Patho Hematologic Disorders

Patho exam 1- lecture 4

plasma

the aqueous component of blood&about 90% water, contains __ proteins: albumin, globulins, fibrinogen, clotting factors and complement proteins

albumin

most abundant plasma protein. carrier molecule and regulates movement of water and solute through capillaries—
– ↓ ___ results in ↓ ability to pull water into vessels
– range: 3.5-5

globulin

plasma protein responsible for immune response. contains antibodies-IgG, IgA, IgM, IgD, IgE
– gamma__ are the most abundant

order of antibodies=

most abundant to least= IgG,A,M,D,E
^{– (Germs And Microbes Dont Exist)}

fibrinogen

plasma protein, most abundant clotting factor (hemostasis), precursor to fibrin clot

true

(T/F) clotting factors are involved in hemostasis and complement proteins are involved in immune response

lymphoid progenitors

produced in bone marrow from Pluripotent stem cell. it produces lymphocytes- a)T-cells, b) B-cells, c) Natural Killer cells

myeloid progenitors

originates from Pluripotent stem cell and produces all other cell types: Erythrocytes, Platelets, Granulocytes (Neutrophil, Eosinophil, Basophil), and Monocytes/Macrophage

erythrocytes

red blood cells, function is tissue oxygenation (due to hemoglobin carrying)
– normal range= 4.2-6.2 mil/mm³

erythropoietin

function is the development of RBCs in bone marrow
– peritubular cells in the kidney release __ after some hypoxia. the __ stimulates bone marrow to make RBCs
^{– requires B12 and folate btw}

hemoglobin

function is to increase oxygen carrying capacity for blood. made up of 2 pairs of proteins (2 α globins and 2 β globins) and 4 hemes.
– each heme can carry 1 O₂ molecule; thus a saturated hemoglobin has 4 O₂ bound.

rbc destruction process

old rbcs are destroyed by enzymes
– heme and globin are separated
– globin is broken down into amino acids &recycled
– heme breaks down into iron and porphyrin. iron is recycled.
– porphyrin is reduced to bilirubin (which can be conjugated in liver [jaundice..] or excreted in urine)

jaundice how?

Conditions that ↑ destruction of RBCs (hemolysis) cause ↑ release of porphyrin and ↑ bilirubin – more than liver can manage → ___.

leukocytes

white blood cells! function: defend against infection, cancer, and remove debris from cellular damage.
– contains Granulocytes (neutrophils, eosinophils, basophils) and Agranulocytes (monocytes/macrophages, lymphocytes, B and Tcells)

neutrophils

most numerous of the WBCs-60%
function: first responders to an infection and chief phagocytic cells of early inflammation

eosinophil

granulocyte and only 3% of WBCs. Function: mildly phagocytic cells—they destroy parasites+worms and are prevalent in allergic reactions

basophil

granulocyte and <1% of WBCs. Function: induce inflammatory response and activate T lymphocyte

lymphocyte

about 30% of WBCs. Function:
1. CD4+ T lymphocytes mature into T-helper cells—
a) create memory B and T cells
b) activate B lymphocytes which mature into plasma cells and make antibodies
c) recruit CD8+ T lymphocytes
2. CD8+ T mature into cytotoxic T cells (which kill cancer and virus infected cells)

monocytes/macrophages

in the blood theyre monocytes but in tissue theyre macrophages
– function: garbage disposal cells. they ingest unwanted materials and act as antigen presenting cells (present antigens to CD4+ cells to initiate adaptive immunity)

thrombocytes (platelets)

cytoplasmic fragments w no DNA. Function: hemostasis.
– platelets block an opening in a blood vessel. when activated, it releases chemical mediators to promote clotting

thrombopoietin (TPO)

produced by the liver and __ stimulates megakaryocytes in bone marrow to produce platelets
– ^{regulation process: platelets contain TPO receptors and TPO binds to those receptors and then cant stimulate megakaryocytes. But when platelets ↓ , TPO has no place to bind and can then continue stimulating megakar}

hematocrit

the measure of packed RBC cell volume when centrifuged
– Rule of 3: HCT = HGB x 3

labs for hematology

“Nobody Likes My Educational Degree”

White blood cell differential is the measure of the percent of each type of leukocyte=
≈ 60% Neutrophils
≈ 30% Lymphocytes
≈ 6% Monocytes/macrophages
≈ 3% Eosinophils
≈ 1% Basophils

