pathophysiology - AIDS/HIV, hematology

what is HIV

retrovirus with single strand RNA with enzymes and regulatory proteins

what does a retrovirus do

type of virus that invades a host cell and the own cells become a “virus making machine”

what is the role of genetics in HIV

okay a big role, since variations of the MHC I will have an effect on the immune response

what are elite controllers

people genetically “immune” to HIV

what is the primary site of infection for HIV

macrophages and dendritic cells, which travel to lymphoid system, and viral replication begins, usually in T-helper cells, and cytotoxic T cells begin killing them

what happens after the cytotoxic cells start destroying t helper cells

when bone marrrow can’t replace the t cells fast enough, the count goes down and immune system dysfunction, which is when AIDS happens

when does AIDS begin

progressive deterioration in immune function resulting in opportunistic infections, and things like Kaposi sarcome, lymphomas, wasting syndrome and AIDs- related dementia

when is the set point of HIV/AIDS

t-cell count is insuffient and constitutional symptoms develop, which is the onset of AIDS

what do myeloproliferative diseases do

cause excessive proliferation of certain blood cells from the myeloid stem cell in bone marrow

what is the different between primary and secondary MPD

primary = JAK2 genetic mutation and cancer, secondary = overproduction of a hormone

what is erythropoietin

glycoprotein hormone/cytokine produced by the peritubular cells of kidneys, stimulates RBC production, EPO binds to EPO receptors to activate protein JAK2, which then activate things like proliferation of new RBC, maturation of RBC etc

what is polycythemia vera

excessive RBC production, primary = JAK2 mutation and causes cancer, secondary = overproduction of erythropoietin

what is the clinical management and treatment of polycythemia vera

diagnosed with CBC, genetic studies, bone marrow aspirate, CMP, treatment: blood letting

what are platelets

thrombocytes arise from myeloid cell line, activated platelets help clot formation, thrombopoietin produced by liver and kidney, regulates production of platelets

what is thrombocythemia

overproduction of platelets, primary: JAK2 mutation, leads to cancer, secondary: overproduction of thrombopoietin

primary thrombocythemia management

diagnosis: CBC, genetic studies of JAK2, bone marrow aspirate, coagulation studies, CMP, inflammatory markers,

treatment: medications to reduce platelets, immunotherapies

what are the leukemia types classified based on

myelogenous or lymphocytic, acute vs. chronic

what is chronic myelogenous leukemia

in chromosomes 9+22 (philadelphia chromosome), characterized by increased proliferation of granulocytes, increased/decreased platelets seen, increased bleeding/bruising, 3 phases

what are the three phases of CML

chronic (5-6 years), accelerated (6-9 months), blast crisis (3-6 months)

what is the onset of CML

incidental findings of elevated WBC, enlarged spleen, fatigue, weight-loss, decreased exercise tolerance, abdominal pain, bleeding, petechiae, bruising

CML diagnosis tools

CBC, peripheral blood smear, bone marrow biopsy, CT scan/ultrasound

CML treatment tools

targeted therapy, immunotherapy, chemotherapy, splenectomy, stem cell transplant

how is anemia often reported

as a decrease in hemoglobin or low hematocrit concentration

what are the two categories for the pathogenesis of anemia

insufficient production of healthy RBC (erythropoiesis, decreased reticulocyte count), increased destruction of RBCs (hemolysis, increased reticulocyte count)

what is the progression of RBC maturation

hemotopoietic stem cells —> myeloid stem cells —> colony forming units —> erythroblasts —> reticulocytes —> erythrocytes

what are reticulocytes 

immature RBC’s, normally mature within a day of release from the bone marrow, during stress they could be released prematurely

what is the reticulocyte count used for

estimate degree of how effective erythropoiesis is, higher in newborns

what could increased reitculocyte be

increase in RBC production, bleeding, hemolysis, bone marrow transplant or response to supplementation

