PATH 370 Week 2 Chap 10, 11, 13, 14, 15

Flashcards covering medical concepts from Chapters 10-15, including hypersensitivity, malignant WBC disorders, anemias, and coagulation disorders.

Hypersensitivity

Describes the mechanism of injury that leads to inflammation and may or may not involve autoimmunity.

Type I Hypersensitivity

The FASTEST hypersensitivity reaction involving IgE antibodies binding to mast cells via Fc receptors; allergen cross-linking induces degranulation and histamine release (e.g., anaphylaxis, food allergies, hay fever). Allergen → IgE → Mast cell activation → Histamine release→ Allergy symptoms

Type II Hypersensitivity

Involves IgG or IgM binding to cell-bound antigens, leading to complement activation, cell lysis, or ADCC mediated by cytotoxic T-cells, NK cells, neutrophils, and macrophages. ON CELL; ANYTHING W BLOOD IS TYPE II

EX: Red blood cell destruction after transfusion with mismatched blood types or during hemolytic disease of the newborn.

Type III Hypersensitivity

Caused by soluble antigen-antibody complexes (IgG and IgM) deposited in tissues, which recruit neutrophils and cause tissue damage via enzyme release. INSIDE OR OUTSIDE CELL

EX: Post-streptococcal glomerulonephritis, rheumatoid arthritis, and systemic lupus erythematosus.

Type IV Hypersensitivity

The SLOWEST reaction (24-48 hrs) mediated by T Cells; $T_H1$ cells secrete cytokines to activate macrophages and cytotoxic T cells

(e.g., contact dermatitis, type I diabetes mellitus).

Autoimmunity WHAT GENES

A condition where the immune system attacks its own tissue due to abnormal, excessive immune responses; associated with MHC (HLA) genes and a higher risk in females.

Autoimmunity Etiology

abnormal, excessive immune responses towards own tissue

Autoimmunity Treatment

Individualized immunosuppressive therapy; corticosteroids and cytotoxins, tumor necrosis factor inhibitors, and immunomodulators, therapeutic plasmapheresis

Anti-Type 1 Hypersensitivity (6)

IgE therapy, Antihistamines, Epinephrine, Beta-Adrenergics, Corticosteroids, Anticholinergics

IgE Therapy

inhibits the binding of IgE to mast cells (only for Type I), stops IgG from activating mast cells.

Antihistamines

block the effects of histamine- prevent histamine from causing symptoms

Epinephrine:

reverses the symptoms of histamine after they’ve already begun; Highly Allergic people can carry an EPIPen; An adrenergic agent given subQ or IV during acute allergic reactions; Used during emergency reaction (anaphylaxis)

Beta-adrenergic

Relax the smooth muscles around the bronchi; decrease bronchoconstriction and open airways

Corticosteroids

decrease inflammatory response

Anticholinergics

block the parasympathetic system by decreasing bronchoconstriction and mucus

Hematologic Neoplasms

Defined as blood cancers that are classified by which blood cell became neoplastic.

Myeloid Lineage

A classification of blood cells that includes RBCs, platelets, Monocytes, and Granulocytes (neutrophils, eosinophils, basophils).

Lymphoid Lineage

A classification of blood cells that includes B Cells, T Cells, and NK (Natural Killer) Cells.

Malignant Disorders of WBCs

Leukemia, lymphoma, and plasma cell myeloma are common neoplastic disorders of the bone marrow and lymphoid tissues.

Leukemia

Circulating tumors that primarily involve the blood and bone marrow.

Typical S/S of Leukemia

malaise, weakness, unexplained fever, night sweats, recurrent infections, enlarged, nontender lymph nodes (lymphadenopathy) with lymphoma and some leukemias, Very high total WBC count or the presence of abnormal cell types

Most Common Clinical Manifestations of Malignant WBC Disorders:

Anemia, thrombocytopenia, leukopenia, neutropenia

Principles of Treatment for Leukemia

combination chemotherapy to remove malignant cells (primary), stem cell transplant to rescue and restore bone marrow function (primary), radiation and tissue-specific drug therapy may be indicated in some cases

List all of the types of Leukemia/Lymphomas:

Chronic Myeloid Leukemia (CML), Acute Myeloid Leukemia (AML), Chronic Lymphoid Leukemia (CLL), Acute Lymphoblastic Leukemia/Lymphoma (ALL), Hodgkin’s/Non-Hodgkin’s, Multiple Myeloma

Chronic Myeloid Leukemia (CML)

A malignancy characterized by granulocytes carrying the Philadelphia ($Ph+$) chromosome, resulting from a translocation of chromosomes $9$ and $22$ creating the BCR/ABL fusion gene that increases cell proliferation and reduces apoptosis. Average onset-> 40-50 years/Adult

Clinical Presentation of CML:

High granulocyte count on CBC and splenomegaly

Treatment/Prognosis of CML:

CML does not respond well to therapy, has poor overall survival time, and untreated patients have a median survival of 2 years.