Anemias

condition characterized by reduction in RBC volume or ↓ in quantity/quality of HGB
— often due to Blood Loss, Impaired RBC Production, ↑ RBC Destruction, or ↓ RBC production

acute blood loss

clinical manifestations:
– Slow blood less: lost plasma replaced by the movement of water from tissue. few symptoms.
– Rapid blood less: ↓ BP, ↓CO _{^{(bc blood volume drops)}}, ↑HR _{^{(reflex tachycardia)}}

iron deficiency anemia

anemia that occurs when Fe is depleted. Reduced Fe→ reduced HGB synthesis→ reduced erythropoiesis →small/pale cells
- causes: continuous low volume blood loss(periods) or pregnancy

chronic disease anemia

mild anemia in pts w/ __ __/inflammation.
- ↓RBC life span. Inflammation→ kidney injury→ reduced erythropoietin

B12 deficiency anemia

anemia due to inadequate/absence of B12 →abnormal synthesis of DNA, RNA, and Proteins. results are large weak RBCs that rupture
- causes: poor dietary intake, lack of intrinsic factor or transport protein for absorption, or excessive alcohol usage

true

(T/F) folic acid deficiency anemia has the same pathologic pathway as B12 anemia deficiency.
- folic acid is necessary for DNA and RNA synthesis

aplastic anemia

anemia characterized by hematopoietic failure (reduction in mature blood cells).
due to drug/chemical exposure which yields bone marrow suppression

sickle cell disease

recessive condition-point mutation in which glutamic acid is replaced by valine.
- result is atypical hemoglobin in RBCs which then precipitates out and stiffens cell.
- sickled cells now have shorter lives (hemolysis) and can obstruct blood vessels→ ischemia

sickle cell manifestations

• Hemolytic anemia → hemoglobin release → jaundice

• Vaso-occlusive crisis → pain from hypoxia/infarction (bones, lungs, brain, etc.)

  • Acute chest syndrome (pain, cough, dyspnea) = leading cause of death

  • Can cause stroke and ischemia of bone → bone necrosis

• Sequestration crisis → sickle cells are removed and trapped in spleen → splenomegaly, shock

• Glomerular disease → sickled cells damage glomerulus → renal failure

thalassemia

recessive autosomal disorder- impaired synthesis of one of the HGB chains. results in ↓oxygen carrying capacity
- hemolysis of immature fragile RBCs and splenomegaly

neutrophilia

Increase in the # of circulating neutrophils. Caused by inflammation, infection, or stress
- overload of neutrophils makes blood viscous→ thrombus can form or occlude a blood vessel
- when demand > supply, bands (immature neutrophils) are released

neutropenia

decrease in # if circulating neutrophils and caused by severe long infection, chemotherapy/rad therapy, or aplastic anemia.
- complications- recurrent, fatal infection

eosinophilia

increase in the # of circulating eosinophils and caused by worms, parasites, allergies/asthma, or collagen vascular diseases
- worms, wheezes, and weird disease^
- allergies/infections stimulate recruitment of __ and production from the bone marrow

infectious mononucleosis

benign self-limiting syndrome characterized by infection and death of B cells by Epstein-Barr virus.
- unaffected B cells then become plasma cells and produce antibodies against EBV
- fatigue, fever, pharyngitis, lymphadenopathy of cervical nodes

leukemia

malignant disorder of uncontrolled proliferation of leukocytes in bone marrow.
- overcrowded bone marrow→ reduced production/function of normal blood cells→ anemia

acute lymphoblastic leukemia

rapid proliferation of lymphocyte progenitor cells in blood and bone marrow.
- differentiation of cell stops. overcrowding of bone and reduction production/function of normal blood cells
- common in children. symptoms: fatigue,fever,anemia,infection,bone,pain

acute myeloblastic leukemia

rapid proliferation of neutrophil progenitor cells in blood and bone marrow.
- differentiation of cell stops
- overcrowding of bone and ↑ in number of immature neutrophils makes blood more viscous (thrombosis/occlusion may occur)

chronic lymphocytic leukemia

slow development of fully differentiated lymphocytes (b cells) in blood & bone marrow
- transformation of fully differentiated but immature B cell, cells cannot mature into plasma cells or make antibodies. no bone marrow crowding
- common in adults. symptoms: usually asymptomatic, lymphadenopathy, high risk of infection

chronic myelocytic leukemia

slow proliferation of fully differentiated granulocytes and other myeloid cells
- Philadelphia chromosome is present in most cases and is thought to initiate CML
- myeloid cells are not mature and dont function right—overproduction of immature blast cells of several myeloid types (no bone marrow crowding)

