1st sem Flashcards

Question

B Cell Cutaneous Lymphoma: Characteristics

Answer 1

Constitute a group of diseases, characterized by B cells similar to those found in germinal centers, such as diffuse large B cell lymphoma, primary cutaneous follicular lymphoma, intravascular large B cell lymphoma.

Answer 2

Intracranial tumor that appears mostly in patients with severe immunosuppression. Highly associated with Epstein-Barr virus infections in immunosuppressed patients but rarely so in immunocompetent patients. Most CNS lymphomas are diffuse large B cell lymphoma.

Answer 3

Symptoms include diplopia (double vision), dysphagia (difficulty swallowing), dementia, and systemic symptoms (fever, night sweats, weight loss).

Answer 4

The precursors of T lymphocytes originate from bone marrow-derived multipotent stem cells. They migrate into the thymus via the bloodstream, where they complete their developmental program. Once mature, they leave the thymus, circulating between blood and lymph, passing through many secondary lymphoid organs/tissues

Answer 5

Mature circulating T cells that have not recognized antigens yet are in a resting state and defined as naive T cells. Activation of naive T cells occurs in the secondary lymphoid organs/tissues where they interact with professional APCs (mainly DCs).

Answer 6

DCs find a pathogen, phagocytose it, transport it to lymph nodes, and present it to a T cell. The T cell recognizes the specific surface MHC-I-peptide complex, leading to T cell activation (naive helper/cytotoxic T cell to effector helper/cytotoxic T cell).

Answer 7

Effector T cells leave the lymphoid tissue, enter the blood circulation, and migrate to infection or inflammation sites in peripheral tissues. Their functions are initiated by recognizing a peptide antigen presented by MHC-I or MHC-II molecules on the target cell surface by TCR.

Answer 8

T helper cells bind to MHC-II on APCs and secrete cytokines that attract other cells of the immune system, such as B cells and macrophages.

Answer 9

T killer cells bind to MHC-I on all nucleated cells and directly kill infected cells by inducing apoptosis or using perforin granzyme. T cells also present the CD28 marker, which helps them bind to APCs.

Answer 10

Whether a lymphoma is of a B, T, or NK cell origin can be determined by specific cell markers (CDs, receptors, enzymes). Whether it is precursor or peripheral depends on the stage of malignant transformation.

Answer 11

Peripheral T-cell lymphomas are characterized by lymphocytic cells (smaller, more cytoplasm, more condensed chromatin), a low rate of proliferation, and more differentiation. These are aggressive tumors that respond poorly to therapy.

Answer 12

Types include: Lymphoepitheloid lymphoma (Lennert's lymphoma) Angioimmunoblastic lymphadenopathy-like T-lymphoma T-zone lymphoma Pleomorphic T-cell lymphoma Large cell anaplastic lymphoma

Answer 13

Small cell (lymphocytic) infiltrate intermingled with a high amount of epithelioid cells and some blasts. Resembles lymphocyte-predominant Hodgkin disease but RS cells are missing.

Answer 14

Mixed infiltrate of small, medium, and large immunoblastic cells. Resembles mixed cellularity Hodgkin disease. Neoplastic cells show clear cytoplasm and wrinkled nucleus. Immunoblasts and plasma cells are basophilic. Hallmarked by proliferation of dendritic reticulum cells (CD23 positive) and HEV.

Answer 15

Spreads within the T-cell areas. Lymph node follicles with germinal centers are preserved. Shows follicular hyperplasia with CD4 positive T-cells.

Answer 16

Characterized by strong nuclear pleomorphism of small, medium, and large lymphoid cells. Clear cells are also present.

Answer 17

T-cells are CD30 positive. Shows cohesive spreading, primarily found within sinuses of lymph nodes. Often mistaken for carcinomas, malignant melanomas, or malignant histiocytosis. Translocation t(2:5) increases tyrosine kinase. May evolve into secondary large cell anaplastic lymphoma. Multinucleated tumor giant cells may be present.

Answer 18

A group of disorders characterized by plasma cell dysfunctions due to gain of function mutations of protooncogenes or loss of function mutations of tumor suppression genes, leading to abnormal proliferation in bone marrow.

Answer 19

Abnormally proliferating plasma cells in these disorders still secrete “M components”; monoclonal antibodies or parts of them: Complete monoclonal antibodies Monoclonal antibodies + excess light chains Heavy chains only (heavy chain disease) Light chains only (light chain disease)

Answer 20

Monoclonal: All secreted antibodies are exactly the same (both heavy and light chains), non-specific, secreted without real stimulation. Polyclonal: Different plasma cells secrete different antibodies with different heavy chains (α IgA, ɤ IgG, μ IgM) and different light chains (κ, λ).

Answer 21

Multiple myeloma (plasma cell myeloma) Monoclonal gammopathy of undetermined significance Solitary plasmacytoma Lymphoplasmacytic lymphoma Heavy-chain disease Primary or immunocyte-associated amyloidosis

Answer 22

t(11,14) Cyclin D protooncogene Deletion of tumor suppression genes on chromosome 13

Answer 23

Primary AL amyloidosis Proteinuria (Bence-Jones protein) Marrow plasma cytosis (>30% of cellularity) Fatigue, bleeding, infections M spike in protein electrophoresis Lytic bone lesions, hypercalcemia, renal failure, depression

Answer 24

Main antibody is IgG, second is IgA. Plasma cell tumors are positive for CD138 (syndecan-1) and often express CD56.

Answer 25

An isolated M spike with none of the other findings of multiple myeloma. Can develop into multiple myeloma.

Answer 26

Extraosseous (soft tissues) - mainly in upper respiratory tract, not very dangerous. Intraosseous (bone marrow) - very dangerous, can develop into full multiple myeloma over 5-10 years.

Answer 27

A single lesion No Bence-Jones proteins Moderate elevation of M proteins in some cases

Answer 28

Abnormal proliferation and infiltration of: Lymphocytes Immunoblasts (intermediate form of lymphocytes trying to convert to plasma cells) Plasma cells

Answer 29

No multiple bony lytic lesions Main antibody is IgM Hyperviscosity syndrome “Waldenstrom's macroglobulinemia” Hepatosplenomegaly with generalized lymphadenopathy No Bence-Jones proteins

Answer 30

α HCD - neoplastic cells in small intestine and respiratory system ɤ HCD - neoplastic cells in liver, spleen, and lymph nodes No Bence-Jones proteins

Answer 31

Overproduction of immunoglobulin light chains, forming aggregations known as AL protein.

Answer 32

A type of non-Hodgkin lymphoma, constituting 50% of NHLs. Aggressive tumors that can affect virtually any organ and are rapidly fatal if not treated.

Answer 33

Mutations/rearrangements of Bcl6 gene on chromosome 3 → overexpression of Bcl6 → increased proliferation of centroblasts. 30% t(14,18); follicular lymphoma which developed into DLBCL. Unknown causes.

Answer 34

Positive for B cell markers (excluding CD10). B-cell receptor (BCR) presence.

Answer 35

Highly aggressive non-Hodgkin lymphoma characterized by rapid growth and proliferation of centroblasts

Answer 36

t(8,14) - chromosomal translocation; MYC gene translocates from chromosome 8 next to the Ig gene for heavy chain on chromosome 14 → MYC gene becomes hyperactive → increased proliferation of centroblasts.

Answer 37

Endemic "African type"; 100% associated with EBV, manifests in the mandible and maxilla. Sporadic "American type"; 20% associated with EBV, manifests in abdominal and pelvic cavities.

Answer 38

"Starry sky appearance" with dark background of neoplastic cells (high chromatin content) and lighter regions of non-neoplastic macrophages with pale cytoplasm and small nuclei.

Answer 39

A type of non-Hodgkin lymphoma, constituting 4% of NHLs. It is aggressive.

Answer 40

t(11,14) - chromosomal translocation; Cyclin D1 gene translocates from chromosome 11 next to the Ig gene for heavy chain on chromosome 14 → Cyclin D1 gene becomes hyperactive → increased proliferation of naive B cells → accumulation in the mantle zone.

Answer 41

Positive for B cell markers. Positive for CD5 (T cell marker).

Answer 42

Non-specific symptoms such as fatigue, fever, weight loss. Lymphadenopathy and generalized disease involving the liver, spleen, bone marrow, and GI tract.

Answer 43

An indolent type of lymphoma. There are 3 types of marginal zone lymphomas: MALT lymphoma – most common form, occurs most frequently in the stomach (also called extra-nodal marginal zone lymphoma). Nodal marginal zone lymphoma – occurs in lymphatic follicles of lymph nodes. Splenic marginal zone lymphoma – B cells replace the normal resident cells of the white pulp of the spleen (T cells, macrophages).

Answer 44

Often arises within tissues involved by chronic inflammatory disorders of autoimmune or infectious etiology, such as Sjögren disease or Helicobacter pylori infection. They may regress if the inciting agent (e.g., Helicobacter pylori) is eradicated.

Answer 45

t(1,14) - chromosomal translocation; Bcl10 gene translocates from chromosome 1 next to the Ig gene for heavy chain on chromosome 14 → Bcl10 gene becomes hyperactive → increased proliferation of lymphocytes.

Answer 46

Positive for B cell markers (excluding CD10). Presence of B-cell receptor (BCR).

Answer 47

Helicobacter-specific T cells produce growth factors which support the formation of the tumor. It often occurs in the stomach due to chronic gastritis caused by H. pylori.

Answer 48

The peripheral lymph node is composed of a cortex and a medulla. The cortex contains lymphocytic nodules (follicles), which primarily consist of B cells and can be either primary (not activated) or secondary (met with an antigen).

Answer 49

Upon activation by an antigen, B cells start to proliferate and differentiate, creating the germinal center of the lymph follicle.

Answer 50

In the germinal center, the differentiating and proliferating B cells undergo: Somatic hypermutation – rearrangement of DNA of the variable region genes to form variations of antibodies. Class switching – rearrangement of the heavy chain genes to switch the class of the antibody.

Answer 51

A type of non-Hodgkin lymphoma, constituting 40% of NHLs. It is characterized by painless lymphadenopathy and poor response to chemotherapy.

Answer 52

B cell markers CD10, CD19, CD20. Cells show somatic hypermutation.

Answer 53

Characteristic translocation of BCL2 gene from chromosome 18 to the loci of IgH gene on chromosome 14, resulting in the overexpression of BCL2 gene. This produces anti-apoptotic proteins, preventing apoptosis.

Answer 54

Painless lymphadenopathy. Bone marrow involvement (RBC, WBC, and platelet levels may be affected). Poor response to chemotherapy.

Answer 55

Follicular lymphoma may progress to diffuse large B-cell lymphoma. Treatment is reserved for symptomatic patients and involves low-dose chemotherapy or rituximab (anti-CD20 antibody).

Answer 56

The classification depends on the stage where the malignant transformation occurs. Precursor lymphoblastic lymphomas/leukemias involve: Lymphoblast cells (bigger, less cytoplasm, less condensed chromatin) High rate of proliferation Less differentiation → Results in acute leukemia/aggressive lymphoma with rapid deterioration (death after 6-12 months). Occurs mainly in children/young adults.

Answer 57

Whether a leukemia/lymphoma is lymphoid or myeloid can be determined by cell markers (CDs, receptors, enzymes).

Answer 58

B cell markers include CD 10, 19, 20, 21, 22.

Answer 59

T cell markers include CD 2, 3 (expressed by all T cells), 4, 7, 8.

Answer 60

NK cell markers include CD 16, 56.

Answer 61

Pre-B cell neoplasms occur in the bone marrow, while pre-T cell neoplasms occur in the thymus. B-ALL is more common (85%) and usually affects children, while T-ALL is less common (10-15%) and usually affects adolescents. NK-ALL is extremely rare.

Answer 62

Mutation → chromosomal abnormality → abnormal transcription factor → malignant transformation. Causes include radiation, chemicals like benzene, genetic factors (e.g., Li-Fraumeni syndrome), or spontaneous mutations.

Answer 63

Chromosomal abnormalities can be numerical (hyperploidy, hypoploidy, trisomy) or structural (deletion, translocation). Hyperploidy Hypoploidy t(12,21) balanced t(9,22) balanced; the resultant chromosome 22 is referred to as the “Philadelphia chromosome”.

Answer 64

Anemia → fatigue Thrombocytopenia → bleeding (epistaxis, petechia, ecchymosis) Neutropenia → infections

Answer 65

Expansion of bone marrow → detachment of periosteum → pain & arthralgia Starry night appearance like in Burkitt lymphoma.

Answer 66

Leukostasis in microcirculation (eyes, kidneys) → thrombi formation.

Answer 67

: Neoplastic cells release their content into the plasma, resulting in: Increased uric acid Increased phosphate Increased H+ Increased Na+ Decreased Ca2+ (forms complexes with phosphate)

Answer 68

Prognosis depends on various factors including the type of chromosomal abnormalities, the stage of detection, and the effectiveness of the treatment plan. Likelihood of survival varies accordingly.

Answer 69

Solid cohesive neoplasms (tumors) of the immune system, mostly originating from lymphoid tissues (bone marrow, thymus, lymph nodes, etc.). In AIDS, they can occur in the CNS. Accumulation of mutations leads to loss of cohesion and potential transition to leukemia.

Answer 70

Malignancies of either lymphoid or myeloid origin, primarily involving the bone marrow with spillage of neoplastic cells into the blood. Sometimes they enter lymphoid tissues and aggregate there, forming lymphomas.

Answer 71

Lymphoid leukemia Myeloid leukemia (affecting RBCs, platelets, and all other WBCs except lymphocytes)

Answer 72

Defines lymphoid tumors based on morphology, cell of origin, clinical features, and genotype. Divides lymphomas into: Tumors of B cells Tumors of T cells and NK cells Hodgkin lymphomas

Answer 73

Precursor B cell neoplasms (B cell ALL) Peripheral B cell neoplasms (mantle cell lymphomas, follicular lymphoma, Burkitt lymphoma)

Answer 74

Precursor T cell neoplasms (T cell ALL) Peripheral T/NK cell neoplasms (NK cell leukemia, mycosis fungoides)

Answer 75

Classical Hodgkin lymphoma Nodular lymphocyte predominance Hodgkin lymphoma (NLPHL)

Answer 76

Identified by B/T/NK cell markers (CDs, receptors, enzymes). Whether it is precursor or peripheral depends on the stage of malignant transformation.

Answer 77

Bigger cells with less cytoplasm and less condensed chromatin High rate of proliferation Less differentiation → Acute leukemia/aggressive lymphoma. Mainly occurs in children/young adults.

Answer 78

Smaller cells with more cytoplasm and more condensed chromatin Low rate of proliferation More differentiation → Chronic leukemia/indolent lymphoma.

Answer 79

Indolent tumors progress slower, are harder to treat, and appear in elderly patients. Aggressive tumors progress fast but are easier to treat and appear in younger patients.

Answer 80

Indolent lymphoma/leukemia caused by trisomy of chromosome 12 (protooncogene) or deletion of chromosome 11/13 (tumor suppressor gene). This interferes with BCRs, causing naive B lymphocytes to stop maturing and die slowly, leading to their accumulation in the bone marrow and transfer to various tissues.

Answer 81

Bone marrow involvement Hepatosplenomegaly (liver and spleen) Lymphadenopathy (lymph nodes) Anemia, thrombocytopenia, neutropenia Autoimmune hemolytic anemia Hypo-ɤ-globulinemia Richter syndrome (progression to DLBL)

Answer 82

Positive for B cell markers Positive for CD5 (T cell marker) Circulating tumor cells are fragile, often disrupted in smears, producing characteristic smudge cells.

Answer 83

Enlargement of a lymph node due to an immune response. It can be acute (painful) or chronic (painless), depending on the underlying cause.

Answer 84

Painful enlargement of a lymph node draining a region with an acute infection. It is often confined to a local group of nodes but can be generalized in the case of systemic infection. Characterized by large germinal centers with numerous mitotic figures.

Answer 85

Painless enlargement of a lymph node. Depending on the causative agent, different areas of the lymph node can be enlarged, such as follicular hyperplasia, paracortical hyperplasia, or sinus histiocytosis.

Answer 86

Enlargement of the follicles, often caused by chronic disorders like rheumatoid arthritis (RA) and early stages of HIV infections.

