PATHO exam 3: heme

Compositon of blood

• % water + % solute ?

• average adult has ___ liters of blood 

Main functions 

• Maintain acid-base balanace

• Delivery substances needed for cellular metabolism 

• Remove waste 

• Immune defense 

When centrifuged: 

• 3 layers + their % makeup of blood + what they contain?

• 91%

• 9%

• 5.5 liters

• plasma coat. makes up 55% of blood. contains 91% water and the remainder are solutes (gas, waste, ions, etc)

• buffy coat. too small of %. contains WBC

• formed elements makeup 45% of blood. contains RBC

Plasma

• 55% of blood volume

• 3 plasma proteins: 

  • ___: controls plasma oncotic pressure 

  • ___: carrier proteins + immunoglobulins

  • ___: clotting factor part of the clotting system

Erythrocytes 

• 45% of blood 

• most abundant cell in blood

  • Responsible for tissue oxygenation

  • Shape: bi-concavity and reversible shape (to squeeze through capillaries)

  • Life cycle is ___ days

• albumin

• globulins

• fibrinogen

• 100-120 days

Granulocytes

• granules that contain enzymes to destroy microbes

• Inflammatory and immune function

• diapedesis movement  

___: act as phagocytes in early stage of inflammation 

• the dominant granulocyte

• shape: polymorphonucelar neutrophil (PMN) bc it has multiple little lobes

___: release is triggered by what type of hypersensitivity?

• Ingests ___

• Increased levels during parasitic infections

____: structurally and functionally similar to mast cells 

Agranulocytes

____: immature macrophages; acts as phagocytes in later stages of inflammation

• When matured, it makes up what “system”?

____: matures into Tcells, Bcells, Plasma cells

___: part of innate defense system; rapidly kills harm to the body

• neutrophils

• eosinophils

• IgE hypersensitivity

• antibody-antigen complexes

• monocytes

• mononuclear phagocyte system (MPS)

• lymphocytes

• natural killer cells

Platelets

• aka called _____

• Irregularly shaped cytoplasmic fragments 

• For blood coagulation/controlling bleeding

• thrombocytes

Lymphoid organs

• Primary lymphoid organs are?

• Secondary lymphoid organs ?

  • Spleen is LARGEST lymphoid organ that is responsible for what 4 things?

  • So if u dont have a spleen = puts you at higher risk for ____

• red bone marrow + thymus

• spleen, liver, lymph nodes, tonsils, peyer patches @ small intestine

• FETAL HEMATOPOIESIS + blood reservoir + initiates immune response (produces antibodies, houses lymphocytes + filters out pathogens to destroy old/used cells)

• infection

Development of RBC

• Red bone marrow (active, hematopoietic): is vascularized + found at which bones?

  • Stem cells usually harvested from which bone?

• Yellow bone marrow (inactive): found @ other bones

Hematopoietic stem cells (HSC)

• where is the primary site of hematopoietic stem cells (HSC)?

• are self renewing (basically infinite division for lifetime supply of blood cells)

• Undergoes hematopoiesis to differentiate into which 2 main categories? 

  • whats the development process of RBC?

  • whats the development process of granulocytes?

  • whats the development process of platelets?

  • (ignoring the lymphocyte development process for now LOL)

____: the production of all blood cells from hematopoietic stem cells

• Occurs where BEFORE birth (in fetal life)?

• Occurs where AFTER birth?

• flat bones (most commonly @ pelvic bones)

• pelvic bones

• red bone marrow

• lymphoid progenitor cells (leads to development of lymphocytes) and myeloid progenitor cells (leads to development of all other blood cells)

• myeloid progenitor cell > pro-eryythroblast > normoblast > reticulocyte > erythrocyte

• myeloid progenitor cell > blast cell > either neutrophil, eosinophil, or basophil

• myeloid progenitor cell > megakaryoblast > megakaryocyte > platelet

• hematopoiesis

• @ spleen and liver

• ONLY @ red bone marrow

Erythropiesis 

• process of RBC development 

• Sequence: myeloid progenitor cell > pro-erythroblast > normoblast > reticulocyte > erythrocyte (RBC)

  • ____: immature RBC that freshly leave red bone marrow = thus they dont function poorly

  • As each step progresses, hemoglobin levels ___ and RBC nucleus size ___

  • In normoblast stage, nucleus shrinks but which organelles remain the unchanged?

