PBL- D2 Block 2

2 major groups of Leukocytes

***granulocytes and agranulocytes, based on the density of their cytoplasmic granules

which main amino acids involved in gluconeogenesis and is the product of proteolysis of skeletal muscle? - Lysine - Arginine - Alanine - glysine

- Alanine (alan- muscle - glucose- workout)

Neutrophils release...?

- Chemokines - Cytokines - Lipid mediators

consequences of DIC

- First, widespread fibrin deposition within the microcirculation -> ischemia - Second, because of depletion platelets and clotting factors + release of plasminogen activators, -> superimposed bleeding tendency. - Plasmin cleaves not only to fibrin (fibrinolysis) but also to factors V and VIII, thereby reducing their concentration further. In addition, fibrinolysis creates fibrin degradation products. These inhibit platelet aggregation, have anti-thrombin activity, and impair fibrin polymerization, all of which contribute to the hemostatic failure

what is α4β7 integrin? where is it found? what is DC-SIGN?

*** Cell adhesion molecule HIV-1 binds to the cellular adhesion molecule ______ which is found on gut-associated lymphoid tissue, and to the DC-SIGN receptor (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin) expressed on dendritic cells. HIV-1 can fuse with certain negatively charged liposomes with no receptors, and the fusion product has a greatly impaired ability to infect cells.

Adult T Cell Leukemia/Lymphoma.

*** neoplasm of CD4+ T cells is caused by a retrovirus, human T cell leukemia virus type 1 (HTLV-1) - HTLV-1 infection also can cause tropical spastic paraparesis, a progressive demyelinating disease affecting the central nervous system and the spinal cord. - associated with skin lesions, lymphadenopathy, hepatosplenomegaly, hypercalcemia, and variable lymphocytosis. - In addition to CD4, the leukemic cells express high levels of CD25, the IL-2 receptor α chain

which anti inflammatory/ painkiller drugs cause hepatotoxicity in excess? how is it eliminated out of the body system? drug overdose?

acetaminophen (paracetamol) is hepatotoxic in excess - it is eliminated by conjugation with glucuronic acid or sulfate, which are then excreted through the kidney - in Aceta overdose - acetaminophen is oxidized by a liver P-450 cytochrome CYP3A4 to N-acetyl benzoquinoneimine (NABQI). NABQI -> cause free radical-mediated peroxidation of membrane lipids and consequently lead to hepatocellular damage NABQI may be detoxified by conjugation with glutathione, but in acetaminophen overdose, glutathione stores also become exhausted, and hepatotoxicity ensues

3 complement pathways converge on a common point, what is it?

activation of C3 complement by enzyme C3 convertase

Polycythemia

aka erythrocytosis, denotes an increase in red cells per unit volume of peripheral blood 1. Absolute (defined as an increase in total red cell mass) or relative. primary when the increased red cell mass results from an autonomous proliferation of erythroid progenitors, and secondary when the excessive proliferation stems from elevated levels of erythropoietin. 2. Relative polycythemia results from dehydration, such as occurs with water deprivation, prolonged vomiting, diarrhea, or the excessive use of diuretics. *** PICTURE***

"Acute phase response" means

all the systemic changes that occur in response to infection or inflammation - acute-phase proteins are synthesized by liver, -> is stimulated by proinflammatory cytokines released by macrophages, and of these, interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF Functions of acute phase protein: Binding proteins, opsonins such as C-reactive protein (CRP), bind to macromolecules released by damaged tissue or infective agents and promote their phagocytosis Complement factors also promote the phagocytosis of foreign molecules. Protease inhibitors, such as α1-antitrypsin and α1-antichymotrypsin, inhibit proteolytic enzymes. The latter two also stimulate fibroblast growth and the production of connective tissue required for the repair and resolution of the injury. amino acids is required as substrates for this increase in hepatic protein synthesis, and these amino acids are derived from the proteolysis of skeletal muscle. TNF and IL-1, again, are involved by stimulating the breakdown of specific intracellular proteins by the ubiquitin-proteasome system

pts w/ STD

- ID all individuals who have active disease. Not always possible. - New cases of syphilis, gonorrhea, and acquired immunodeficiency syndrome (AIDS) should be reported to the local or state health department. - Reasonable suspicion of sexual abuse in children, such as the identification of oral condylomata, should also be reported.

which Ig is the first class of antibodies to produce during primary immune response? where to find them? they are effective against which antigents? (proteins, saccharides, or polysaccharides, or lipopolysaccharides)

- Ig M (M- priMary) - pentameric structure, with five immunoglobulin units connected via sulfhydryl bonds and a J chain - found on plasma membrane of B cells, bind component - effective against polysaccharides

what is the role of NO in the circulatory system? NO binding to hemoglobin

- NO : vasodilator - hemoglobin: vasoconstrictor and a scavenger (heme destroys NO) - when O2 binds to hemoglobin, No binds to a.a on hemoglobin -> bounded NO is protected from degradtion by hemoglobin Fe, cysteine group - when O2 is unloaded -> No is released -> causing vasodilation - as deoxygeneted hemoglobin picks up CO2, it binds NO & carries to lungs for unloading

what is long terminal repeat (LTR)

- RNA sequences that comprise promoter and enhancer gene sequences that bind transcription factors.

ch 12- Histo blood

- Serum contains growth factors and other proteins released from platelets during clot formation, which confer biological properties very different from those of plasma.

- Vasculitis - Glomerulonephritis - Arthritis

- Vasculitis- resultant inflammatory lesion if occur in blood vessels - Glomerulonephritis- occurs renal glomeruli - Arthritis- occurs in joints

Hemolytic anemia

- accelerated red cell destruction (hemolysis). life span of RBCs < 120 days

types of vaccines: - attenuated/ live viral vaccines - Inactivated vaccines - Subunit vaccines

- attenuated/ live viral vaccines - live weak viruses - Inactivated vaccines- dead viruses/ bacteria - Subunit vaccines- components of viruses/ bacteria ** Conjugated vaccines

which conditions link to Vit B12 deficiency?

- chronic atrophic gastritis marked by a loss of parietal cells - serum of most affected patients contains several types of autoantibodies that block the binding of vitamin B12 to intrinsic factor or prevent binding of the intrinsic factor-vitamin B12 complex to cubilin

where do you find IgA

- found in blood, tears, colostrum, intestinal and respiratory secretions, and saliva

hematoma hemostasis

- hematoma is a common problem that occurs as a result of damage to one of the larger blood vessels in the body. it looks like a bruise - hemostasis- stopping of a flow of blood.

Extranodal Marginal Zone Lymphoma

- indolent B cell tumor arises most commonly in epithelial tissues such as the stomach, salivary glands, small and large bowel, lungs, orbit, and breast. - ancer that arises within and is sustained by chronic inflammation. It tends to develop within tissues that are involved by chronic inflammation triggered by autoimmune disorders (Sjögren syndrome and the thyroid gland in Hashimoto thyroiditis) - tumor of mature B cells expressing CD20 and surface immunoglobulin, usually IgM. - swelling of the salivary gland, thyroid or orbit or are discovered incidentally in the setting of H. pylori-induced gastriti

what is preintegration complex where is it being transported to ?

- is form when double-stranded cDNA is circularized and then complexes with cellular and viral proteins - get transported thru nuclear pore to nucleus

- substrates for gluconeogenesis are derived from________released by glycolysis in the peripheral tissues and from hepatic deamination of amino acids (mainly alanine) generated from the proteolysis of skeletal muscle

- lactase

IL-1

- mediator of inflammation that recruits leukocytes and induces fever

Lymphocytes

- smallest leukocytes - subtypes by CD markers (cluster of differentiation)

form of folate that is needed for DNA synthesis? and is recycled by?