Answer 87

Enlargement of the paracortex, often caused by viral infections like EBV (Epstein-Barr Virus), certain vaccinations (e.g., smallpox), and sometimes by Burkitt lymphoma.

Answer 88

Enlargement of the sinuses of the medulla, often caused by draining of cancers like breast cancer. It is characterized by an increase in the number of histiocytes (macrophages).

Answer 89

Caused by infection with the protozoan Toxoplasma gondii. Characterized by the presence of melanin-filled macrophages, eosinophils, and plasma cells in the affected area of the lymph node.

Answer 90

Neoplastic proliferation of mature cells of the myeloid lineage, commonly associated with mutated tyrosine kinases. Includes Chronic Myeloid Leukemia (CML), Polycythemia Vera (PCV), Primary Myelofibrosis, and Essential Thrombocythemia. These diseases result in high WBC counts (neutrophils > 100,000 cell/µL) and hypercellular bone marrow.

Answer 91

Increased proliferation of mature myeloid cells, especially granulocytes. Affects adults between 25 and 60 years of age.

Answer 92

t(9,22) balanced translocation, resulting in the Philadelphia chromosome.

Answer 93

Basophilia Low leukocyte alkaline phosphatase (LAP) Presence of t(9,22) translocation (Philadelphia chromosome)

Answer 94

Imatinib, which blocks tyrosine kinase activity.

Answer 95

Increased proliferation of mature myeloid cells, especially erythrocytes.

Answer 96

Mutation in JAK2, a tyrosine kinase, leading to hypersensitivity of cells to erythropoietin (EPO).

Answer 97

Increased RBC mass → increased blood viscosity → stasis → blurry vision, flushed face, thrombosis (e.g., Budd-Chiari syndrome) Serum EPO levels decreased Itching after bathing (due to high number of basophils)

Answer 98

Phlebotomy. Without treatment, death typically occurs within a year.

Answer 99

Increased proliferation of mature myeloid cells, especially megakaryocytes.

Answer 100

Mutation in JAK2, a tyrosine kinase, leading to overproduction of PDGF by megakaryocytes, which stimulates fibroblasts to deposit collagen, causing marrow fibrosis.

Answer 101

Hepatosplenomegaly (due to extramedullary hematopoiesis) Leucoerythroblastic smear (presence of immature cells in circulation) Fatigue, infections, thrombosis (due to insufficient cell production) Tear-drop cells (RBCs squeezed out of fibrosed marrow)

Answer 102

Increased proliferation of mature myeloid cells, especially platelets.

Answer 103

Mutation in JAK2, a tyrosine kinase, leading to abnormal platelet production, causing bleeding or thrombosis.

Answer 104

Usually asymptomatic. No significant risk for hyperuricemia or gout.

Answer 105

Acute Leukemia: Rapid increase in immature blood cells (blasts >20%), suppressing normal hematopoiesis and decreasing WBCs, RBCs, and platelets. Chronic Leukemia: Slow progression with excessive buildup of relatively mature, but abnormal leukocytes.

Answer 106

Lympho/myeloBLASTIC cells (bigger, less cytoplasm, less condensed chromatin) High rate of proliferation Less differentiation Pre-B cell neoplasms occur in the bone marrow, pre-T cell neoplasms in the thymus Occurs mainly in children/young adults Rapid progression (death after 6-12 months if untreated)

Answer 107

AML usually affects adults over 50 years old. Characterized by the accumulation of myeloid lineage cells at earlier stages of development.

Answer 108

Lineage is determined by cell markers and other characteristics. AML is identified by myeloid markers, while ALL is identified by lymphoid markers.

Answer 109

Acquired mutations in transcription factors inhibit normal myeloid differentiation, leading to the accumulation of immature cells. Examples include: Acute promyelocytic leukemia (t(15,17) causing PML/RARα fusion protein, blocking differentiation) Transformation from CML or other dysplastic syndromes to AML

Answer 110

t(15,17) translocation leading to PML/RARα fusion protein Promyelocytic cells contain Auer rods, increasing coagulation risk (DIC) Treatment: ATRA (vitamin A derivative) promotes maturation into neutrophils; combination with arsenic trioxide is more effective.

Answer 111

Surface markers: CD 13, 14, 15 Cell types: Erythroblast AML Megakaryoblast AML (no myeloperoxidase, associated with Down syndrome under age 5) Monoblast AML (acute monocytic leukemia, no myeloperoxidase, infiltrated gums)

Answer 112

Bone marrow is replaced by clonal progeny of mutant multipotent stem cells that differentiate into defective RBCs, granulocytes, or platelets. These syndromes are genetically unstable, often transforming into AML.

Answer 113

Defective megaloblastoid erythroid precursors Transformation into AML in 10%-40% of cases Karyotype abnormalities include loss of chromosome 5 or 7, deletion of their long arm, and trisomy 8 Poor response to chemotherapy

Answer 114

The most common form of nutritional deficiency anemia, characterized by a decrease in total body iron content.

Answer 115

Women: 2.5g, Men: 3.5g 80% in hemoglobin 20% in myoglobin and iron-containing enzymes Iron storage pool in hemosiderin and ferritin-bound iron (liver, spleen, bone marrow, skeletal muscle)

Answer 116

Iron is absorbed in the duodenum. Hepcidin, synthesized in the liver, regulates iron transfer between transferrin receptor and ferritin expression by inducing internalization of ferroportin.

Answer 117

Low dietary intake (vegetarians) Malabsorption (e.g., celiac disease) Increased demands (pregnancy, infancy) Chronic blood loss (GI tract ulcers, colonic cancer, female genital tract issues like menorrhagia)

Answer 118

RBCs are microcytic and hypochromic (low MCV, low MCHC) Increased platelet count Elevated erythropoietin levels due to hypoxia, but bone marrow cannot meet RBC production demands

Answer 119

Mostly asymptomatic but may include weakness, pallor, and pica (consumption of non-food items like dirt or clay).

Answer 120

Anemia with microcytic and hypochromic RBCs, low serum ferritin, low serum iron, low transferrin saturation, and a good response to iron treatment.

Answer 121

Anemia resulting from inflammation-induced depletion of iron, commonly due to chronic infections, immune disorders, or neoplasms.

Answer 122

Low serum iron level RBCs are either normocytic and normochromic, or microcytic and hypochromic Increased iron storage in bone marrow, high serum ferritin level, reduced iron-binding capacity

Answer 123

High level of hepcidin due to cytokines produced during inflammation (e.g., IL-6).

Answer 124

Caused by deficiencies in folate or vitamin B12, both required for DNA synthesis, leading to enlarged erythroid precursors (megaloblasts) and abnormal RBCs (macrocytes).

Answer 125

Impaired DNA synthesis causes cell division delay, while RNA and cytoplasmic synthesis proceed normally, resulting in nuclear-cytoplasmic asynchrony.

Answer 126

: Hypercellular bone marrow, nuclear-cytoplasmic asynchrony of megaloblasts and granulocyte precursors. In peripheral blood: hyper-segmented neutrophils and macrocytes.

Answer 127

Poor diet or increased metabolic need (e.g., pregnancy) Absorption blocked by drugs (e.g., Phenytoin) or malabsorptive disorders (e.g., Celiac disease) Metabolism blocked by drugs (e.g., Methotrexate)

Answer 128

Same as vitamin B12 deficiency but without neurological abnormalities.

Answer 129

Same as folate deficiency but also includes demyelinating disorders of peripheral nerves and spinal cord.

Answer 130

Absorbed through intrinsic factor (produced by parietal cells in the fundus mucosa) in the ileum, and delivered to the liver by transcobalamins.

Answer 131

Malabsorption due to gastric mucosal atrophy Autoimmune reaction against parietal cells or intrinsic factor Malabsorption in the distal ileum (e.g., Crohn's disease, Whipple disease)

Answer 132

A disorder where multipotent myeloid stem cells are suppressed, leading to marrow failure and pancytopenia. Most cases are idiopathic or caused by exposure to myelotoxic agents.

Answer 133

Autoreactive T cells attack the bone marrow. The trigger for the T cell attack is unclear, but may involve inherited defects in telomerase.

Answer 134

Bone marrow is hypocellular, with more than 90% of inter-trabecular spaces occupied by fat.

Answer 135

Affects all ages and sexes. Causes slow-progressing anemia with weakness, pallor, dyspnea, thrombocytopenia, and granulocytopenia. No splenomegaly.

Answer 136

Reduction of oxygen transport capacity of the blood due to a decrease in RBC number or hemoglobin concentration. Causes include bleeding, increased destruction, decreased production, or reduced hemoglobin concentration.

Answer 137

Decreased tissue oxygen tension triggers increased production of erythropoietin from kidney cells, leading to compensatory hyperplasia of erythroid precursors in the bone marrow and extramedullary hematopoiesis in severe cases.

Answer 138

Microcytic (iron deficiency, thalassemia) Macrocytic (folate/B12 deficiency) Normocytic with abnormal shape (hereditary spherocytosis, sickle cell) By color (normo/hypo/hyper-chromic)

Answer 139

Iron levels (iron deficiency anemia, chronic disease anemia, thalassemia) Plasma unconjugated bilirubin, LDH, haptoglobin (hemolytic anemias) Folate/B12 levels (megaloblastic anemias) Hemoglobin electrophoresis Coombs test (immunohemolytic anemia) Bone marrow examination (in case of associated thrombocytopenia/granulocytopenia)

Answer 140

Determined by severity, rapidity of onset, and underlying mechanism. Common symptoms include pallor, fatigue, and dyspnea. Severe anemia can lead to myocardial hypoxia, angina, CNS hypoxia, and systemic complications.

Answer 141

Acute: >20% blood volume loss, immediate threat of hypovolemic shock, normocytic and normochromic RBCs, elevated erythropoietin, leukocytosis. Chronic: Anemia when loss exceeds marrow regenerative capacity or iron depletion, leading to microcytic and hypochromic RBCs.

Answer 142

Characterized by accelerated RBC destruction, increased erythropoiesis (reticulocytosis), and retention of RBC destruction products (iron - hemosiderosis). Can be due to intra-corpuscular (inherited) or extra-corpuscular (acquired) defects.

Answer 143

Intravascular: Occurs within vascular compartments, caused by mechanical trauma, biochemical/physical agents, leading to hemoglobinemia, hemoglobinuria, hemosiderinuria. Extravascular: Occurs within phagocytic cells (spleen/liver), more common, leads to systemic hemosiderosis, jaundice, and splenomegaly.

Answer 144

Includes hereditary membrane defects (spherocytosis), hemoglobin synthesis defects (sickle cell anemia, thalassemias), and enzyme deficiencies (G6PD deficiency).

Answer 145

Includes immunohemolytic anemias (warm/cold antibody), erythroblastosis fetalis, mechanical trauma to RBCs, and infections (malaria).

Answer 146

Low dietary intake (especially in vegetarians) Malabsorption (e.g., celiac disease) Increased demands (e.g., pregnancy, infancy) Chronic blood loss (e.g., GI tract ulcers, colonic cancer, menorrhagia)

Answer 147

RBCs are microcytic and hypochromic (low MCV, low MCHC). Increased platelet count, elevated erythropoietin levels, but bone marrow cannot meet RBC production demands.

Answer 148

Low serum iron level, RBCs either normocytic/normochromic or microcytic/hypochromic. Increased iron storage in bone marrow, high serum ferritin, reduced iron-binding capacity. Caused by high levels of hepcidin from cytokines during inflammation.

Answer 149

Caused by deficiencies in folate or vitamin B12, necessary for DNA synthesis. Leads to enlargement of erythroid precursors (megaloblasts) and abnormal RBCs (macrocytes).

Answer 150

Disorder where multipotent myeloid stem cells are suppressed, leading to marrow failure and pancytopenia. Most cases are idiopathic or caused by exposure to myelotoxic agents.

Answer 151

Autoreactive T cells attack the bone marrow, trigger unclear. Bone marrow is hypocellular with over 90% inter-trabecular spaces occupied by fat.

Answer 152

Affects all ages and sexes, causes slow-progressing anemia with weakness, pallor, dyspnea, thrombocytopenia, and granulocytopenia. No splenomegaly.

Answer 153

The most common vasculitis, affecting individuals >50 years, more common in females. Primarily affects arteries of the head, especially temporal arteries.

Answer 154

Headache: Especially in the temporal arteries. Visual disturbances: When ophthalmic artery is affected. Jaw pain: Claudication in maxillary arteries.

Answer 155

Immunologic mechanisms: Antibodies against endothelial cells. Cell-mediated (autoreactive T cells).

Answer 156

Elevated ESR (erythrocyte sedimentation rate). Biopsy: Presence of giant cells (granulomas) in the internal elastic lamina.

Answer 157

Segmental nature of the disease. Requires at least a 2- to 3-cm length of artery for adequate biopsy. Negative biopsy does not exclude the diagnosis

Answer 158

Corticosteroids to treat inflammation.

Answer 159

Mostly seen in Asian women <40. Affects the aorta and its branches, especially those from the aortic arch (elastic arteries).

Answer 160

Weak or absent pulse in upper extremities due to affected branches. Visual and neurological symptoms due to affected branches serving the head. Corneal ostial stenosis. Aortic stenosis

Answer 161

Similar clinical features to giant cell arteritis, except for segmentation. Treatment is the same as giant cell arteritis (corticosteroids).

Answer 162

Caused by direct invasion of an infectious agent, primarily bacteria (e.g., Aspergillus and Mucor spp.) which release exotoxins.

Answer 163

Caused by bacteria-induced inflammation, damaging endothelial cells through harmful cytokines. Example: Molecular mimicry in streptococcus causing endocarditis and vasculitis.

Answer 164

Affects children <5 years old. Primarily affects coronary arteries (transmural inflammation), which can lead to myocardial infarction.

Answer 165

Conjunctivitis Rash Adenopathy (enlarged lymph nodes) Strawberry tongue Hands and feet are swollen with rash

Answer 166

Primarily affects young adults. Targets multiple visceral arteries (mainly renal, not pulmonary). Segmental appearance (beads on angiogram).

Answer 167

Molecular mimicry: Endothelium confused with HBV (Hepatitis B Virus). Causes transmural inflammation (affects tunica intima, media, and adventitia). Frequently accompanied by fibrinoid necrosis. Not associated with ANCA (antineutrophil cytoplasmic antibodies).

Answer 168

Corticosteroids to treat inflammation.

Answer 169

Affects men 20-40 years old, often associated with tobacco use. Causes blood clots in small arteries, especially in the fingers and toes (mainly tibial and radial arteries).

Answer 170

Leads to dead tissue and possible autoamputation. Spreads to adjacent veins and nerves. Segmental nature of the disease.

Answer 171

Affect arterioles, capillaries, and venules. B cells produce antibodies ANCA (anti-neutrophilic cytoplasmic antibodies, mainly IgG) against granules made by self-neutrophils.

Answer 172

Affects middle-aged males. Involves vessels in the nasopharynx, lungs, and kidneys. Associated with cANCA (cytoplasmic ANCA) which targets proteinase 3 in neutrophils.

Answer 173

Sinusitis leading to chronic pain. Ulcers causing bloody mucous. Saddle nose deformity. Can spread to the ear causing otitis media.

Answer 174

Lungs: Difficulty breathing, ulcers causing bloody cough. Kidneys: Glomeruli damage leading to decreased urine production and increased blood pressure.

Answer 175

Treatment: Corticosteroids and cyclophosphamide (immunosuppressor). If untreated, death within one year. Disease characterized by relapses.

Answer 176

Similar to Wegener’s Granulomatosis but only affects blood vessels of lungs and kidneys. Not associated with nasopharynx involvement. No granulomas present. Characterized by pANCA (perinuclear ANCA) which targets myeloperoxidase.

Answer 177

Symptoms: Lung and kidney damage. Treatment: Corticosteroids and cyclophosphamide. Disease characterized by relapses.

Answer 178

Associated with pANCA. Involves symptoms similar to Wegener’s but also affects GI, skin, nerves, and heart. Granulomas can form. Increased eosinophils, often mistaken for an allergy.

Answer 179

Symptoms: Sinusitis, lung damage, kidney damage, GI issues, skin rashes, nerve damage, and heart problems. Presence of granulomas and high eosinophil count.

Answer 180

Inflammation of vessel walls of virtually any type of vessel.

