD, while extended courses of steroid therapy are often needed in chronic GVHD. Second-line therapies include anti-TNF, mTOR inhibitors, and extracorporeal photopheresis. Topical steroid therapy may be sufficient in mild disease with limited cutaneous involvement. However, excessive immunosuppression may increase the risk of infection and limit the beneficial graft-versus-tumor effect of the transplant.

The primary cause of vitamin B12 deficiency is pernicious anaemia. This condition occurs when the stomach lining is destroyed by autoimmune factors, leading to reduced production of intrinsic factor. Intrinsic factor is responsible for binding B12 in the gut, and without it, B12 absorption is impaired. This can result in a deficiency of vitamin B12 and macrocytic anaemia, as well as neurological symptoms due to damage to spinal cord myelination.

While a strict vegan diet and alcoholism can also lead to B12 deficiency, they are not the most common causes.

Microcytic sideroblastic anaemia, on the other hand, is caused by lead poisoning, which impairs haem production.

Vitamin B12 is essential for the development of red blood cells and the maintenance of the nervous system. It is absorbed through the binding of intrinsic factor, which is secreted by parietal cells in the stomach, and actively absorbed in the terminal ileum. A deficiency in vitamin B12 can be caused by pernicious anaemia, post gastrectomy, a vegan or poor diet, disorders or surgery of the terminal ileum, Crohn’s disease, or metformin use.

Symptoms of vitamin B12 deficiency include macrocytic anaemia, a sore tongue and mouth, neurological symptoms, and neuropsychiatric symptoms such as mood disturbances. The dorsal column is usually affected first, leading to joint position and vibration issues before distal paraesthesia.

Management of vitamin B12 deficiency involves administering 1 mg of IM hydroxocobalamin three times a week for two weeks, followed by once every three months if there is no neurological involvement. If a patient is also deficient in folic acid, it is important to treat the B12 deficiency first to avoid subacute combined degeneration of the cord.

Hydroxyurea is utilized in the prophylactic management of sickle cell anemia to prevent painful episodes by increasing the levels of HbF. The management of sickle cell disease involves two aspects: acute episodes and chronic management. Acute episodes are treated with adequate hydration and effective analgesia, while chronic management aims to prevent acute episodes and treat complications. Hydroxyurea has been proven to reduce the frequency of painful crises and the need for blood transfusions by increasing HbF levels, which has a higher affinity for oxygen than haemoglobin A. Acetaminophen is an analgesic that inhibits the cyclooxygenase enzyme and is only useful in mild pain cases. Methotrexate is a chemotherapeutic agent that has no role in sickle cell disease management.

Managing Sickle-Cell Anaemia

Sickle-cell anaemia is a genetic blood disorder that causes red blood cells to become misshapen and break down, leading to a range of complications. When a crisis occurs, management involves providing analgesia, rehydration, oxygen, and potentially antibiotics if there is evidence of infection. Blood transfusions may also be necessary, and in some cases, an exchange transfusion may be required if there are neurological complications.

In the longer term, prophylactic management of sickle-cell anaemia involves the use of hydroxyurea, which increases the levels of HbF to prevent painful episodes. Additionally, it is recommended that sickle-cell patients receive the pneumococcal polysaccharide vaccine every five years to reduce the risk of infection. By implementing these management strategies, individuals with sickle-cell anaemia can better manage their condition and improve their quality of life.

The correct diagnosis for the patient is sideroblastic anaemia, which is characterized by hypochromic microcytic anaemia, high levels of ferritin iron and transferrin saturation, and basophilic stippling of red blood cells. This condition is caused by vitamin B6 deficiency due to frequent alcohol consumption, leading to abnormal heme production. The peripheral smear shows basophilic stippling of red blood cells, and there is iron overload causing iron deposition in the bone marrow, observed as increased staining with Prussian blue.

Anaemia of chronic disease, iron deficiency anaemia, and aplastic anaemia are incorrect diagnoses. Anaemia of chronic disease is usually normocytic normochromic and has significantly low levels of folate, B12, and iron while ferritin is high. Iron deficiency anaemia may be microcytic hypochromic, but serum iron, ferritin, and transferrin levels would be reduced. Aplastic anaemia presents with pancytopenia and is rarely found in the given age group.

Understanding Sideroblastic Anaemia

Sideroblastic anaemia is a medical condition that occurs when red blood cells fail to produce enough haem, which is partly synthesized in the mitochondria. This results in the accumulation of iron in the mitochondria, forming a ring around the nucleus known as a ring sideroblast. The condition can be either congenital or acquired.