- tetrahydrofolate - Vit B12 -> anemia of vitamin B12 deficiency is reversed with the administration of folate.

Buffy coat - 1% - oxygen content in different type of BV

- thin layer of leukocytes and platelets Between the sedimented erythrocytes and the supernatant light-colored plasma - PIC highest in lung capillaries and arteries

Disorders of the Thymus:

- thymus hyperplasia - thymoma PIC

Burkitt Lymphoma- fastest growing human tumor

- translocations involving the MYC gene on chromosome 8 that result in overexpression of the MYC transcription factor. - MYC is a master regulator of Warburg metabolism (aerobic glycolysis), a cancer hallmark that is associated with rapid cell growth. -Most translocations fuse MYC with the IgH gene on chromosome 14, but variant translocations involving the κ or λ light chain loci also are observed. -tumors express surface IgM, the B cell marker CD20, and the germinal center B cell markers CD10 and BCL6.

Inflammatory Myopathies

- uncommon, heterogeneous group of disorders characterized by injury and inflammation of mainly the skeletal muscles that are probably immunologically mediated

is NO a vasodilator or vasoconstrictor?

- vasodilator - laughing gas -> for anxiety / stress relief - relaxing

how can HIV genome be transferred from cell -> cell? and what does it lead to?

- via cell- cell fusion - leads to multinucleated syncytia. multiple nuclear??? lk

Amniotic Fluid Embolism

an uncommon, grave complication of labor and the immediate postpartum period occurring in 1 in 40,000 deliveries. - most common cause of maternal death in the developed world - Onset is characterized by sudden severe dyspnea, cyanosis, and hypotensive shock, followed by seizures and coma. If the patient survives the initial crisis, pulmonary edema typically develops, along with (in about half the patients) disseminated intravascular coagulation secondary to release of thrombogenic substances from amniotic fluid - underlying cause is the entry of amniotic fluid (and its contents) into the maternal circulation via tears in the placental membranes and/or uterine vein rupture. Histologic analysis shows squamous cells shed from fetal skin, lanugo hair, fat from vernix caseosa, and mucin derived from the fetal respiratory or gastrointestinal tracts in the maternal pulmonary microcirculation

Myelodysplastic Syndromes

Are clonal stem cell disorders, which may progress to AML. They are characterized by Pancytopenia - 3 genes: Epigenetic factors RNA splicing factors Transcription factors

Nef gene regulates what?

CD4 & MHC I

know 5 different types of heavy chains that define antibody - isotypes Isotypes vs Allotypes, Idiotypes

IgG, IgM, IgA, IgE, and IgD Allotypes are additional genetic features of immunoglobulins that vary among individuals. (allo- add) Idiotypes are antigenic determinants formed by the specific protein sequence in the variable region of an immunoglobulin that generate the large number of antigen-binding regions.

what is the Hutchinson's triad?

Late stage congenital syphilis is rare, and there is a classic triad of congenital syphilis known as Hutchinson's triad that includes: interstitial keratitis of the cornea, eighth nerve deafness dental abnormalities

ALL

Terminal deoxynucleotidyl transferase (TdT), an enzyme specifically expressed in pre-B and pre-T cells. Further subtyping of ALL into pre-B and pre-T cell types relies on stains for lineage-specific markers, such as the B cell marker CD19 and the T cell marker CD3.

epitope spreading

activation of such autoreactive T cells is called epitope spreading, because the immune response spreads to epitopes that were not recognized initially. This is one of the mechanisms that may contribute to the chronicity of autoimmune diseases.

Thalassemia

both reduced red cell production (aregenerative anemia) and early destruction contribute to anemia Pic- cont from the previous slide

Anemia of Diminished Erythropoiesis: - Fe deficiency anemia - Folic acide - Vit B12

caused by an - inadequate dietary supply of nutrients, particularly iron, folic acid, and vitamin B12

- Early in the infection of a person, this co-receptor is the _________, expressed primarily on ________. The virus is initially _________ - Later, chronic infection of a person, the ______ gene undergoes mutations and the new _______ binds to the chemokine receptor ________, expressed primarily on ________ cells; the virus is then said to be ________ The interaction of gp120 with the co-receptor displaces gp120 to a sufficient extent that the ______________ into the host cell membrane, thereby mediating membrane fusion.

chemokine receptor CCR5 macrophages and dendritic cells "M-tropic" or an "R5 virus." gp120 gene gp120 CXCR4 T cells "T-tropic" or an "X4 virus." trimeric transmembrane gp41 can insert its hydrophobic N-terminus

Systemic Lupus Erythematosus

chronic autoimmune inflammatory disease of collagen in skin, joints, kidney and serosal membranes and internal organs - involving multiple organs, characterized by a vast array of autoantibodies, particularly antinuclear antibodies (ANAs), in which injury is caused mainly by deposition of immune complexes and binding of antibodies to various cells and tissues.

Bilirubin is metabolized by the _____________ and excreted in ________

hepatocytes , bile

platelet hyalomere granulomere

hyalomere- very lightly stained peripheral zone granulomere = darker staining central zone rich in granules

what types of vaccines are Diphtheria and tetanus vaccines

inactivated bacterial vaccines- inactivated toxins

platelet Alpha granules (αG)

larger and contain platelet-derived growth factor (PDGF), platelet factor 4, and several other platelet-specific proteins.

what is indicated INR to treat pt?

less than 2.5

Terms used to describe the abnormal immunoglobulins associated with plasma cell neoplasms include

monoclonal gammopathy, dysproteinemia, and paraproteinemia.

which organ stores/ tissues most glycogen? - liver - muscle - fat

muscle - no glucose -6 - phosphatase-> can not contribute Gucose to blood

dental considerations for pts with recent Gonorhea infection takes antibiotic?

ok to do dental procedure wihtin days of beginning antibiotic tx - pts with active phryngitis & other oral signs or symptoms suggestive an infection of unclear etiology -> refer to physician

Multiple Myeloma

one of the most common lymphoid malignancies - most frequent M protein produced by myeloma cells is IgG - In the remaining cases, the plasma cells produce only κ or λ light chains. Because free light chains are small in size, they are also excreted in the urine, where they are referred to as Bence Jones proteins -In the remaining cases, the plasma cells produce only κ or λ light chains. Because free light chains are small in size, they are also excreted in the urine, where they are referred to as Bence Jones proteins -myeloma often has chromosomal translocations that fuse the IgH locus on chromosome 14 to oncogenes such as the cyclin D1 and cyclin D3 genes.

what is paratope?

region of antibody interacts with epitopes

Follicular Lymphoma

t 14;18 translocation causing BCL-2 fusion gene on chromosome 18 to IgH lcus on chromosome 14 -> overexpression of BCL 2 protein- prevents apoptosis (remember through the prevention of cytochrome c release from mitochondria) - - tumors express B cell markers such as CD20 and the germinal center B cell markers CD10 and BCL6 (transcription factor)

Hemostasis

to stop or control bleeding

Anti-Nuclear Antibodies 4 categories

(1) antibodies to DNA, (2) antibodies to histones, (3) antibodies to nonhistone proteins bound to RNA (4) antibodies to nucleolar antigens

Neoplastic Proliferations of White Cells

*-Lymphoid neoplasms* *-Myeloid neoplasms* *-Histiocytoses*

Complications of Transfusion

- Allergic Reactions Severe, potentially fatal allergic reactions may occur when blood products containing certain antigens are given to previously sensitized recipients. - Hemolytic Reactions Acute hemolytic reactions usually are caused by preformed IgM antibodies against donor red cells that fix complement. - Delayed hemolytic reactions are caused by antibodies that recognize red cell antigens that the recipient was sensitized to previously, for example, through a 492previous blood transfusion.

