Blood – PATHOLOGY

Sickle cell anemia is a normocytic hemolytic anemia caused by a mutation in the beta-globin gene, leading to the production of abnormal hemoglobin S. Under low oxygen conditions—such as high-altitude exposure during hiking—deoxygenated HbS polymerizes, distorting red blood cells into a sickled shape. These sickled cells are prone to hemolysis and vascular occlusion, leading to symptoms like pain crises, fatigue, and low hemoglobin.

This patient’s normocytic anemia (MCV 90 fL), environmental trigger (altitude), and systemic symptoms strongly point to sickle cell disease or sickle cell trait with complications.

Why the other options are incorrect:

• Thalassemia: Typically presents with microcytic anemia and does not cause pain crises after altitude exposure.

• Acute blood loss anemia: Would present with signs of trauma or bleeding and not typically be triggered by altitude or cause pain crises.

• Iron deficiency anemia: Presents with microcytic, hypochromic red cells and is not associated with altitude-related complications.

• Megaloblastic anemia: Characterized by macrocytosis (MCV >100 fL) and neurologic signs—not acute pain episodes.

Human papillomavirus (HPV), particularly types 16 and 18, is the primary cause of cervical cancer. These high-risk strains integrate into host DNA and produce viral oncoproteins E6 and E7, which inactivate tumor suppressor proteins p53 and Rb, respectively.

Cervical warts are usually caused by low-risk HPV types 6 and 11, but the presence of warts and a history of multiple sexual partners indicates a high risk for co-infection with high-risk oncogenic strains.

Why the other options are incorrect:

• Herpes simplex virus (HSV): Can cause genital ulcers, but does not lead to cervical cancer.

• Hepatitis B virus (HBV): Associated with hepatocellular carcinoma, not cervical cancer.

• Epstein-Barr virus (EBV): Linked to nasopharyngeal carcinoma, Burkitt lymphoma, and other lymphoproliferative disorders.

• Cytomegalovirus (CMV): Commonly causes congenital infections and disease in immunocompromised individuals, but not cervical cancer.

Liver cells (hepatocytes) are classified as stable cells. These cells are normally quiescent (in G₀ phase) but have the capacity to re-enter the cell cycle and proliferate in response to injury or partial resection, such as in liver donation.

Stable cells do not divide regularly like labile cells, but unlike permanent cells, they retain the capacity to proliferate when stimulated. This property underlies the remarkable regenerative ability of the liver.

Why the other options are incorrect:

• Permanent: These cells (e.g., neurons, cardiac muscle) cannot regenerate. Liver cells do not belong in this category.

• Labile: These cells (e.g., skin, GI epithelium, bone marrow) divide continuously. Hepatocytes are not constantly dividing.

• Quiescent: This describes the state of stable cells at rest, not a cell type. It overlaps with “stable,” but is not a classification on its own.

• Senescent: These are aged or damaged cells that have lost the ability to divide. Hepatocytes after resection are not senescent.

Granulation tissue is a hallmark of the proliferative phase of wound healing. It consists primarily of:

• Fibroblasts, which produce collagen and extracellular matrix

• Newly formed capillaries, which provide nutrients and oxygen to the healing tissue

• Loose connective tissue and inflammatory cells, but the dominant components are fibroblasts and angiogenic capillaries

Granulation tissue is pink, soft, and granular in appearance and is essential for wound closure and tissue repair.

Why the other options are incorrect:

• Epithelioid cells: These are activated macrophages found in granulomatous inflammation, not granulation tissue.

• Multinucleated giant cells: Also part of granulomatous inflammation, especially in infections like tuberculosis.

• Keratinocytes: These are epithelial cells involved in re-epithelialization, but not a major component of granulation tissue.

• Neutrophils and eosinophils: Present during the early inflammatory phase, not the proliferative granulation phase.

A keloid is an abnormal proliferation of scar tissue that extends beyond the original wound margins and does not regress spontaneously. It results from excessive collagen (mostly type III) deposition during wound healing and is more common in darker-skinned individuals and in certain body areas like the ears, chest, and shoulders.

This is different from a hypertrophic scar, which remains within the boundaries of the original injury and may regress over time.

Why the other options are incorrect:

• Proud flesh: Refers to excessive granulation tissue that prevents re-epithelialization; it does not extend beyond the wound boundaries like a keloid.

• Fibrosis: A general term for excess collagen deposition in tissues, often internal (e.g., liver, lung), not specific to skin wounds.

• Scar: A normal outcome of wound healing; it does not imply overgrowth or abnormal extension.

• Hypertrophic scar: Overgrown scar that stays within the original wound boundary, unlike a keloid.

Secondary hemostasis refers to the formation of a stable fibrin clot through the coagulation cascade, involving clotting factors like factor VIII and IX. When there’s a defect in secondary hemostasis (e.g., Hemophilia A or B), patients experience deep tissue bleeding, which includes:

• Hemarthrosis (bleeding into joints)

• Muscle hematomas

• Delayed bleeding after trauma or surgery

These are not typical of platelet disorders (primary hemostasis), which affect mucosal surfaces.

Why the other options are incorrect:

• Epistaxis: Common in primary hemostasis defects like platelet disorders or von Willebrand disease.

• Petechiae: Small pinpoint hemorrhages seen in thrombocytopenia or platelet dysfunction, not coagulation factor defects.

• Bruising: While can be seen in both, easy bruising is more common in platelet-related disorders.

• Purpurae: Larger hemorrhages than petechiae, but still typically related to platelet or vascular disorders, not coagulation factor deficiencies.

Superficial cuts typically involve small vessels and should stop bleeding quickly due to the action of platelets forming a temporary plug. If the bleeding continues to ooze and is not profuse, it suggests a problem with primary hemostasis, which is mediated by platelets.

A defect in platelet function—such as seen in conditions like von Willebrand disease or drug-induced platelet dysfunction (e.g., aspirin use)—leads to mucocutaneous bleeding, including easy bruising, nosebleeds, and prolonged bleeding from small cuts.

Why the other options are incorrect:

• Thrombocytosis: An increased platelet count, often asymptomatic, and does not cause bleeding—in fact, it may cause thrombosis.

• Defect in factor VIII: This is seen in Hemophilia A, which typically causes deep tissue bleeding, joint bleeds, and prolonged bleeding after trauma, not superficial oozing.

• Vitamin K deficiency: Affects clotting factors II, VII, IX, and X leading to coagulation defects, but bleeding tends to be more systemic and is not limited to minor cuts.

• Hemophilia: Refers to factor VIII or IX deficiency (Hemophilia A or B), which causes deep bleeding, not prolonged bleeding from superficial skin injuries.

Yellowish skin and eyes (jaundice) happen when red blood cells break down too quickly. This releases a substance called bilirubin, which builds up in the blood.

In this case, the patient has:

• Painful episodes

• Low red blood cell count

• Abnormal red cells on blood test

These are signs of a condition like sickle cell disease, where red blood cells are destroyed faster than normal. That fast breakdown is what causes the yellow color — so it points to a red blood cell disorder.

Why the other options are wrong:

• Bacterial infection – May cause fever or pain, but not jaundice like this.

• Bleeding disorder – Causes bruising or bleeding, but not yellowing.

• Viral infection – Only certain ones (like hepatitis) cause jaundice, not likely here.

• Iron disorder – Affects blood production, not breakdown.

Hookworms such as Ancylostoma duodenale and Necator americanus attach to the mucosa of the small intestine and feed on host blood. Chronic blood loss caused by these parasites leads to iron deficiency. This results in microcytic, hypochromic anemia, especially in individuals with heavy infestations or poor nutritional intake.

Why the other options are incorrect:

• Vitamin B12 deficiency is typically due to malabsorption or pernicious anemia, not blood loss from parasitic infection.

• Folate (Vitamin B9) deficiency can also cause anemia, but it results in megaloblastic anemia, not commonly associated with hookworm.

• Vitamin B6 deficiency may cause sideroblastic anemia, but it is not linked to blood loss from parasites.

• Vitamin C plays a supportive role in iron absorption but is not the primary deficiency caused by hookworm infection.

Hookworms, such as Ancylostoma duodenale and Necator americanus, attach to the mucosa of the small intestine and feed on host blood. Each worm can cause chronic blood loss, and in heavily infected individuals, this leads to iron deficiency anemia.

This type of anemia is typically microcytic and hypochromic, and may present with fatigue, pallor, and reduced physical development in children.