The congenital cause of sideroblastic anaemia is delta-aminolevulinate synthase-2 deficiency. On the other hand, acquired causes include myelodysplasia, alcohol, lead, and anti-TB medications.

To diagnose sideroblastic anaemia, doctors may conduct a full blood count, iron studies, and a blood film. The results may show hypochromic microcytic anaemia, high ferritin, high iron, high transferrin saturation, and basophilic stippling of red blood cells. A bone marrow test may also be done, and Prussian blue staining can reveal ringed sideroblasts.

Management of sideroblastic anaemia is mainly supportive, and treatment focuses on addressing any underlying cause. Pyridoxine may also be prescribed to help manage the condition.

In summary, sideroblastic anaemia is a condition that affects the production of haem in red blood cells, leading to the accumulation of iron in the mitochondria. It can be congenital or acquired, and diagnosis involves various tests. Treatment is mainly supportive, and addressing any underlying cause is crucial.

Dilutional anemia can occur as a result of saline administration, which does not improve oxygen transport or coagulopathy.

When the blood group of a patient is unknown, O rhesus negative blood may be administered as it is considered the universal donor. However, to conserve O negative blood stocks, transfusion guidelines now recommend giving male patients O positive blood in such situations, as Rhesus status is only relevant in pregnancy.

It is crucial to ensure that the correct blood product is prescribed and administered to the right patient, as transfusion reactions can be severe and fatal.

Blood Products and Cell Saver Devices

Blood products are essential in various medical procedures, especially in cases where patients require transfusions due to anaemia or bleeding. Packed red cells, platelet-rich plasma, platelet concentrate, fresh frozen plasma, and cryoprecipitate are some of the commonly used whole blood fractions. Fresh frozen plasma is usually administered to patients with clotting deficiencies, while cryoprecipitate is a rich source of Factor VIII and fibrinogen. Cross-matching is necessary for all blood products, and cell saver devices are used to collect and re-infuse a patient’s own blood lost during surgery.

Cell saver devices come in two types, those that wash the blood cells before re-infusion and those that do not. The former is more expensive and complicated to operate but reduces the risk of re-infusing contaminated blood. The latter avoids the use of donor blood and may be acceptable to Jehovah’s witnesses. However, it is contraindicated in malignant diseases due to the risk of facilitating disease dissemination.

In some surgical patients, the use of warfarin can pose specific problems and may require the use of specialised blood products. Warfarin reversal can be achieved through the administration of vitamin K, fresh frozen plasma, or human prothrombin complex. Fresh frozen plasma is used less commonly now as a first-line warfarin reversal, and human prothrombin complex is preferred due to its rapid action. However, it should be given with vitamin K as factor 6 has a short half-life.

If a patient has a history of gastrectomy and is experiencing macrocytic anaemia, it is likely that they are suffering from B12 deficiency.

Vitamin B12 is essential for the development of red blood cells and the maintenance of the nervous system. It is absorbed through the binding of intrinsic factor, which is secreted by parietal cells in the stomach, and actively absorbed in the terminal ileum. A deficiency in vitamin B12 can be caused by pernicious anaemia, post gastrectomy, a vegan or poor diet, disorders or surgery of the terminal ileum, Crohn’s disease, or metformin use.

Symptoms of vitamin B12 deficiency include macrocytic anaemia, a sore tongue and mouth, neurological symptoms, and neuropsychiatric symptoms such as mood disturbances. The dorsal column is usually affected first, leading to joint position and vibration issues before distal paraesthesia.

Management of vitamin B12 deficiency involves administering 1 mg of IM hydroxocobalamin three times a week for two weeks, followed by once every three months if there is no neurological involvement. If a patient is also deficient in folic acid, it is important to treat the B12 deficiency first to avoid subacute combined degeneration of the cord.

Aplastic anemia is a condition where there is a shortage of blood cells from all types of progenitor lines. It is most commonly seen in individuals between the ages of 15 to 25 and those over 60.

The causes of aplastic anemia can be attributed to various factors such as infections (including Epstein-Barr), toxic exposure (such as benzene and radiation), idiopathic, and rarely hereditary.

Haematopoietic stem cells in the bone marrow generate immune cells. These cells produce two main types of progenitors, myeloid and lymphoid progenitor cells, which give rise to all immune cells.