Red infarcts vs white infarcts

- Infarcts caused by venous occlusion or occurring in spongy tissues typically are hemorrhagic (red);- ovarian torsion, loose tissue in lung, lung and small intestine - those caused by arterial occlusion in compact tissues typically are pale (white). heart, spleen , kidney, wedged shaped, occluded vessel at the apex & organ periphery form the base

Clinical feature of Primary herpes vs Recurrent herpes infections which one is more severe

- Primary herpes- lymphadenopathy and viremia are prominent features also headache, malaise, myalgia, and symptoms of fever - Recurrent herpes- less severe than primary sacral ganglia, HSV-2 is more efficient in reactivating HSV2 recurrence 4x more likely than HSV1 localized itching, tingling, paresthesia, pain, and burning -> vesicular eruption

what are retroviruses? are they envleoped viruses RNA or DNA what is reverse transcriptase

- Retroviruses are enveloped viruses with a positive-strand RNA genome. Retroviruses - R -> RNA - Replicate through a DNA intermediate, which requires an enzyme that can transcribe RNA into DNA. - This enzyme, an RNA-dependent DNA polymerase - reverse transcriptase (RT). This mechanism was a new addition to what had been known as the "central dogma of molecular biology," from DNA to RNA to protein.

inflammasome

- Several of the NLRs signal via a cytosolic multiprotein complex - activates an enzyme (caspase-1) that cleaves a precursor form of the cytokine interleukin-1 (IL-1) to generate the biologically active form -

Deficiencies of factors below causes: - factor V, VII, VIII, IX, and X - factor XI - factor XII

- V, VII, VIII, IX, and X are associated with moderate to severe bleeding disorders, and prothrombin deficiency is likely incompatible with life- VII most important activator activator of factor IX, and IX or VIII important for X - XI- mild bleeding- ability of thrombin to activate factor XI, feedback mechanism - XII- do not bleed and in fact may be susceptible to thrombosis

how is the HIV envelop glycoproteins being produced?

- cleavage of the precursor gp160 by cellular proteases-> produce 2 gycoproteins

The most widely used method for detecting ANAs is....?

- indirect immunofluorescence, which can identify antibodies that bind to a variety of nuclear antigens, including DNA, RNA, and proteins (collectively called generic ANAs)

Atherosclerosis

- major cause of arterial thromboses because it is associated with the loss of endothelial integrity and with abnormal blood flow

Hemostasis

- process of blood clotting that prevents excessive bleeding after blood-vessel damage - Inadequate hemostasis may result in hemorrhage, which can compromise regional tissue perfusion and, if massive and rapid, may lead to hypotension, shock, and death

Folate (Folic Acid) Deficiency Anemia

- result of inadequate dietary intake, sometimes complicated by increased metabolic demands

can HIV-1 infect cells that are CD4-negative? such as ___________cells , and how?

- yes - fibroblasts and certain brain cells - most likely via its interaction with a co-receptor and the fusion activity of gp41.

Aplastic anemia- pathogenesis

-60%- 70% activated T cells suppress hematopoietic stem cells. * stem cells are first antigenically altered by exposure to drugs, infectious agents, or other unidentified environmental insults. -> provoke cellular response-> activated TH1 cells produce cytokines such as interferon-γ (IFN-γ) and TNF that suppress and kill hematopoietic progenitors. - 5% to 10% of patients have inherited defects in telomerase,- short telomeres

Coagulation factor deficiencies

8,9,11 fibrinogen- cogenital 2,7,9,10 vitamin K deficiency

hemophilia

A hereditary disease where blood does not coagulate to stop bleeding

Disorders Caused by Immediate Hypersensitivity

Atopic dermatitis, food allergies, hay fever, and certain forms of asthma are examples of localized allergic reactions.

Air embolism decompression sickness bends- Rapid formation of gas bubbles within skeletal muscles and supporting tissues in and about joints is responsible for the painful condition

Gas bubbles within the circulation can coalesce and obstruct vascular flow and cause distal ischemic injury. articular form of gas embolism called decompression sickness is caused by sudden changes in atmospheric pressure. (Scuba diving) When air is breathed at high pressure (e.g., during a deep sea dive), increased amounts of gas (particularly nitrogen) become dissolved in the blood and tissues. If the diver then ascends (depressurizes) too rapidly, the nitrogen expands in the tissues and bubbles out of solution in the blood to form gas emboli, which cause tissue ischemia.

which infections is th most common STD?

Genital warts

which HPV subtype has strong tedency to induce epithelial hyperplasia -> leading to condylomata

HPV-6 and -11 have a strong tendency to induce epithelial hyperplasia, leading to condylomata (anogenital warts)

which of the following is not HIV genome's main gene clusters: - gag, pol, hal, env *** PICTURE from book

Hal is not gag, pol env- 3 main gene clusters (gagging in envelop at pool)

Sickle cell disease: A common hemoglobinopathy

In sickle cell disease (SCD), distortion of erythrocyte structure (sickling) limits capillary blood flow hemolytic anemia, resulting from chronic lysis of red cells, and painful vasoocclusive crises. impaired growth, increased susceptibility to infections, and multiple-organ damage. In the African American population in the United States, SCD is caused by an inherited single-point mutation in the gene encoding β-globin, leading to the expression of the Hb variant HbS. HbS - leading to a greater release of O2 in the capillaries and increased propensity for sickling.

Chronic or recurrent external blood loss (due to peptic ulcer or menstrual bleeding) cause what type of anemia? How about internal bleeding- does it cause the same type of anemia?

Iron deficiency anemia (consequence of loss of Iron in hemoglobin)4 - Internal bleeding does not cause iron deficiency anemia because Fe is efficiently recycles from phagocytosed red cells

histone deacetylase (HDAC) de-acetylase

One enzyme involved in enabling histone proteins to compact DNA is histone deacetylase (HDAC), which removes acetyl groups bound to lysines The exposed lysines as well as arginines can interact with negatively charged DNA and condense it, thereby preventing transcription

what is the main oral manifestations of HIV/ AIDS? The main bacterial opportunistic infections are caused by ________

Oral candidiasis & hairy leukoplakia caused by EBV Mycobacterium tuberculosis, Mycobacterium avium-intracellulare complex, and the gastrointestinal pathogens Salmonella, Shigella, and Campylobacter. - TB

which type of HIV initially infect a persion via sexual contact?

R5. binds to both the CD4 receptor and the CCR5 chemokine receptor that are found on monocytes, macrophages, and dendritic cells

Disorders of the Spleen and Thymus

Splenomegaly - PIC

what happens in severe anemia

The appearance of extramedullary hematopoiesis within the secondary hematopoietic organs (the liver, spleen, and lymph nodes).

what is migratory thrombophlebitis?