Answer 181

Immunologic Mechanisms: Immune Complex Deposition: Type III hypersensitivity; e.g., SLE. ANCA Mediated: cANCA: Target proteinase 3. pANCA: Target myeloperoxidase. Antibodies Against Endothelial Cells. Cell-Mediated: Autoreactive T cells. Infectious Mechanisms: Direct invasion by infectious pathogens (e.g., varicella zoster virus, some fungi). Physical / Chemical Injuries.

Answer 182

Distinguishing between etiologies is crucial for treatment. Corticosteroids useful for immunologic causes but harmful for infectious causes.

Answer 183

Weakening of Blood Vessels: Leads to aneurysm and rupture of small vessels → microhemorrhage (purpura). Exposure of Underlying Collagen and TF: Triggers coagulation. Healing Process: Fibrin deposition → vessel stiffness. Reduced lumen diameter → organ ischemia.

Answer 184

Severe inflammation activates many inflammatory cells. High cytokine levels affect the hypothalamus → fever, fatigue, and weight loss. Cytokines affect hepatocytes → CRP production → sticky RBCs → increased ESR.

Answer 185

Most common vasculitis, affects people >50 years, more common in females. Affects arteries of the head, especially temporal arteries. Symptoms: Headache, visual disturbances, jaw pain (claudication). Immunologic mechanisms: Antibodies against endothelial cells, cell-mediated (autoreactive T cells). Clinical features: ↑↑ESR, biopsy shows giant cells in internal elastic lamina. Treatment: Corticosteroids.

Answer 186

Large Vessel Vasculitides. Medium Vessel Vasculitides. Small Vessel Vasculitides.

Answer 187

Mostly seen in Asian women <40. Affects the aorta and its branches. Symptoms: Weak pulse in upper extremities, visual/neurological symptoms, aortic stenosis. Treatment: Same as giant cell arteritis.

Answer 188

Affects children <5 years old. Primarily affects coronary arteries, may lead to MI. Symptoms: Conjunctivitis, rash, adenopathy, strawberry tongue, swollen hands/feet.

Answer 189

Primarily affects young adults. Involves multiple visceral arteries, mainly renal (not pulmonary). Cause: Molecular mimicry with HBV. Segmental appearance, causes transmural inflammation. Treatment: Corticosteroids.

Answer 190

Affects men 20-40 years old, associated with tobacco use. Causes blood clots in tiny arteries, mainly in fingers/toes → tissue death → autoamputation. Segmental spread to adjacent veins and nerves.

Answer 191

Affects middle-aged males. Involves vessels in the nasopharynx, lungs, and kidneys. Symptoms: Sinusitis, bloody mucous, saddle nose deformity, otitis media, difficulty breathing, bloody cough, glomeruli damage. Associated with cANCA targeting proteinase 3. Treatment: Corticosteroids and cyclophosphamide.

Answer 192

Similar to Wegener’s but affects only lungs and kidneys. No granulomas present. Associated with pANCA targeting myeloperoxidase. Treatment: Corticosteroids and cyclophosphamide.

Answer 193

Associated with pANCA. Symptoms: Sinusitis, lung and kidney damage, GI, skin, nerve, and heart damage. Presence of granulomas, increased eosinophils.

Answer 194

Disordered, non-neoplastic cellular growth. Often arises from longstanding pathologic hyperplasia (e.g., endometrial hyperplasia) or metaplasia (e.g., Barrett esophagus). Dysplasia is reversible with alleviation of inciting stress; if stress persists, it progresses to carcinoma (irreversible). Term used when cellular abnormality is restricted to the originating tissue.

Answer 195

Increased population of immature cells restricted to the mucosal surface, not invading deeper tissues. If dysplastic cells span the entire thickness of the epithelium, it is referred to as carcinoma in situ. Myelodysplastic syndromes show increased immature cells in bone marrow and decreased mature, functional cells in blood.

Answer 196

Epithelial Dysplasia of the Cervix: Increased immature cells in the mucosal surface without invasion through the basement membrane. Myelodysplastic Syndromes: Increased immature blood-forming cells in bone marrow, decreased mature cells in blood.

Answer 197

Abnormalities with increased risk of developing into cancer. Early removal may prevent cancer development. Genetically and phenotypically altered cells with higher risk to develop into malignant tumors. Arise in settings of chronic tissue injury or inflammation

Answer 198

Chronic tissue injury or inflammation increases likelihood of malignancy. Stimulating regenerative proliferation or exposing cells to byproducts of inflammation leads to somatic mutations.

Answer 199

Squamous Metaplasia and Dysplasia of Bronchial Mucosa: Seen in habitual smokers, risk factor for lung cancer. Endometrial Hyperplasia and Dysplasia: Seen in women with unopposed estrogenic stimulation, risk factor for endometrial carcinoma. Leukoplakia of Oral Cavity, Vulva, or Penis: May progress to squamous cell carcinoma. Villous Adenomas of the Colon: Associated with a high risk of transformation to colorectal carcinoma.

Answer 200

Dysplasia is reversible with alleviation of stress. If stress persists, dysplasia progresses to carcinoma, which is irreversible. Early intervention in precancerous lesions can prevent progression to cancer.

Answer 201

Location and Impingement on Adjacent Structures: Small tumor in the pituitary gland may compress and destroy the gland (hypopituitarism). Leiomyoma in the renal artery may lead to ischemia and hypertension. Functional Activity (e.g., hormone synthesis/paraneoplastic syndrome): Neoplasms of endocrine glands. Adenoma/carcinoma in beta cells of the pancreatic islets of Langerhans can cause hyperinsulinism. Adenoma/carcinoma of adrenal cortex can affect aldosterone secretion (Na retention), hypertension, hypokalemia. Ulceration: Tumors may cause ulceration through a surface, leading to bleeding and infection. Cancer Cachexia: Loss of body fat, wasting, profound weakness. Rupture/Infarction

Answer 202

Definition: Symptoms not directly related to tumor spread or hormone hypersecretion by the tumor (ectopic secretions). Importance: May represent early manifestations of neoplasm. Can cause significant clinical problems, potentially lethal. May mimic metastatic disease, confounding treatment. Examples: Cushing Syndrome: Cortisol → ACTH → Small cell lung/pancreatic carcinoma. Hypercalcemia: PTH → Squamous cell carcinoma of lung/breast cancer. Hyponatremia: ADH → Small cell lung carcinoma. Dehydration and Diarrhea: VIP → GI tumor. Non-bacterial Thrombotic Endocarditis.

Answer 203

Mechanism: Increased cortisol production. ACTH secretion by tumor cells. Associated Cancers: Small cell lung carcinoma. Pancreatic carcinoma. Symptoms: Hypercalcemia. Hypertension. Obesity. Moon facies.

Answer 204

Characteristics: Progressive loss of body fat and skeletal muscle mass. Profound weakness and anemia. Incidence: Occurs in 50% of cancer patients. Accounts for 20% of cancer deaths. Cause: Action of cytokines produced by the tumor, not by nutritional demands of the tumor. Mechanisms: High calorie expenditure and basal metabolic rate (BMR) despite reduced food intake. Suspected mediators: TNF (cachectin), IL-1. TNF inhibits neuropeptide Y (NPY) → no signal to feeding center in hypothalamus. TNF inhibits lipoprotein lipase → no release of free fatty acids (FFAs) from lipoproteins. Mobilizing factor: Proteolysis-inducing factor causing skeletal muscle protein breakdown.

Answer 205

Causes: Bone marrow suppression by tumor factors (e.g., leukemia, monoclonal expansion of antibodies). Toxicity of chemotherapy. Irradiation of bone marrow. Malnutrition and anorexia.

Answer 206

Rate of Growth: How quickly the tumor grows. Invasiveness: Whether the tumor invades nearby tissues. Presence or Lack of Metastasis: Whether the tumor spreads to other parts of the body. Clinical Features: Symptoms and signs presented by the tumor.

Answer 207

Excision or Biopsy: Removal of the tumor with margin or a large mass of the tumor for histopathological examination. Frozen Section: Sample is quick-frozen and sectioned for immediate histologic evaluation. Fine-Needle Aspiration: Aspiration of cells from a palpable mass (e.g., breast, thyroid) for cytologic examination. Cytologic Smears: Evaluation of cells shed into fluids or secretions for anaplastic features.

Answer 208

Keratin +: Indicates epithelial cells. Vimentin +: Indicates mesenchymal cells. Desmin +: Indicates muscle cells. PSA +: Indicates prostate origin. ER +: Indicates breast tissue origin. Technique: Detection of characteristic proteins by specific monoclonal antibodies labeled with peroxidase.

Answer 209

Use: Classification of leukemias and lymphomas. Method: Antibodies against cell surface molecules and differentiation markers labeled with fluorescence dye. Purpose: To obtain the phenotype of malignant cells.

Answer 210

Full Name: Prostate Specific Antigen. Use: Screening for prostatic adenocarcinoma.

Answer 211

Full Name: Carcino-Embryonic Antigen. Associated Cancers: Colon, pancreas, breast, and stomach cancers.

Answer 212

Full Name: Alpha-Fetoprotein. Produced By: Hepatocellular carcinoma, yolk sac remnants in gonads. Elevated In: Cancers of testes, ovary, pancreas, and stomach.

Answer 213

Purpose: Contribute to determination of therapy effectiveness or recurrence monitoring. Limitations: Low sensitivity and specificity, produced in non-neoplastic conditions, not definitive for cancer diagnosis. Requirement: A biopsy is always needed for definitive diagnosis.

Answer 214

Pleomorphism: Assessing variation in size and shape of cells to determine if the tumor is benign or malignant. Histopathological Examination: Microscopic analysis of tumor tissue. Immunocytochemistry: Staining cells to detect specific antigens using monoclonal antibodies.

Answer 215

Definition: The process by which normal cells are transformed into cancer cells. Key Process: Tumors arise from the monoclonal growth of a progenitor cell with non-lethal mutations.

Answer 216

Growth-promoting Proto-oncogenes Mutation in one allele is sufficient. Growth-inhibiting Tumor Suppressor Genes Both alleles must be mutated to lose cell function. Genes that Regulate Apoptosis Genes Involved in DNA Repair

Answer 217

Definition: Tumor progression results from mutations that accumulate independently in different cells. Outcome: Generates sub-clones with different characteristics and greater malignant potential.

Answer 218

Monoclonal Origin: Tumors start from a single progenitor cell. Heterogeneity: Tumors become heterogeneous over time due to continuous multiple mutations. Sub-clone Survival: Sub-clones with different characteristics emerge, with some becoming adept at survival, growth, invasion, and metastasis.

Answer 219

Origin: Malignant tumors start from a single cell but become heterogeneous by the time they are clinically evident. Process: Continuous mutations in different cells generate new sub-clones. Host Defense Interaction: Sub-clones are subjected to immune and non-immune defenses; some are destroyed, while others survive and thrive.

Answer 220

Selection Pressure: Host defenses create a selection pressure. Adaptation: Sub-clones that survive become "experts" in survival, growth, invasion, and metastasis.

Answer 221

1. Autosomal Dominant Mutation in protooncogenes transforming into oncogenes. One-hit Hypothesis: Mutation in one allele is sufficient for malignant transformation. Example: Retinoblastoma (can be sporadic or familial). 2. Autosomal Recessive Syndromes Mutation of tumor suppressor genes or DNA repair genes. Two-hit Hypothesis: Both alleles must be mutated for malignant transformation. Example: Xeroderma pigmentosum. 3. Familial Cancers of Uncertain Inheritance Occur more often in family members than expected by chance. Transmission pattern is unclear. Examples: Carcinomas of colon, breast, ovary, and brain.

Answer 222

Mechanism: Mutation in protooncogenes transforming into oncogenes. One-hit Hypothesis: A mutation in one allele is enough for malignant transformation. Example: Retinoblastoma (can be sporadic or familial).

Answer 223

Type: Cancer of the retina. Forms: Sporadic (60%) or Familial (40%). Familial Retinoblastoma: Genetics: Autosomal recessive RB gene, but presents clinically as autosomal dominant. Characteristics: Bilateral tumors, younger age onset, high risk of secondary cancers (e.g., osteosarcoma).

Answer 224

Mechanism: Mutation of tumor suppressor genes or DNA repair genes. Two-hit Hypothesis: Both alleles must be mutated for malignant transformation. Example: Xeroderma pigmentosum.

Answer 225

Characteristics: Occur more often in family members than by chance. Transmission: Pattern is not clear. Examples: Carcinomas of colon, breast, ovary, and brain.

Answer 226

Preneoplastic Conditions: Conditions that predispose to malignant neoplasms. Examples: Liver cirrhosis → Hepatocellular carcinomas Smoking → Squamous metaplasia and dysplasia of the bronchial mucosa → Lung cancer Unopposed estrogenic stimulation → Endometrial hyperplasia and dysplasia → Endometrial carcinoma Leukoplakia of the oral cavity, vulva, or penis → Squamous cell carcinoma Benign Tumors: Usually not precancerous, but exceptions like adenomas of the colon can undergo malignant transformation in 50% of cases.

Answer 227

Prevalence: Mutation present in 50% of cancers. Role: Tumor suppressor gene involved in regulating cell cycle and apoptosis.

Answer 228

Loosening (Dissociation) of Cells: Cells detach from neighbors by downregulation of E-cadherins.

Answer 229

2. Attachment to Laminin: Tumor cells attach to laminin in the basement membrane (BM).

Answer 230

. Destruction of Basement Membrane: Tumor cells destroy BM by producing type IV collagenase or inducing stromal cells like fibroblasts to produce proteases.

Answer 231

4. Attachment to Fibronectin: Tumor cells attach to fibronectin in the extracellular matrix (ECM).

Answer 232

. Locomotion: Tumor cells propel themselves through degraded BM and zones of matrix proteolysis.

Answer 233

6. Vascular Dissemination and Homing of Tumor Cells: Tumor cells circulate as single cells or form emboli with WBCs for protection. Extravasation involves adhesion to vascular endothelium and egress through BM into organ parenchyma.

Answer 234

Predicted by Location: Primary tumor's location and vascular/lymphatic drainage. Specific Distal Tissues: Tumors like lung cancer may involve adrenals. Factors: Adhesion molecules specific to endothelia of target cells. Chemokines and receptors (e.g., CXCR4/7 in breast cancer). Nonresponsive environments (e.g., skeletal muscle).

Answer 235

Carcinomas: Spread via lymphatics to regional lymph nodes. Sarcomas: Spread through blood (lungs characteristic site). Exceptions: Renal cell carcinoma: Renal vein. Hepatocellular carcinoma: Hepatic vein. Follicular carcinoma of the thyroid. Choriocarcinoma. Ovarian carcinoma: Spreads via body cavities, usually omentum.

Answer 236

Tumor Growth: Individual cells accumulate mutations, creating subclones. Metastatic Signature: Intrinsic property developed during carcinogenesis, requiring additional mutations for metastasis. Metastasis Oncogenes: SNAIL and TWIST promote epithelial-to-mesenchymal transition (EMT). Downregulate epithelial markers (e.g., E-cadherin). Upregulate mesenchymal markers (e.g., smooth muscle actin).

Answer 237

Purpose: Based on size of primary lesion, spread to regional lymph nodes, and presence/absence of bloodborne metastases. TNM System: T (Primary Tumor): T1 to T4 (increasing size), T0 (in-situ lesion). N (Regional Lymph Node Involvement): N0 (no nodal involvement), N1 to N3 (increasing number/range of nodes). M (Metastases): M0 (no distant metastases), M1 or M2 (presence and extent of metastases).

Answer 238

Definition: Translocation of neoplastic cells across tissue barriers within the same organ or to adjacent tissues. Steps: Loosening of cells (downregulation of E-cadherins). Attachment to laminin in the basement membrane (BM). Destruction of BM by type IV collagenase or proteases from stromal cells. Attachment to fibronectin in the extracellular matrix (ECM). Locomotion through degraded BM and zones of matrix proteolysis.

Answer 239

Functions: Blood Supply: Crucial for tumor growth. Consistency: Determines the neoplasm's consistency; desmoplasia in certain cancers. Encapsulation: In benign tumors, stroma can encapsulate the tumor.