Acute Myeloid Leukemia (AML)

A blood cancer with an abrupt onset where the bone marrow aspirate must contain > 20 \% blasts for diagnosis; median age of onset is $64$ year; 80% of cases are adults.

Prognosis for AML

Worse than ALL (Acute Lymphoblastic Leukemia/Lymphoma), Less than 50% of children survive and 30% of adults survive long term.

Chronic Lymphoid Leukemia (CLL)

The most common leukemia in the United States (30%), 95% of cases involve malignant B-cell precursors and follow an indolent (slow-growing) course; 5% associated with more aggressive T-cell transformation; asymptomatic; Usually found by accident in routine blood examinations

If CLL becomes symptomatic: S/S of CLL

fatigue, weight loss, anorexia, increased susceptibility to infections, enlarged painless lymph nodes, enlarged spleen.

Pathogenesis of CLL:

Malignant lymphocytes invade lymphoid tissues and bone marrow--disrupts function; Reduces production of red blood cells/platelets; too many (preponderance) of lymphoid cells

Acute Lymphoblastic Leukemia/Lymphoma (ALL)

The most common malignancy in children, peaking between ages $3$ and $7$(second peak middle age)

Symptom onset for ALL:

Abrupt; Bone pain, bruising, fever, infection; Children may refuse to walk (Hematothrosis= bleeding joints); Loss of appetite, fatigue, abdominal pain; Enlarged spleen, liver, lymph nodes; 3% may present with CNS signs

Treatment/Prognosis of ALL:

85% 5-year survival rate in children; 30% to 50% in adults (Better prognosis in children than adults); Certain forms of ALL more responsive to therapy; Chemotherapy for remission inductionare

Hematothrosis

A condition in children with ALL that causes them to refuse to walk due to bone/joint pain.

Hodgkin Lymphoma

A B-cell malignancy characterized by Reed-Sternberg Cells and contiguous spread through lymphatic pathways, Cervical Nodes (predictable); risk factors include the EB virus. 20-40 yo males; radiation + chemo survival rate >85%.

Reed-Sternberg Cells

Large, abnormal lymphocytes found in Hodgkin Lymphoma.

Non-Hodgkin Lymphoma

A group of cancers involving B, T, and NK cells that spread in a non-predictable manner; risk factors include HIV, Burkitt Lymphoma, and Epstein-Barr Virus. Prominent in older males—survival rate about 50%. Complications include superior vena cava obstruction or spinal cord compression.

Multiple Myeloma

A malignant disorder of mature B cells, antibody-secreting plasma cells that invade bone (hypercalcemia) and produce excessive identical monoclonal antibodies known as Bence Jones Protein. occurs exclusively in adults (>40); median age 65

Pathogeneses of Multiple Myeloma:

malignant plasma cells produce excessive identical monoclonal antibodies called Bence Jones Protein; accumulate in the blood stream and urine, detected by protein electrophoresis, and form a characteristic spike.

Bence Jones Protein

Identical monoclonal antibodies produced in Multiple Myeloma that accumulate in blood and urine and are detected via protein electrophoresis.

Erythrocytes

RBCs with a normal count of $4.2-6.2\operatorname{mi}llioncells/mm^3$ ; they contain hemoglobin to carry oxygen and remove $CO_2$.

Hematopoiesis:

Making blood cells; Erythopoietin (EPO hormone) helps stimulate blood cell production in the kidneys (adults) or liver and kidneys (fetus/newborn). Renal (kidney) disease disrupts EPO production, decreasing blood cells, causing anemia.

Nutritional requirements for Erythopoiesis:

Requires adequate amounts of iron, protein, vitamins, and minerals; iron for hemoglobin; folate (B9) and Vitamin B12 for DNA synthesis.

Hemoglobin

contains iron (Ferrous Fe2+ and ferric Fe 3+ forms). MCV: 80-100fl (Microcytic, normocytic, and macrocytic)

Erythropoietin (EPO)

A hormone produced by the kidneys (adults) or liver/kidneys (fetus) that stimulates the production of blood cells.