Tumor-associated procoagulant release is largely responsible for the increased risk of thromboembolic phenomena seen in disseminated cancers. These are sometimes referred to as migratory thrombophlebitis, because of the tendency to involve several different venous beds transiently

Major plasma proteins

albumins, globulins (a & b globulins), immunoglobulins (antibodies or y globulins), fibrinogen (largest plasma protein), complement proteins

what is live attenuated polio vaccine

attenuated viruses replicate at a localized site, such as the gastrointestinal tract, but do not reach the target tissue where the disease occurs, for example neurons in the case of the live attenuated polio vaccine

Histiocytic Neoplasms

histiocytosis is an "umbrella" designation for a variety of proliferative disorders of dendritic cells or macrophages.

pathogenesis of folate clinical features?

in cells: ***dihydrofolate -> tetrahydrofolate by dihydrofolate reductase - Tetrahydrofolate acts as an acceptor and donor of one-carbon units in rxns for synthesis of (dTMP). If intracellular stores of folate fall, insufficient dTMP is synthesized and DNA replication is blocked, leading to megaloblastic anemia. *** clinical features: - nonspecific symptoms such as weakness and easy fatigability *** no neurologic abnormalities occur (do occur in Vit B12 deficiency)

Thrombosis vs Embolism

inappropriate clotting (thrombosis) or migration of clots (embolism) can obstruct blood vessels, potentially causing ischemic cell death (infarction)

what is viral load-

number of viral RNA copies per milliliter of plasma.

Auxiliary proteins / accessory gene

six gene products that regulate HIV gene expression

Cholecystectomy

surgical removal of the gallbladder

criteria for effective vaccines to be developed?

(1) The infectious agent should not establish latency; for example, human immunodeficiency virus integrates its genome into the host chromosome and is not accessible to vaccine prevention when it is in this state. (2) The agent should not undergo antigenic variation. (3) The infectious agent should not interfere with the immune response.

Causes/ abnormalities that lead to intravascular thrombosis

(1) endothelial injury in heart & arterial circulation, clots r rich in platelets (reason to use aspirin & other platelet inhibitors in coronary artery disease & acute MI) (2) stasis or turbulent blood flow -> causing endothelial injury or dysfunction, forming countercurrents & local pockets of stasis (3) hypercoagulability of the blood (the so-called "Virchow triad")

how does Defective synthesis of β-globin in β-thalassemia contributes to anemia?

(1) inadequate HbA formation, resulting in small (microcytic), poorly hemoglobinized (hypochromic) red cells; (2) by allowing the accumulation of unpaired α-globin chains, which form toxic precipitates that severely damage the membranes of red cells and erythroid precursors

other tests used to eval anemia

(1) serum iron indices (iron levels, iron-binding capacity, transferrin saturation, and ferritin concentrations), which help distinguish among microcytic anemia caused by iron deficiency, chronic inflammation, and thalassemia; (2) plasma unconjugated bilirubin, haptoglobin, and lactate dehydrogenase levels, which are abnormal in hemolytic anemia; (3) serum and red cell folate and vitamin B12 concentrations, which are low in megaloblastic anemia; (4) hemoglobin electrophoresis, which is used to detect abnormal hemoglobin; and (5) the Coombs test, which is used to detect antibodies or complement bound to red cells in suspected cases of antibody-mediated hemolytic anemia

Disadvantages of inactivated vaccines

(1) the induced immunity is usually just humoral and not long-lasting, (2) a local IgA response is not elicited, and (3) booster shots are required. The diphtheria and tetanus vaccines must be re-administered every 10 years.

ineffective hematopoiesis

(the premature death of marrow erythroid progenitors) is associated with inappropriate increases in iron absorption from the gut, which can lead to iron overload (secondary hemochromatosis) with consequent damage to endocrine organs and the heart. If left untreated, a severe congenital anemia such as β-thalassemia major inevitably results in growth retardation, skeletal abnormalities, and cachexia. *** PICTURE

Which bacteria causes Syphilis? natural host? stages of Syphilis? primary site? pregant women transmits syphillis to fetus? early as 9-10 wks in utero -> Hudchinson triad in late stage include interstitial keratitis of the cornea, eighth nerve deafness, and dental abnormalities

*** Treponema pallidum*** - natural host- humans - primary & secondary syphilis - early infectous stages primary- round, painless, firm lesion- 2-3 wks after exposure secondary- 6-8 wks after initial exposure- hematogenous, associated systemic immunologic response to T . Pad- fever, malaise, headache, arthalgias, lymphadenopathy, and patchy hair loss and a generalized eruption of the skin and mucous membranes, including the oral cavity, skin rash is maculopapular. Lues maligna is a rare and severe manifestation of secondary syphilis in immunocompromised patients, such as those with HIV infection - latent stage- seroreactive, asymptomatic, no clinical evidence of disease. 1st 4 yrs mucocutaneous relapses & infectious. after 4 yrs, no relapse, non infectious. last many yrs or thruout life - nonifectious late stage = tertiary syphilis destructive stage, noninfectious, many organs involved three subtypes: *neurosyphilis- meningitis like syndrome, difficult movements *cardiovascular- vascular in nature -> lead to carotid, aortic stenosis, aneurysm of ascending aorta *gummatous disease- localized lesion, involve skin, mucous membranes, bone, end result of hypersensitivity rxn- noninfectious inflammatory granulomatous lesion with a central zone of necrosis. late stage - no risk of transmission occur in this stage - Primary site- genitalia, but also be in the oral cavity

Induction and competitive inhibition of cytochrome P-450 enzymes underpin mechanisms of drug interactions Cytochrome P-450 gene polymorphisms determine the response to many drugs

***CYP1A2 metabolizes- caffeine and theophylline. It can be inhibited by grapefruit juice, which contains a substance known as naringin, or by the antibiotic ciprofloxacin. CYP1A2 are metabolized more slowly, and their plasma levels increase. ***drugs that induce induction or repression of CYP3A enzymes often act through the nuclear receptor mechanism. They combine with nuclear receptors (i.e., in the case of CYP3A4, the pregnane X receptor [PXR]), which then form heterodimers with retinoid X receptors. Such complexes upregulate CYP3 synthesis by binding to response elements in the gene promoter. ***CYP2D6, in person w/ slow to hydroxylate debrisoquine, a now little-used blood pressure-lowering drug. Clopidogrel is a prodrug that undergoes hepatic biotransformation by CYP2C19 into its active metabolit -> lower capacity to transform clopidogrel to its active metabolite and are therefore at significantly higher risk of adverse cardiovascular events. (19-> use gel lk)

Thrombocytopenia

***low platelet count - Isolated thrombocytopenia is associated with a bleeding tendency and normal coagulation tests. A count less than 150,000 platelets/µL generally is considered thrombocytopenia. - 20,000 to 50,000 platelets/µL is there an increased risk of posttraumatic bleeding - spontaneous bleeding is unlikely until counts fall below 5000 platelets/µL. - When the cause is the accelerated destruction of platelets, the bone marrow usually shows a compensatory increase in the number of megakaryocytes. - one of the most common hematologic manifestations of AIDS

HIV envelop consists of ... the envelop surrounds... what is in

- 2 glycoproteins that are produced by cleavage of the precursor gp160 by cellular proteases - envelop surrounds the capsid composed viral p24 protein - Inside the capsid are two copies of viral RNA and two tRNA molecules that hybridize to the RNA and act as primers

Basophils

- A circulating leukocyte that produces histamine. - nucleus with 2 irregular lobes - specific grannules stain purpe w/ basic dye - Strong basophilia of granules- bc of Heparin & sulfated GAGs - contain histamine + platelet activating factor, , eosinophil chemotactic factor, and the enzyme phospholipase A that catalyzes an initial step in producing lipid-derived proinflammatory factors called leukotrienes. - has surface receptor for IgE

Hypercoagulability

- Abnormally high tendency of the blood to clot, and is typically caused by alterations in coagulation factors. - important underlying risk factor for venous thrombosis 1. primary (genetic) 2. secondary (acquired) disorders read book chapter 4 page 109

Hemorrhage = Anemia of blood loss 1. Acute 2. Chronic

- Acute bleeding are mainly due to the loss of intravascular volume, which if massive can lead to cardiovascular collapse, shock, and death. (>20% -> hypovolemic shock)- normocytic & normochromic - Chronic bleeding- Fe stores're gradually depleted Iron is essential for hemoglobin synthesis and erythropoiesis- decrease RBCs production

lacking mitochondria, what does RBC rely on for their energy needs?