multiple myeloma

plasma cell cancer → masses in bone marrow and lytic bone lesions
- excessive proliferation of malignant plasma cells which produce M protein—this makes blood viscous and ↑ infections
- also produces Bence-Jones protein (nonfunctional and toxic to renal tissue)
- myeloma cells promote activation of osteoclasts→ bone reabsorption and absorbs calcium from it (↑Ca²⁺ in blood)

hodgkin lymphoma

neoplasm that develops from malignant lymphocytes
- reed-sternberg cell is the malignant lymphocyte, spreads to adjacent nodes, inflammatory cytokines release symptoms: enlarged, painless lymph nodes

non-hodgkin lymphoma

group of neoplasms arising from lymphoid tissue (usually B-cell neoplasms)
- chromosomal abnormalities→ activation of oncogenes→ inactivation of tumor suppressor genes→ ↑cellular proliferation
- symptoms: swollen, painless peripheral nodes and extranodal involvement

hodgkin vs non-hodgkin

hemostasis platelet response: Activation

step 1- platelets are recruited to damaged endothelium by thromboxane
- platelets are activated by inflammatory mediators and change shape and express receptors on their surface

hemostasis platelet response: Adhesion

step 2- von Willebrand factor is produced by endothelial cells and binds to collagen in subendothelium. vWF also binds to receptor on the activated platelets—which is now attached to subendothelial

hemostasis platelet response: Aggregation

platelets bound to subendothelial collagen send chemicals to recruit more
- fibrinogen binds to the Gp IIb/IIIa receptors of adjacent platelets and theyre bound together forming a hemostatic plug

hemostasis- clotting factor response

a fibrin mesh will form to stabilize the platelet plug and the coagulation/clotting cascade occurs in 2 pathways
- extrinsic pathway(faster): initiated by release of tissue factor from endothelial cells
- intrinsic pathway: initiated when clotting factors come in contact w subendothelial collagen
These two converge in the activation of factor X which converts prothrombin into thrombin. Thrombin converts fibrinogen into fibrin

true

(T/F) during the clotting factor response, activated Xa converts prothrombin into thrombin. and thrombin is responsible for converting fibrinogen into fibrin

intrinsic vs extrinsic

antithrombin and thrombomodulin

regulates coagulation cascade- reduces thrombin function→ fibrinogen cannot convert into fibrin

thrombocytopenia

not enough platelets. results in ↓platelet production, ↑platelet consumption, and congenital conditions
^{- ↑platelet consumption can be caused by ITP, HIT, or TTP and ↓platelet production by viral infection/ chemotherapy/ nutritional deficiencies}

immune thrombocytopenic purpura (ITP)

most common cause of thrombocytopenia (immune mediated platelet destruction)
- autoantibodies (IgG) produced against antigens on the surface of the platelet. macrophages bind to autoantibody and engulf the platelet
- purpura- red/purple discoloration. also bleeding can occur

thrombotic thrombocytopenic purpura (TTP)

disorder characterized by thrombocytopenia and occlusion of vessels
- ADAMTS13 is absent/inadequate and thus cannot shorten the vWF.
- platelets aggregate on the large vWF molecule and aggregates eventually break free and obstruct vessels. RBC become stressed and fragment

heparin induced thrombocytopenia (HIT)

immune mediated drug reaction
- antibodies are produced against heparin and platelet factor 4. this leads to over activation of platelets and widespread clotting

thrombocythemia

overproduction of platelets due to defect in megakaryocyte progenitor, occlusions
- platelets have abnormal TPO receptors on surface and TPO cannot bind to these receptors. this TPO continues stimulating bone marrow to produce megakaryocytes and ↑platelet production
- DVT and PE can occur

disseminated intravascular coagulation (DIC)

trauma event leads to widespread clotting and depletes the body of clotting factors, fibrinogen,& platelets which then leads to hemorrhage

factor v leiden

genetic mutation of factor V which alters the site of attachment of protein C.
- factor V cant be inactivated by protein C, levels of factor V remain↑ , and clotting persists (risk for thrombosis)

hemophilia A

classic __, most common cause of life threatening bleeding, X-linked recessive trait
- genetic mutation of gene causing Factor VIII deficiency. clotting factors ↓= reduced coagulation and higher risk of bleeding

hemophilia B

genetic mutation of gene causing factor IX, X-linked recessive traight
- clotting factors ↓= reduced coagulation and higher risk of bleeding