Circulatory Flashcards

Question

**White Blood Cells by Hematopoietic Lineage**

Answer 1

*Myeloid Lineage*: 1. **Neutrophils** – phagocytose bacteria and fungi; degranulate, release ROS, and form NETs 2. **Eosinophils** – fight parasites; contribute to late-phase allergy and inflammation 3. **Basophils** – release histamine, herapin and cytokines; support allergic responses and inflammation 4. **Monocytes** – circulate and become macrophages; perform phagocytosis, secrete cytokines, aid in inflammation 5. **Mast cells** – tissue-resident; trigger allergy and inflammation via histamine and cytokines - *Lymphoid Lineage*: 1. **B lymphocytes** – Produce antibodies 2. **T lymphocytes** – Regulate immune response; kill infected cells 3. **NK (Natural Killer) cells** – Destroy virus-infected and tumor cells - *Key Point*: - **Myeloid** = innate immunity & phagocytosis - **Lymphoid** = adaptive immunity & targeted killing

Answer 2

- *All WBCs* contain **azurophilic (nonspecific) granules** - These are **lysosomes** used in digestion of pathogens - Often appear faint, making cytoplasm look clear - **Granulocytes** (neutrophils, eosinophils, basophils): - Contain specific granules in addition to azurophilic ones - Specific granules hold enzymes, histamine, or antimicrobial compounds - Important for **immune defense** and **inflammatory response** - **Agranulocytes** (lymphocytes, monocytes): - Lack specific granules, but still have azurophilic granules - *Key point*: Only granulocytes have visible, function-specific granules

Answer 3

- *% of WBCs*: 60–70% - *Triggered by*: Bacterial infections, acute inflammation. Also will see increase under acute stress. - *Role*: First-line defense in innate immunity *Functions* 1. **Phagocytosis**: Engulf and digest bacteria and fungi 2. **Degranulation**: Release antimicrobial enzymes such as myeloperoxidase, defensins, and proteases 3. Respiratory burst: Produce and release **reactive oxygen species (ROS)** and **reactive nitrogen species (RNS)** to kill pathogens 4. NET formation: Expel chromatin and granule proteins to form **neutrophil extracellular traps (NETs)** 5. Chemotaxis: Migrate toward infection in response to chemical signals *Appearance* - 3–5 lobed nucleus - Fine, pale violet granules - Size: 9–12 µm

Answer 4

- 1–4% of circulating leukocytes - *Myeloid lineage* → granulocyte *Primary roles* 1. **Defend against multicellular parasites** - targets helminths, some protists, and fungi - IgE exposure -> upregulate IgE receptors on eosinophil surface -> bind IgE-coated parasites upon re-exposure - **degranulate** → release major basic protein, eosinophil peroxidase, other toxic proteins - produce **reactive oxygen species (ROS)** enzymatically (not from granules) - result: combined damage to parasites and coordination of immune defense 2. **Modulate allergic inflammation** - active in late-phase allergic responses (e.g. asthma, eczema) - bind IgE-coated allergens → trigger degranulation and release of toxic granule proteins - degrade histamine via enzymes → helps limit early allergic signals - cause tissue damage if granule toxins and ROS outweigh histamine-degrading effects 3. **Perform minor phagocytosis** - engulf antigen-antibody complexes and debris - functionally limited; not a major phagocyte *Increased in*: parasitic infections, asthma, allergies, autoimmune diseases - levels fluctuate diurnally and with the menstrual cycle

Answer 5

**Basophils** - *% of WBCs*: <0.5% count is relatively stable under normal conditions - Increases in certain viruses (chickenpox, sinusitis), and certain diseases (diabetes mellitus, myxedema, and polycythemia) often found in connective tissue / skin. 1. Mediate **inflammatory response** → Secrete **cytokines**, **histamine** (→ vasodilation), and **heparin** (→ anticoagulant) → Increase **capillary permeability** to recruit immune cells and proteins 2. Contribute to **allergic reactions and anaphylaxis** → After first exposure to an allergen, B cells produce allergen-specific IgE → IgE binds to FcεRI receptors on the surface of basophils - The basophils now “carry” IgE on their surface → On re-exposure, the allergen binds to and cross-links these surface-bound IgE antibodies → This activates the basophil, triggering release of histamine and inflammatory mediators (histamine/heparin/leukotriens/prostaglandins/cytoines) → Results in allergy symptoms like itching, swelling, runny nose, and watery eyes