Answer 240

Definition: Development of new blood vessels from existing vessels, primarily venules. Processes: Vasculogenesis: Formation of primitive vascular system from angioblasts (embryonic development). Angiogenesis: New vessel development from existing vessels. Steps: Vasodilation and Permeability: Induced by NO and VEGF. Tip Cell Selection: Cells bind VEGF, form filopodia, secrete proteolytic enzymes to break BM. Migration of Tip Cells: Toward angiogenic center, proliferation of stalk cells. Tubulogenesis: Remodeling into capillary tubes. Fusion: Two stalks fuse. Suppression of Proliferation and Migration: BM deposition. Recruitment of Peri-endothelial Cells: Pericytes (small capillaries) and fibroblasts (larger vessels).

Answer 241

Factors: Angiopoietins 1 & 2, PDGF, TGFβ: Stabilize new vessels, recruit pericytes and smooth muscle cells, deposit connective tissue. FGF2: Stimulates endothelial cell proliferation, promotes macrophage and fibroblast migration, stimulates epithelial cell migration for wound coverage.

Answer 242

Perfusion: Supplies nutrients and oxygen. Growth Stimulation: New endothelial cells secrete growth factors like IGFs and PDGF, stimulating adjacent tumor cells.

Answer 243

Leaky Vessels: Due to incompletely formed inter-endothelial junctions and presence of VEGF. Consequence: Permits tumor cells to metastasize.

Answer 244

G1 Phase: Presynthetic growth phase 1 – high rate of biosynthetic activities, mainly production of proteins necessary for DNA replication. S Phase: DNA synthesis phase – replication of DNA, forming two sister chromatids for each chromosome. G2 Phase: Premitotic growth phase 2 – continuation of protein production needed for division. M Phase: Mitosis – nuclear division (karyokinesis) and cytoplasm division (cytokinesis).

Answer 245

Prophase: Chromatin condenses into chromosomes, centrosomes and microtubules appear. Metaphase: Nuclear membrane disintegrates, chromosomes align along the equatorial plane. Anaphase: Sister chromatids are separated and pulled apart. Telophase: Formation of nuclear membrane, chromosomes decondense to form chromatin.

Answer 246

Checkpoints: Prevent replication of damaged DNA or mitosis of abnormal cells. Cyclins and CDKs: Proteins that regulate the transition between cell cycle stages. CDIs: Inhibit CDKs, controlling the cell cycle

Answer 247

Carcinogenesis: Transformation of normal cells into cancer cells due to mutations in: Growth-promoting proto-oncogenes. Growth-inhibiting tumor suppressor genes. Genes regulating apoptosis. Genes involved in DNA repair.

Answer 248

Function: Essential for cell growth and differentiation. Mutation: Gain of function mutation transforms protooncogenes into oncogenes, leading to unregulated cell growth. Examples: PDGF: Brain tumors like astrocytoma. HER2/NEU: Breast cancer. RAS: Signal transducer, mutation leads to excess signaling. ABL: Unregulated tyrosine kinase activity. MYC: Increased cell proliferation. Cyclin D1: Increased cell proliferation.

Answer 249

Function: Dampen cell cycle and promote apoptosis. Mutation: Loss of function leads to unregulated cell growth. Examples: RB: Inhibits E2F transcription factor, preventing transcription of cyclin E. P53: Arrests cell cycle, repair mechanisms, induces apoptosis. TGFβ: Inhibits proliferation by activating growth-inhibiting genes.

Answer 250

Normal Cells: Telomerase not expressed, telomeres shorten, activating cell cycle checkpoints. Cancer Cells: Telomerase adds DNA sequences to telomeres, preventing apoptosis.

Answer 251

Tumors: Require blood supply, trigger formation of new blood vessels from existing ones. Mechanism: Hypoxia activates HIF1α, leading to transcription of VEGF and angiogenesis.

Answer 252

Dividing Cells: Continuously proliferate (e.g., hematopoietic cells, surface epithelia). Quiescent Cells: In G0 state, can enter cell cycle in response to stimulus (e.g., parenchymal cells). Non-dividing Cells: Cannot undergo division post-natally (e.g., neurons, skeletal and cardiac muscle).

Answer 253

Definition: The extent to which parenchymal cells resemble their normal cells of origin, both morphologically and functionally. Importance: Differentiation is crucial for identifying the tumor type but stroma, although vital for blood supply, does not determine benign or malignant status. Consistency: Amount of stromal tissue affects the tumor's consistency (desmoplasia leads to hard tumors).

Answer 254

Characteristics: Well-differentiated cells that closely resemble normal tissue. Examples: Lipoma (mature fat cells), Chondroma (mature chondrocytes). Low mitotic figures in normal configuration.

Answer 255

Characteristics: Wide range of parenchymal differentiation, from well-defined to completely undifferentiated cells. Often resemble primitive, undesignated cells. More rapidly growing and less likely to retain specialized functional activity.

Answer 256

Definition: Lack of differentiation in cells, characteristic of malignant tumors. Implications: Loss of structural and functional differentiation of normal cells. Features: Pleomorphism, high nucleus/cytoplasm ratio, hyperchromatic nuclei, clumped chromatin, atypical mitotic figures, loss of normal cell polarity, large nucleoli.

Answer 257

Definition: Variation in size and shape of cells within a tumor. Characteristics in Anaplastic Cells: Nucleus/cytoplasm ratio approaches 1:1. Large, hyperchromatic nuclei. Rough, clumped chromatin. Numerous and atypical mitotic figures. Loss of normal cell polarity. Large nucleoli.

Answer 258

Definition: Disorderly but non-neoplastic proliferation; loss of uniformity and architectural orientation. Features: Displays pleomorphism. Carcinoma in situ: When dysplastic changes involve the entire thickness of the epithelium.

Answer 259

Purpose: Estimates the aggressiveness or level of malignancy based on cytologic differentiation and mitotic rate. Grades: I: Well-differentiated (low grade, benign). II: Moderately differentiated (intermediate grade). III: Poorly differentiated (high grade). IV: Undifferentiated (high grade, malignant). Grading Systems: Gleason system: Prostate cancer. Bloom-Richardson system: Breast cancer. Fuhrman system: Kidney cancer.

Answer 260

Characteristics: Low mitotic rate, less aggressive. Less mitotic figures, reduced metastatic capability. Well differentiated, minimal pleomorphism. Prognosis: More difficult to treat (chemotherapy less effective), usually non-curable, less favorable.

Answer 261

Characteristics: High mitotic rate, many mitotic figures. Little differentiation, increased pleomorphism. Very aggressive, spreads fast. Prognosis: Easier to treat (dividing cells more easily destroyed), faster treatment results, more favorable, potentially curable.

Answer 262

Mesenchymal Origin: Suffix "-oma" added to the cell type from which the tumor arises. Examples: Fibroma: Tumor of fibroblasts. Chondroma: Tumor of chondroblasts. Osteoma: Tumor of osteoblasts. Epithelial Origin: Based on histogenesis and architecture. Examples: Adenoma: Glandular origin, may have glandular structure. Papilloma: Microscopic finger-like projections. Cystadenoma: Cystic structure. Polyp: Macroscopic finger-like projections into a lumen.

Answer 263

Mesenchymal Origin: Suffix "-sarcoma". Examples: Fibrosarcoma: Malignant tumor of fibroblasts. Chondrosarcoma: Malignant tumor of chondroblasts. Leukemia/Lymphoma: Malignant neoplasms of blood mesenchymal cells. Epithelial Origin: Suffix "-carcinoma". Examples: Adenocarcinoma: Cancer of glandular epithelium. Squamous Cell Carcinoma: Cancer of squamous epithelium.

Answer 264

Mixed Tumors: Derived from one germ-cell layer differentiating into more than one cell type. Examples: Pleomorphic Adenoma: Salivary gland tumor with epithelial and stromal/cartilage-like tissue. Fibroadenoma: Mixed tumor of the female breast. Teratoma: Special mixed tumor derived from totipotent germ cells with potential to differentiate into any cell type. Choristoma: Congenital anomaly with functional cells in the wrong place (e.g., pancreatic tissue in stomach submucosa). Hamartoma: Disorganized masses of mature tissue characteristic of the normal surrounding tissue (e.g., disorganized hepatic cells, blood vessels, and bile ducts in the liver).

Answer 265

Defects affecting the structure and/or function of organs, present at birth.

Answer 266

Primary errors of morphogenesis due to multifactorial gene defects. Can result in abnormally formed, partially formed, or absent structures (agenesis). Example: Neural tube defects, atresia of the esophagus.

Answer 267

Change in the normal shape or size of normally forming structures, usually due to mechanical effects. Example: Oligohydramnios (too little amniotic fluid) → restricted fetal movement → micrognathia (small jaw).

Answer 268

Defects in organs that were previously normally developing due to outer/extrinsic influences. Example: Diabetes in the mother → increased insulin crossing the placenta → macrosomia (excessive fetal birth weight).

Answer 269

Abnormal organization of cells in a tissue. Example: Osteogenesis imperfecta.

Answer 270

A single major anomaly alters the subsequent development of other structures. Example: Posterior urethral valves defect → obstruction of urine flow → oligohydramnios → micrognathia.

Answer 271

Abnormalities that occur together more frequently than expected by chance alone. Example: Congenital abnormalities of the spine consistently associated with characteristic urinary tract malformations.

Answer 272

Environmental influences: Viral infections (e.g., CMV causing vision problems, hearing loss, developmental delay), drugs, irradiation during pregnancy. Multifactorial inheritance: Combination of environmental influence on the expression of 2 or more genes.

Answer 273

Timing of prenatal defect: First 3 weeks: Injurious agents can cause abortion or minor defects. 3rd-9th weeks: Embryo extremely susceptible to injuries as organs are being formed. After the 9th week: Fetal period with organ growth and maturation; less susceptible to injuries but sensitive to growth retardation. Genes regulating morphogenesis: Valproic acid disrupts HOX gene expression (controls body plan along the head-tail axis) leading to abnormalities. All-trans-retinoic acid (vitamin A derivative) essential for normal development and differentiation (e.g., cleft lip and cleft palate).

Answer 274

Structural abnormality in one or more chromosomes. Usually occur due to errors in cell division following mitosis or meiosis. Karyotype: Photographic representation of stained metaphase chromosomes arranged in order of decreasing length.

Answer 275

Caused by the presence of a 3rd copy of chromosome 21, or part of it. Non-disjunction during meiosis (95% cases): Non-disjunction of a homologous pair of chromosomes at the 1st meiotic division. Non-disjunction of sister chromatids during the 2nd meiotic division. Result in trisomic (3 copies) or monosomic (1 copy) zygotes. Robertsonian translocation: Fusion of the long arms of acrocentric chromosomes (13, 14, 15, 21, 22) after loss of their short arms.

Answer 276

Some patients can be mosaic, having a mixture of cells with either 46 or 47 chromosomes.

Answer 277

Flat facial profile, mental retardation, cardiac malformations. 40% have congenital heart disease, most commonly endocardial defects. 10- to 20-fold increased risk of developing acute leukemia (ALL and AML). Neuropathologic changes characteristic of Alzheimer’s disease by age 40. Abnormal immune responses, leading to serious infections (particularly lungs) and thyroid autoimmunity.

Answer 278

Reciprocal translocation: Genetic material exchanged between nonhomologous chromosomes. Robertsonian translocation: Loss of short arms and fusion of long arms of acrocentric chromosomes (13, 14, 15, 21, 22). Isochromosome: Centromere divides horizontally, resulting in loss of one arm. Deletion: A portion of the chromosome is removed. Inversion: A portion of the chromosome breaks off, turns upside down, and reattaches. Insertion: A portion of DNA is inserted into the chromosome.

Answer 279

Transmitted by heterozygous female carriers to sons, who are hemizygous. Males express the disorder, females are carriers and will express if homozygous. Affected males will not transmit to sons, but all daughters will be carriers.

Answer 280

Duchenne muscular dystrophy: Mutation in dystrophin gene → no dystrophin protein → muscle weakness. Hemophilia A/B: Factor VIII/IX deficiency → impaired hemostasis → bleeding. SCID: Mutated ɤ chain of cytokine receptors → impaired humoral and cellular immunity. Hunter syndrome: Mucopolysaccharidosis type 2. Lesch-Nyhan syndrome: HGPRT deficiency → hyperuricemia.

Answer 281

Rare variant of inheritance. 50% transmission to sons and daughters of heterozygous females. Affected males transmit to all daughters but not to sons. Examples: Rett syndrome, vitamin D-resistant rickets.

Answer 282

Inheritance of traits attributed to 2 or more genes, possibly influenced by the environment. Risk of expressing a disorder depends on the number of mutant genes inherited. Recurrence rate in first-degree relatives is the same as in affected individuals (2%-7%). Characteristic for diabetes mellitus, hypertension, gout, schizophrenia, and bipolar disorders.

Answer 283

Increased purine intake/production or increased cell degradation → hyperuricemia. Formation of uric acid crystals in joints/kidney tubules → inflammation and tissue destruction. Two forms: Primary Gout: 90% of cases; enzymatic defect unknown or partial HGPRT deficiency . Secondary Gout: Hyperuricemia caused by another condition (e.g., Lesch-Nyhan syndrome).

Answer 284

Asymptomatic hyperuricemia: Elevated uric acid levels without symptoms. Acute arthritis: Sudden onset of joint inflammation. Asymptomatic inter-critical period: No attacks during this time. Chronic tophaceous gout: Long-term joint damage and formation of tophi (urate crystal deposits).

Answer 285

Result from malfunctioning lysosomal enzymes, leading to accumulation of partially degraded metabolites. Disorders are caused by the absence of specific lysosomal enzymes or related proteins.

Answer 286

Deficiency in hexoaminidase A enzyme. Causes accumulation of gangliosides in neurons and glial cells. Forms: Infantile: Normal development for 6 months, then mental and physical deterioration, blindness, deafness, paralysis, death by age 4. Juvenile: Onset 2-10 years, cognitive and motor skill decline, dysarthria, dysphagia, ataxia, death by 5-15 years. Adult (Late Onset): Symptoms in 30s-40s, loss of walking coordination, neurological decline, dysphagia, dysarthria, cognitive decline, psychiatric issues, usually not fatal.

Answer 287

Caused by mutations in SMPD1 gene. Type A: Severe sphingomyelinase deficiency, accumulation in neurons and phagocytic cells, severe visceromegaly and neurologic deterioration, death by age 3. Type B: Visceromegaly without neurologic symptoms.

Answer 288

Caused by defect in lipid transport (NPC1/2 gene mutations). Accumulation of cholesterol and gangliosides. Symptoms: Ataxia, vertical supranuclear gaze palsy, dystonia, dysarthria, psychomotor regression.

Answer 289

Mutation in glucocerebrosidase gene, accumulation of glucosylceramide. Types: Type I: Hepatosplenomegaly, skeletal weakness, no CNS involvement. Type II: Acute, early onset, liver and spleen enlargement, extensive brain damage, spasticity, limb rigidity, death by age 2. Type III: Chronic, mild neurologic symptoms, hepatosplenomegaly, anemia, respiratory issues.

Answer 290

Defective degradation of mucopolysaccharides (GAGs). Accumulation leads to rough facial features, corneal clouding, joint stiffness, mental retardation. Types 1 to 7, all autosomal recessive except type 2 (Hunter syndrome), which is X-linked.

Answer 291

Caused by deficiencies in enzymes involved in glycogen metabolism. Types: Hepatic Type: Liver enlargement, hypoglycemia (e.g., Von Gierke disease - lack of G-6-phosphatase). Myopathic Type: Muscle weakness, cramps, no lactate after exercise (e.g., McArdle syndrome - defective muscle phosphorylase). Pompe Disease: Deficiency in lysosomal acid maltase, glycogen in organs, prominent cardiomegaly. Brancher Disease: Deposition of abnormal glycogen.

Answer 292

Defects affecting structure/function of organs present at birth. Types: Malformation: Primary morphogenesis errors (e.g., neural tube defects). Deformation: Mechanical impact on developing structures (e.g., oligohydramnios). Disruption: External influences on normal development (e.g., maternal diabetes). Dysplasia: Abnormal tissue organization (e.g., osteogenesis imperfecta).

Answer 293

Parents are usually not affected; siblings may show the disease. Siblings have a 25% chance of being affected. Higher likelihood of occurrence due to relatives' marriage if the mutant gene is rare in the population. Common features: Uniform expression of the defect. Complete penetration is common. Early onset of disease. New mutations rarely detected clinically. Often affects enzyme proteins.