MCV (Mean Corpuscular Volume)

A measure of the average volume of a red blood cell, with normal levels between $80-100\,fL$.

Folate and B 12 deficiencies

disruption in DNA synthesis of blast cells producing megaloblast (macrocytic).

Folate Deficiency:

stem from dietary deficiencies, alcoholism, cirrhosis, pregnancy, or infancy.

Absorption of B12:

in the small intestine requires an intrinsic factor, which is produced by the parietal cells of the stomach; B12 is stored in the liver.

Pernicious Anemia

Anemia caused by a deficiency in intrinsic factor, leading to vitamin $B_{12}$ deficiency.

Clinical Manifestations of Pernicious Anemia:

Low RBC, WBC, and platelet counts w increased MCV; megaloblastic dysplasia; peripheral nerve degeneration, shillings t’s test indicates low B12, and achlorhydria (NO HCL in gastric secretions)

Intrinsic factor

A substance produced by the parietal cells of the stomach required for the absorption of vitamin $B_{12}$ in the small intestine.

Treatment/Prognosis for Folate and B12 Deficiency:

Administer B12 parenterally or orally + potassium supplements. Administer Folic acid. Prognosis: majority respond well to treatment- reversibility of neurologic damage is slow.

Anemia

RBC deficiency (reduction in circulating RBC mass); Low oxygen-carrying capacity leads to hypoxia; Hb <13.5g/dL in males and Hb<12.5 g/dL in females

Clinical Manifestations of Anemia:

weakness, fatigue, dyspnea, pale conjunctiva + skin, headache, lightheadedness, angina (chest pain; esp with preexisting coronary artery disease); Increased heart rate, hypertension, heart failure, Dysrhythmia

Polycythemia

Opposite of anemia- excess of RBCs; primary or acquired; increases blood viscosity + volume, endothelium injury, Systolic BP Increase, left ventricle hypertrophy + failure, systemic hypoxia due to low O2 sat in RBCs.

Aplastic Anemia

A condition characterized by panocytopenia and fatty marrow replacement; normal RBC size, disease of the young (15-25) or old (>60)

Etiology of Aplastic Anemia:

Caused by toxic, radiant, or immunologic injury to the bone marrow stem cells

Diagnosis of Aplastic Anemia:

with bone marrow biopsy

Treatment/Prognosis of Aplastic Anemia:

determine efficacy of bone marrow transplantation, administer immunosuppressive therapy or stimulate hematopoiesis and bone marrow regeneration; fatal unless bone marrow transplant successful

Iron Deficiency Anemia

The most common nutritional deficiency worldwide, characterized by hypochromic, microcytic RBCs, low MCV, and low MCHC. Insufficient iron for hemoglobin synthesis. Serum ferritin level and serum iron decrease, and total iron binding capacity increases.

MCV & MCHC for Iron Deficiency Anemia

Low MCV = microcytic (<80 fL), Low MCHC (hypochromic)(<32 g/dL)

S/S for Iron Deficiency Anemia:

Pica (craving for nonfood substances such as dirt, clay, ice, laundry starch, cardboard, or hair). Koilonychias (spoon-shaped nails), blue sclerae

Treatment/Prognosis for Iron Deficiency Anemia:

Oral administration of ferrous sulfate or IV ferric gluconate (only in severe cases); continue for 4-6 months, treat underlying cause; prognosis excellent

Sickle Cell Anemia

A genetic defect in hemoglobin synthesis leading to hemoglobin instability and sickled cells that cause vascular occlusion. Severe anemia, RBCs of different shapes and sizes, and recurrent painful episodes.

Hemolytic Disease of the Newborn

Occurs when maternal antibodies from an $Rh-$ mother cross the placenta and destroy fetal cells of an $Rh+$ fetus. Maternal antibodies cross into the fetal circulation causing destruction of fetal cells (ABO incompatibility most common; Rh incompatibility more clinically relevant)

Hemophilia

most common coagulation disorder resulting in excessive bleeding due to missing a clotting factor. Inherited as X-linked recessive (mostly affects males). Prolonged bleeding time and prolonged aPTT. Platelet count stays the same.