❌ Why the other options are incorrect:

• Folic acid deficiency:
  Not typically caused by hookworms. Folic acid is absorbed in the jejunum and is more affected by diet or medications, not blood loss.

• Vitamin A deficiency:
  Not directly linked to hookworm. This vitamin is fat-soluble and more associated with malnutrition or fat malabsorption.

• Vitamin B12 deficiency:
  Seen in conditions affecting the ileum (e.g., Diphyllobothrium latum infection), not typically due to hookworms, which reside in the duodenum/jejunum.

• Vitamin C deficiency:
  Results from poor dietary intake, not blood loss from parasitic infection.

The alternative complement pathway is part of the innate immune system and is triggered directly by foreign surfaces, such as bacterial walls, viruses, or venoms, without the need for antibodies. Cobra venom, being a non-self protein that enters the bloodstream, can directly initiate the alternative pathway.

In this pathway, C3 spontaneously hydrolyzes, and C3b binds to the foreign surface. This leads to the formation of the C3 convertase (C3bBb), amplifying the response and generating C3a and C5a, which promote inflammation and recruit immune cells.

Factor H plays a regulatory role in this pathway, preventing damage to host cells by inactivating C3b when bound to self-surfaces.

❌ Why the other options are incorrect:

• Classical pathway (antigen-antibody complex dependent):
  This requires antibodies (IgG or IgM) bound to antigens to initiate the cascade. Since the cobra venom exposure is an acute event and antibodies may not yet be present, this is unlikely to be the primary pathway.

• Lectin pathway (triggered by mannose-binding lectin):
  This pathway targets microbial surfaces with mannose residues, such as those on bacteria or fungi. Cobra venom does not activate this pathway.

• Activation of factor H and C3b regulation:
  While factor H is a regulator of the alternative pathway (not a trigger), it prevents complement activation on host cells, not foreign ones like venom. This is a regulatory mechanism, not the main activation pathway.

• Direct activation of C3a and C5a without initial antibody involvement:
  While C3a and C5a are products of complement activation, this option describes an effect, not a pathway. It’s better to identify the specific pathway (alternative) that leads to their activation in this context.

The presence of epithelioid cells (activated macrophages with a squamous-like appearance) and multinucleated giant cells is characteristic of granulomatous inflammation. This form of chronic inflammation occurs in response to indigestible substances, such as persistent pathogens (e.g., Mycobacterium tuberculosis), foreign bodies, or autoimmune triggers.

Granulomas are organized collections of macrophages surrounded by lymphocytes, and often contain Langhans-type giant cells (with peripheral nuclei) or foreign body-type giant cells.

❌ Why the other options are incorrect:

• Serous inflammation:
  This is characterized by a watery, protein-poor fluid, such as that seen in blisters or viral pleuritis—not by cellular infiltrates like giant cells.

• Ulcerative inflammation:
  Involves necrosis and sloughing of the surface epithelium (e.g., peptic ulcers). It does not typically feature giant cells or epithelioid macrophages.

• Fibrinous inflammation:
  Characterized by fibrin-rich exudate due to increased vascular permeability (e.g., in pericarditis). It lacks granuloma formation.

• Acute inflammation:
  Dominated by neutrophils, not macrophages or giant cells. The features here indicate a chronic process.

Megaloblastic anemia is a type of macrocytic anemia caused primarily by deficiency of vitamin B12 or folate, leading to impaired DNA synthesis in the bone marrow.

Characteristic features of megaloblastic anemia:

• Bone marrow hypercellularity:
  Despite the peripheral anemia, the bone marrow in megaloblastic anemia is hypercellular with abundant megaloblasts (large, immature red blood cell precursors). The ineffective erythropoiesis results in many precursor cells dying within the marrow (intramedullary destruction), hence hypercellularity.

• Serum iron:
  Usually normal or increased due to ineffective erythropoiesis and increased iron release from dying marrow cells, not reduced.

• Reticulocyte count:
  Usually decreased or low-normal because of impaired DNA synthesis and ineffective erythropoiesis; the marrow cannot produce mature RBCs efficiently.

• Serum vitamin B12:
  Usually decreased in vitamin B12 deficiency anemia, not increased.

• TIBC (Total iron-binding capacity):
  Generally normal or decreased in megaloblastic anemia; increased TIBC is more typical of iron deficiency anemia.

Why other options are incorrect:

• Serum iron reduced: Not typical; iron is often normal or high in megaloblastic anemia.

• Reticulocyte count increased: No, it decreases due to impaired erythropoiesis.

• Serum vitamin B12 increased: No, B12 is deficient or low in megaloblastic anemia.

• TIBC increased: Usually not elevated; this is more seen in iron deficiency anemia.

The clinical picture and laboratory findings in this patient suggest pernicious anemia, a common cause of vitamin B12 deficiency and megaloblastic anemia.

Breakdown of clinical and lab clues:

• Fatigue and numbness in limbs: These symptoms suggest neurological involvement common in vitamin B12 deficiency.

• Long history of diarrhea: Indicates possible autoimmune gastritis or malabsorption.

• Thyroid replacement therapy: Patient has hypothyroidism, possibly due to autoimmune thyroiditis (Hashimoto’s); autoimmune diseases tend to cluster.

• CBC findings:

  • Low WBC and platelets (pancytopenia tendency)

  • Low Hb with macrocytosis (MCV 120 fL) typical of megaloblastic anemia

• Vitamin B12 deficiency confirmed.

Why anti-intrinsic factor antibodies?

• Pernicious anemia results from autoimmune destruction of gastric parietal cells or neutralization of intrinsic factor (IF) by antibodies, impairing vitamin B12 absorption.

• Anti-intrinsic factor antibodies are highly specific and diagnostic for pernicious anemia.

• The neurological symptoms are due to subacute combined degeneration caused by B12 deficiency.

Why other options are incorrect:

• Antigliadin antibodies: Found in celiac disease, related to gluten sensitivity; this causes malabsorption but is not directly linked to intrinsic factor or pernicious anemia.

• Antimitochondrial antibodies: Seen in primary biliary cholangitis (PBC), an autoimmune liver disease.

• Anticentromere antibodies: Associated with limited systemic sclerosis (CREST syndrome).

• Antismooth muscle antibodies: Found in autoimmune hepatitis.

This patient presents with a 2-month history of fever, lethargy, and night sweats—these are classical “B symptoms” often associated with lymphomas (both Hodgkin and non-Hodgkin types).

Key clinical features supporting lymphoma:

• Palpable cervical and axillary lymph nodes: Painless lymphadenopathy is a hallmark of lymphoma.

• Splenomegaly: Commonly seen in lymphoproliferative disorders including lymphoma.

• B symptoms: Fever, night sweats, and weight loss (sometimes present), characteristic systemic symptoms in lymphoma.

Why other options are less likely:

• Viral fever: Usually acute, shorter duration, lymphadenopathy may occur but persistent lymphadenopathy with B symptoms over months is less typical.

• Chronic myeloid leukemia (CML): Usually presents with splenomegaly and symptoms related to hypermetabolism, but lymphadenopathy is not prominent.

• Chronic malaria: Can cause splenomegaly and fever, but lymphadenopathy is not a typical feature; also, symptoms tend to be intermittent.

• Metastatic cancer: Typically presents with firm, fixed lymph nodes and usually the primary site is known; lymphadenopathy distribution and systemic B symptoms less characteristic.

This patient presents with persistent cervical lymphadenopathy and splenomegaly with no signs of recent infection (e.g., sore throat or flu), and the swelling has persisted for 10–12 days. These red flags raise suspicion for underlying malignancy or a granulomatous disease (e.g., lymphoma, tuberculosis, or sarcoidosis).

➤ Why is lymph node biopsy correct?

• A biopsy is the gold standard to evaluate unexplained lymphadenopathy that persists >2 weeks without obvious infection and is non-tender, firm, mobile, or accompanied by splenomegaly.

• Biopsy helps in histopathological diagnosis, especially for ruling out Hodgkin’s or non-Hodgkin’s lymphoma, tuberculosis, or metastatic cancer.

❌ Why the other options are incorrect:

• Reassure the patient and send him home
  → ❌ Dangerous. With persistent lymphadenopathy and splenomegaly, this may delay diagnosis of a serious disease.