Answer 294

Widespread disorder of epithelial transport causing thick viscous secretions. Critically affects lungs, GI tract, exocrine glands (e.g., pancreas), and reproductive system. Abnormal function of epithelial Cl- channel protein encoded by CFTR gene on chromosome 7. Most common mutation: ΔF508 (deletion of three nucleotides for phenylalanine). CFTR misfolding leads to impaired Cl- transport and viscous secretions.

Answer 295

Sweat glands: Hypertonic sweat (high salt concentration). Respiratory and intestinal epithelium: Increased mucus secretion → defective mucociliary action → airway obstruction. Pancreas: Mucous accumulation in ducts: Mild: Small ducts dilated, some gland dilation. Advanced: Ducts plugged, gland atrophy, fibrosis → pancreatic enzymes do not reach the duodenum → defective lipid/protein absorption → steatorrhea. Intestine: Meconium ileus in infants due to mucus plugs. Pulmonary changes: Viscous mucus in respiratory tree, distended bronchioles, hyperplasia, hypertrophy of mucus-secreting cells, chronic bronchitis from infections. Liver: Bile canaliculi plugged, hepatic steatosis common, potential cirrhosis development. Vas deferens: Absent or obstructed by thick secretions.

Answer 296

CFTR gene mutations cause impermeability to Cl- ions, leading to viscous secretions. Tissue-specific impacts: Sweat glands: Increased salt concentration in sweat. Respiratory/Intestinal epithelium: Mucus obstruction. Pancreas: Enzyme blockage, malabsorption, steatorrhea. Intestine: Obstruction in infants. Lungs: Chronic bronchitis, distended bronchioles. Liver: Hepatic steatosis, potential cirrhosis. Reproductive system: Vas deferens abnormalities.

Answer 297

Affects both males and females, expressed in heterozygotes. Features include: Some patients may have new mutations (not inherited). Reduced penetrance: some individuals inherit the gene but are phenotypically normal. Variable expressivity: same mutant gene expressed differently among individuals. Delayed age of onset. 50% reduction in normal gene product associated with clinical symptoms. Non-enzymatic proteins affected: regulatory proteins (membrane receptors, transport proteins) and structural proteins (collagen, cytoskeletal components). Dominant negative effect: mutated allele impairs the function of the normal allele in multimeric proteins.

Answer 298

Autosomal dominant disorder of connective tissue affecting fibrillin-1. Fibrillin-1, a glycoprotein secreted by fibroblasts, is a major component of microfibrils in ECM. Microfibrils serve as scaffolding for elastic fiber deposition. FBN1 gene on chromosome 15 encodes fibrillin-1. Mutant FBN1 gene acts as a dominant negative by preventing normal microfibril assembly. Dysregulation of TGFβ production also contributes to Marfan syndrome features. 75% of cases are familial; 25% are sporadic (new mutations).

Answer 299

Skeletal abnormalities: Tall and thin stature with abnormally long legs, arms, and fingers (arachnodactyly). High arch palate, hyper-extensible joints, spinal and chest deformities. Ocular changes: Bilateral dislocation of the lens (weak suspensory ligaments). Cardiovascular system: Fragmentation of elastic fibers in the tunica media of the aorta, leading to aneurysm and potential aortic rupture. Cardiac valves, mainly the mitral valve, may be extensively distended, leading to regurgitation.

Answer 300

Characterized by defects in collagen synthesis or structure; single gene disorders. Inherited as autosomal recessive, autosomal dominant, or X-linked. Affects tissues rich in collagen (skin, joints, ligaments)

Answer 301

Skin: Hyper-extensible, extremely fragile, lacks normal tensile strength. Joints: Hyper-mobile, prone to dislocations. Internal organs: Risk of rupture (colon, large vessels), cornea may rupture.

Answer 302

Deficiency of lysyl hydroxylase (kyphoscoliosis, type VI): Hydroxylation of lysyl residues decreases in collagen types I & III. Interferes with normal cross-links of collagen molecules. Inherited as autosomal recessive disorder. Deficient synthesis of type III collagen (vascular, type IV): Resulting from mutations affecting the COL3A1 gene. Inherited as an autosomal dominant disorder. Characterized by weakness of vessels and intestinal wall. Deficient synthesis of type V collagen: Mutations in COL5A1 and COL5A2. Inherited as an autosomal dominant disorder. Results in classical EDS.

Answer 303

Caused by: Human Immunodeficiency Virus (HIV) Targets: Immune system cells (macrophages, DCs, T helper cells) Results: Profound immunosuppression, increased risk of opportunistic infections and tumors Transmission: Sexual contact (75% of cases, especially male to male transmission) Parenteral transmission (intravenous drug abuse) Mother-to-child transmission (transplacental, during delivery, or via breast milk)

Answer 304

Lipid Envelope: Contains transmembrane glycoproteins gp-120: Primary attachment to CD4 molecule gp-41: Fusion with host cell membrane Matrix Protein: gp-17 Capsid Protein: gp-24 Nucleocapsid Protein: gp-7 (encloses nucleic acid) Genetic Material: 2 copies of (+)SSRNA Viral Enzymes: Reverse Transcriptase Integrase Protease

Answer 305

HIV Type 1: Common in the US, Europe, and Central Africa M (major): Divided into subtypes A-J O (outlier) HIV Type 2: Found principally in West Africa and Southern Asia Both types are genetically different but antigenically similar

Answer 306

Attachment: gp120 binds to CD4, exposing recognition sites for CCR5 and CXCR4 Fusion: gp41 inserts into target cell membrane Internalization: Viral genome undergoes reverse transcription, forming complementary DNA (cDNA) Integration: cDNA integrates into the host genome (latent infection) Progression: Viral particles formation eventually leads to cell death Post-exposure prophylaxis: Maraviroc (within 72 hours)

Answer 307

Acute Phase: R5 strain binds CCR5 co-receptor on DCs DCs present virus to CD4+ cells in lymph nodes Large spike in virus replication (viremia), with non-specific symptoms (sore throat, fever, rash) Chronic Phase: Clinical latency period with immune competence Steady decline in CD4+ T cells No symptoms detectable Crisis Phase: Low CD4+ T cells count (<500 cells/μL) Serious opportunistic infections, secondary neoplasms, neurologic manifestations

Answer 308

Opportunistic Infections: Pneumonia, herpes, tuberculosis, influenza Neoplasms: Kaposi sarcoma, non-Hodgkin lymphoma, cervical cancer CNS Involvement: Aseptic meningitis, vascular myelopathy, progressive encephalopathy

Answer 309

Type: X-linked recessive Defect: Mutation in BTK gene (Bruton’s tyrosine kinase) on the X chromosome Pathogenesis: Pre-B cells cannot mature into B cells → absence of B cells and γ-globulins (antibodies) in the blood Symptoms: Onset after 6 months (after maternal antibodies wane) Recurrent bacterial infections Gender Prevalence: Almost exclusively in males Treatment: Life-long intravenous immunoglobulin infusion and antibiotics for infections

Answer 310

Type: Congenital B cell immunodeficiency Defect: Block in terminal differentiation of IgA-secreting B cells to plasma cells Pathogenesis: Lack of IgA antibodies → increased mucosal antigen exposure → increased IgE production → hyperallergy Symptoms: Often asymptomatic but may include diarrhea and pulmonary infections

Answer 311

Type: Congenital disorder caused by a microdeletion on chromosome 22 (22q11.2) Defect: Deletion of TBX1 gene affecting the development of the 3rd and 4th pharyngeal pouches Pathogenesis: Partial or complete thymic dysfunction → deficiency in mature T cells (B cells and serum immunoglobulins are unaffected) Symptoms: Cardiac abnormalities Facial abnormalities (e.g., cleft palate, long face) Mental disorders Variable thymic dysfunction (mild to severe)

Answer 312

Type: Genetic disorder affecting both humoral and cell-mediated immunity Defect: Mutations in genes encoding the common γ-chain of cytokine receptors (IL-2, 4, 7, 9, 15) Pathogenesis: IL-7 is crucial for immature B and T cell survival and expansion Different mutations affect T, B, and NK cells in various ways: X-linked SCID (T- B+ NK-): Common γ-chain mutation Autosomal Recessive SCID: ADA deficiency (T- B- NK-): Accumulation of adenosine inhibits DNA synthesis MHC-II gene mutation (T- B+ NK+): CD4+ T-cell defect RAG gene mutation (T- B- NK+): DNA rearrangement defect Symptoms: Severe infections early in life Treatment: Bone marrow transplantation and gene therapy

Answer 313

Definition: Chronic systemic autoimmune disease causing destruction of exocrine glands. Affected Glands: Lacrimal: Dry eyes "keratoconjunctivitis sicca" Salivary: Dry mouth "xerostomia" → increased risk of caries Sweat: Dry skin "xerosis" Mucous: Dry vagina and pain during intercourse "dyspareunia", dry nose, decreased smell sensation

Answer 314

Demographics: Most common in middle-aged women Forms: Primary: Isolated disorder, autoantibodies against SS-A (Ro) and SS-B (La) Secondary: Associated with another autoimmune disease (most commonly rheumatoid arthritis) Complications: High risk of non-Hodgkin B cell lymphoma (Marginal zone) → unilateral enlargement of the parotid gland

Answer 315

Pathogenesis: Loss of tolerance in helper T cells → duct obstruction → atrophy

Answer 316

Definition: Chronic systemic autoimmune disease causing fibrosis of the skin and internal organs (GI tract, lungs, kidneys, heart, skeletal muscle) Types: Diffuse Scleroderma: Widespread skin involvement, rapid progression, early visceral involvement Limited Scleroderma (CREST Syndrome): Mild skin involvement (fingers, face), late visceral involvement, relatively benign course CREST: Calcinosis, Raynaud syndrome, Esophageal dysmotility, Sclerodactyly, Telangiectasia

Answer 317

Pathogenesis: Fibroblast activation → excessive fibrosis Helper T cells activation → cytokine release → fibrosis B cell activation → hypergammaglobulinemia, ANAs Microvascular disease → fibrosis and narrowing of microvasculature

Answer 318

Antibodies: Anti-DNA topoisomerase I (anti-Scl70): Specific for diffuse scleroderma (70% of patients) Anti-centromere antibodies: Specific for limited scleroderma (90% of patients) Morphology: Skin: Diffuse sclerotic atrophy, fibrosis, thickened basement membrane, endothelial cell damage GI Tract: Progressive atrophy, collagenous replacement, dysfunction of esophageal sphincter, malabsorption

Answer 319

Musculoskeletal System: Synovial hyperplasia, inflammation, fibrosis Lungs: Fibrosis of small pulmonary vessels, pulmonary hypertension Kidneys: Thickened intertubular artery walls, hypertension with fibrinoid necrosis Heart: Patchy myocardial fibrosis, thickening of intramyocardial arterioles, right ventricular hypertrophy and failure

Answer 320

Clinical Course: Affects women 3x more than men, peak age 50-60 Distinctive cutaneous involvement Almost all patients exhibit Raynaud phenomenon

Answer 321

Definition: A systemic, chronic inflammatory disease primarily affecting the synovial joints. Affected Joints: Symmetrical involvement of 5 or more joints; initially small joints (MCP, MTP), later larger joints (shoulders, elbows, knees, ankles).

Answer 322

Involvement: Can extend to skin, heart, blood vessels, muscles, and lungs.

Answer 323

Interplay of Factors: Environmental: Infections, smoking leading to citrullination. Genetic: Susceptibility genes like HLA-DR4, polymorphism in PTPN22 gene. Process: APCs do not recognize citrullinated antigens → present to TH1 and TH17 in lymph nodes. TH cells stimulate B cells to secrete specific antibodies. Antibodies and T helper cells reach synovial joints → chronic inflammation and cell injury → angiogenesis → more immune cells. Formation of pannus → cartilage and bone erosion → fibrosis and calcification → ankylosis.

Answer 324

T-Cells: Cause chronic inflammation and stimulate synovial cells. Antibodies: Bind to citrullinated antigens, forming immune complexes → inflammation and joint damage.

Answer 325

Synovium Changes: Synovial cell hyperplasia and proliferation. Infiltration of inflammatory cells forming lymphoid follicles (helper T cells, plasma cells, macrophages). Increased vascularity due to angiogenesis. Fibrin aggregates on synovial surface. Increased osteoclast activity.

Answer 326

Symptoms: General: Weakness, fever, malaise. Joints: Swelling, limited movement, morning stiffness. Deformities: Radial deviation of the wrist. Ulnar deviation of the fingers. Bending of fingers due to destruction of tendons, ligaments, and joint capsules.

Answer 327

Definition: A multisystem autoimmune disease affecting various parts of the body, primarily the skin, kidneys, serosal membranes, joints, and heart. Diagnosis: Established if the patient shows at least 4 of the following symptoms: Malar rash (butterfly) Discoid rash Photosensitivity Oral ulcers Serositis (pleuritis, pericarditis) Neurological disorders Renal disorders Arthritis Hematologic disorders (anemia, thrombocytopenia, leukopenia) Positive ANA (Anti-Nuclear Antibodies)

Answer 328

Factors: Environmental: UV light, smoking, medications, estrogen. Genetic: Ineffective clearance of nuclear antigens and failure of T and B cell tolerance. Major Defect: Failure to maintain self-tolerance. Tissue Damage Pathways: Deposition of antigen-antibody complexes (type III hypersensitivity). Production of autoantibodies, mainly ANA (type II hypersensitivity).

Answer 329

Anti-Nuclear Antibodies (ANAs): Produced against nuclear antigens (e.g., DNA, Smith antibodies, histones, nucleolar antigens). Anti-Phospholipid Antibodies: Target phospholipids of cell membranes, disrupting coagulation processes. Antibodies Against Blood Cells: Target RBCs (causing hemolytic anemia), platelets (causing thrombocytopenia), and lymphocytes (causing lymphopenia).

Answer 330

Blood Vessels: Necrosis and fibrinous deposits leading to fibrous thickening and lumen narrowing. Joints: Swelling and non-specific mononuclear cell infiltration in synovial membranes. Skin: Malar rash (butterfly pattern), photosensitivity, liquefactive degeneration of the basement membrane, and edema at the dermis-epidermis junction. CNS: Focal neurologic deficits, often due to vascular lesions causing cerebral microinfarctions. Spleen: Moderate enlargement with capsular fibrous thickening and follicular hyperplasia. Serous Membranes: Inflammatory changes in pericardium and pleura. Heart: Endocarditis, myocarditis, valvular lesions (Libman-Sacks endocarditis). Kidneys: Various forms of glomerulonephritis due to antigen-antibody complex deposition.

Answer 331

Class I (5%): Rare, no histological signs of inflammation. Class II (10%-25%): Mesangial lupus glomerulonephritis with immune complex deposition in the mesangium. Class III (20%-35%): Focal proliferative glomerulonephritis with endothelial and mesangial cell proliferation and neutrophil infiltration. Class IV (35%-60%): Diffuse proliferative glomerulonephritis, most severe form, with extensive endothelial and mesangial proliferation, subendothelial immune complex deposition. Class V (10%-15%): Membranous glomerulonephritis with widespread capillary wall thickening due to immune complex deposition, severe proteinuria.

Answer 332

Definition: The lack of immune response to an antigen. Antigen Specific: Unlike general immunosuppression, immunological tolerance is specific to particular antigens

Answer 333

Definition: The immune system's lack of response to self-antigens. Failure: Results in autoimmunity. Mechanisms: Central tolerance (primary lymphoid organs) and peripheral tolerance.

Answer 334

Location: Occurs in primary lymphoid organs (bone marrow & thymus). Mechanism in BM: B cells undergo "receptor editing" to eliminate self-reactivity. Non-reactive B cells mature, while autoreactive ones are deleted or become anergic. Mechanism in Thymus: T cells that recognize self-antigens are eliminated by apoptosis. AIRE gene helps present self-antigens for T cell negative selection.

Answer 335

Purpose: Eliminates or inhibits autoreactive B and T cells that escape central tolerance. Mechanisms: B cells require multiple activation signals; lacking any leads to anergy. T cells experience anergy without co-stimulation, suppression by regulatory T cells, or deletion through apoptosis.