    • their roles + what do they develop into?

  • Regulation of eryhthropoiesis is controlled by ____ → allows for increased RBC production in specific conditions like hypoxia  

    • Process: hypoxia detected by kidneys → kidneys release erythropoietin which triggers erythropoiesis → more RBC made → increased hemoglobin → increased O2 levels detected by kidneys → kidneys stop releasing erythropoeitin → bone marrow stops making RBC

• reticulocyte

• increase

• shrinks

• ribosome and mitochondria

• ribosome develops into globulin + mitochondria devlops into heme —> they form hemoglobin

• negative feedback loop with erythropoietin (produced by kidney)

Erythropoeisis continued 

• Rmb that erythropoiesis lowk depends on hemoglobin synthesis (bc if not enough oxygenation via hemoglobin carrying O2 in blood = kidney negative feedback loop with erythropoeitin is triggered = makes more erythrocytes which means more hemoglobin)

• Globulin is composed of what?

• A single heme is composed of what + binds to what?

  • ____: a non-reduced ferric iron (Fe+3) that CANNOT bind to oxygen (so it just serves other important functions) 

• ____: condition of excess ferric iron (Fe+3)

• SX: cyanosis, fatigue, headache, dyspnea

• Diagnosis?

• Treatment: methylene blue, vitamin C, oxygen support

Nutritional requirements for proper erythropoiesis 

• Important to have proper intake of?

• 2 pairs of polypeptide chains (2 alpha + 2 beta)

• 4 iron-protoporphyrin complexes which binds to reduced FERROUS iron (Fe+2)

• non-reduced FERRIC iron (Fe+3)

• chocolate-brown blood + SpO2

• all the B vitamins + vitamin E + iron + copper 

Iron and development of blood cells

• circulating ferrous iron is bound to what?

• stored iron is bound to what? 

Iron cycle

• what is it?

• what hormone is it controlled/regulated by?

• Process?

• Daily iron requirement for erythropoeisis is 25 mg, and only 2mg of that is dietary = so what im tryna say is that the majority of iron is from recycling!

• Pregnant women require increased iron intake to meet the needs of growing fetus/placenta nutrition 

• transferrin

• ferritin

• an iron recycling process

• controlled/regulated by hepcidin (produced by liver)

• macrophages of MPS @ spleen breakdown ingested erythrocytes (into heme + globin) → heme releases the iron → iron either returned directly to bloodstream (via binding to transferrin in bloodstream to float to RB marrow) OR iron is stored as ferritin inside spleen or liver

Leukocytes development 

____: development of granulocytes and agranulocytes from myeloid progenitors 

• Matures at ____ → granulocytes differentiate into 2 things (functional circulating granulocytes OR stored inside blood vessel walls) 

Lymphocyte development

____: development of lymphocytes from lymphoid progenitors 

• Matures at ____ → then released into bloodstream 

Platelet development 

• Process: megakaryoblast > megakaryocyte > platelets 

  • how does the megakaryocyte turn into platelets?

• Regulation: via which hormone?

• Life cycle: ___ days

  • what happens to the old/used up platelets?

• Myelopoiesis

• bone marrow

• Lymphopoiesis

• Lymphoid organs (red bone marrow + thymus)

• megakaryocyte undegoes DNA replication BUT doesnt divide; instead, the cell elongates and then fragments into little pieces = platelets

• thrombopoietin (produced by liver)

• 10 days

• destroyed by spleen

Hemostasis

Hemostasis: stopped bleeding via formation of blood clots @ site of vascular injury 

Steps

1. Vascular injury triggers ____

2. Endothelial cell damage leads to ____

3. Clotting cascade activated to produce ____

4. (repair stage) Fibrin clot ___ → eventually the clot will dissolve

Blood vessels

• Endothelial cells adhere to their own subendothelial matrix (connective tissue) which normally produces nitric oxide and prostaglandin to inhibit platelet aggregation (under normal conditions) 

• BUT damage to endothelium exposes the underlying subendothelial matrix → triggers endothelial cells to release platelet activators (primarily which platelet activator?)