Answer 6

- ~20–40% of circulating leukocytes - *Lymphoid lineage* → adaptive immunity (T & B cells), innate (NK cells) 1. **T lymphocytes (T cells)** - *Develop in*: Thymus - *Types & Functions*: - **Helper T cells (CD4⁺)**: Activate B cells, cytotoxic T cells, and macrophages - **Cytotoxic T cells (CD8⁺)**: Kill virus-infected and cancerous cells via perforin/granzymes - **Regulatory T cells**: Suppress autoimmunity and modulate immune responses - *Key role*: Cell-mediated immunity - *Memory T cells*: Long-term adaptive memory 2. **B lymphocytes (B cells)** - *Mature in*: Bone marrow - *Function*: Humoral immunity (antibody production) - *Differentiate into*: - **Plasma cells**: Secrete large amounts of specific antibodies - **Memory B cells**: Provide long-term immunity 3. **Natural Killer (NK) cells** - *Lymphoid origin*, but part of innate immunity - *Function*: Kill virus-infected or tumor cells without prior activation - *Mechanism*: Use perforin and granzymes - *No antigen-specific receptors* (no TCR or BCR) *Increased in*: Viral infections, chronic immune activation, some cancers

Answer 7

**Monocytes, Macrophages, and Dendritic Cells** - **3–8%** of circulating leukocytes - *Lineage*: **Myeloid** → **Monocytes** (circulate in blood) → Differentiate into **macrophages** or **dendritic cells** in tissues - marcrophages named for location ex / **Dust cells** alveolar macrophages (lungs) *Functions* 1. **Phagocytosis** → Engulf pathogens & debris via receptors (e.g. TLRs, Fc, C3b) → Digest in lysosomes 2. **Antigen presentation** → Display pathogen peptides on **MHC II** to **CD4⁺ T cells** → Requires co-stimulatory signals (CD80/86) 3. **Cytokine secretion** → Release **IL-1**, **IL-6**, **TNF-α** to amplify inflammation 4. **Tissue repair** → Secrete growth factors after inflammation to promote healing **Dendritic cells** (professional APCs) - Found in **skin, mucosa, lymphoid tissue** (not just skin) - Capture antigen in periphery → migrate to lymph nodes - Present antigen to **naïve T cells** to activate adaptive immunity - Some arise from monocytes; others from distinct precursors - *Increased in*: Chronic inflammation, immune activation, some viral infections

Answer 8

- *Definition*: Low white blood cell count (<5,000/µL) - *Causes*: Radiation, poisons, infectious disease - *Effects*: Increased susceptibility to infection due to reduced immune surveillance

Answer 9

- *Definition*: Elevated white blood cell count (>10,000/µL) - *Causes*: Infection, allergy, inflammation, disease - *Notes*: - Often evaluated using a **differential WBC count** - Determines relative percentages of each leukocyte typ

Answer 10

- *Definition*: Cancer of **hematopoietic tissues** (bone marrow and blood) - *Types*: - **Myeloid** or **lymphoid** origin (based on affected stem cell line) - **Acute**: Rapid progression, death within months if untreated - **Chronic**: Slower onset, median survival ~3 years untreated - *Pathology*: - Uncontrolled proliferation of **immature or abnormal WBCs** - Crowds out normal hematopoiesis → **anemia**, **thrombocytopenia**, **immunosuppression** - *Why it may go undetected*: - Malignant WBCs are often recognized as **"self"** by the immune system - No early pain or inflammation signals; changes in blood counts may be gradual - *Clinical consequence*: - Immunocompromised state allows **opportunistic pathogens** to cause infection - Especially vulnerable to fungi, viruses, and atypical bacteria Bone transplants can be cure

Answer 11

- *Definition*: IV transfer of healthy donor bone marrow into a patient - *Procedure*: 1. Destroy patient's diseased marrow with radiation and chemotherapy 2. Ensure donor and recipient share matching surface antigen (HLA compatibility) 3. Infuse donor marrow into patient's vein for reseeding of hematopoietic stem cells 4. Success depends on histocompatibility - *Used to treat*: - **Leukemia** - **Sickle cell disease** - **Aplastic anemia** - **Lymphoma** - **Breast, ovarian, or testicular cancers**