• Antibiotics/antivirals
  → ❌ Not appropriate without signs of infection (e.g., fever, sore throat). Empirical treatment can mask symptoms and delay diagnosis.

• Observe the patient for 3–4 weeks
  → ❌ Acceptable only if no splenomegaly and node is <1 cm, soft, tender, and recent. In this case, with systemic signs, immediate evaluation is warranted.

• Send viral serology/VDRL/PCR
  → ❌ May be helpful adjunctively, but biopsy is essential to determine the cause definitively.

Step 1: Understanding macrocytic anemia

Macrocytic anemia is characterized by large red blood cells, usually caused by impaired DNA synthesis, leading to fewer but larger red cells. The two main causes of macrocytic anemia are:

• Vitamin B12 deficiency (Cobalamin)

• Folic acid deficiency

Since vitamin B12 levels are normal, B12 deficiency can be ruled out.

Step 2: Understanding the other lab finding: increased serum transferrin

• Serum transferrin is a transport protein that carries iron in the blood.

• Increased transferrin usually occurs in iron deficiency anemia, as the body tries to capture more iron.

• However, iron deficiency typically causes microcytic anemia (small red blood cells), not macrocytic.

Step 3: Considering pregnancy and folic acid deficiency

• Pregnancy increases folate requirements because of rapid cell division and fetal growth.

• Folic acid deficiency results in macrocytic anemia.

• Folic acid deficiency typically shows increased serum transferrin because iron metabolism can be secondarily affected.

• Serum vitamin B12 is normal, which helps distinguish folate deficiency from B12 deficiency.

Step 4: Why other options are incorrect?

• Iron deficiency → causes microcytic anemia, not macrocytic.

• Intrinsic factor deficiency → causes B12 deficiency (pernicious anemia).

• Cobalamin (vitamin B12) → levels are normal here.

• Erythropoietin deficiency → causes normocytic anemia, often seen in kidney disease.

Final conclusion:

The patient’s macrocytic anemia with normal B12 but increased transferrin in pregnancy suggests folic acid deficiency.

This clinical picture and lab results are classic for von Willebrand Disease (vWD), the most common inherited bleeding disorder.

Hemostasis and von Willebrand factor:

Hemostasis has three major steps:

1. Vasoconstriction: Narrowing of blood vessels to reduce blood flow.

2. Platelet adhesion: Platelets stick to exposed collagen in the damaged vessel wall. This step requires von Willebrand factor (vWF) as a bridge between platelet surface glycoprotein Ib and exposed collagen.

3. Platelet aggregation: Platelets stick to each other to form a platelet plug.

4. Prothrombin generation: Activation of the coagulation cascade producing thrombin.

5. Prothrombin inhibition: Inhibiting clot formation (negative regulation).

Why platelet adhesion?

• vWF is essential for platelet adhesion to the vessel wall.

• Decreased vWF → impaired platelet adhesion → mucocutaneous bleeding symptoms (nosebleeds, easy bruising, menorrhagia).

• Normal platelet count means platelets are present but cannot adhere properly.

• Normal APTT/PT means coagulation cascade is intact (except severe vWD can prolong APTT).

Analysis of options:

• Vasoconstriction: Initial step; usually not affected in vWD.

• Platelet adhesion: Correct answer, since vWF is essential here.

• Prothrombin generation: This is part of coagulation cascade, normal here.

• Platelet aggregation: Aggregation happens after adhesion; vWD mainly affects adhesion.

• Prothrombin inhibition: Not relevant here.

Summary:

The defect in von Willebrand disease is in platelet adhesion due to decreased or dysfunctional vWF.

The major histocompatibility complex (MHC) is a set of genes that code for cell surface proteins essential for the immune system to recognize foreign molecules in vertebrates, which in turn determines histocompatibility.

• MHC molecules present peptide antigens to T cells, which is critical for the adaptive immune response.

• This antigen presentation is essential for the immune system to distinguish self from non-self.

• Due to this, MHC molecules are central to transplantation biology, as mismatched MHC molecules lead to immune rejection of transplanted organs or tissues.

• The variability in MHC molecules between individuals is why transplant rejection happens, unless immunosuppressive therapy is used.

Option analysis:

1. Muscle contraction

   • Incorrect. Muscle contraction is regulated by calcium ions and actin-myosin interactions, unrelated to MHC.

2. Blood clotting

   • Incorrect. Blood clotting involves platelets and clotting factors, independent of MHC.

3. Neurotransmitter release

   • Incorrect. Neurotransmitter release is a neuronal process, not linked to MHC.

4. Hormone regulation

   • Incorrect. Hormone regulation involves endocrine glands and receptors, not MHC.

5. Transplant rejection

   • Correct. MHC molecules are central to the immune recognition of self vs. non-self, making them the key factor in transplant rejection.

Summary:

MHC is involved in transplant rejection because it presents antigens that trigger the immune system to recognize and potentially reject non-self tissues.

The complement system is a crucial part of innate immunity, helping to clear pathogens, especially bacteria, through opsonization, recruitment of inflammatory cells, and direct lysis via the membrane attack complex (MAC).

Deficiencies in complement components can predispose individuals to specific problems:

• Early complement component deficiencies (C1, C2, C4) are strongly linked with autoimmune diseases, especially systemic lupus erythematosus (SLE). This is because defective clearance of immune complexes and apoptotic cells leads to immune system dysregulation.

• Terminal complement component deficiencies (C5–C9) increase susceptibility to recurrent infections with Neisseria species (meningococcal infections), due to inability to form MAC and lyse bacteria.

Therefore, the hallmark of complement deficiency is increased risk of bacterial infections, particularly with encapsulated organisms and Neisseria species.

Option analysis:

1. Allergic reactions

   • Incorrect. Complement deficiencies do not primarily increase allergic reactions.

2. Hypergammaglobulinemia

   • Incorrect. This refers to increased antibody production, which is not a direct consequence of complement deficiency.

3. Autoimmune diseases

   • Partially correct. Some complement deficiencies (especially early components) are associated with autoimmune diseases, but this is not the most universal or classic consequence.

4. Hypersensitivity

   • Incorrect. Hypersensitivity reactions are related to immune response types but not specifically linked to complement deficiency.

5. Bacterial infections

   • Correct. Complement deficiencies increase the risk of recurrent bacterial infections due to impaired opsonization and lysis.

Summary:

Complement deficiencies most commonly lead to an increased risk of bacterial infections

Osteoarthritis is primarily a degenerative joint disease characterized by cartilage degradation, bone remodeling, and some degree of synovial inflammation. However, it is not a classic inflammatory arthritis like rheumatoid arthritis. The inflammation in OA is low-grade, chronic, and mostly involves repair and remodeling rather than intense immune cell infiltration.

Option Analysis:

1. Cytokines and growth factors having no role in this type of inflammation

   • Incorrect. OA involves inflammatory cytokines (like IL-1, TNF-alpha) and growth factors that contribute to cartilage breakdown and repair. These mediators play a crucial role, even if the inflammation is mild.

2. Granuloma formation as a constant feature in these patients

   • Incorrect. Granulomas are a hallmark of chronic granulomatous inflammation (e.g., tuberculosis, sarcoidosis). OA does not involve granuloma formation.

3. Neutrophilic exudate with pus formation on biopsy

   • Incorrect. Neutrophilic exudate and pus formation are typical of acute bacterial infections or abscesses, not OA. OA inflammation is chronic and non-suppurative.

4. Alternatively activated macrophages promoting tissue repair

   • Correct. OA synovium shows an infiltration of macrophages polarized towards the M2 phenotype (alternatively activated), which are involved in tissue repair and fibrosis rather than classical inflammatory damage. These macrophages release anti-inflammatory cytokines and growth factors promoting repair and remodeling.

5. Plasma cells and B lymphocytes being almost never found

   • Incorrect. Plasma cells and B cells are generally sparse in OA; however, they are not almost never found. Some low-level infiltration of lymphocytes can occur, but it’s minimal compared to autoimmune arthritis.

Summary:

The correct answer is:
Alternatively activated macrophages promoting tissue repair

The classical pathway of complement activation is one of three major pathways (classical, lectin, and alternative) that activate the complement system to fight infections. Understanding what triggers each pathway is key to distinguishing them.

Let’s analyze the options:

1. Antigen-antibody complexes:

   • This is the correct initiator of the classical pathway.

   • When antibodies (mainly IgG or IgM) bind to antigens on a pathogen’s surface, the C1 complex (C1q, C1r, and C1s) recognizes and binds to the Fc region of the antibody, initiating the cascade.