Mechanisms of hemostasis

***basically describes hemostasis steps***

• Platelets function basically describes hemostasis steps (regulate bloodflow via transient vasoconstriction, forms platelet plug, activates clotting cascade to stabilize plug w/fibrin, initiates repair process)

• Damaged vessel initiates platelet activation:

1. Platelet adhesion to damaged wall

2. Activation leading to degranulation of platelet activators (von willebrand factor)

3. Platelet aggregation 

4. Activated clotting system and formation of stabilizing meshwork of fibrin and platelets

• transient vasoconstriction (temporary vasoconstriction for 30 sec before u actually start bleeding)

• platelet adhesion to form temporary platelet plug

• fibrin to STABILIZE the temporary platelet plug = fibrin-platelet meshwork

• will contract to pull the injured vessel together

• von willebrand factor (which calls out to the circulating platelets to come here and aggregate!)

Clotting factors

• A bloodclot is a meshwork of platelet and fibrin strands (which stabilizes the platelet plug)

• Fibrin strands are produced from the Clotting Cascade

  • describe Intrinsic pathway?

  • describe Extrinsic pathway?

  • describe Common pathway?

• Excessive bleeding is caused by low platelet count, clotting factor deficiency, or Aspirin (which irreversibly COX-1)

• triggered by vascular endothelial injury; activated by Hageman factor (factor 7) makes contact with exposed vessel subendothelial substances

• triggered by tissue injury; activated when thromboplastin (factor 9) released by damaged endothelial cells

• activation of factor Xa → prothrombin → thrombin → fibrinogen → fibrin → fibrin clot → stable clot yayyy

Retraction and lysis of blood clots (repair phase of hemostasis)

• Clot retraction: fibrin strands shorten and contract to pull edges of injured vessel/or site of injury together 

• Lysis of blood clots: happens via Fibrinolytic System 

  • Fibrinolytic system process: ____ binds to the fibrin (but theres 2 types bc ___ will lyse intravascular clots VS ___ will lyse of tissue clots) > the whicever-plasmin digests fibrin into small pieces called ____ → clot is gone

• elevated levels of fibrin degradation products in blood tell us that a clot is being broken up right now!!!

• plasminogen

• tissue plasminogen activator (tPA)

• urokinase plasminogen activator (uPA)

• fibrin split products or fibrin degradation products

Older adults

• Erythrocyte lifespan is normal, but SLOW replacement due to what reason?

• Lymphocyte function decreased with age (thus older adult higher risk for infxns) + humoral immune system overall less responsive 

• iron deficiency

Anemia 

Anemia: reduced total number of RBC OR reduced hemoglobin quantity or quality 

Caused by 3 main categories:

• Impaired RBC production (evidenced by decreased reticulocytes)

• Blood loss

• Increased RBC destruction

  • Results in increased reticulocytes as a poor compensation attempt (bc why r we releasing hella immature RBCs…)

Anemia classifications

• Based on size and hemoglobin content 

• ___ = the size of RBC

  • ends in what suffix?

• ___= the amount of hemoglobin “packed inside” an RBC

  • ends in what suffix?

• mean corpuscular volume (MCV)

• -cytic

• mean corpusuclar hemoglobin content (MCHC)

• -chromic

Anemia type classification continued

___: macrocytic-normochromic anemia caused by intrinsic factor (IF) deficiency = leads to B12 deficiency

• often seen in GI malabsorption or vegans

• manifestations: basic anemia SX + also neurologic SX which only develop later when hemoglobin level is very low at ____

  • SX?

• treatment?

____: macrocytic-normochromic anemia caused by B9 deficiency (folate deficiency)

• often seen in malnutrition or alcoholism

• manifestations?

• treatment?