Answer 336

Gene Mutations: Often run in families, linked to HLA locus on chromosome 6, and non-HLA genes like CTLA4 and PTPN22. Infections: Pathogens with proteins similar to self-antigens can trigger autoimmunity (e.g., Rheumatic heart disease). Privileged Sites: Areas with no BVs or lymphatics; damage can expose self-antigens as foreign (e.g., cornea). Modification of Antigen: Drug metabolites change antigen conformation. Epitope Spreading: T cells reactive to less dominant epitopes are not eliminated. Failure of T Cell Suppression: Insufficient IL-10 production. Lack of AICD: Defect in Fas-Fas ligand interaction (e.g., SLE).

Answer 337

Type I Diabetes Mellitus: Mechanism: T cells destroy pancreatic β cells, no insulin production, blood glucose increases. Multiple Sclerosis: Mechanism: T cells attack myelin proteins, causing demyelination in CNS, leading to neurologic deficits. Rheumatoid Arthritis: Mechanism: Chronic inflammation targets joints, causing synovitis and destruction of cartilage and bone.

Answer 338

Rheumatic Heart Disease: Cause: Streptococcal infections with antigens similar to those in the heart. Sjogren's Syndrome: Effect: Destruction of exocrine glands causing dry eyes, mouth, skin, and other symptoms. Systemic Sclerosis (Scleroderma): Effect: Fibrosis and thickening of skin and internal organs. Systemic Lupus Erythematosus (SLE): Effect: Multi-system involvement, particularly kidneys, joints, and skin.

Answer 339

Definition: Infections by microorganisms that normally do not cause disease but become pathogenic when the immune system is impaired. Significance: Account for the majority of deaths in AIDS and other diseases with immunosuppression.

Answer 340

Superficial Infections: Affect skin, hair, and nails (dermatophytes). Deep Fungal Infections: Can spread systemically and invade tissues, destroying vital organs in immunocompromised hosts

Answer 341

Endemic Species: Invasive fungi limited to specific geographic regions. Opportunistic Species: Include Candida, Aspergillus, Mucor, Cryptococcus; infect immunocompromised individuals, often from environmental sources.

Answer 342

Cause: Pneumocystis jiroveci. Effects: Pneumonia or disseminated disease, often fatal in AIDS patients. Transmission: Respiratory tract. Treatment: Treatable, prophylaxis possible

Answer 343

Cause: Candida albicans. Affected Areas: Oral cavity, trachea, lungs, esophagus. Common in: Immunocompromised individuals.

Answer 344

Cause: Cryptococcus fungi. Transmission: Enters via respiratory tract, spreads to lepromeninges causing meningitis. Other Affected Areas: Skin, skeletal system, urinary tract. Mortality: High, but treatable.

Answer 345

Cause: Histoplasma capsulatum. Transmission: Inhalation (bird and bat droppings). Pathology: Intracellular parasite in macrophages, forming epitheloid cell granulomas with necrosis. Differential Diagnosis: TB, sarcoidosis, coccidioidomycosis. Severe Cases: No granulomas, macrophages filled with fungal yeasts throughout the body.

Answer 346

Types: TB (Tuberculosis): Pulmonary or extrapulmonary; M. tuberculosis blocks phagolysosome fusion. Atypical Mycobacteria: M. avium intracellulare, often disseminated. Common Bacterial Pathogens: S. aureus, S. pneumoniae, H. influenzae, Salmonella. Common Infections: Pneumonia, enteritis, meningitis, sepsis.

Answer 347

Prevalence: Very common, most people have had CMV by 40 years old. Transmission: Via saliva, blood, semen. Affected Areas: Throat, lung, GI, meningoencephalitis, retinitis. Histology: Enlarged cells with large eosinophilic nuclear inclusion and smaller basophilic cytoplasmic inclusion.

Answer 348

Types: HSV-1 (gingivostomatitis), HSV-2 (genital herpes). Other Infections: Keratitis, encephalitis, hepatitis, pneumonia. Histology: Large nuclear inclusion surrounded by a clear halo.

Answer 349

Disease: Causes Kaposi sarcoma, common in immunocompromised patients.

Answer 350

Disease Association: B-cell lymphomas, such as Burkitt lymphoma.

Answer 351

Diseases: Chickenpox and shingles. Complications in Immunosuppressed: Encephalitis, transverse myelitis, necrotizing visceral lesions.

Answer 352

Definition: Air-borne, chronic granulomatous disease typically attacking the lungs. Causing Agent: Mycobacterium tuberculosis. Characteristic Lesion: Tubercular granulomas with caseous necrosis. Two Forms: Pulmonary TB and Non-Pulmonary TB

Answer 353

Transmission: Inhalation of droplets containing Mycobacterium tuberculosis. Characteristic Lesion: Ghon focus and Ghon complex, which can progress to Ranke complex. Primary TB: Develops in previously unexposed individuals. Secondary TB: Reactivation of dormant Ghon complexes or exogenous reinfection, often localized to the lung apices.

Answer 354

Cause: Often Mycobacterium bovis, usually from ingestion of infected milk. Forms: Can affect various organs including lymph nodes (lymphadenitis), bones (Pott disease), meninges, kidneys, and intestines.

Answer 355

Development: In previously unexposed individuals. Lesion: Ghon focus in distal airspaces of the lung. Complex: Ghon complex (parenchymal lesion + lymph node involvement), can become Ranke complex (fibrosis and calcification). Histology: Granulomatous inflammation with giant cells and epitheloid histiocytes.

Answer 356

Occurs: In previously sensitized hosts. Localization: Apices of one or both upper lobes. Lesions: Sharply defined, firm, gray-white to yellow areas with caseous necrosis and fibrosis. Complications: Cavitations, miliary pulmonary disease, systemic miliary TB, isolated-organ TB, lymphadenitis, and intestinal TB.

Answer 357

Initial Stage: Mycobacteria ingested by macrophages, inhibit bactericidal responses, proliferate within alveolar macrophages. Immune Response: Cell-mediated immunity develops after 3 weeks; TH1 cells secrete IFNγ, activating macrophages. Macrophage Activation: Release TNF, NO, reactive oxygen species, recruit monocytes that form granulomas.

Answer 358

Mantoux Test: Positive tuberculin skin test indicates cell-mediated hypersensitivity but does not differentiate between infection and active disease. False Negatives: Can be produced by viral infections, Hodgkin lymphoma, etc.

Answer 359

Onset: Often asymptomatic. Systemic Symptoms: Malaise, anorexia, weight loss, fever. Progression: Increasing sputum production (mucoid to purulent), hemoptysis, pleuritic pain. Complications: Amyloidosis in persistent cases.

Answer 360

Progressive Pulmonary TB: Enlargement of apical lesion, cavitation, hemoptysis. Miliary Pulmonary Disease: Dissemination through lymph vessels, forming small, solid masses throughout lungs. Systemic Miliary TB: Spread through pulmonary veins to systemic circulation.

Answer 361

Isolated-Organ TB: Involves meninges, kidneys, adrenal glands, bones, fallopian tubes. Pott Disease: TB infection in the vertebrae. Lymphadenitis: Frequent extra pulmonary form, especially in the cervical region. Intestinal TB: Ingestion of contaminated milk, affecting lymphoid tissue in intestines.

Answer 362

Definition: Immunological reaction to a transplanted tissue, except in identical twins or autografts. Allograft: Transplant from one individual to another of the same species.

Answer 363

Direct Recognition: Recipient T-cells recognize donor APCs directly through MHC molecules. Indirect Recognition: Recipient APCs process donor MHC molecules and present them to T-helper cells.

Answer 364

T-cell Mediated Rejection: Cytotoxic T cells directly kill graft cells. Helper T cells secrete cytokines, triggering DTH reaction. Antibody-Mediated Rejection: Host antibodies target graft MHC, activate complement, and recruit leukocytes.

Answer 365

Timing: Minutes to hours post-transplantation. Cause: Pre-existing antibodies. Characteristics: Acute arteritis, vessel thrombosis, ischemic necrosis.

Answer 366

Timing: Days to weeks post-transplantation. Types: Acute Cellular Rejection: Interstitial infiltration of T cells, edema, mild hemorrhage, renal failure. Acute Humoral Rejection: Necrotizing vasculitis, endothelial cell necrosis, antibody and complement deposition.

Answer 367

Timing: Late post-transplantation. Characteristics: Vascular changes, interstitial fibrosis, renal parenchyma loss, increased serum creatinine.

Answer 368

Occurrence: In compromised recipients during bone marrow transplantation or solid organs with lymphoid tissue. Mechanism: Donor T cells recognize recipient tissues as foreign

Answer 369

Timing: Days to weeks post-transplantation. Symptoms: Epithelial cell necrosis in liver, skin, and gut; jaundice, bloody diarrhea, generalized rash.

Answer 370

Occurrence: Can follow acute GVHD or occur independently. Symptoms: Skin lesions, manifestations mimicking autoimmune diseases.

Answer 371

Methods: MHC matching. Depletion of donor T cells before transplantation.

Answer 372

Purpose: Suppress the immune system to prevent graft rejection. Risks: Increased susceptibility to infections, higher cancer risk.

Answer 373

Definition: Immune complexes not adequately cleared deposit in blood vessel walls, causing inflammation and tissue damage. Mechanism: Immune complex formation → deposition in basement membranes (BVs) → complement activation.

Answer 374

Damaged cell releases DNA. Autoreactive B cell binds Ag, presents to T helper cell. T helper cell activates B cell → antibody secretion. Formation of small soluble immune complexes. Complexes deposit in basement membranes. Complement activation: C3a, C4a, C5a: Increase BV permeability (edema) and degranulate neutrophils (vasculitis).

Answer 375

Systemic Lupus Erythematosus (SLE): Immune complex deposition affects multiple organs. Glomerulonephritis: Deposition in glomeruli BVs. Arthritis: Immune complexes in synovial fluid. Serum Sickness: Reaction to foreign serum proteins. Farmer's Lung: Inhaled allergens cause lung inflammation.

Answer 376

Definition: Cell-mediated immune response, not antibody-mediated. Types: Delayed Type Hypersensitivity (DTH): T helper cell-mediated. Direct Cell Cytotoxicity: Cytotoxic T cell-mediated.

Answer 377

Tuberculin Test: Small tuberculin Ag injected. DCs present Ag to naïve T helper cells on MHCII. IL-12 secretion → TH1 cell differentiation. TH1 cells secrete IFN-γ & TGF-β → inflammation. Contact Dermatitis: Caused by agents like nickel or poison ivy.

Answer 378

DCs present Ag on MHC-I to naïve T cells. T cells differentiate into cytotoxic T cells. Cytotoxic T cells secrete perforin & granzymes. Target cell destruction. Examples: Type I Diabetes Mellitus: Destruction of pancreatic β cells. Rheumatoid Arthritis (RA): WBCs infiltrate synovial joints, produce antibodies against human IgG.

Answer 379

Timeframe: Delayed (48-72 hours for TH1 cells recruitment). Antigen Requirement: Higher antigen amount needed than in antibody-mediated hypersensitivity.

Answer 380

Autoimmune diseases, excessive reactions against microbes, and immune responses against common environmental substances.

Answer 381

It is antibody-mediated and targets antigens on the patient’s own cell surfaces.

Answer 382

1. Target cell depletion/destruction without inflammation. Complement/Fc receptor mediated inflammation. Antibody-mediated cell dysfunction.

Answer 383

Antibodies bind to cell surface antigens, and their Fc regions are recognized by phagocytes, promoting phagocytosis or opsonization.

Answer 384

Hemolytic anemia (warm type), thrombocytopenia, ABO incompatibility, erythroblastosis fetalis.

Answer 385

Antibodies activate the complement system via the classical pathway, recruiting neutrophils and macrophages, leading to inflammation.

Answer 386

Acute rheumatic fever.

Answer 387

Antibodies bind to cell surface receptors, blocking normal ligands and disrupting cell signaling.

Answer 388

Myasthenia gravis.

Answer 389

Conditions like hemolytic anemia and erythroblastosis fetalis can benefit from treatments like splenectomy, reducing phagocytic activity of the spleen.

Answer 390

Through activation of the complement system and recruitment of inflammatory cells leading to an inflammatory response.

Answer 391

Antibodies block acetylcholine receptors at the neuromuscular junction, causing muscle weakness.

Answer 392

They recognize and bind to the Fc region of antibodies attached to cell surface antigens, promoting cell destruction.

Answer 393

It reduces the phagocytic activity of the spleen, decreasing the destruction of opsonized cells

Answer 394

Complement proteins and inflammatory cells like neutrophils and macrophages.

Answer 395

By blocking receptors or altering signaling pathways, preventing normal cell function.

Answer 396

The ability of tissues to repair themselves is critically influenced by their intrinsic proliferative capacity. Tissues of the body are divided into three groups: Labile (continuously dividing) tissues – cells are continuously replaced by maturation of stem cells. Include hematopoietic cells in BM and majority of surface epithelia (skin, oral cavity, vagina, cervix, ducts of exocrine organs, GI and urinary tract). Stable tissues – minimal replicative activity in normal state, yet can proliferate in response to injury/loss of tissue mass. Can reconstruct parenchyma of liver, kidney, and pancreas. Permanent tissues – cells of these tissues are permanently differentiated and nonproliferative, such as neurons and cardiac muscle.

Answer 397

Repair begins within 24 hours of injury by emigration of fibroblasts and their induction, as well as endothelial cell proliferation. 3-5 days: granulation tissue is apparent. Granulation tissue accumulates CT matrix, resulting in scar formation. Components of CT repair: Angiogenesis – formation of new blood vessels. Migration and proliferation of fibroblasts. Scar formation – deposition of CT, called granulation tissue. Maturation and reorganization of the fibrous tissue.

Answer 398

Steps of blood vessel formation: Vasodilation by NO and permeability of existing blood vessels by VEGF (vascular endothelial growth factor). Migration of endothelial cells to the site of injury. Proliferation and remodeling of endothelial cells => tube formation. Recruitment of pericytes and smooth muscle cells to form mature vessel. Newly formed vessel is leaky during angiogenesis since the interendothelial junctions are not completely formed, and because VEGF increases permeability. Structural ECM proteins participate in the process by interactions with endothelial cells through integrin receptors.

Answer 399

Scar formation (deposition of CT) occurs in 2 steps: Migration of fibroblasts into the site of injury and their proliferation there. Deposition of ECM produced by these cells. Recruitment and stimulation of fibroblasts are driven by growth factors: PDGF – platelet-derived growth factor; promotes proliferation of fibroblasts and smooth muscle cells. FGF2 – fibroblast growth factor. TGFβ – transforming growth factor; controls proliferation and differentiation. Macrophages clear tissue debris and secrete mediators that induce fibroblast proliferation and ECM production.

Answer 400

Collagen synthesis by fibroblasts starts at day 3-5 from the onset of injury. The same GFs that induce fibroblasts proliferation mediate collagen synthesis. Net collagen accumulation depends on increased synthesis and diminished degradation of collagen. The granulation tissue evolves into a scar composed of inactive, spindle-shaped fibroblasts, dense collagen, and ECM components. As the scar matures, there is progressive vascular regression, transforming the vascularized granulation tissue into a pale, avascular scar.

Answer 401

Transition from granulation tissue into scar tissue involves a shift in composition of the ECM. Collagen and ECM components are degraded by metalloproteins (MMPs) that are dependent on zinc ions for their activity. MMPs are produced by many cell types including fibroblasts, macrophages, and neutrophils. Production is inhibited by TGFβ or by steroids.

Answer 402

Involves both epithelial regeneration and the formation of connective tissue scar. Based on the nature of the wound, healing can occur by 1st or 2nd intention.

Answer 403

Occurs in clean, uninfected surgical incision. Minor disruption of epithelial basement membrane continuity. Death of relatively few epithelial and connective tissue cells. Epithelial regeneration predominates over fibrosis, forming a small scar.

Answer 404

Day 1: Incision filled with fibrin-clotted blood, followed by infiltration of neutrophils. Increased mitotic activity in basal cells. Day 2: Epithelial cells from both edges migrate and proliferate, depositing basement membrane components. Day 3: Neutrophils replaced by macrophages, granulation tissue invades incision space. Day 5: Maximal blood vessel formation, granulation tissue fills incision space, collagen fibers bridge incision. Week 2: Continued collagen accumulation and fibroblast proliferation, diminished WBC infiltration, edema, and vascularity. Week 4: Scar comprises cellular connective tissue devoid of inflammatory cells, covered by normal epidermis.