2. Binding of mannose-binding lectin (MBL) to microbial surfaces:

   • This initiates the lectin pathway, not the classical pathway.

   • MBL binds specific sugars on pathogen surfaces to activate complement independently of antibodies.

3. Breakdown of C3:

   • C3 breakdown is part of the complement cascade but is not an initiating event.

   • It occurs downstream after the activation of C3 convertase.

4. Binding of C-reactive protein (CRP) to microbial surfaces:

   • CRP can activate the classical pathway by binding to microbial surfaces and interacting with C1q, but this is a less common and indirect initiation method. The main initiation is through antigen-antibody complexes.

5. Activation of C3 convertase:

   • C3 convertase is an enzyme complex formed during the complement cascade to cleave C3, but its formation occurs after the pathway is initiated. It is not the starting event.

Summary:

• The classical complement pathway is primarily initiated by antigen-antibody complexes.

• Antibodies bound to antigen recruit the C1 complex, triggering the cascade leading to pathogen destruction.

The Membrane Attack Complex (MAC) is the terminal product of the complement system activation and is crucial for the destruction of target cells such as bacteria. It forms pores in the membrane of the pathogen, leading to cell lysis.

Let’s break down the options:

1. C5b, C6, C7, C8, and C9:

   • This is the correct composition of the MAC.

   • Activation proceeds with cleavage of C5 into C5a and C5b; C5b then sequentially binds C6, C7, C8, and multiple C9 molecules.

   • The complex inserts into the pathogen’s membrane, forming a pore that disrupts the membrane integrity, causing cell death.

2. C1, C2, C4, and C6:

   • These components belong to the early classical pathway of complement activation.

   • C1 initiates the classical pathway; C2 and C4 form the C3 convertase.

   • C6 is part of MAC but not in isolation with C1, C2, C4.

3. C5a and C5b:

   • These are split products of C5 cleavage.

   • C5a acts as an anaphylatoxin (inflammation mediator), while C5b initiates MAC formation but alone is not the entire MAC.

4. C1, C3b, and C4b:

   • These are involved in complement activation steps, like opsonization and C3 convertase formation, but are not the MAC components.

5. C3a, C3b, and C5b:

   • C3a and C5a are anaphylatoxins; C3b is an opsonin.

   • C5b initiates MAC assembly, but C3a and C3b are not MAC components.

Summary:

• The Membrane Attack Complex (MAC) consists of C5b, C6, C7, C8, and C9.

• This complex creates pores in pathogen membranes, causing osmotic lysis and cell death.

This patient has an ulcer in the gastric antrum with biopsy showing infiltration of lymphocytes, macrophages, and plasma cells, along with granulation tissue formation and fibrosis. These features give us clues about the type of inflammation.

Let’s analyze the terms:

1. Acute inflammation:

   • Characterized mainly by infiltration of neutrophils, edema, and vascular changes.

   • It is a rapid, short-term response to injury or infection.

   • Does not involve granulation tissue or fibrosis.

2. Serous inflammation:

   • This is a mild form of acute inflammation with clear, protein-poor fluid (serous exudate).

   • It lacks significant cellular infiltration and tissue damage.

3. Chronic inflammation:

   • Characterized by infiltration of mononuclear cells: lymphocytes, plasma cells, and macrophages.

   • Accompanied by tissue destruction, fibrosis, and granulation tissue formation.

   • This type of inflammation occurs when acute inflammation fails to resolve and the process becomes prolonged.

4. Fibrinous inflammation:

   • Marked by deposition of fibrin in tissues or serous cavities.

   • Seen in some severe acute inflammations, especially of serous membranes.

   • No mention of fibrin or fibrin deposition here.

5. Granulomatous inflammation:

   • A special form of chronic inflammation characterized by granulomas, which are collections of activated macrophages (epithelioid cells), often with multinucleated giant cells.

   • Usually seen in diseases like tuberculosis, sarcoidosis, and some fungal infections.

Why Chronic inflammation is the best answer:

• The biopsy shows lymphocytes, macrophages, plasma cells (mononuclear cells) typical of chronic inflammation.

• The presence of granulation tissue and fibrosis confirms ongoing tissue repair and chronicity.

• There is no mention of granulomas, ruling out granulomatous inflammation.

Why the other options are incorrect:

• Acute inflammation would show mainly neutrophils, not plasma cells or granulation tissue.

• Serous inflammation involves clear fluid without much cellular infiltration.

• Fibrinous inflammation involves fibrin deposition, which is not mentioned here.

• Granulomatous inflammation requires granuloma formation, which is not described.

Correct answer: Chronic

The symptoms described—excessive sneezing and watery eyes every year during spring and summer—strongly suggest allergic rhinitis, which is an IgE-mediated hypersensitivity reaction typically triggered by environmental allergens like pollen.

In allergic reactions:

• The immune system overreacts to harmless antigens (allergens).

• This activates mast cells and basophils to release histamine, causing symptoms like sneezing and watery eyes.

• However, the cell type that notably increases in the peripheral blood and tissues in allergic reactions, especially seasonal allergies, is the eosinophil.

Let’s break down the options:

1. Basophils:

   • Basophils, like mast cells, play a role in allergic reactions by releasing histamine and other mediators.

   • However, their numbers in blood usually remain normal or slightly elevated, not markedly increased.

   • Basophils are relatively rare in circulation.

2. Lymphocytes:

   • These are key players in adaptive immunity and viral infections but are not typically increased specifically in allergic reactions.

3. Eosinophils:

   • These cells are the hallmark of allergic responses and parasitic infections.

   • They accumulate in tissues affected by allergy and increase in peripheral blood during active allergic reactions.

   • Eosinophils release toxic granules that contribute to tissue inflammation and symptoms of allergy.

4. Monocytes:

   • These are precursors to macrophages and dendritic cells, involved in chronic inflammation and infection, not specifically elevated in allergies.

5. Neutrophils:

   • These are first responders in bacterial infections and acute inflammation but are not elevated specifically in allergic conditions.

Correct Answer: Eosinophils

Eosinophils are the most characteristic cells increased during allergic reactions like seasonal allergic rhinitis.

The question describes a classic pattern where an affected male does not transmit the disorder to his sons, but all daughters become carriers. This inheritance pattern is highly characteristic of X-linked recessive disorders.

Let’s analyze why:

1. X-linked recessive inheritance:

   • Males have one X and one Y chromosome (XY). If a male inherits a mutated gene on his single X chromosome, he will express the disease because he has no second X chromosome to compensate.

   • Affected males cannot pass the mutation to their sons because sons inherit their father’s Y chromosome, not the X.

   • All daughters inherit their father’s X chromosome (the one with the mutation), so they become carriers if the disorder is recessive, typically unaffected but carriers of the mutated gene. This fits perfectly with the scenario described.

2. Autosomal dominant inheritance:

   • An affected male can transmit the mutation to both sons and daughters equally. Sons and daughters have a 50% chance of being affected. So this option does not fit the pattern.

3. Sex chromosome abnormality:

   • This term usually refers to disorders like Turner syndrome (XO) or Klinefelter syndrome (XXY), which are not inherited in a simple Mendelian pattern. This option is not relevant here.

4. X-linked dominant inheritance:

   • Affected males transmit the disease to all daughters (who will be affected) and none of their sons (because sons get the Y).

   • However, in this pattern, daughters are affected, not just carriers. Since the question states daughters are carriers, X-linked dominant is unlikely.

5. Autosomal recessive inheritance:

   • Both males and females are equally affected, and the pattern is typically horizontal in families. Sons and daughters can both be affected if they inherit two mutated alleles.

   • The described pattern of no transmission to sons but all daughters being carriers does not fit autosomal recessive.

Summary:

• The correct answer is X-linked recessive inheritance because:

  • Affected males do not pass the mutation to sons (sons get Y chromosome).

  • All daughters inherit the mutated X and become carriers.

Autosomal dominant disorders have several hallmark features related to their genetics and clinical presentation:

• Reduced penetrance and variable expressivity are classic features of many autosomal dominant disorders.

  • Reduced penetrance means that not all individuals who carry the mutant gene show clinical symptoms of the disease.

  • Variable expressivity means that the severity and features of the disease can vary widely among affected individuals, even within the same family.