Hemophilia A + Treatment

A coagulation disorder caused by a deficiency in factor VIII. treatment: cryoprecipitate or factor VIII concentrate

Hemophilia B + Treatment

Also known as Christmas disease, it is caused by a deficiency in factor IX. BT and aPTT time prolonged; Hallmark: hemarthrosis; treatment: fresh frozen plasma or cryoprecipitate

Vitamin K Deficiency

Normal BT, normal platelet count, increased PT/INR

PT/INR

Measures the clotting speed of the EXTRINSIC pathway; Increase = problem with Factor VII or warfarin use.

aPTT

Measures the clotting speed of the INTRINSIC pathway; increase indicates problem by heparin use or problems with factors VIII, IX, XI, or XII.

Bleeding time (BT)

Measures how well platelets form the initial plug; often prolonged by aspirin or platelet disorders.

Hepatic Disease:

increases bleeding risk by reducing vitamin K absorption, decreasing clotting factor production (V and XI), impairing clearance of fibrinolytic proteins, and causing thrombocytopenia.

Treatment of Hepatic Disease:

Vitamin K administration; Platelet transfusion, fresh frozen plasma, or whole/packed blood

What can cause thrombocytopenia?

CHEMOTHERAPY

Stages of Hemostasis:

Primary, Secondary, Clot Retraction.

Primary Hemostasis:

initial response to vascular injury involving the interaction between platelets and the endothelium of the injured vessel; Injured vessel vasoconstricts to prevent blood loss; Formation of a platelet plug.

Secondary Hemostasis:

involves the formation of a fibrin clot through intrinsic and extrinsic pathways; coagulation

Fibrinolysis

The final hemostasis stage involves clot dissolution, where plasminogen is converted to plasmin to digest fibrin and inactivate factors V and VIII.

Von Willebrand Disease (vWD)

An autosomal dominant disorder causing excessive bleeding, characterized by prolonged BT and aPTT but normal platelet count and PT/INR.

Treatment for Von Willebrand Disease

Desmopressin, which releases von Willebrand factor and factor VIII from vascular endothelial cells; Cryoprecipitate and humate-P used to manage severe bleeding; Avoid aspirin use

Disseminated Intravascular Coagulation (DIC)

An acquired hemorrhagic syndrome where clotting and bleeding occur simultaneously; Widespread clot formation in small vessels; Hypoxia; edema. clotting factors and platelets consumed, resulting in bleeding—lethal!!! increased aPTT, PT/INR, BT, D-Dimers

Etiology of DIC

trauma, malignancy, burns, shock, and abruptio placentae; Decreased fibrinogen and platelets; Increased bleeding time; Elevated PT/INR and aPTT, and D-dimer/fibrin split products.

Treatment of DIC

Removal/correction of underlying cause; Support major organs; Fresh frozen plasma, packed red blood cells, platelets, or cryoprecipitate; Heparin used to minimize further consumption of clotting factors (controversial)

Arterial Occlusion

Obstruction that blocks blood flow TO tissue (decreased blood flow downstream, ischemia), resulting in pale, cold, and painful tissue (ischemia).

Venous Occlusion

Obstruction that blocks blood flow FROM tissues, leading to increased pressure upstream (congestion), swelling, warm tissue, and edema.

Thrombus

A stationary blood clot formed within a vessel or a chamber of the heart.

Treatment for Thrombosis

anticoagulant therapy; thrombolytic drugs; surgery to remove thrombus

Venous Thrombosis causes:

peripheral edema

Embolus

Material that forms a traveling clot within the bloodstream; Embolus leaving L ventricle = ischemic stroke; Embolus leaving R ventricle = pulmonary embolus.

Treatment for Embolus

embolectomy/filter in the IVC

Atherosclerosis

The hardening and narrowing of medium and large-sized arteries initiated by endothelial surface damage to the arterial intima which initiates inflammatory damage.

Nonmodifiable Risk Factors:

age, gender, family history, history of coronary artery disease(CAD), ethnicity

Modifiable Risk Factors

Physical activity, tobacco use, Hypertension, hypercholesterolemia, glucose intolerance/metabolic syndrome & diabetes, obesity.

The 6 Ps

Classic signs of acute arterial occlusion: Pallor, Paresthesia, Paralysis, Pain, Polar, and Pulseless.

Deep Vein Thrombosis (DVT)

The formation of a thrombus in a deep vein (usually the leg) that can block venous return and always carries the risk of pulmonary embolism; causes pain, swelling, warmth, redness.

Varicose Veins

Dilated, twisted superficial veins caused by weak valves; not typically life-threatening.