- Anaerobic glycolysis. and also Lacking nuclei, they cannot replace defective proteins.

hemolytic anemia

- Anemia caused by the premature destruction of red cells (hemolytic anemia) is associated with hyperbilirubinemia, jaundice, and pigment gallstones (if hemolysis is chronic), all related to increases in the turnover of hemoglobin

signs and symptomsof genital warts dx tests ? Tx?

- Anogenital warts (condylomata) are predominantly external, but also found intraanally, intravaginally, or involving the cervix and urethral meatus. - Externally- small multiple confluent sessile papules (<1 mm) to grossly exophytic papillary or warty cauliflower-like lesions Dx test: - use of commercial DNA and RNA in situ hybridization kits to detect HPV - Alternative diagnostics include PCR and immunohistochemistry using anti-HPV antibodies. Tx: - genital warts: surgical, ablative technique (sapel excision, electrosurgery, laser removal,...), administration of antiproliferative or immunomodulatory agents - Topical agents: podophyllotoxin, podophyllin, imiquimod, sinecatechins (e.g., Polyphenon E), cidofovir, and 5-fluorouracil - systemic retinoids and interferon, which may be used topically, intralesionally, or systemically

Type II hypersensititvity

- Antibody-mediated (type II) hypersensitivity disorders are caused by antibodies directed against target antigens on the surface of cells or other tissue components - Antibodies cause disease by targeting cells for phagocytosis, activating the complement system, or interfering with normal cellular functions

Type III hypersensitivity Immune Complex-Mediated Diseases - Sequential phases in the induction of systemic immune complex- medicated disease

- Antigen-antibody (immune) complexes that are formed in the circulation may deposit in blood vessels, leading to complement activation and acute inflammation. Immune complex-mediated diseases tend be systemic, but often preferentially involve the kidney (glomerulonephritis), joints (arthritis), and small blood vessels (vasculitis), all of which are common sites of immune complex deposition. 1. Formation of immune complexes- form antibodies -> secrete into blood react w/ antigen -> form antibodies antigen complexes 2. Deposition of immune complexes- deposit into tissue 3. Inflammation & tissue injury- complexes initiate acute inflam rxn via complement activation & engagement of leukocyte Fc receptors. Ig G or IgM.

Autoimmune diseases

- Autoimmune diseases may be organ-specific, in which the immune responses are directed against one particular organ or cell type and result in localized tissue damage, or systemic, characterized by lesions in many organs. - diseases are often referred to as collagen vascular diseases or connective tissue diseases -unresponsive (tolerant) to their own (self) antigens, and autoimmunity results from a failure of self-tolerance. -Self-tolerance refers to lack of immune responsiveness to one's own tissue antigens. - Two broad mechanisms are recognized: central tolerance and peripheral tolerance

hypersensitivity - 4 types - can be subdivided into four types based on the principal immune mechanism responsible for injury - three are variations on antibody-mediated injury, and the fourth is T-cell mediated PIC

- Autoimmunity : reactions against self antigens - Reactions against microbes - Reactions against enviromental antigens (pollens, animal fander, dust mites)

tx of HIV

- Azidothymidine - highly active antiretroviral therapy (HAART)- Antiretroviral drugs are currently given as a combination to lower the development of drug resistance is lower and the blood levels of HIV can be reduced to undetectable levels Postexposure prophylaxis, for example following a needlestick injury, is essential to prevent infection.

***Micro chapter 2- Antibodies & Complement B cells & T cells

- B cells Precursor -> recognize particular epitopr, or antigent determinant via specific antibodies on B cel surface -> proliferate & differentiate -> plasma cells produce antibodies , some differentitate into mermoryB cells - T cells Stem cells -> pre T cell -> CD4 or CD8 which interact w/ MHC I (CD8) or MHC II (CD4) -> cause apoptosis of cells -> provide tolerance for self antigens if cells fo not recognize MHC w/ peptides -> apoptosis, clonal deletion

Some characteristic about EBV virus

- B-lymphotropic herpesvirus - transmitted primarily after exposure to oropharyngeal secretions, predominantly by kissing. Infrequently, it is transmitted through shared infected drinks, eating utensils, or infected blood products. - incubation time is approximately 6 weeks. A prodromal period of 3 to 5 days precedes the clinical phase, which typically lasts 7 to 20 days. During the prodromal phase, the virus infects oropharyngeal epithelial cells and spreads to B lymphocytes in the tonsillar crypts. Infected B lymphocytes circulate through the reticuloendothelial system, triggering a marked CD8+ T-lymphocytic response - combination of reactive lymphocytes + cytokines they produce, and + B cell-produced (heterophile) antibodies directed against EBV antigens -> acute infection. - After the acute infection, the virus remains latent in B lymphocytes for the life of the host. About 40% of asymptomatic herpesvirus-seropositive adults carry EBV in their saliva on any given day

HIV drugs these drugs inhibit HIV replication or infection , but they can NOT cure HIV/AIDS

- Binding of gp120 to the CCR5 co-receptor is inhibited with a receptor agonist (maraviroc). - Gp41-mediated virus-cell fusion is inhibited by a peptide drug (T-20, enfuvirtide). - RT is inhibited by nucleoside analog drugs, including AZT, dideoxyinosine, and dideoxycytidine, that are phosphorylated by cellular enzymes and incorporated into the cDNA, thereby causing DNA chain termination. RT is also inhibited by other mechanisms by non-nucleoside inhibitors (efavirenz). - Raltegravir inhibits viral integrase, preventing the incorporation of the viral genome into the cell chromosome. - Protease inhibitors such as ritonavir and indinavir block the cleavage of the Gag and Gag-Pol polyproteins, thereby preventing the maturation of the virus structure The protease inhibitor darunavir,

Coagulation tests - PT - PTT - Platelet count Tests of platelet function

- Bleeding resulting from vascular fragility is seen with vitamin C deficiency (scurvy) - systemic amyloidosis ( Chapter 5), chronic glucocorticoid use, rare inherited conditions affecting the connective tissues, and a large number of infectious and hypersensitivity vasculitides. - Deficiencies of platelets (thrombocytopenia) also are an important cause of bleeding. von Willebrand disease - easy bruising, nosebleeds, excessive bleeding from minor trauma, and menorrhagia. - bleeding disorders stemming from defects in one or more coagulation factors, the PT, PTT, or both are prolonged. Unlike platelet defects, petechiae and mucosal bleeding are usually absent. Instead, hemorrhages tend to occur in parts of the body that are subject to trauma, such as the joints of the lower extremities. Massive hemorrhage may occur after surgery

Immune Thrombocytopenic Purpura

- Chronic ITP is a relatively common disorder that tends to affect women between the ages of 20 and 40 years. - Acute ITP is a self-limited form seen mostly in children after viral infections. - Antibodies directed against platelet membrane glycoproteins IIb/IIIa or Ib/IX complexes can be detected in roughly 80% of cases of chronic ITP. - spleen is an important site of anti-platelet antibody production and the major site of destruction of the IgG-coated platelets. Although splenomegaly is not a feature of uncomplicated chronic ITP - Clinical signs: petechiae, easy bruising, epistaxis, gum bleeding, and hemorrhages after minor trauma

path of Fe deficiency type of Fe deficiency anemia? neurobehavioral complication? - PICA