Let’s analyze each option:

1. Protein shows loss of function
   This is not universally true for autosomal dominant disorders. Many dominant disorders are caused by gain-of-function mutations or dominant-negative effects. For example, achondroplasia involves a gain-of-function mutation in FGFR3, not loss of function. Loss-of-function mutations often cause autosomal recessive diseases. So, this option is incorrect as a general statement.

2. New mutations detected early clinically
   New mutations (de novo mutations) can occur in autosomal dominant disorders, but the clinical detection timing varies greatly. Early clinical detection is not a defining feature. Thus, this statement is not the best descriptor.

3. Reduced penetrance and variable expressivity
   This is a hallmark of autosomal dominant disorders. Many such diseases show incomplete penetrance and variable expressivity, meaning symptoms might be mild or absent in some carriers and severe in others. This makes this option correct.

4. Onset usually early in life
   Autosomal dominant disorders can have variable onset ages; some appear in childhood (e.g., Huntington’s disease appears in mid-adulthood), and others much later. Early onset is not a universal feature. Hence, incorrect as a generalization.

5. Disease in homozygous state
   Autosomal dominant disorders manifest even in the heterozygous state. Homozygosity is often rare and may cause more severe disease but is not necessary for disease. This statement better describes autosomal recessive diseases, so incorrect here.

This clinical scenario describes a patient who developed pneumonia and then, after discharge, has symptoms indicating a localized collection of thick, foul-smelling sputum with imaging showing a localized collection of fluid in the lung.

Understanding the Outcome of Acute Inflammation:

Acute inflammation in the lung (such as pneumonia) can have several outcomes depending on the extent of tissue damage, the nature of the infecting organism, and host response:

1. Resolution:

   • Complete restoration of normal tissue architecture and function.

   • Occurs when the injury is mild, and the tissue can regenerate fully.

   • No scarring or permanent damage.

2. Fibrosis:

   • Replacement of normal tissue by fibrous connective tissue (scar formation).

   • Happens when tissue damage is severe and regeneration is incomplete.

   • Leads to permanent loss of function in the affected area.

3. Abscess formation:

   • Localized collection of pus (neutrophils, dead cells, and microbes) surrounded by a fibrous capsule.

   • Caused by pyogenic bacteria that cause localized tissue necrosis and liquefactive necrosis.

   • Characterized by foul-smelling, thick purulent material, often with cavitation seen on imaging.

   • Common in bacterial pneumonia caused by organisms like Staphylococcus aureus or anaerobes.

4. Granuloma formation:

   • A chronic inflammatory response characterized by aggregates of activated macrophages (epithelioid cells) often with multinucleated giant cells.

   • Seen in infections like tuberculosis, fungal infections, or foreign body reactions.

   • Not typical in acute bacterial pneumonia.

5. Ulcer formation:

   • Localized loss of epithelial surface, usually on mucosal surfaces (e.g., GI tract).

   • Not a typical pulmonary lesion.

Why Abscess formation fits best:

• The presence of thick, foul-smelling sputum indicates pus and necrotic material.

• The CT scan shows a localized fluid collection (cavity) within the lung, a classic sign of a lung abscess.

• The time frame (2 weeks after discharge) suggests a complication of pneumonia, likely due to tissue necrosis and pus accumulation.

Why the other options are incorrect:

• Resolution: Would imply no residual collection or symptoms.

• Fibrosis: Happens later and usually not associated with pus or foul smell.

• Granuloma formation: Typical for chronic infections, not acute bacterial infections.

• Ulcer formation: Not common in lung infections; more typical for mucosal surfaces

This case describes a young woman with breast cancer, a strong family history (sister with ovarian cancer, aunt with breast cancer), and early age at onset — all highly suggestive of a hereditary cancer syndrome.

The key genetic culprit in familial breast and ovarian cancer syndromes is the BRCA1 gene.

🔬 BRCA1: A Tumor Suppressor Gene

• BRCA1 (Breast Cancer 1) is located on chromosome 17q21.

• It functions in DNA repair — specifically, homologous recombination of double-stranded DNA breaks.

• Loss-of-function mutations in BRCA1 impair this repair process, increasing the risk of mutations accumulating, which predisposes to:

  • Breast cancer (especially premenopausal)

  • Ovarian cancer (especially high-grade serous carcinoma)

This patient’s history (young age, family members with breast and ovarian cancer) fits a classic BRCA1 mutation pattern.

❌ Why the Other Options Are Incorrect:

• ERBB2 (HER2/neu):

  • A growth factor receptor gene often amplified in sporadic breast cancer, especially HER2-positive types.

  • Not associated with familial inheritance or ovarian cancer.

• BCL2:

  • An anti-apoptotic protein, commonly overexpressed in follicular lymphoma.

  • Not typically involved in familial breast or ovarian cancer.

• HST1 (Fibroblast Growth Factor gene):

  • Involved in cell proliferation and angiogenesis but not known for hereditary cancer syndromes.

• EGF (Epidermal Growth Factor gene):

  • Similar to ERBB2 in function, but not associated with inherited cancer syndromes.

To understand carcinoma, we must first grasp the basic classification of malignant neoplasms:

There are two major categories:

1. Carcinomas → arise from epithelial tissues

2. Sarcomas → arise from mesenchymal tissues (connective tissue, bone, muscle, etc.)

🔍 Carcinoma Defined:

A carcinoma is a malignant tumor of epithelial origin. Epithelial cells line the outer and inner surfaces of the body, including:

• Skin

• Gastrointestinal tract lining

• Glandular ducts

• Respiratory passages

• Urinary tract

✅ Key feature: Tissue of origin is the epithelium, regardless of embryological germ layer (ectoderm, endoderm, or mesoderm).

For example:

• Basal cell carcinoma (from skin — ectoderm)

• Adenocarcinoma of colon (from glandular lining — endoderm)

• Renal cell carcinoma (from renal tubular epithelium — mesoderm)

Thus, the correct classification is by tissue type (epithelium), not embryonic origin.

❌ Why the Other Options Are Incorrect:

• Arising exclusively from the cells of mesodermal origin → describes sarcomas, not carcinomas.

• Arising from sheets of solid mesenchyme → again, refers to mesenchymal origin tumors, i.e., sarcomas.

• Arising exclusively from the cells of ectodermal origin → misleading. While many epithelia are derived from ectoderm, carcinomas can originate from endoderm (e.g., GI tract) or mesoderm (e.g., renal tubules) too.

• Arising exclusively from the cells of endodermal origin → same problem. Not all carcinomas come from endoderm.

This clinical scenario describes a malignant tumor in the neck that has been growing for months, associated with weight loss, and shows a firm, fixed mass. The key histological clue is that “all areas of the tumor have similar morphology,” which implies a lack of differentiation across the tumor.

Let’s unpack this carefully.

🔍 Key Clues from the Question:

• Age: 58 years → increased risk of malignancy

• Symptoms: Neck fullness and weight loss → suggest systemic impact of a malignant tumor

• Physical exam: Firm, fixed mass → classic sign of invasive carcinoma

• Histology: All areas look the same → implies undifferentiation, pleomorphism, and loss of structural organization, which are key features of anaplasia.

🧬 Why Anaplastic Carcinoma Is Correct:

Anaplastic carcinoma is a high-grade, poorly differentiated malignant tumor.

• “Anaplastic” literally means without form.

• It often arises in the thyroid gland, particularly in older individuals, and has a very aggressive course.

• Microscopically, these tumors show:

  • Marked cellular pleomorphism

  • Giant cells

  • Atypical mitotic figures

  • No glandular or squamous differentiation

Thus, a tumor that looks the same throughout — despite being aggressive and fast-growing — reflects uniform undifferentiation, not benign uniformity.

❌ Why the Other Options Are Incorrect:

• Adenoma: A benign epithelial tumor that is usually well-circumscribed and does not invade local tissue or cause systemic signs like weight loss.

• Leiomyoma: A benign tumor of smooth muscle (e.g., in uterus). Not expected in the neck or thyroid region.

• Well-differentiated adenocarcinoma: Shows glandular differentiation. Histologically, you’d expect regions that resemble glandular tissue. Not the case here — no evidence of differentiation.

• Squamous cell carcinoma: Characterized by keratin pearls, intercellular bridges, and squamous differentiation. Again, the question implies lack of differentiation, which argues against this.