Myeloid progenitor cells give rise to cells such as macrophages/monocytes, dendritic cells, neutrophils, eosinophils, basophils, and mast cells. On the other hand, lymphoid progenitor cells give rise to T cells, NK cells, B cells, and dendritic cells.

Aplastic anaemia is a condition characterized by a decrease in the number of blood cells due to a poorly functioning bone marrow. It is most commonly seen in individuals around the age of 30 and is marked by a reduction in red blood cells, white blood cells, and platelets. While lymphocytes may be relatively spared, the overall effect is a condition known as pancytopenia. In some cases, aplastic anaemia may be the first sign of acute lymphoblastic or myeloid leukaemia. A small number of patients may later develop paroxysmal nocturnal haemoglobinuria or myelodysplasia.

The causes of aplastic anaemia can be idiopathic, meaning that they are unknown, or they can be linked to congenital conditions such as Fanconi anaemia or dyskeratosis congenita. Certain drugs, such as cytotoxics, chloramphenicol, sulphonamides, phenytoin, and gold, as well as toxins like benzene, can also cause aplastic anaemia. Infections such as parvovirus and hepatitis, as well as exposure to radiation, can also contribute to the development of this condition.

The primary cause of hypercalcemia in multiple myeloma is increased osteoclast activity in response to cytokines released by the myeloma cells. This neoplasm of bone marrow plasma cells is most commonly seen in males aged 60-70 years old, which fits the demographic of the patient in this scenario. It is important to investigate patients presenting with hypercalcemia for an underlying diagnosis of multiple myeloma. Decreased osteoblast function, elevated PTH-rP levels, and impaired renal function are less contributing factors to hypercalcemia in myeloma compared to increased osteoclastic activity. Although impaired renal function is commonly seen in multiple myeloma, it is not stated whether this patient has decreased renal function.

Understanding Multiple Myeloma: Features and Investigations

Multiple myeloma is a type of cancer that affects the plasma cells in the bone marrow. It is most commonly found in patients aged 60-70 years. The disease is characterized by a range of symptoms, which can be remembered using the mnemonic CRABBI. These include hypercalcemia, renal damage, anemia, bleeding, bone lesions, and increased susceptibility to infection. Other features of multiple myeloma include amyloidosis, carpal tunnel syndrome, neuropathy, and hyperviscosity.

To diagnose multiple myeloma, a range of investigations are required. Blood tests can reveal anemia, renal failure, and hypercalcemia. Protein electrophoresis can detect raised levels of monoclonal IgA/IgG proteins in the serum, while bone marrow aspiration can confirm the diagnosis if the number of plasma cells is significantly raised. Imaging studies, such as whole-body MRI or X-rays, can be used to detect osteolytic lesions.

The diagnostic criteria for multiple myeloma require one major and one minor criteria or three minor criteria in an individual who has signs or symptoms of the disease. Major criteria include the presence of plasmacytoma, 30% plasma cells in a bone marrow sample, or elevated levels of M protein in the blood or urine. Minor criteria include 10% to 30% plasma cells in a bone marrow sample, minor elevations in the level of M protein in the blood or urine, osteolytic lesions, or low levels of antibodies in the blood. Understanding the features and investigations of multiple myeloma is crucial for early detection and effective treatment.

The leading cause of cancer deaths in the UK is lung cancer, while malignant melanoma does not rank in the top 10. Prostate cancer is the most prevalent cancer in men and the second most common cause of cancer-related deaths in men. Breast cancer is the second most common cause of cancer deaths in women.

Cancer in the UK: Common Types and Causes of Death

Cancer is a major health concern in the UK, with several types of cancer affecting a significant number of people. The most common types of cancer in the UK are breast, lung, colorectal, prostate, bladder, non-Hodgkin’s lymphoma, melanoma, stomach, oesophagus, and pancreas. However, when it comes to causes of death from cancer, lung cancer tops the list, followed by colorectal, breast, prostate, and pancreatic cancer. Other types of cancer that contribute to cancer-related deaths in the UK include oesophageal, stomach, bladder, non-Hodgkin’s lymphoma, and ovarian cancer. It is important to note that non-melanoma skin cancer is not included in these statistics. Despite the prevalence of cancer in the UK, there are various treatments and support available for those affected by the disease.