- Chronic blood loss - low intake and poor biovailability bc of predominantly vegan diets - malabsorbtion *** microcytic anemia - cells are microlytic & hypochromic - Low serum Ferretin & Fe levels, low transferrin saturation, increase total Fe- binding capacity - EPO levels are elevated, but marrow respinse is blunted by Fe deficiency, only slightly increasedPlatelet count is elevated Iron stores are depleted first, marked by a decline in serum ferritin and the absence of stainable iron in the bone marrow - Pica, compunction to consume nonfoodstuffs such as dirt or clay (an eating disorder)

Unconjugated bilirubin vs Conjugated bilirubin

- Conjugated bilirubin is water soluble > may be secreted by the hepatocyte into the biliary canaliculi. The hydrophilicity of bilirubin is increased by esterification, usually known as conjugation, of one or both of its carboxylic acid side chains with glucuronic acid, xylose, or ribose.

D dimer

- D-dimer test is a blood test that can be used to help rule out the presence of a serious blood clot. - D-dimer is a protein fragment from the break down of a blood clot. Blood clots generally start to slowly break down after they are formed, and this process releases D-dimer into the blood - you can get high levels of D-dimer in your blood if you have a major clot like with deep vein thrombosis (DVT)

Difference between petechiae & ecchymosis? which one does Coville have?

- Ecchymosis is subcutaneous. - - Palatal petechiae can be caused by Streptococcus, viral infection, trauma, tonsillitis Coville has palatal petechiae ***Bleeding into the skin can occur from broken blood vessels that form tiny red dots (called petechiae). ***Blood also can collect under the tissue in larger flat areas (called purpura) ***or in a very large bruised area (called an ecchymosis)

what types of cells are central regulators of hemostasis

- Endothelial cells the balance between the anti-thrombic and prothrombotic activities of endothelium determines whether thrombus formation, propagation, or dissolution occurs

2 types of hemolytic: - intrinsic (intracorpuscular) - extrinsic (extracorpuscular)

- Extravascular hemolysis is caused by defects that increase the destruction of red cells by phagocytes, particularly in the spleen. (macrophages ) • Hyperbilirubinemia and jaundice, stemming from degradation of hemoglobin in macrophages • Varying degrees of splenomegaly due to "work hyperplasia" of phagocytes in the spleen • If long-standing, formation of bilirubin-rich gallstones (pigment stones) and an increased risk of cholelithiasis - Intravascular hemolysis, by contrast, is characterized by injuries so severe that red cells literally burst within the circulation • Hemoglobinemia, hemoglobinuria, and hemosiderinuria. Hemoglobin released into the circulation is small enough to pass into the urinary space. Here, it is partially resorbed by renal tubular cells and processed into hemosiderin, which is then lost in the urine when renal tubular cells are sloughed. • Loss of iron, which may lead to iron deficiency if hemolysis is persistent. By contrast, iron recycling by phagocytes is very efficient, and so iron deficiency is not a feature of extravascular hemolytic anemias.

- Transferrin - which form of Fe - Ferretin site of Fe absorption? form of Fe that is transported transporters for Fe newly absorbed Fe is next oxidized by?

- Ferretin- iron stores. - Transferrin- Iron is transported in the plasma bound to the protein transferrin. - Duodenum (DJ I) - Fe2+ by divalent metal transporter-1 (DMT1), & ferroportin - oxidized by -hephaestin and ceruloplasmin to ferric iron (Fe3+), the form of iron that binds to transferrin

roles of the gene clusters of HIV genome? gag, pol, env Basically: capsid- envelop - antigen gag stands for pol stands for env stands for

- Group-specific antigen gene, gag, encodes the capsid (p24), nucleocapsid (p7), and matrix (p17) genes. - gang capsid lk - polymerase, pol, gene encodes RT integrase, and protease (- merase = enzyme -> intergrase & protease). - envelope, env, gene codes for the transmembrane gp41 protein and the surface protein gp120, which form trimers and are trafficked to the plasma membrane. *** notes - These genes are initially in the form of polyproteins, which are cleaved by proteases to form the final protein products. - In the case of Gag and Pol, the HIV protease carries out this function within the newly synthesized virion. All of the viral components are assembled at the plasma membrane, and the virus buds, taking with it some cellular membrane proteins, including the major histocompatibility complex (MHC). The HIV genome can be transferred from cell to cell via cell-cell fusion, leading to multinucleated syncytia.

which is the first vaccine given soon after birth? after 2 mons, after 12 mons, after 18 mons, after 2 yrs

- HBV vaccine - Subunit - diphtheria, tetanus, acellular pertussis (DTaP); rotavirus; Η influenzae B; the pneumococcal conjugate vaccine; and inactivated poliovirus- after 2 mons - hepatitis A vaccine (inacticvated), the MMR vaccine (attenuated), and the varicella vaccine (attenuated)- after 12 mons - -Inactivated influenza virus can be given yearly- at 18 months (rabies, Diphtheria, tetanus, Vibrio cholerae, Bacillus anthracis, Yersinia pestis, and Coxiella burnetii) - live attenuated influenza virus is administered yearly- after age 2 years (BCG, Salmonella, polio, influenza)

Oncoviriance- Human t cell lymphotropic

- HTLVTax protein is a transcriptional activator of the viral LTR, and Rex facilitates the transport of mRNA encoding structural proteins into the cytoplasm. Gp46 and gp21 are the envelope proteins of the virus, and p24 is the capsid protein. Although HTLV-1 can penetrate and infect different cell types, productive infection is restricted to a few cell types, including T lymphocytes. - dx- HTLV-1 causes adult T-cell leukemia/lymphoma then decades-long latency. The syndromes include hepatosplenomegaly, lymphadenopathy, and lesions in the skin and bones. Fungal and viral opportunistic infections, especially following treatment with chemotherapy. HTLV-1 also causes HTLV-associated myelopathy/tropical spastic paraparesis, whose symptoms include weakness in the lower limbs, low back pain, and spasticity during walking. HTLV-2 causes hairy cell leukemia of T-cell origin. - Tax protein of the virus binds to the LTR of HTLV-1 and enhances the transcription of proto-oncogenes, which leads to transformation. Tax also causes an increase in the production of interleukin-2 (IL-2) and IL-2 receptor, causing uncontrolled growth. Syncytia formation of infected T lymphocytes has been observed. HTLV-associated myelopathy/tropical spastic paraparesis is a demyelinating disease, especially in motor neurons, most likely via an autoimmune reaction and CTL-mediated killing of neurons. HTLV-1 is transmitted via blood, including sexual intercourse, blood transfusion, and intravenous drug use. Breastfeeding appears to be the main source of mother-to-child transmission tx- - Adult T-cell leukemia/lymphoma is usually treated with anticancer medicines. - Patients with HTLV-associated myelopathy/tropical spastic paraparesis may benefit from a combination of interferon and antiretroviral agents such as AZT and lamivudine.