This clinical scenario describes a malignant melanoma—a potentially aggressive skin cancer originating from melanocytes, the pigment-producing cells in the skin. The classic red flag features of melanoma are captured in the ABCDE rule:

• Asymmetry

• Border irregularity

• Color variation

• Diameter >6 mm

• Evolving lesion

In this case, the patient presents with a 1.2 cm, darkly pigmented, and bleeding lesion that has changed recently—all hallmark features of melanoma.

🔬 Why Ultraviolet Radiation Is the Key Risk Factor:

Ultraviolet (UV) radiation—particularly UVB (290–320 nm)—is the most important environmental risk factor for melanoma development. UV light induces DNA damage in skin cells, particularly pyrimidine dimers, and can impair the function of tumor suppressor genes (e.g., p53). Repeated exposure and sunburns in early life dramatically increase melanoma risk.

People with light skin, frequent sun exposure, sunburns, or use of tanning beds are at high risk. This patient has the lesion on the dorsum of the hand, a site frequently exposed to sunlight, making UV radiation the most likely contributing factor.

❌ Why the Other Options Are Incorrect:

• Smoking tobacco: Strongly associated with lung cancer, oral cancers, bladder, and pancreatic cancers, but not significantly linked with melanoma.

• Asbestos exposure: Associated with mesothelioma and lung cancer, particularly in those with a smoking history—not melanoma.

• Chemotherapy: May increase the risk of secondary malignancies, especially leukemias, but melanoma is not commonly linked to chemo-induced transformation.

• Allergy to latex: This is an immunological hypersensitivity, not a carcinogen. There’s no link between latex allergies and skin cancers.

Thyroid carcinoma, especially papillary thyroid carcinoma, is strongly associated with a history of radiation exposure during childhood. This is one of the most well-established risk factors for developing thyroid malignancies. Exposure to ionizing radiation, especially during early development when tissues are more sensitive to mutagenic effects, leads to DNA damage and increases the likelihood of oncogenic transformation in thyroid follicular cells.

Now let’s critically analyze each option:

❌ A. Chronic alcoholism

• Chronic alcohol use has no direct link with thyroid carcinoma.

• It is more commonly associated with liver disease, pancreatitis, and certain GI tract cancers, but not thyroid neoplasms.

❌ B. Exposure to arsenic compounds

• Arsenic exposure is linked with skin cancer, lung cancer, and bladder cancer, but not typically with thyroid carcinoma.

❌ C. Blunt trauma from a fall

• While trauma may occasionally draw attention to a previously unnoticed thyroid lesion, it does not cause cancer.

• There is no evidence suggesting trauma as a carcinogenic factor for the thyroid.

✅ D. Radiation therapy in childhood

• This is the most relevant clinical clue.

• Historical cases, such as those treated with radiation for acne, thymic enlargement, or tonsillar hypertrophy in the 1940s–60s, have shown a significantly higher incidence of thyroid cancers.

• Chernobyl disaster survivors also showed increased rates of thyroid carcinoma, particularly in children.

❌ E. Ataxia telangiectasia

• This is a genetic disorder involving DNA repair defects and immunodeficiency.

• It is associated with leukemias and lymphomas, but there is no strong link to thyroid cancer.

This patient has:

• MCV = 105 fL → Macrocytic anemia

• Low hemoglobin

• No hypersegmented neutrophils → Not megaloblastic

• Normal lung exam and imaging

• Shortness of breath at rest → Symptom of anemia, not necessarily pulmonary disease

💡 Interpretation:

Macrocytic anemia without hypersegmented neutrophils rules out:

• Folate deficiency

• Vitamin B12 deficiency
  These cause megaloblastic anemia with hypersegmented neutrophils.

So we are dealing with a non-megaloblastic macrocytic anemia.

🔬 Common Causes of Non-Megaloblastic Macrocytic Anemia:

❌ Why Others Are Incorrect:

• Iron deficiency anemia → Microcytic, hypochromic anemia (MCV ↓)

• Sickle cell anemia → Normocytic; presents earlier with crises and pain

• Thalassemia → Microcytic anemia; often shows target cells

• Aplastic anemia → Normocytic or mildly macrocytic; pancytopenia and hypocellular marrow

Hepatic angiosarcoma is a rare, aggressive malignant tumor of vascular origin in the liver. It is strongly associated with occupational exposure to:

• Vinyl chloride (used in PVC/plastic pipe manufacturing)

• Arsenic

• Thorium dioxide (Thorotrast) – historically used as a radiologic contrast agent

🧪 Vinyl Chloride Exposure:

• Industrial use: Manufacturing of polyvinyl chloride (PVC) pipes and plastics

• Target organ: Liver

• Typical cancer: Hepatic angiosarcoma

• Latency: Long—symptoms often appear years after exposure

🧾 Why Others Are Incorrect:

• Benzene → Associated with bone marrow suppression and leukemias, especially acute myeloid leukemia (AML)

• Beryllium → Linked with chronic beryllium disease (lung granulomas)

• Asbestos → Strongly associated with mesothelioma and bronchogenic carcinoma

• Arsenic → Can also cause angiosarcoma, but vinyl chloride is more specifically linked to liver angiosarcoma, especially in PVC workers

The most characteristic feature of granulation tissue is the proliferation of fibroblasts and the formation of new capillaries (angiogenesis).

This tissue appears during the healing process, particularly in secondary intention wound healing, and is essential for tissue regeneration and scar formation.

🔍 Histological Features of Granulation Tissue:

• Numerous newly formed capillaries (giving it a pink, granular appearance).

• Proliferating fibroblasts (synthesize collagen).

• Scattered inflammatory cells: mostly macrophages, sometimes neutrophils in early stages.

• Loose extracellular matrix.

🚫 Incorrect Options Explained:

• Monocytes and fibroblasts → monocytes are not dominant; fibroblasts alone are not enough.

• Granuloma resemblance → granulomas are organized collections of macrophages (not related to granulation tissue).

• Neutrophils and macrophages → seen more in acute inflammation, not as specific to granulation tissue.

• Exudate → present in inflammation, not characteristic of granulation tissue.

✅ Correct Answer: Selectin

Why?
Selectins are cell adhesion molecules expressed on activated endothelial cells. They are the primary mediators of margination and rolling of neutrophils during the early stages of inflammation.

• When inflammation begins, cytokines like TNF-α and IL-1 stimulate endothelial cells to express:

  • E-selectin

  • P-selectin

• These selectins bind weakly to Sialyl-Lewis⁺ receptors on neutrophils, causing them to tether and roll along the vascular endothelium — a process known as margination and rolling.

• This is the first step before firm adhesion (via integrins) and transmigration.

❌ Why the other options are incorrect:

Tumor necrosis factor (TNF)

• A pro-inflammatory cytokine that helps upregulate selectins and integrins, but does not directly cause margination.

Integrin

• Responsible for firm adhesion, not margination.

• Integrins on neutrophils bind to ICAM-1 on endothelial cells after rolling has occurred.

Interleukin-8 (IL-8)

• A chemokine that promotes chemotaxis and activation of neutrophils, not margination.

Adherin

• Not a standard term in leukocyte adhesion pathways. Possibly a confusion with adherens junctions, which relate to epithelial cell-cell adhesion, not neutrophil margination.

✅ Correct Answer: Factor VII deficiency

Why?
A prolonged PT with a normal aPTT points to a defect in the extrinsic pathway of the coagulation cascade.

• Factor VII is the only clotting factor in the extrinsic pathway.

• The prothrombin time (PT) test measures the extrinsic and common pathways, especially sensitive to Factor VII.

• The aPTT evaluates the intrinsic and common pathways (Factors VIII, IX, XI, XII).

Therefore:

• If PT is prolonged but aPTT is normal, Factor VII deficiency is the most likely cause.

❌ Why the other options are incorrect:

Factor IV deficiency

• Factor IV = Calcium, an essential cofactor, but deficiency is not a clinical condition in isolation affecting PT selectively.

Factor VIII deficiency

• Associated with Hemophilia A → causes prolonged aPTT, not PT.

Factor II deficiency

• Prolongs both PT and aPTT (since it is part of the common pathway).

Platelet

• Platelet disorders affect bleeding time, not PT or aPTT, which measure coagulation factors, not platelets.

✅ Correct Answer: Platelet adhesion

Why?
von Willebrand factor (vWF) is a multifunctional glycoprotein synthesized by endothelial cells and megakaryocytes, and it plays a crucial role in primary hemostasis by mediating platelet adhesion.