Answer 405

Occurs when tissue loss is more extensive (large wound, abscess, ulceration, ischemic necrosis). Intense inflammatory reaction due to greater volume of necrotic debris. Abundant development of granulation tissue. Wound contraction by action of myofibroblasts. Differences from 1st intention: Larger clot at the wound surface. Intense inflammation. Larger amount of granulation tissue. Involves wound contraction.

Answer 406

Sutures give wounds up to 70% of the strength of unwounded skin. After sutures are removed, the wound strength is 10% of unwounded skin strength but increases rapidly. Recovery of tensile strength results from collagen synthesis exceeding its degradation and structural modifications of collagen. Wound strength reaches up to 70%-80% of unwounded skin strength.

Answer 407

Resolution Scarring (fibrosis) Chronic inflammation

Answer 408

Limited injury, minimal damage. Restoration to normal structure/function. Involves: decay of mediators, normalization of permeability, cessation of leukocyte emigration, debris clearance. Leukocytes secrete cytokines: blood vessels grow, fibroblasts lay collagen, tissue cells proliferate.

Answer 409

Substantial tissue destruction. Tissue can't regenerate. Extensive CT deposition. Outcome is fibrosis.

Answer 410

Prolonged inflammation, injury, and healing. Caused by persistent infections, toxic agents, hypersensitivity. Features: macrophages, lymphocytes, fibrosis. Mediated by cytokines (TNF, IL-1, INFγ).

Answer 411

Aggregations of activated macrophages. Causes: persistent T-cell response, immune diseases, unknown etiology. Macrophages present pathogens, T-cells release cytokines (IL-1, IL-2, TNF-α, IFN-ɤ). Multinucleated giant cells = Langerhans cells in TB.

Answer 412

Epitheloid cells: pink granular cytoplasm. Surrounding lymphocytes secrete cytokines. Older granulomas: rim of fibroblasts/CT. Multinucleated giant cells: fusion of >20 macrophages. Caseous necrosis in infections. Noncaseating in Crohn's, sarcoidosis, foreign body reactions.

Answer 413

No necrotic centers. Found in Crohn's, sarcoidosis, foreign body reactions. Microscopically: amorphous, structureless debris.

Answer 414

Fluid derived from serum or secretions of mesothelial cells (peritoneum, pericardium, pleura). Fluid in a serous cavity is called effusion. Example: skin blister – fluid accumulates beneath or within the epidermis.

Answer 415

Consequence of more serious injuries. Greater vascular permeability allows fibrinogen to cross the endothelial barrier. Fibrinous exudate in body cavity linings (meninges, pericardium, pleura). Degradation by fibrinolysis and macrophages leads to resolution. Incomplete removal leads to organization and scar tissue formation. Example: fibrous scar tissue in pericardium restricts myocardial function.

Answer 416

Presence of pus (neutrophils, fibrin, necrotic cells, edema fluid, cell debris, bacteria). Pyogenic organisms (e.g., staphylococci) induce pus formation. Abscess: focal pus collection with central necrosis, surrounded by preserved neutrophils, dilated vessels, and fibroblasts. Outcome: abscess replaced by connective tissue, leading to scarring.

Answer 417

Local defect due to cell necrosis and shedding of inflammatory necrotic tissue. Common in mouth, stomach, intestine, urogenital tract, and lower extremities with circulatory issues. Can be acute or chronic: Acute: intense PMN infiltration, vascular dilation at margins. Chronic: scarring, accumulation of lymphocytes, macrophages, and plasma cells.

Answer 418

A protective response to eliminate the cause of cell injury and necrotic cells. Rapid onset, short duration (minutes to days), characterized by fluid/plasma protein exudation and neutrophilic leukocyte accumulation. 5 cardinal signs: heat, redness, swelling, pain, loss of function. Causes: infections, trauma, tissue necrosis, foreign bodies, hypersensitivity.

Answer 419

Vascular changes Cellular events

Answer 420

Vasodilation: increased local blood flow, stasis, margination. Increased permeability: endothelial contraction, direct injury, transcytosis, new vessel leakage. Adhesion of leukocytes: selectins and integrins promote extravasation.

Answer 421

Recruitment and activation of leukocytes (mainly neutrophils). Steps: margination, rolling (E & P selectins), firm adhesion (integrins), extravasation (diapedesis), invasion (chemotaxis). Leukocyte activation: phagocytosis, intracellular destruction, extracellular microbe destruction, inflammatory ampli

Answer 422

Stimuli: microbes, necrotic cells, mediators. Responses: phagocytosis, intracellular destruction (phagolysosomes), extracellular microbe destruction (NETosis), inflammatory amplification. Injury to normal cells possible

Answer 423

Decay/degradation of chemical mediators. Normalization of vascular permeability. Cessation of leukocyte emigration, neutrophil apoptosis. Production of inhibitory mediators. Clearance of debris by lymphatic drainage and macro

Answer 424

Vasoactive amines: histamine (permeability, epithelial contraction), serotonin (similar to histamine). Amino acid metabolites: COX pathway (thromboxane A2, prostaglandins), LOX pathway (leukotrienes). Cytokines: TNF, IL-1 from macrophages. Kinin system: links kinin, coagulation, plasminogen, complement. Complement system: C3a, C5a (anaphylatoxins), C3b (opsonization).

Answer 425

Due to severe CO↓ (pump failure in LV). Causes: Myocardial infarction Ventricular arrhythmias Cardiac tamponade (fluid in pericardium compresses heart) Outflow obstruction

Answer 426

Results from loss of blood or plasma volume. Causes: Hemorrhage Severe burns Trauma Vomiting, diarrhea

Answer 427

Septic shock: microbial infection (G(+), G(-), fungi) Neurogenic shock: anesthetic accident or spinal injury, loss of vascular tone Anaphylactic shock: systemic vasodilation and increased vascular permeability, type I hypersensitivity (IgE)

Answer 428

Compensatory Stage: Short-term: SNS↑ → CO=HR↑∙SV → CO↑ → MAP↑ Long-term: RAS↑, ADH↑, ANP↓(volume↑) Progressive Stage: Anaerobic metabolism → lactic acidosis, low ATP Confusion, decreased consciousness Irreversible Stage: Tissue/organ damage irreparable → death NO increased synthesis worsens myocardial contraction Lysosomal enzyme leakage

Answer 429

Affected organs: brain, heart, kidneys, adrenals, GI tract. Brain: ischemic encephalopathy Liver: fatty change, nutmeg liver (venous congestion) Kidney: tubular ischemic injury – electrolyte imbalance, fibrin thrombi Adrenals: cortical cell lipid depletion – decreased cortical production, reduced perfusion GI: focal mucosal hemorrhage and necrosis Heart: ischemic coagulative necrosis Tissues recover if patient survives, except for neuronal and cardiomyocyte loss.

Answer 430

Intravascular solid, liquid, or gaseous mass carried by blood to a distant site. Most emboli derive from dislodged thrombus (thromboembolism). Less common: fat droplets, air/nitrogen bubbles, atherosclerotic debris, tumor fragments, bone marrow bits, amniotic fluid. Emboli lodge in small vessels causing partial or complete occlusion. Systemic embolization: ischemic necrosis (infarction). Pulmonary embolization: hypoxia, hypotension, right-sided heart failure.

Answer 431

Originates from DVT above the knee. Passes through right heart into pulmonary circulation. Causes occlusion of main pulmonary artery, bifurcation (saddle embolus), or arterioles. 60%-80% are small and silent, large embolus can cause sudden death. Consequences: cardiovascular impact, left heart affected, respiratory alkalosis. Rarely, paradoxical embolism through heart defects.

Answer 432

Emboli in systemic circulation, mostly from intracardial mural thrombi. Associated with left ventricular wall infarcts. Major sites: lower extremities, CNS; also kidneys, intes

Answer 433

Caused by long bone fractures or soft tissue trauma. Mechanical obstruction: occlude pulmonary/cerebral vasculature. Biochemical injury: fat enters circulation, FFA released causing endothelial injury. Fat embolism syndrome (10%): pulmonary insufficiency, neurological symptoms, anemia, thrombocytopenia. Symptoms: tachypnea, dyspnea, tachycardia (1-3 days after injury

Answer 434

Gas bubbles obstruct vascular flow. Air embolism: >100ml causes clinical effects, from chest injury or obstetric procedures. Nitrogen embolism: decompression sickness in divers, rapid ascent causing nitrogen bubbles.

Answer 435

Complication of labor/postpartum period. Mortality rate ~80%, leading cause of maternal death in developed world. Amniotic fluid enters maternal circulation, contains tissue factor (TF), induces coagulation (DIC). Symptoms: sudden severe dyspnea, cyanosis, hypotensive shock, pulmonary edema.

Answer 436

Clot (thrombus) in an uninjured vessel or after minor injury. Three risk factors (Virchow's triad): endothelial injury, stasis/turbulence of blood flow, blood hypercoagulab

Answer 437

Endothelium normally prevents clotting by being a barrier, releasing antithrombotic substances (NO, PGI2), and anticoagulants (TFPI, TPA). Dysfunction (not just damage) can cause imbalance, leading to thrombosis (e.g., hypertension, bacterial endotoxins, vasculitis

Answer 438

Turbulence injures endothelium, forming countercurrents and local stasis. Causes: aneurysm, MI, bed-rest, hyper-viscosity syndromes, sickle cell anemia, ulcerated atherosclerosis, mitral valve stenosis.

Answer 439

Primary (inherited): Factor V Leiden, mutations in anticoagulant genes (AT III, proteins C&S). Secondary (acquired): HIT (autoantibodies to heparin-platelet complexes), antiphospholipid syndrome (autoantibodies to phospholipids), oral contraceptives, age-related changes.

Answer 440

Can develop anywhere in the cardiovascular system. Arterial/cardiac thrombi: sites of endothelial injury/turbulence. Venous thrombi: sites of stasis. Thrombi are attached to the vascular surface, with distinct growth directions for arterial (retrograde) and venous (direction of blood flow). Lines of Zahn: laminations indicating antemortem thrombosis. Types: mural thrombi, arterial thrombi, venous thrombi, postmortem clots, vegetations.

Answer 441

Propagation: thrombus enlarges, increasing obstruction/embolism risk. Embolization: fragments transported elsewhere. Dissolution: removed by fibrinolysis, inefficient in older thrombi. Organization and recanalization: endothelial cells, smooth muscle, fibroblasts ingrow; capillary channels form, reestablishing lumen continuity.

Answer 442

Sudden onset of widespread microvascular thrombosis. Thrombi cause ischemia in brain, lungs, heart, kidneys, and hemolysis. Consumes platelets and clotting factors, leading to bleeding. Not a primary disease; potential complication of various conditions. Causes: obstetric complications, advanced malignancy, sepsis (increased TF, IL-1, TNF).

Answer 443

Active process with increased blood flow due to increased activity (e.g., inflammation, exercise). Tissue becomes redder due to oxygenated blood accumulation. Vasodilation causes: sympathetic tone, vasodilators (histamine, bradykinin), inflammation. Increased activity releases metabolites (CO2, adenosine) causing vasodilation, increasing blood flow.

Answer 444

Passive process with impaired venous outflow (systemic due to heart failure, local due to vein obstruction). Tissue becomes cyanotic due to deoxygenated blood accumulation. Acute or chronic; chronic congestion can cause hypoxia, parenchymal death, tissue fibrosis, edema, vessel rupture, and focal hemorrhage.

Answer 445

Extravasation of blood into extravascular space. Causes: trauma, atherosclerosis, inflammatory/neoplastic vessel erosion, chronic congestion. External or confined within tissue (hematoma).

Answer 446

Petechia: 1-2 mm, associated with thrombocytopenia, defective platelets, vitamin C deficiency. Purpura: 3-5 mm, associated with trauma, vasculitis, vascular fragility. Ecchymoses: 1-2 cm subcutaneous hematoma; RBC degradation (Hb → bilirubin → hemosiderin).

Answer 447

Hemothorax, hemopericardium, hemoperitoneum, hemarthrosis (joints). Extensive hemorrhage can cause jaundice (increased bilirubin). Recurrent external bleeding can lead to iron deficiency anemia. Blood loss >20% may cause hemorrhagic shock.

Answer 448

Swelling due to fluid accumulation in extravascular spaces. Can accumulate in body cavities: hydrothorax, hydropericardium, hydroperitoneum/ascites. Anasarca: severe edema with swelling of subcutaneous tissue and fluid in body cavities. Types of fluid: transudate (low protein, <1.012 specific gravity), exudate (high protein, >1.012 specific gravity).

Answer 449

Systemic: mostly due to congestive heart failure. CO↓ → renal perfusion↓ → RAS activation → Na⁺ and water retention → increased hydrostatic pressure in veins → edema. Treatment: anti-aldosterone/diuretics. Local: venous obstruction (e.g., thrombosis) causes local edema distal to thrombus.

Answer 450

Causes: reduced synthesis or increased loss of albumin. Nephritic syndrome: increased glomerular permeability. Liver diseases (e.g., cirrhosis): reduced synthesis. Protein malnutrition. Result: fluid moves from plasma to interstitium, causing edema.

Answer 451

Causes: inflammatory/neoplastic obstruction (e.g., parasites causing fibrosis), surgical removal of lymph nodes (e.g., breast cancer therapy). Result: localized lymphedema.

Answer 452

Primary: associated with renal dysfunction. Na⁺ retention increases hydrostatic pressure and decreases oncotic pressure. Secondary: due to congestive heart failure.

Answer 453

Microscopically: clearing and separation of ECM elements, cell swelling. Common sites: subcutaneous tissues, lungs, brain. Subcutaneous: dependent edema (gravity-dependent, common in cardiac failure), pitting edema. Pulmonary: seen in left ventricular failure, lungs weigh 2-3 times normal weight. Brain: localized (injury, infarct, abscess, neoplasm) or generalized (encephalitis, venous outflow obstruction).

Answer 454

Misfolded proteins aggregate, forming insoluble amyloid fibrils. Deposits in extracellular space, causing tissue damage and functional compromise. Normal proteins degraded via proteasome (IC) or macrophages (EC).

Answer 455

Amyloid: insoluble fibrous protein with β-pleated sheet configuration, eosinophilic in H&E, apple-green birefringence with Congo red stain. 95% fibrillar proteins + 5% P proteins (PG, GAG, SAP). Types: AL (Amyloid Light-chain): plasma cells, immunoglobulin light chains, multiple myeloma. AA (Amyloid-Associated): SAA protein from liver, chronic inflammation. Aβ: amyloid precursor protein (APP), Alzheimer'

Answer 456

Primary: monoclonal plasma cell proliferation (AL type), multiple myeloma, monoclonal gammopathy, Bence Jones proteins. Deposits in kidneys, heart, PNS, GI tract. Secondary: chronic inflammatory process (AA type), TB, RA, renal carcinoma, Hodgkin lymphoma. IL-1, IL-6 → SAA → AA. Hemodialysis-associated: β2-microglobulin not filtered, deposits in joints.

Answer 457

Amyloid deposition in a single organ: lungs, larynx, skin, urinary bladder, tongue. Senile cerebral: Aβ amyloid, Alzheimer's disease, chromosome 21 (Down syndrome). Endocrine: medullary thyroid carcinoma (calcitonin-derived), Type II diabetes (amylin in pancreas).

Answer 458

Familial Mediterranean fever: autosomal recessive, pyrin gene, overproduction of IL-1, SAA → AA. Periodic fever, serosal inflammation. Familial amyloidotic polyneuropathies: autosomal dominant, mutant transthyretin (TTR) deposition in nerves. Senile systemic amyloidosis: amyloid of aging, systemic TTR deposition, involves heart.

Answer 459

Kidneys: large, pale, gray, firm, deposits mainly in glomeruli. Spleen: enlarged (200-800g), deposits in splenic follicles and sinusoids, gray, waxy. Liver: massive enlargement (up to 9kg), deposits in space of Disse, hepatic parenchyma, sinusoids. Heart: minimal to moderate enlargement, gray-pink subendocardial elevations, mainly between myocardial fibers. Other organs: adrenal, thyroid, pituitary, starts in epithelial cells, progresses to parenchyma, no functional disturbance.

Answer 460

Phagocytosed by alveolar macrophages, transported to tracheobronchial lymph nodes. Anthracosis: blackening of lymph nodes and pulmonary parenchyma. Heavy accumulation: indicates emphysema or fibroblastic reaction (coal workers' pneumonia).