Answer 12

- *Purpose*: Measures percentages and absolute counts of circulating blood cells - Detects: Infection, leukemia, anemia, parasites, chemotherapy effects, allergies, toxicity - **Neutrophils**: 60–70% → ↑ in bacterial infections, stress, inflammation - **Lymphocytes**: 25–33% → ↑ in viral infections, some leukemias - **Monocytes**: 3–8% → ↑ in viral, fungal, or chronic inflammation - **Eosinophils**: 2–4% → ↑ in parasitic infections, allergic reactions, asthma. Normally fluctate from day to night, seasonally, with phase of menstral cycle. - **Basophils**: <1% → ↑ in allergic reactions, hypothyroidism, diabetes, chickenpx, sinusitis, polycythemia **Reticulocyte count**: - *Reticulocytes*: Immature RBCs normally ~0.5–2% of total RBCs - ↑ Reticulocytes indicate -> Increased RBC production by bone marrow -> hemolytic anemia, acute blood loss - ↓ Reticulocytes suggest Bone marrow suppression or failure (e.g. aplastic anemia, chemotherapy)

Answer 13

**Platelets (Thrombocytes)** - *Definition*: Small, anucleate fragments of **megakaryocyte** cytoplasm - Circulate as functional, cell-like elements - Also called **thrombocytes** (though not true cells) - *Structure*: - Contain **granules**, mitochondria, and an **open canalicular system** (membrane invaginations for secretion) - Capable of **amoeboid movement** via pseudopods - May engage in limited **phagocytosis** (e.g., viruses, immune complexes) - *Relative abundance*: - **Second most abundant formed element** (after erythrocytes) - *Functions*: 1. Secrete **vasoconstrictors** → reduce blood loss 2. Chemotactically attract **neutrophils** and **monocytes** to injury/inflammation 3. Aggregate to form **platelet plugs** at damaged vessels 4. Release **polyphosphates** → activate **Factor XII** → initiate the **intrinsic coagulation pathway** 5. Support **fibrinolysis** by promoting **plasmin formation** through Factor XII–mediated activation of **kallikrein** 6. Secrete **platelet-derived growth factor (PDGF)** → stimulate **fibroblast** and **smooth muscle** mitosis for vessel repair

Answer 14

- *Definition*: Formation of platelets from stem cells in the bone marrow - *Hormonal control*: Stimulated by **thrombopoietin** secrted by liver **Steps**: 1. Stem cells develop receptors for thrombopoietin and become **megakaryoblasts** 2. **Megakaryoblasts** undergo repeated mitosis without cytokinesis → large **megakaryocytes** (≈100 µm, multilobed nucleus) 3. **Megakaryocytes** reside adjacent to bone marrow sinusoids 4. Extend long cytoplasmic projections (proplatelets) into the blood sinusoids 5. Blood flow shears off fragments → pro platelets -> **platelets** 6. Platelets **circulate 5–6 days**; ~40% stored in the **spleen** *Platelets are small cytoplasmic fragments essential for clotting, inflammation, and vessel repair.*

Answer 15

Physiological process that stops bleeding through vascular, platelet, and coagulation responses. All involve platelets 1. **Vascular Spasm** - Caused by pain receptors, smooth muscle injury, and serotonin release from platelets - Results in vasoconstriction of broken vessels - Provides time for next hemostatic steps - Short duration (nerve-based) or longer (muscle injury) 2. **Platelet Plug Formation** - Intact vessels have a smooth endothelium coated with **prostacyclin** which repels platelets. - Vessel injury exposes collagen → platelets adhere via pseudopods - Platelets pseudopods contract to form a plug - Platelets degranulate releasing: - **Serotonin** -> vasoconstriction - **ADP** -> attracts more platelets - **Thromboxane A₂** (paracrine / eocosanaid) -> promotes aggregation and degranulation -> Positive feedback loop until vessel break is sealed 3. **Coagulation (Clotting)** Last and most effective defense. Conversion of plasma protein fibrinogen into insoluble fibrin threads to form framework of clot (scab). - Procoagulants (clotting factors) - usually produced by the liver are present in plasma. Activate one factor and it will activate the next to form a reaction cascade. - Two activation pathways: - **Extrinsic**: Tissue factors released from damaged tissue - **Intrinsic**: Factors in blood -> specifically platelets

Answer 16

- *Coagulation factors* = **plasma proteins** (usually made by liver) that circulate in inactive form and activate in a cascade during clotting - *Purpose*: Convert **fibrinogen** → **fibrin** → forms stable clot - *Calcium (Ca²⁺)* is required for both pathways 1. **Extrinsic Pathway** - Trigger: Tissue damage → release of Factor III - Cascade: Factor III with help of factor VII → activates X 2. **Intrinsic Pathway** - **Factor XII** (from plasma) is activated by **negatively charged surfaces**, including **polyphosphates released by activated platelets** - Cascade: XII → XI → IX (+ VIII + Ca²⁺) → activates **Factor X** Usually both pathways are activated at the same time. Extrinsic happens faster (fewer steps) - *Common Pathway* - both need calcium - Activated **Factor X** converts **prothrombin (Factor II)** → **thrombin** - Thrombin converts **fibrinogen (Factor I)** → **fibrin** -> mesh network This pathway is a positive feed back look also the signal is amplified. Clinical note: disease when coagulation just happens don't know name