• When a blood vessel is injured, subendothelial collagen is exposed.

• vWF binds to this collagen and forms a bridge between the damaged vessel wall and platelets by attaching to:

  • Collagen on one side

  • Glycoprotein Ib (GpIb) receptors on platelets on the other side

This enables platelets to adhere to the site of injury and initiate platelet plug formation.

❌ Why the other options are incorrect:

Activation of thrombin

• Part of the coagulation cascade (secondary hemostasis), involving Factor X and prothrombin, not vWF.

Clot dissolution

• Performed by the fibrinolytic system, primarily via plasmin, not vWF.

Platelet aggregation

• Involves fibrinogen binding to GpIIb/IIIa receptors on activated platelets, not vWF.

Clot formation

• Refers to fibrin clot development via thrombin and fibrinogen; vWF plays no direct role here.

✅ Correct Answer: Endothelin

Why?
Endothelin is one of the most potent vasoconstrictors produced immediately by injured endothelial cells.

• It is released locally at the site of vascular injury.

• It acts paracrinally on smooth muscle cells to cause vasoconstriction, reducing blood flow and minimizing blood loss — a first-line hemostatic response.

• This sets the stage for platelet plug formation and clotting.

Endothelin is crucial during the vascular spasm phase of hemostasis.

❌ Why the other options are incorrect:

Thromboxane A₂

• Produced by activated platelets, not endothelial cells.

• Promotes vasoconstriction and platelet aggregation, but is not the first responder from endothelium.

Serotonin (5-HT)

• Also released by platelets during aggregation.

• Contributes to vasoconstriction, but again, not endothelial in origin, and not immediate.

Bradykinin

• A vasodilator, not a vasoconstrictor.

• Increases vascular permeability and causes pain and inflammation.

Vasopressin (ADH)

• A systemic hormone secreted by the posterior pituitary, regulating water balance and vasoconstriction, but not locally released by vascular endothelium after injury.

✅ Correct Answer: Plasminogen

Why?
Fibrinolytic agents (e.g., tissue plasminogen activator [tPA], streptokinase, urokinase) work by activating plasminogen, which is a zymogen (inactive precursor) circulating in the blood.

• Once activated to plasmin, this enzyme breaks down fibrin — the structural protein that stabilizes blood clots.

• This process dissolves the thrombus, restores blood flow, and minimizes damage to heart tissue after an MI.

This approach is part of thrombolytic therapy, especially in ST-elevation myocardial infarction (STEMI) when percutaneous coronary intervention (PCI) is not immediately available.

❌ Why the other options are incorrect:

Fibrinogen

• Precursor to fibrin, the clotting mesh — not broken down directly by fibrinolytics.

• It is not activated by thrombolytics; it is part of clot formation, not breakdown.

Bradykinin

• A vasodilator peptide involved in inflammation and pain signaling — has no role in clot lysis.

Clotting factor XII (Hageman factor)

• Initiates the intrinsic coagulation pathway, not involved in fibrinolysis.

• Plays a role in clot formation, not breakdown.

Prothrombin

• Converted to thrombin during coagulation — part of the clotting cascade, not the fibrinolytic system.

• Activated in clot formation, not targeted by fibrinolytic drugs.

When assessing iron deficiency, various components of the iron profile are evaluated. However, the most reliable and earliest indicator of iron deficiency is serum ferritin.

🔬 Why Ferritin?

• Ferritin is the primary intracellular iron storage protein.

• A decrease in ferritin reflects depletion of body iron stores.

• It is the earliest lab abnormality seen in iron deficiency.

• Normal ferritin rules out iron deficiency in the absence of inflammation.

Ferritin <15–20 ng/mL is diagnostic of iron deficiency anemia in most cases.

⚠️ Note: Ferritin is an acute-phase reactant. In infections or inflammation, it may be falsely elevated, which must be considered.

❌ Why Other Options Are Incorrect:

The key diagnostic clue here is the total leukocyte count (TLC) of 2500/μL, which is lower than the normal range of 4000–11000/μL. This reduced white blood cell count is medically termed leukopenia.

🔬 Leukopenia — What is it?

• Definition: A decrease in the total number of white blood cells (WBCs).

• Normal TLC range: ~4000 to 11000/μL

• Leukopenia: TLC < 4000/μL

• Causes:

  • Viral infections (common!)

  • Certain medications (chemotherapy, antipsychotics)

  • Bone marrow suppression (e.g., aplastic anemia, leukemia)

  • Autoimmune diseases

In this case, the patient has a febrile illness with low WBC count, suggestive of a viral etiology causing transient leukopenia.

❌ Why the Other Options Are Incorrect:

Anemia due to reduced erythropoiesis means that the bone marrow is not producing enough red blood cells (RBCs). This is exactly what happens in aplastic anemia — a condition characterized by pancytopenia (deficiency of all blood cell lines) due to bone marrow failure.

🔍 Let’s break it down:

🩸 Aplastic Anemia

• Caused by destruction or suppression of hematopoietic stem cells in the bone marrow.

• Leads to:

  • Low RBCs → anemia

  • Low WBCs → infections

  • Low platelets → bleeding

• Bone marrow biopsy shows hypocellular marrow with fatty replacement.

• Common causes: drugs (e.g., chloramphenicol), radiation, viral infections (like hepatitis), autoimmune diseases.

❌ Why the Other Options Are Incorrect:

The presentation described is textbook for Hodgkin lymphoma, especially the nodular sclerosis or mixed cellularity subtype. Let’s analyze why.

🔍 Clinical Features of Hodgkin Lymphoma:

• Fever (often low-grade or intermittent) – Can follow Pel-Ebstein pattern: cyclic fevers that rise and fall over days.

• Lymphadenopathy:

  • Painless

  • Discrete, rubbery, and firm

  • Most commonly cervical or supraclavicular

• Systemic symptoms (B symptoms):

  • Fever

  • Night sweats

  • Weight loss

• Often occurs in young adults or middle-aged males

• Lymph nodes are typically non-tender

• No significant findings on general physical examination initially besides lymphadenopathy

🧪 Confirmatory Test:

• Excisional biopsy of lymph node: shows Reed-Sternberg cells (large binucleated cells with “owl’s eye” nuclei)

❌ Why Other Options Are Incorrect:

This child has a classic atopic triad:

1. Eczema (atopic dermatitis)

2. Allergic rhinitis

3. Asthma

These conditions are type I hypersensitivity reactions, which are IgE-mediated and involve eosinophil activation in response to allergens.

🔬 What Happens in the Blood?

• The immune response in atopic diseases is skewed towards a Th2 (T-helper 2) profile, which promotes:

  • IgE production

  • Mast cell activation

  • Eosinophil recruitment

• In such patients, peripheral eosinophilia (increased eosinophils in blood) is commonly seen—this is called eosinophilic leukocytosis.

❌ Why the Other Options Are Incorrect:

🔹 Context: Deep Vein Thrombosis (DVT)

• DVT is the formation of a blood clot (thrombus) in a deep vein, usually in the legs.

• The classic causes of thrombosis are described by Virchow’s triad:

  1. Stasis of blood flow

  2. Endothelial injury

  3. Hypercoagulability

• In this patient, immobilization (due to pain and inability to move the leg) causes venous stasis, which predisposes to thrombus formation.

• Immobile muscles do not pump blood efficiently, causing pooling and clotting.

🔹 Why Other Options Are Incorrect:

🔹 Clinical Background:

• The patient has rheumatoid arthritis (RA).

• She presents with splenomegaly, neutropenia, and anemia.

🔹 What is Felty Syndrome?

• Felty syndrome is a rare complication of long-standing rheumatoid arthritis.

• It is characterized by the triad of:

  • Rheumatoid arthritis

  • Splenomegaly

  • Neutropenia

• The neutropenia increases the risk of infections.

• Anemia is also common due to chronic inflammation or hypersplenism.

• Splenomegaly occurs due to increased destruction and sequestration of blood cells in the spleen.

🔹 Why Other Options Are Incorrect:

🔹 What is Immune Memory?

• Memory is a hallmark feature of the adaptive immune system.

• After initial exposure to an antigen, memory B and T cells are formed.

• Upon subsequent exposures, these memory cells trigger a faster, stronger, and more effective immune response compared to the primary response.

• This leads to an exaggerated (amplified) response that can rapidly clear the pathogen.