CD4+ T Cell-Mediated Inflammation

- In CD4+ T cell-mediated hypersensitivity reactions, cytokines produced by the T cells induce inflammation that may be chronic and destructive. - The prototype of T cell-mediated inflammation is delayed-type hypersensitivity (DTH), a tissue reaction to antigens given to immune individuals. - an antigen administered into the skin of a previously immunized individual results in a detectable cutaneous reaction within 24 to 48 hours -The classic example of DTH is the tuberculin reaction (known in clinical medicine as the PPD skin test), which is produced by the intracutaneous injection of purified protein derivative (PPD, also called tuberculin), a protein-containing antigen of the Mycobacterium tuberculosis bacillus. -Prolonged DTH reactions against persistent microbes or other stimuli may result in a special pattern of reaction called granulomatous inflammation

Reactive Lymphadenitis

- Infections and nonmicrobial inflammatory stimuli often activate immune cells residing in lymph nodes, which act as defensive barriers. - Any immune response against foreign antigens can lead to lymph node enlargement (lymphadenopathy) - occurs with cat-scratch disease

rxn of innate immunity: -

- Inflammation. Cytokines and products of complement activation, leukocytes destroy pathogens and ingest and eliminate damaged cells. -Anti-viral defense. Type I interferons produced in response to viruses act on infected and uninfected cells and activate enzymes that degrade viral nucleic acids and inhibit viral replication.

which antibodies are produced initially and how does it switch to different class of Ig? Which part of the antibody actually changing in response to class switching? light chain or heavy chain? Control of class switching depends on conc of?

- Initial IgM -> then switch to Ig G -> IgA - Change in the heavy chain - depend on conc of Interleukins Ex; IL4 enhances production of IgE, IL 5 enhances IgA

where do most plasma proteins synthesized? - blood - kidney - liver - bone marrow which is the most abundant protein in blood and where is it synthesized?

- Liver - albumin. synthesized in liver in liver disease ->low plasma albumin (increased vascular endothelial permeability that allows the leakage of albumin into the interstitial space.) - liver also synthesize most of the plasma α- and β-globulins

MHC molecules

- Major Histocompatibility Complex Molecules: The Peptide Display System of Adaptive Immunity - fundamental to T-cell recognition of antigens, and genetic variations in MHC molecules are associated with many immunologic diseases; - the normal function of MHC molecules is to display peptides for recognition by CD4+ and CD8+ T lymphocytes

Subunit vaccines - they were isolated biochemically from the pathogen or synthesized by recombinant DNA technology

- Molecular components of bacteria or viruses: include capsular polysaccharides and surface proteins of bacteria and viral envelope glycoproteins - Ex: . hepatitis B virus (HBV) vaccine consists of HBsAg, which is expressed in yeast from its gene . human papillomavirus (HPV) vaccine and are more immunogenic than the individual antigens.

monoclonal antibodies, what they do? Myeloma cells Hybridoma Chimeric antibodies Use of monoclonal antibodies ? ELISAs (enzyme linked immunosorbent assays)

- Monoclonal antibodies- an antibody produced by a single clone of cells or cell line and consisting of identical antibody molecules. Antibodies that were copied and made in the lab -> they can recognize a single epitope on an antigen - lymphocytes from the spleen of mice immunized with a particular antigen and fused them with myeloma cells to produce hybridomas that could divide indefinitely Hybridomas are produced by injecting a specific antigen into a mouse, collecting an antibody-producing cell from the mouse's spleen, and fusing it with a tumor cell called a myeloma cell. *** role of monoclonal antibodies - use in the construction of enzyme-linked immunosorbent assays (ELISAs) to detect or quantify particular antigens, since antibodies to different epitopes would be required: one to capture the antigen onto the plastic surface of the well of a microtiter plate and another to recognize the bound antibody - used in therapeutics; monoclonal antibodies against the epidermal growth factor receptor are used in the treatment of colorectal cancer and head and neck cancer. -> they are genetically engineered to produce chimeric antibodies with a murine variable region and a human constant region to reduce the immunogenicity of murine antibodies. *** chimeric antibodies- antibody made by fusing the antigen binding region (variable domains of the heavy and light chains, VH and VL ) from one species like a mouse, with the constant domain (effector region) from another species such as a rabbit.

what are 2 other minor hemoglobins found in human?

- Neuroglobin (Ngb)in central nervous system and some endocrine tissues; - Cytoglobin (Cygb) in cells of fibroblast origin. Both human proteins share only about 25% sequence identity with Mb and Hb. Yet all key elements of the globin fold are present: 3 over 3 α-helix sandwich; proximal and distal His residues; hydrophobic, heme-containing pocket. - Ngb and Cygb contain hexacoordinate hemes for both the Fe2+ and the Fe3+ valency states.

- clinical features of Vit B12 deficiency? - dx of vit B12 deficiency, how about pernicous anemia

- Non specific: pallor, easy fatigability, and, in severe cases, dyspnea and even congestive heart failure - mild jaundice, beefy red tongue *** dx: (1) low serum vitamin B12 levels, (2) normal or elevated serum folate levels, (3) moderate to severe macrocytic anemia, (4) leukopenia with hypersegmented granulocytes, (5) a dramatic reticulocytic response (within 2 to 3 days) to parenteral administration of vitamin B12. ***Pernicious anemia is associated with all of these findings plus the presence of serum antibodies to intrinsic factor.

which test to use to dx Syphillis

- Nontreponemal testing- Venereal Disease Research Laboratory (VDRL) slide test and the rapid plasma reagin (RPR) test. both equally valid but noncomparable, detect antibody like substance reagin - Treponemal testing- fluorescent treponemal antibody absorption test (FTA-ABS) highly specific but positive test result can not differentiate bw current and past infection bc antibodies remain positive in most pts

Is Infectious Mononucleosis an STD? caused by which virus?

- Not classically STD. - EBV virus - Children, adolescents, and young adults are most commonly affected - transmission- oropharyngeal route during close personal contact (i.e., intimate kissing). - clinical triad of fever, sore throat, and lymphadenopathy and is associated with lymphocytosis.

Holton- 34 yrs old: - white spots in mouth , tongue, funny taste, fever, weight loss, SOB w/ minimaL EXERTION, dry cough, diarrhea, occasional night sweat (can be caused by TB or lymphoma), sore throat, pain when swallowing - persistent scaling facial rash, cotton wool spots - test for candiasis in oral cavity- rub it off w/ cotton swab, should be rub off; if not rub off -> hairy leukoplakia pts with EBV, HIV - tachicardia - high neutrophils, low lymphocytes, low platelets (- Possible Acute infection, anemia, thrombocytopenia (Low lymphocytes can be caused due to viral infections)We would see high lymphocytes in lymphoma, but since we don't have high lymphocyte - we can cross out lymphoma.) - EKG demonstrated sinus tachycardia at a rate of 125, axis +60, non specific S-T changes V4 -V5. EKG otherwise within normal limits. - The normal QRS axis should be between -30 and +90 degrees. Left axis deviation is defined as the major QRS vector, falling between -30 and -90 degrees. Right axis deviation occurs with the QRS axis and is between +90 and +180 degrees. Nonspecific ST-T wave abnormalities, is frequently used when the clinical data are not available to correlate with the ECG findings. - - LD is high Lactate dehydrogenase is an enzyme found in nearly all living cells. LDH catalyzes the conversion of lactate to pyruvate and back, as it converts NAD⁺ to NADH and back. - - pH: 7.48 - pCO2: 28 - pO2: 55 - HCO3: 20 - Respiratory alkalosis with partial metabolic compensation - Hyperventilation - Lung disease with hyperventilation - Anemia - - Smear of the anal ulcer releaveled multinucleated giant cells consistent with herpes. - HSV -2 - chest xray -

- Nystatin- antifungal -> worsen his cough and breathing - Rhonchi & Crackles Rhonchi (sonorous wheeze): loud, low, coarse sounds like a snore most often heard continuously during inspiration or expiration; coughing may clear sound (usually means mucus accumulation in the trachea or large bronchi) Crackles are the sounds you will hear in a lung field that has fluid in the small airways. As stated before, crackles and rales are the same thing - Periungual mycosis: overgrowth of fungi in the toenail area. Candidiasis - Serial sevens, counting down from one hundred by sevens, is a clinical test used to test mental function - KOH Test for Candida albicans, also known as a potassium hydroxide preparation or KOH prep, is a quick, inexpensive fungal test to differentiate dermatophytes and Candida albicans symptoms from other skin disorders like psoriasis and eczema.