Answer 17

- *Definition*: **Clotting factors**—mostly plasma proteins made by the **liver**, circulating in inactive form - Activated in a **reaction cascade**, where one factor activates the next in sequence *Reaction Cascade Overview* 1. **Initiation**: Intrinsic (platelets/F XII) or extrinsic (tissue damage/F III) triggers cascade 2. **Amplification**: Each activated factor enzymatically activates the next (e.g., XIIa → XIa → IXa, etc.) 3. **Common Pathway**: - Factor X → Xa - Xa + Factor V → converts **prothrombin (F II)** → **thrombin** - Thrombin converts **fibrinogen (F I)** → **fibrin** - **Factor XIII** cross-links fibrin into stable mesh - *Key concept*: Cascade = **positive feedback loop** → rapid clot formation

Answer 18

**Clot Retraction** - Begins within 30 minutes*of clot formation - Platelets contract and pull on **fibrin strands**, compacting the clot and drawing damaged vessel edges together - Platelets and endothelial cells secrete **platelet-derived growth factor (PDGF)**: - Stimulates **fibroblasts and smooth muscle cells** to undergo mitosis and repair vessel wall **Fibrinolysis (Clot Dissolution)** - Goal: **Remove the clot once tissue repair is complete** - **Factor XII** (Hageman factor) initiates a cascade that accelerates: - Formation of **kallikrein** (enzyme) - Kallikrein converts **plasminogen** (inactive) → **plasmin** (active enzyme) - **Plasmin** breaks down **fibrin polymer** into degradation products → positive feedback: **plasmin** promotes formation of more **kallikrein**, accelerating clot dissolution - **Platelets** support this process by releasing **polyphosphates**, which help activate **Factor XII** ``` Platelets play a multifaceted role in fibrinolysis, acting as both promoters and inhibitors of clot degradation. They release fibrinolytic inhibitors like PAI-1 and promote clot retraction, which can impede lysis. However, they also contribute to fibrinolysis by binding plasminogen, a key component of the fibrinolytic system ```

Answer 19

*Hemophilia* - Group of hereditary disorders caused by **deficiencies in clotting factors** - **Hemophilia A**: deficiency of **factor VIII** (∼83% of cases) -> Sex-linked recessive - **Hemophilia B**: deficiency of **factor IX** (∼15% of cases) -> Sex-linked recessive - **Hemophilia C**: deficiency of **factor XI** -> autosomal *Effects and Treatment* - Physical exertion leads to painful internal bleeding due to lack of clotting - Treated with **transfusion** of plasma or **purified clotting factors** - **Factor VIII** can be synthesized using **transgenic bacteria** *Other Disorders* - **Hematomas**: masses of clotted blood that pool within tissues

Answer 20

**Thrombus** - A **stationary blood clot** that forms in an unbroken vessel, often in veins or arteries - Can obstruct blood flow, leading to **ischemia** (reduced oxygen supply) - Particularly dangerous in coronary arteries (→ myocardial infarction) **Embolus** - A **thrombus that dislodges** and travels through the bloodstream - May lodge in smaller vessels, causing **embolism** -> Can block blood flow to critical organs such as the **lungs (pulmonary embolism)** or **brain (stroke)** *Clinical Note*: Both are medical emergencies and may require anticoagulants or surgical intervention

Answer 21

- **Platelet repulsion**: Intact endothelium is coated with **prostacyclin**, which repels platelets → prevents activation unless **collagen is exposed** - **Thrombin dilution**: Normal, rapid blood flow disperses **thrombin** → prevents clot formation; **slow flow** (e.g., in shock) allows thrombin buildup and promotes clotting - **Natural anticoagulants**: - **Heparin** (from basophils and mast cells): Inhibits formation of **prothrombin activator** - **Antithrombin** (from liver): Inactivates **thrombin** before it can convert fibrinogen to fibrin

Answer 22

- Goal: Prevent formation of clots or dissolve existing ones. 1. **Vitamin K antagonists**: Vitamin K is required for clotting factor synthesis. 2. **Aspirin**: Inhibits formation of chemicals that promote platelet aggregation. 3. **Heparin**: Used in hemodialysis and surgery to inhibit clotting. 4. **Other anticoagulants**: - **Hirudin**: From medicinal leeches (used since 1884). - **Arvin**: From viper venom.

Circulatory Flashcards

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