Answer 461

Brownish-yellow, insoluble pigment from lipid peroxidation. Accumulates in elderly, mainly in heart, liver, brain. Indicates past free radical injury, not harmful. Brown atrophy: large amounts in atrophied tissue.

Answer 462

Brown-black pigment produced by melanocytes (epidermis). Synthesized by tyrosinase, transferred to keratinocytes. Protects against UV radiation. Increased pigmentation: sun tanning. Decreased pigmentation: albinism, vitiligo.

Answer 463

Yellowish pigment, end product of heme degradation. Accumulation causes jaundice, staining mucous membranes, sclera, and organs.

Answer 464

Golden-yellow to brown pigment, derived from hemoglobin, contains iron. Ferritin aggregates (hemosiderin granules), identified by Prussian blue stain. Local excess: results from hemorrhage (bruise). Red-blue: hemoglobin (RBC lysis). Green-blue: biliverdin, bilirubin. Golden-yellow: hemosiderin. Hemosiderosis: systemic iron overload, deposits in liver, bone marrow, spleen, lymph nodes. Causes: increased iron absorption, impaired iron utilization, hemolytic anemia, transfusions. Hereditary hemosiderosis: Hfe gene mutation (chromosome 6), "bronzed diabetes" (micronodular cirrhosis, diabetes mellitus, skin pigmentation).

Answer 465

Abnormal deposition of Ca²⁺ salts along with iron and Mg²⁺ in tissues. Two forms: dystrophic and metastatic calcification

Answer 466

Occurs in dying/dead cells as a response to injury (common in necrosis). Normal serum Ca²⁺ levels. Pathogenesis: crystalline Ca²⁺-phosphate formation. Extracellular: in membrane-bound vesicles, Ca²⁺ and phosphate from degenerating cells. Intracellular: in mitochondria of cells with lost Ca²⁺ regulation. Seen in aortic valves (aortic stenosis) and atherosclerosi

Answer 467

Due to hypercalcemia. Causes: Endocrine dysfunction: increased PTH secretion (tumors). Bone destruction: increased turnover (Paget's disease), immobilization, tumors. Vitamin D disorders: hypervitaminosis, sarcoidosis (macrophages activate vitamin D precursors). Renal failure: phosphate retention, secondary hyperparathyroidism. Excess Ca²⁺ intake. Morphology: affects kidneys, lungs, and gastric mucosa.

Answer 468

Genetic or acquired defects in folding, packaging, transport, or secretion of endogenous substances. Accumulation of exogenous substances due to lack of enzymatic degradation or transport out of the cell.

Answer 469

Abnormal TAG accumulation in parenchymal cells, mainly liver, also heart, kidney, skeletal muscle. Causes: toxins, malnutrition, diabetes mellitus, obesity, anoxia. FFA processes in hepatocytes: esterified into TAGs, converted to cholesterol/phospholipids, oxidized to ketone bodies. Defects in TAG processing lead to accumulation (e.g., alcohol, CCl4, protein malnutrition, anoxia).

Answer 470

Appears as clear vacuoles in parenchymal cells. Special stains: Sudan IV/oil red O (fat appears orange-red), PAS (glycogen appears red-violet). Liver: yellow, enlarged (3-6 kg), soft and greasy. Heart: zebra-like pattern (prolonged hypoxia) or uniformly affected (profound hypoxia).

Answer 471

Component of cell membranes, steroids, bile acids, vitamin D synthesis. Macrophages phagocytose excess lipids forming foam cells. Conditions: Xanthomas: foamy macrophages in subepithelial tissue. Atherosclerosis: foam cells in intimal layer of arteries. Cholesterolosis: cholesterol-laden macrophages in gallbladder lamina propria. Niemann-Pick disease, type C: lysosomal storage disease, enzyme mutation affecting cholesterol trafficking.

Answer 472

Eosinophilic droplets of abnormal proteins, primarily in extracellular spaces. Kidney: increased protein reabsorption in proximal tubules, appearing as pink hyaline droplets. Plasma cells: accumulation of immunoglobulins in RER forming Russell bodies. Liver: Mallory bodies ("alcoholic hyaline") - eosinophilic cytoplasmic inclusions. α1-antitrypsin deficiency: aggregates in ER of liver cells. Brain: Alzheimer's disease - neurofibrillary tangles of aggregated proteins.

Answer 473

Excessive glycogen due to glucose/glycogen metabolism abnormalities. Glycogen appears as clear vacuoles, PAS stain (rose-to-violet color). Glycogen storage diseases: enzymatic defects in glycogen synthesis/breakdown. Diabetes mellitus: glycogen accumulates in renal tubules, hepatocytes, cardiac myocytes, pancreatic β cells.

Answer 474

Pathologic premature cell death in living tissue, can lead to organ death. Characterized by loss of membrane integrity, cellular content leakage, inflammation.

Answer 475

Protein denaturation (low pH from hypoxia-induced glycolysis). Plasma membrane disruption. Enzymatic digestion: Autolysis: by intracellular enzymes (lysosomes). Heterolysis: by extrinsic enzymes (leukocyte enzymes). Cytoplasmic changes: increased eosinophilia. Nuclear changes: karyolysis, pyknosis, karyorrhexis. Necrotic cells may be replaced by myelin, phagocytosed, and degraded to FA, which may calcify.

Answer 476

Ischemia → infarction (necrosis). Red infarct: loosely organized organ, blood reentry. White infarct: arterial occlusion. Characteristic of ischemic infarcts in all solid organs except the brain. Dead tissue cells, preserved architecture (for days), firm texture. Protein denaturation predominates, no proteolysis, eosinophilia. Digested by leukocytes, debris removed by phagocytes

Answer 477

Affects lower limbs due to blood supply loss, secondary to coagulative necrosis. Wet gangrene: bacterial infection modifies coagulative necrosis by liquefaction. Dry gangrene: coagulative necrosis without liquefaction.

Answer 478

Bacterial/fungal infections stimulate inflammatory cells, enzymes digest tissue. Hypoxic death in CNS causes liquefactive necrosis (microglial cells with hydrolytic enzymes), also seen in abscesses and pancreatitis. Dead cells fully digested, tissue becomes liquid viscous mass. Loss of basophilia, pus formation if initiated by acute inflammation.

Answer 479

"Cheese-like" white, friable tissue (mycobacterium tuberculosis, fungal infection). Tissue architecture obliterated, amorphous granular appearance, no cellular outlines. Enclosed within inflammatory border, characteristic of granulomas. Granulomatous reaction: necrotic area with multinucleated giant cells, epithelial cells, T cells, fibroblasts.

Answer 480

Necrotic adipose tissue from activated pancreatic lipases (pancreatitis). Pancreatic enzymes leak to peritoneal cavity, liquefying fat cell membranes. Digestion of TAGs releases FFAs, combine with Ca²⁺, forming chalky white areas (saponification). Characteristic of trauma to fat (e.g., car accidents) and pancreatitis.

Answer 481

Seen in immune reactions involving blood vessel damage. Antigen-antibody complexes and fibrin deposited in vessel walls. Bright pink, amorphous appearance in H&E stains ("fibrinoid"). Causes: malignant hypertension, vasculitis (protein leakage into vessel wall).

Answer 482

Ischemia: diminished blood flow due to arterial obstruction. Anemia: reduced RBCs or Hb molecules. CO poisoning: CO's high affinity for Hb. Decreased perfusion: CHF, shock, hypertension. Poor oxygenation: pulmonary diseases.

Answer 483

Mitochondrial damage: reduced ATP production, pro-apoptotic enzyme release. Plasma membrane damage: loss of osmotic balance, fluid/ion influx, content loss. Lysosomal damage: digestive enzyme leakage into cytopla

Answer 484

High conduction channels ("mit. permeability transition pores") → membrane potential loss. ATP depletion, ROS formation, pro-apoptotic molecule leakage. Cyt-C diffusion to cytosol → caspase stimulation → apoptosis. Oxidative stress: excess ROS due to increased production or ineffective scavenging.

Answer 485

Anaerobic glycolysis: decreased glycogen, lactic acidosis, pH↓ → chromatin clumping, enzymatic activity↓. Na⁺/K⁺ pump failure: IC Na⁺↑, water retention, cell/ER swelling, microvilli loss, ribosome detachment → protein synthesis↓. Ca²⁺ pump failure: IC Ca²⁺↑, enzyme activation (proteases, caspases, phospholipases).

Answer 486

Mitochondrial and lysosomal swelling. Extensive plasma membrane damage. Massive Ca²⁺ influx. Release of IC enzymes into circulation (AST, LDH, CK, troponin, ALT, alkaline phosphatase, gamma-glutamyl transferase).

Answer 487

Neurons: 3-5 minutes; purkinje cells of cerebellum & hippocampus more sensitive. Myocardial and hepatic cells: 1-2 hours. Skeletal muscle cells: several hours.

Answer 488

Increased eosinophilia: eosin binds to denatured proteins, loss of RNA basophilia. Glassy, homogenous appearance: loss of glycogen particles. Vacuolated cytoplasm: enzyme digestion of organelles. Myelin figures: large masses of phospholipids from damaged membranes. Calcification: eventual fate of dead cells. Electron microscopy: discontinuous membranes, mitochondrial dilation, lysosomal disruption, cytoplasmic myelin figures, nuclear changes (pyknosis, karyorrhexis, karyolysis).

Answer 489

Occurs when the adaptive capability of the cell is exceeded. Reversible within limits; severe/persistent stress leads to irreversible injury and cell death. Cellular function may be lost before cell death, with morphologic changes lagging.

Answer 490

Cell can return to normal state if stress is removed (early stages/mild injury). Significant structural/functional abnormalities, but no severe membrane damage/nuclear dissolution. Types: Cellular swelling: due to ion pump failure, Na⁺↑, water retention. Fatty change: lipid vacuoles in cells involved in fat metabolism (liver, heart).

Answer 491

Cellular swelling: clear vacuoles in cytoplasm, organ pallor, turgor, increased weight. Fatty change: lipid vacuoles, displaced nucleus, fatty cysts, eosinophilic staining. Plasma membrane: blebbing, blunting, microvilli distortion, IC attachment loosening. Mitochondria: swelling, phospholipid-rich densities. ER: dilation, ribosome detachment. Nucleus: chromatin clumping.

Answer 492

Inability to reverse mitochondrial damage. Profound membrane dysfunction. Necrosis: morphological changes from enzyme degradation, autolysis, heterolysis. Apoptosis: programmed cell death

Answer 493

Functional/biochemical abnormalities in: Mitochondria (ATP generation) Cell membranes (ionic/osmotic homeostasis) Protein synthesis Cytoskeleton DNA

Answer 494

Hypoxia/toxins/ROS/radiation → mitochondrial damage. High conduction channels ("mit. permeability transition pores") → membrane potential lost. ATP depletion, ROS formation, pro-apoptotic molecule leakage. Cyt-C diffusion to cytosol → caspase stimulation → apoptosis

Answer 495

Hypoxia/toxins/ETC disruption → ATP depletion. Anaerobic glycolysis: glycogen↓, lactic acidosis, pH↓, chromatin clumping, decreased enzymatic activity. Na⁺/K⁺ pump failure: IC Na⁺↑, water retention, cell/ER swelling, microvilli loss, ribosome detachment, protein synthesis↓. Ca²⁺ pump failure: IC Ca²⁺↑, enzyme activation (proteases, caspases, phospholipases).

Answer 496

Ischemia/toxin → release of sequestered Ca²⁺ from mitochondria/SER. Increased IC Ca²⁺ → mitochondrial permeability transition pores, apoptosis. Enzyme activation (ATPase, phospholipase, protease, endonuclease).

Answer 497

Ischemia/toxin/lytic complement components → damage to plasma/lysosomal membranes. Loss of osmotic balance, fluid/ion influx, cellular content l

Answer 498

Genetic mutations and environmental factors can cause DNA damage and protein misfolding. Misfolded proteins accumulate, leading to cellular dysfunction

Answer 499

Reversible changes in size, number, phenotype, or function of cells in response to environmental changes. Achieves a new steady state to preserve cell function

Answer 500

Response to normal stimulation by hormones or endogenous mediators. Examples: Opening/closing of ion channels. Enlargement of breast and uterus during pregnancy.

Answer 501

Response to stress that allows modulation of cell structure to escape injury. Types: Atrophy Hypertrophy Hyperplasia Metaplasia Dysplasia

Answer 502

An organ is in homeostasis with the physiologic stress placed on it. Changes in stress (increase, decrease, or change) result in growth adaptations. Adaptation: cell response to stimuli (stress) to achieve a new steady state and preserve function.

Answer 503

Responses to normal stimulation by hormones or endogenous mediators. Examples: Opening/closing of ion channels. Enlargement of breast and uterus during pregnancy.

Answer 504

Responses to stress that allow modulation of cell structure to escape injury. Types: Atrophy Hypertrophy Hyperplasia Metaplasia Dysplasia

Answer 505

Decrease in size of an organ due to decreased stress. Causes: decreased hormonal stimulation, disuse, nutrient supply, blood supply, denervation, aging. Mechanisms: decreased cell number (apoptosis), decreased cell size (ubiquitin-proteasome degradation, autophagy).

Answer 506

Energy-dependent, genetically programmed cell death. Characterized by nuclear dissolution without complete loss of membrane integrity, no inflammation. Examples: Physiological: endometrial shedding, embryogenesis, T cell-mediated killing, cell loss in proliferating populations, elimination of self-reactive lymphocytes. Pathological: DNA damage, misfolded proteins, cell injury due to infections, pathologic atrophy after duct obstruction.

Answer 507

Mediated by caspases, which activate proteases (cytoskeleton breakdown) and endonucleases (DNA breakdown). Pathways: Intrinsic mitochondrial: loss of growth factor stimulation, DNA damage, misfolded proteins; activation of Bax, Bak; cytochrome c release, caspase activation. Extrinsic death receptor: FAS ligand, tumor necrosis factor; receptor binding, caspase activation. Cytotoxic CD8+ T cell-mediated: perforins create pores, granzyme activates caspases.

Answer 508

Developmental loss of tissue size. Examples: Uterus: returns to normal size after childbirth. Thymus: begins to atrophy during puberty, replaced by fat.

Answer 509

Continuous exchange of nutrients, fluids, and temperature with the external environment. Stress: any stimulus interrupting cell homeostasis, can be physiological or pathological.

Answer 510

Hypoxia: interferes with aerobic oxidative respiration. Causes: ischemia, hypoxemia, anemia, CO poisoning. Infectious agents: viruses, bacteria, fungi. Genetic defects: congenital malformations, damaged DNA, misfolded proteins. Chemical agents: glucose, salts, pollutants, CO, asbestos. Physical agents: trauma, extreme temperatures, radiation, pressure. Aging: affects cell replication and repair. Immunologic reactions: autoimmune, allergic reactions. Nutritional imbalance: lack of proteins, vitamins.

Answer 511

Reversible changes in size, number, phenotype, or function of cells in response to environmental changes to achieve a new steady state and preserve function. Physiological adaptation: response to normal stimulation by hormones or endogenous chemicals. Pathological adaptation: response to stress to avoid cell injury. Types: hyperplasia, hypertrophy, metaplasia, atrophy, dysplasia.

Answer 512

Occurs when the cell is exposed to severe stress exceeding its adaptive capability. Can be acute or chronic

Answer 513

Reversible: cell can return to normal if stress is removed. Morphological correlates: cellular swelling, fatty change. Irreversible: cell will eventually die (necrosis or apoptosis). Characterized by mitochondrial dysfunction and profound membrane disturbance.

Answer 514

Cellular swelling: failure of energy-dependent ion pumps, ATP depletion, ion pump failure, IC Na⁺↑, water retention, swelling, loss of microvilli, bulging, rER swelling, ribosome detachment. Fatty change: lipid vacuoles in cytoplasm, abnormal TAG accumulation, seen in liver, heart, kidney.

Answer 515

Necrosis: always pathological, loss of membrane integrity, cell lysis. Apoptosis: programmed cell death, no inflammation, due to lack of growth factors or DNA/protein damage.

Answer 516

Causes: various types of stress. Distinctive alterations in organelles: Autophagy: lysosomal digestion of the cell's own components. Hypertrophy of sER: exposure to chemicals (e.g., barbiturates). Mitochondrial alterations: changes in number, size, shape. Cytoskeletal abnormalities: drug interference, polymerization disruption, fibrillar material accumulation, defective organelle mobility.