what could decrease in reticulocyte count be

bone marrow prolems (infection, leukemia), deficiency of: iron, b-12, folic acid, erythropoietin

what to look at to find underlying cause of anemia

size, color

what test looks at the size of the RBC, and what test looks at the color

size: mean corpuscle volume (MCV), color: mean corpuscular hemoglobin concentration (MCHC)

for insufficient production leading to anemia, why would there be normocytic RBC’s

blood loss, bone marrow problem, anemia of chronic disease

for insufficient production leading to anemia, why would there be microcytic RBC’s

iron deficiency anemia

for insufficient production leading to anemia, why would there be macrocytic RBC’s

B-12/folate, chronic alcoholism, dietary deficiency, pernicious anemia

what is the clinical presentation of insuffient production cauing anemia

fatigue, leg cramps, craving ice, cold, easily infected, altered beahvior, impaired growth, pale mucus membranes

what tools to diagnose insuffienct production of RBC

blood tests: CBC, reticulocyte count, iron, b-12, folate, complete metabolic panel

what are the types of anemia from increased destruction of RBCs

inherited hemolytic anemia: genetic, like sickle cell disease or thalassemia, aquired hemolytic anemia: autoimmune (antibody) mediated, complement cascade, warm autoimmune hemolytic anemia, cold agglutination disease

what is sickle cell anemia

cells misformed and reduced oxygen carrying, pain crisis, triggers; hypoxemia, dehydration, infection, fever, many have increased reticulocyte count

what is thalassemia

genetic deficiency in synthesis of globin chains, leads to hemolysis and impaired erythropoies

what is autoimmune hemolytic anemia

body makes antibodies that target RBC, antibodies that attach to RBC, cause warm autoimmune hemolytic anemia, cold agglutinatin-mediatied autoimmune hemolytic anemia

what detects endothelial injury

nerves and smooth muscle cells —> then vasoconstriction to reduce blood loss

why does collagen exposure occur

due to endothelial cell damage —> release of von willebrand factor, that binds with collagen

what do the surface proteins on platelets to

bind to vWF via adhesion —> cause platelet activation, then leads them to attract more platekets and secrete vFW and other chemicals

what does thromboxane A2 and ADP cause platelets to do

express proteins on surfaces that bind to fibrinogen

what is von willebrand disease

most common bleeding disorder, deficiency of vWF, mostly impacts primary hemostasis, equally occurs between sexes

what might cause the vWF defiency

autosomal dominant genetic mutation, secondary to disease, medication

what are the types of vWD

type 1: most common, mildest, low levels of VWF, type 2: normal levels of VWF but functionally impaired, type 3: rarest, most severe, little to no VWF and low factor VIII

VWD clinical presentation + diagnosis

nosebleeds, ecchymosis, heavy menstrual bleeding, prolonged bleeding, diagnosis with CBC, PT/INR, PTT, serum vWF

VWD managament

pharmacotherapy and risk reduction

what is hemophilia

coagulation factor deficiency, can be inherited via genetic mutation (sex-linked, recessive, mostly men), or aquired (rare) either secondary to disease or medication

what is hemophelia A

factor VIII deficiency, 30% no family history, 85% of cases

what is hemophilia B

factor IX defiency, less severe than A

hemophelia presentation

hemorrhage into joints, muscles or intracranial (esp in minors), diagnosis: CBC, PT/INR and PTT, factor VIII or IX, clinical management: emergency treatment of factor VIII concentrations, risk reduction

vitamin k deficiency

vit k deficiency in neonates: vit k not crossed by placenta, liver doesn’t produce, lack of bacterial colonization of gut, hemorrhagic disease of newborn can be prevented by IM injection of vit K, in adults: malnutrition, liver disease, alcoholism

vitamin k clinical presentation, diagnosis, clinical management

excessive bleeding, hematoma, menstruation, diagnosis: CBC, PT/INR and PTT, serum vit k, clinical management: vit k supp, treat underlying diseae, risk reduction