Abnormalities on FBC and Possible Causes

The FBC shows a normal Hb but an elevated MCV, which could be indicative of alcohol abuse. This is further supported by the patient’s increased confusion and withdrawal, suggesting acute withdrawal. Alcohol is known to cause an increase in MCV, while other causes such as B12 and folate deficiencies would also result in anemia. However, hypothyroidism and hematological malignancies are also associated with high MCV, but they are not likely causes in this clinical picture. Overall, the FBC abnormalities and clinical presentation suggest alcohol abuse and acute withdrawal as the most probable cause.

The patient is displaying typical signs and symptoms of cervical carcinoma, with a constant dull pelvic pain indicating possible invasion of pelvic structures and nerves. The strongest risk factor for this patient is having had multiple sexual partners at a young age, which increases the likelihood of being infected with the human papillomavirus.

1: Multiple sexual partners are the strongest risk factor for cervical carcinoma due to the increased chance of contracting the human papillomavirus, specifically the 16 and 18 viral strains that inhibit the tumor suppressor genes p53 and RB, triggering carcinogenesis.
2: While cigarette smoking can have an oncogenic effect, it is not the primary risk factor in this case.
3: HIV is a risk factor for cervical carcinoma, but it is less common than the human papillomavirus.
4: The human papillomavirus is the primary risk factor, but it does not activate oncogenes. Instead, it inhibits tumor suppressor genes.
5: Age alone is not a risk factor for cervical carcinoma. However, an older person who has been exposed to the human papillomavirus may have a higher risk due to the longer exposure time for the virus to induce carcinogenesis via the inhibition of tumor suppressor genes.

HPV Infection and Cervical Cancer

Human papillomavirus (HPV) infection is the primary risk factor for cervical cancer, with subtypes 16, 18, and 33 being the most carcinogenic. Other common subtypes, such as 6 and 11, are associated with genital warts but are not carcinogenic. When endocervical cells become infected with HPV, they may undergo changes that lead to the development of koilocytes. These cells have distinct characteristics, including an enlarged nucleus, irregular nuclear membrane contour, hyperchromasia (darker staining of the nucleus), and a perinuclear halo. These changes are important diagnostic markers for cervical cancer and can be detected through Pap smears or other screening methods. Early detection and treatment of HPV infection and cervical cancer can greatly improve outcomes and reduce the risk of complications.

Chronic Lymphocytic Leukaemia (CLL) Prognostic Indicators

Chronic lymphocytic leukaemia (CLL) is a type of cancer that affects the blood and bone marrow. Patients with CLL often have genetic mutations, with trisomy 12 being a bad prognostic indicator. ZAP-70, a tyrosine kinase involved in cell signalling, is also measured in CLL patients, and high expression is associated with a poor prognosis. On the other hand, lactate dehydrogenase (LDH) is a marker of tumour burden, and a normal level suggests less tumour bulk, which is a good prognostic marker.

Many patients with CLL may not require treatment and may die with the disease rather than from it. It is often diagnosed in asymptomatic patients who undergo blood tests for other reasons. Treating the disease too early may actually lead to a worse outcome than monitoring the patient initially. Therefore, patients who do not need to start treatment immediately have a more favourable outlook.

B cells in secondary lymphoid tissue undergo somatic hypermutation when they recognise an antigen. This process fine-tunes antibody specificity, and cells that have undergone somatic hypermutation are more mature. If CLL arises from one of these cells, it is associated with a more favourable prognosis. these prognostic indicators can help healthcare professionals determine the best course of treatment for patients with CLL.

The thymus is where T-cells undergo maturation, while they are produced in the bone marrow. Once mature, they can be found in the spleen and lymph nodes where they interact with antigen presenting cells. To investigate the impact of HIV on T-cell maturation, a thymus sample is necessary.

Understanding the Lymphatic System

The lymphatic system is composed of primary and secondary lymphatic organs, as well as lymph vessels. The primary lymphatic organs are the thymus and red bone marrow, which are responsible for the formation and maturation of lymphocytes. These organs contain pluripotent cells that give rise to immunocompetent B cells and pre-T cells. To become mature T cells, pre-T cells must migrate to the thymus.

On the other hand, secondary lymphatic organs include lymph nodes, the spleen, tonsils, mucosa-associated lymphoid tissue (MALT), and Peyer’s patches. These organs filter lymphocytes and activate them to mount an immune response. Understanding the lymphatic system is crucial in comprehending how the body’s immune system works. By knowing the different organs and their functions, we can appreciate how the body fights off infections and diseases.