🔹 Why Other Options Are Incorrect:

🔹 Pathophysiology:

• Parietal cells in the stomach secrete intrinsic factor (IF), which is essential for the absorption of vitamin B12 in the terminal ileum.

• Atrophy of the stomach mucosa, such as in autoimmune gastritis or chronic atrophic gastritis, leads to loss of parietal cells.

• Without intrinsic factor, vitamin B12 absorption is impaired, resulting in vitamin B12 deficiency.

• Vitamin B12 deficiency causes megaloblastic anemia, characterized by the production of large, immature RBCs due to defective DNA synthesis.

🔹 Why Other Options Are Incorrect:

🔹 Context:

• The patient has a malignant eye tumor (likely retinoblastoma given the location and tumor suppressor gene involved).

• Molecular analysis shows deletion of both copies of a gene regulating the G1 to S phase transition in the cell cycle.

• This gene is a classic tumor suppressor gene.

🔹 Role of the Rb Gene:

• The Rb (retinoblastoma) gene produces retinoblastoma protein (pRb).

• pRb regulates the cell cycle checkpoint at the G1/S transition by controlling E2F transcription factors.

• When both alleles of Rb gene are deleted or mutated, this checkpoint is lost, leading to uncontrolled cell proliferation.

• This mechanism is the classic cause of retinoblastoma, a malignant eye tumor in children.

• Loss of both copies of Rb is consistent with Knudson’s “two-hit” hypothesis for tumor suppressor genes.

🔹 Why Other Options Are Incorrect:

🔹 Clinical Features:

• Patient has gum bleeding and epistaxis (nosebleeds).

• CBC shows a normal platelet count.

• Prolonged bleeding time indicates a platelet function disorder, not a platelet number problem.

• Positive family history suggests an inherited condition.

🔹 What is Glanzmann Thrombasthenia?

• It is a rare inherited platelet function disorder caused by deficiency or dysfunction of the glycoprotein IIb/IIIa receptor on platelets.

• This receptor is essential for platelet aggregation (platelets sticking together to form a plug).

• Platelet count is normal, but platelets cannot aggregate properly, leading to prolonged bleeding time and mucocutaneous bleeding symptoms like gum bleeding and epistaxis.

🔹 Why Other Options Are Incorrect:

🔹 What is an Adenoma?

• The term “adenoma” refers to a benign tumor originating from glandular epithelium.

• It arises from epithelial cells that form glands or gland-like structures.

• It is not malignant, meaning it does not invade or metastasize, but it can sometimes progress to malignancy.

🔹 Why the Other Options Are Incorrect:

🔹 Sickle Cell Anemia Basics:

• Caused by a mutation in the β-globin gene producing HbS (α₂β^S₂).

• Under low oxygen conditions, HbS polymerizes, causing RBC sickling, hemolysis, and vaso-occlusion.

• This leads to chronic anemia and recurrent transfusions, as seen in the patient.

🔹 Protective Role of HbF:

• HbF (α₂γ₂) is the fetal hemoglobin normally dominant in newborns.

• HbF does not contain β chains, so it does not sickle.

• Increased HbF levels in sickle cell patients reduce polymerization of HbS by inhibiting sickling.

• Hence, HbF ameliorates symptoms and severity of sickle cell disease.

• Treatments like hydroxyurea work by increasing HbF production.

❌ Why the Other Options Are Incorrect:

In erythroblastosis fetalis, the key pathological event is immune-mediated destruction of fetal red blood cells (RBCs) due to maternal antibodies (usually anti-Rh IgG) crossing the placenta and attacking fetal RBC antigens.

What happens next?

• Due to massive hemolysis (breakdown of RBCs), the fetus develops severe anemia.

• To compensate, the fetal bone marrow increases production of RBC precursors, including erythroblasts (nucleated red blood cells).

• These immature RBCs enter the circulation in large numbers, which is an abnormal finding known as erythroblastosis.

Therefore, the blood culture (or peripheral blood smear) shows increased immature red blood cells, not just mature RBCs.

Why not the other options?

🔹 What is Beta-Thalassemia Minor?

Beta-thalassemia minor is the heterozygous form of beta-thalassemia, where one of the two beta-globin genes is mutated. It typically causes mild microcytic anemia and is often asymptomatic or discovered incidentally.

🔹 Hemoglobin Types in Adults:

🔹 Key Change in Beta-Thalassemia Minor:

• The production of β chains is reduced, so less HbA (α₂β₂) is made.

• The body compensates by increasing production of δ chains, which form HbA₂ (α₂δ₂).

• Therefore, HbA₂ is elevated, usually to >3.5%, which is a diagnostic hallmark of beta-thalassemia minor.

❌ Why the Other Options Are Incorrect:

• HbF (α₂γ₂): Slightly increased in some cases, but not consistently or diagnostically significant in minor form.

• HbS: Found in sickle cell disease, not thalassemia.

• HbC: Abnormal variant associated with HbC disease, unrelated to thalassemia.

• HbA: Actually reduced due to the β-chain production defect.

🔹 The 5 Cardinal Signs of Inflammation

(Originally described by Celsus and later expanded by Virchow):

These signs result from vasodilation, increased vascular permeability, and inflammatory mediator release (e.g., prostaglandins, bradykinin, histamine).

• Redness (Rubor): Caused by increased blood flow (hyperemia)

• Swelling (Tumor): Due to fluid extravasation (edema)

• Warmth (Calor): From increased perfusion and metabolism

• Pain (Dolor): From chemical mediators stimulating nerve endings

• Loss of function: May result from pain, swelling, or tissue damage

❌ Why the Other Options Are Incorrect:

1. Pain – A key symptom due to chemical irritation of nerve endings.

2. Warmth – Caused by hyperemia (increased blood flow).

3. Swelling – Due to fluid accumulation (edema) in tissues.

4. Redness – Also a result of increased perfusion.

❌ Confusion is not a cardinal sign:

• Confusion is a neurological symptom, not a classic sign of localized inflammation.

• It may be seen in systemic inflammatory responses (e.g., sepsis or delirium), but it is not one of the classical signs of inflammation.

🔹 Complement Protein C3:

• C3 is the central component of the complement cascade, activated in all three pathways:

  • Classical

  • Alternative

  • Lectin

• Upon activation:

  • C3 is cleaved into C3a and C3b.

  • C3a promotes inflammation (anaphylatoxin).

  • C3b aids in opsonization (marking pathogens for phagocytosis) and helps in the formation of the C5 convertase.

🔹 Clinical Importance:

• Serum levels of C3 are commonly measured to assess complement activity.

• Low levels of C3 can indicate:

  • Autoimmune diseases (e.g., lupus)

  • Complement consumption due to infections or immune complex diseases

  • Inherited complement deficiencies

Hence, C3 is the most widely used marker to monitor complement activity and immune function.

❌ Why the Other Options Are Incorrect:

1. C2:

   • Involved in the classical and lectin pathways, but not typically used alone for diagnostic purposes.

2. C1q:

   • Initiates the classical pathway, but not used routinely to measure overall complement activity.

3. C5:

   • Leads to formation of the membrane attack complex (MAC) but is less commonly measured.

4. C9:

   • Final component of the MAC, not a good indicator of general immune activity.

🔹 Post-streptococcal glomerulonephritis (PSGN):

• PSGN is a classic example of a Type 3 hypersensitivity reaction, which is immune complex–mediated.

• After a streptococcal infection (often throat or skin), immune complexes form between streptococcal antigens and antibodies.

• These immune complexes deposit in the glomerular basement membrane of the kidneys.

• The deposition leads to activation of the complement system, recruitment of inflammatory cells, and resultant glomerular inflammation and damage.

Key features:

• Immune complexes → complement activation → inflammation → tissue injury.

Why not the others?

1. Type 2 hypersensitivity

   • Antibody-mediated cytotoxicity targeting specific cells (e.g., hemolytic anemia).

   • PSGN is not caused by direct antibody binding to cell surface antigens.

2. Type 1 hypersensitivity

   • Immediate hypersensitivity mediated by IgE (allergic reactions like anaphylaxis).

   • PSGN is not an allergic reaction.

3. Type 4 hypersensitivity

   • Delayed-type, T-cell mediated immunity (e.g., contact dermatitis).

   • PSGN is immune complex–mediated, not T-cell mediated.

4. Type 2 and 3 hypersensitivity

   • PSGN is primarily Type 3. No significant Type 2 mechanism.