• percicious anemia

• 7-8

• parasthesia (tingling toes/fingers) + walking difficulty + sore tongue (glossitis)

• lifelong B12 replacement

• folate deficiency anemia

• same as pernicuos anemia except DOESNT cause neuro SX

• oral B9 supplements

Anemia classification continued

____: microcytic-hypochromic anemia caused by low ferrous iron serum levels primarily due to chronic blood loss

• common in pregnancy

• manifestations?

• treatment?

• iron deficiency anemia

• brittle thin ridged spooned fingernails (koilonchyia), cheilosis, painful mouth ulcers

• iron and vitamin C + less Ca intake

____: Normocytic-normochromic anemia caused by chronic disease (ex: cancer, chronic organ diseases, chronic infection, etc…)

• treatment?

____: Normocytic-normochromic anemia caused by bone marrow failure

• associated with autoimmune disorders, radiation, drugs, etc

• manifestations?

• treatment?

• anemia of chronic disease

• treating the underlying disorder

• aplastic anemia

• easy bruising, frequent nosebleeds

• bone marrow transplant

Anemia classification continued

____: Anemia of increased RBC destruction

• Caused by either intrinsic reason (example?) OR extrinsic reason (example?)

Acute hemolytic reaction

• adverse reaction due to blood type incompatability during blood transfusion 

• manifestations?

• nursing process on what to do if this happens?

• hemolytic anemia

• sickle cell anemia (an inherited disease)

• acute hemolytic reaction from failed blood transfusion, type 2 hypersensitivity reactions, etc…)

• sickness SX (fever, chills), hypotension, back or flank pain, red/brown urine, disseminated intravascular coagulation (DIC)

• STOP transfusion > HANG normal saline > NOTIFY the HCP and the blood bank

Polycythemia 

• what is it?

Types

• Primary polythycemia (aka Polythycemia Vera) is caused by?

• Secondary polythycemia is caused by?

Manifestaions 

• ?

• overproduction of RBC

• due to genetic mutation

• due to either: NORMAL kidney response of producing more erythropoietin in response to hypoxia OR PATHOLOGIC erythropoetin-secreting tumors

• increased blood volume + hypercoagulable state due to increased blood thickness

Alteration of leukocyte function 

2 categories: 

• Quantitative disorders: either increase/decrease in amount due to bone marrow dysfunction or premature cell death

  • Leukocytosis: high WBC levels; normal physiological response to infection

  • Leukopenia: low WBC level; pathological response that puts patient at higher infxn risk 

• Qualitative disorders: disruption to leukocyte function

Qualitive leukocyte disorders

___: increased granulocytes levels evident in early stages of infection/inflammation

• how does this relate to left/right shift?

___: decreased granulocyte levels

• Caused by:

  • Prolonged infection

  • Decreased production 

  • Early death 

  • Abnromal distribution 

• ____ (severe neutropenia) and ____ (absence of granulocytes) often due to chemotherapy or certain drugs

• granulocytosis/neutrophilia

• during early stage of infection, there is a left shift (increased in immature neutrophils due to high demand and supply of mature neutrophils being used up). later on, right shift will occur (level of mature neutrophils return to normal)

• granulocytopenia

• agranulocytosis

Leukemia

• A malignant disorder of bone marrow and blood

• Involves proliferation + accumulation

  • Excess accumulation of leukemic cells is bad because:

    • crowds bone marrow

    • decrease function of hematopoietic stem cells

2 categories

• Acute leukemia: presence and rapid proliferation of ____

  • Is this disease a slow or rapid progression?

  • short survival time → Needs ASAP treatment

• Chronic leukemia: mainly partially matured leukocytes that dont function correctly

  • Is this disease a slow or rapid progression?

• immature blast cells

• rapid

• slow

Acute leukemia 

____: excess lymphoblasts

___: excess myeloblasts

• whats notable abt this type of cancer?

Chronic leukemia 

___: excess immature lymphocytes 

• whats notable abt this type of cancer?

• Treatment: observe and SX treatment overtime

____: excess WBC produced from bone marrow 

• what unique factor does this involve?
  

• acute lymphocytic leukemia (ALL)

• acute myleogenous leukemia (AML)

• AML is the most aggressive type of leukemia ***think: M as in “mad and aggressive”***

• chronic lymphocytic anemia (CLA)

• most common adult leukemia in the western world ***think: most Common Leukemia Adult **

• chronic myleogenous leukemia (CML)

• involves philadelphia chromsome (related to chromosome translocation or something) ***think: CM as in ChroMosome = philadelphia chromsome ****

Alterations in lymphoid function

Lymphadenopathy: enlarged lymph node

• Localized: drainage occurs at/near the enlarged node usually due to infection

• Generalized: drainage occurs in multiple nodes; occurs due to infection, autoimmune disease, metastisized cancer

Malignant lymphoma:

• ***Most common blood cancer in the US!!!**

• diverse neoplasms that develop from proliferated malignant lymphocytes 

2 types:

____: spreads to just one neighboring lymph node (contiguous spread aka localized)

• RARE

• involves the presence of what type of cells?

• Manifestations?

____: spreads to distant lymph nodes (non-contiguous aka non-localized)

• COMMON

• what demographic is at higher risk of this cancer?

• manifestations?

• Poor prognosis ☹ (which makes this type hard to detect….)

• hodgkins lymphoma

• reed-sternberg cells

• a mediastinal mass + nightsweats, fever, chills

• non-hodgkins lymphona

• older white men

• fever + painless generalized lymphadenopathy

____ malignant proliferation of plasma cells

• Infiltrates bone marrow → develops ___ (tumors inside bone that lyse)

• Manifestations:

  • _____ (from a popped tumor)

  • Renal failure 

  • Anemia (duh! bc bone marrow is damaged)

  • Immune dysfunction 

• multiple myeloma

• hypercalcemia

Platelet disorders 

Thrombocythemia: high platelet levels

• caused by many things, but professor wants u to primarily think of ___ (= results in concentrated blood)

Thrombocytopenia: defined by platelet count below what value?

• below what platelet count does thrombocytopenia become clinically significant?

• below what platelet count is indicated by SEVERE bleeding?

Thrombocytopenia manifestations:

• Bleeding in gums, GI tract, genitourinary tract, lung’s mucosal lining

• Petechiae

• Purpura

• Ecchymosis (large bruise)

• dehydration

• 150,000

• 100,000

• 10,000

Types of thrombocytopenia

1. Heparin induced thrombocytopenia (HIT): adverse drug rxn where ____ will target platelet factors → platelet count drops by HALF → serious bleeding risk

• Treatment?

2. IDIOPATHIC thrombocytopenia purpura (ITP)

• begins as petechia —> progresses into major hemorrhage

3. _____: basically thrombotic micro-angiopathy

• Process: platelet aggregation > micro-thrombi > occlusion of capillaries + arterioles 

• IgG (immunoglobulin G)

• stop giving the heparin

• thrombotic thrombocytopenia purpura (TTP)

Alterations in coagulation 

• Caused by issues with clotting factors (NOT caused by platelet issues)

Types

• Impaired hemostasis: inability to form fibrin clot

  • associated with which organ dysfunction and which vitamin deficiency?

• Thrombo-embolic disorders

  • localized

  • caused by acquired hypercoagulability or hereditary thrombophilia 

• Consumptive thrombo-hemorrhagic disorders

  • systemic

  • primary example of this is?

Disseminated intravascular coagulation (DIC)

• what is this disorder in basic terms?

• DIC occurs secondary to sepsis, cancer, trauma, immunologic rxns, etc → ultimately leads to _____

• Manifestations?

• Diagnosis: lab tests + D-dimer blood test

• Treatment?

• liver dysfunction (since liver produces all the clotting factors) + vitamin K deficiency

• disseminated intravascular coagulation

• systemic clotting AND bleeding

• end organ failure

• BLACK cyanosis hands/feet + bleeding from arterial lines or puncture sites + petechiae/purpura/hematoma

• ironically u gotta give a heparin drip (bc we gotta stop the clots first bc hypoxia > blood volume replacement) + also manage organ function