3 human retrovirus:

- Oncovirinae, which includes human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 - Lentivirinae, which includes HIV-1 and HIV-2 - Spumavirinae. The first human retrovirus to be isolated was a spumavirus, but it does not cause human disease. ***Endogenous retroviruses have been found throughout the human chromosomes, but they do not produce virions.

Oral manifestations of Syphilis?

- Oral chancres and mucous patches are usually painless unless they become secondarily infected- highly infectous Oral chancres - solitary lesions that may involve the lips, tongue, oropharynx, may be associated with lymphadenopathy begin round papule-> erodes into painless ulcer Hutchin incisors, peg shaped permanent central incisors w/ notching of incisal edge, multiple supernumerray cusps (mulberry MLs), skin fissure- congenital ....

Know - extrinsic pathway - intrinsic pathway PT, PTT

- PT: prothrombin time assesses the function of the proteins in the extrinsic pathway (factors VII, X, V, II (prothrombin), and fibrinogen). In brief, tissue factor, phospholipids, and calcium are added to plasma and the time for a fibrin clot to form is recorded. - PTT: partial thromboplastin time assay screens the function of the proteins in the intrinsic pathway (factors XII, XI, IX, VIII, X, V, II, and fibrinogen). Clotting of plasma is initiated by the addition of negative-charged particles (e.g., ground glass) that activate factor XII (Hageman factor) together with phospholipids and calcium, and the time to fibrin clot formation is recorded.

Malaria

- Plasmodium falciparum - other four species of Plasmodium that infect humans—Plasmodium malariae, Plasmodium vivax, Plasmodium knowlesi, and Plasmodium ovale—cause relatively benign disease transmitted by the bite of female Anopheles mosquitoes - PICTURE - During their asexual reproduction in red cells, each of the four forms of malaria develops into trophozoites. The asexual phase is completed when the trophozoites give rise to new merozoites, which escape by lysing the red cells.

Anti thrombotic properties:

- Platelet inhibitory effects: PGI2, NO, adenosine diphosphatase, ADp -> inhibit platelet activation & aggregation - Anticoagulant effects: thrombomodulin, endothelial protein C receptor bind thrombin & protein C -> thrombin can not activate coagulation factors& platelets, but cleave & activate protein C, a vit K dependent protease need cofactor protein S -> inhibit factors Va & VIIIa, heparin-like molecules bind & activate antithrombin III -> inhibit thrombin & factors IXa, Xa, XIa, XIIa, and tissue factor pathway inhibitor like protein C, needs protein S as cofactor -> bind & inhibits tisue factor VIIa complexes - Fibrinolytic effects: t-PA, key component of fibrinolytic pathway

what are platelets? and its role? their functions depend on what?

- Platelets: cell fragments that are shed from megakaryocytes in the bone marrow into the bloodstream - role in hemostasis by forming the primary plug - their function depends on several glycoprotein receptors, contractile cytoskeleton, 2 types of cytoplasmic granules : . α-Granules have the adhesion molecule P-selectin on their membranes . Dense (or δ) granules contain adenosine diphosphate (ADP) and adenosine triphosphate, ionized calcium, serotonin, and epinephrine.

role of platelets in controlling blood loss (hemorrhage)

- Primary aggregation: Disruptions in the microvascular endothelium, which are very common, allow the platelet glycocalyx to adhere to collagen in the vascular basal lamina or wall. Thus, a platelet plug is formed as a first step to stop bleeding - Secondary aggregation: Platelets in the plug release a specific adhesive glycoprotein and ADP, which induce further platelet aggregation and increase the size of the platelet plug. - Blood coagulation: During platelet aggregation, fibrinogen from plasma, von Willebrand factor and other proteins released from the damaged endothelium, and platelet factor 4 from platelet granules promote the sequential interaction (cascade) of plasma proteins, giving rise to a fibrin polymer that forms a three-dimensional network of fibers trapping RBCs and more platelets to form a blood clot, or thrombus (Figure 12-14). Platelet factor 4 is a chemokine for monocytes, neutrophils, and fibroblasts, and proliferation of the fibroblasts is stimulated by PDGF. - Clot retraction: The clot initially bulges into the blood vessel lumen, but soon contracts slightly due to the activity of platelet-derived actin and myosin. - Clot removal: Protected by the clot, the endothelium and surrounding tunic are restored by new tissue, and the clot is then removed, mainly dissolved by the proteolytic enzyme plasmin, which is formed continuously through the local action of plasminogen activators from the endothelium on plasminogen from plasma.

- granulomatous inflammation - epitheloid cells - giant cells - granuloma - contact dermatitis

- Prolonged DTH reactions against persistent microbes or other stimuli may result in a special pattern of reaction called granulomatous inflammation. - accumulated macrophages typically exhibit morphologic evidence of activation; that is, they become large, flat, and eosinophilic, and are called epithelioid cells - epithelioid cells occasionally fuse under the influence of cytokines (e.g., IFN-γ) to form multinucleate giant cells - aggregate of epithelioid cells, typically surrounded by a collar of lymphocytes, is called a granuloma - Contact dermatitis is a common example of tissue injury resulting from DTH reactions

Dx tests for herpes infection? when should the samples be taken ?

- Samples taken from active genital lesions may be cultured or undergo NAATs or direct immunofluorescence (DIF) of viral antigens to confirm viral types - Real-time PCR assays are highly accurate, rapid, and less technique sensitive; can provide quantitative results; and, importantly, can be used to assess asymptomatic viral shedding. DIF is a rapid test but can only be used on rich fresh samples. - Serology to detect HSV-1 or HSV-2 immunoglobulin (Ig) G is reliable to show past infection x Cytopathologic testing is typically not recommended, although staining for HSV infection may be helpful. x HSV IgM serology is not reliable for a recent or early infection. - Samples should be taken ideally within 24 hours of the initial clinical manifestations and taken from the base of the vesicular lesions.

Hemophilia B—Factor IX Deficiency

- Severe factor IX deficiency is an X-linked disorder - less common PTT prolonged dx is made using specific assay of factor IX

3 major route of HIV transmission

- Sexual tranmission - via blood - needle stick - vertical transmission - mom-> fetus HIV is not transmitted by touching, kissing, coughing, sneezing, insect bites, water, food, or via swimming pools.

Infectious Complications

- Significant bacterial contamination (sufficient to produce symptoms) is much more common in platelet preparations than red cell preparations, because of the fact that platelets (unlike red cells) must be stored at room temperature, which favors growth of bacterial contaminants.

what is the reverse transcriptase (RT)

- This enzyme - RNA-dependent DNA polymerase

medical tx for IM

- Tx tailors symptoms: bedrest, fluids, acetaminophen or NSAIDs for pain control, and gargling and irrigation with saline solution or lidocaine to relieve sore throat symptoms. - Antiviral drugs such as acyclovir can inhibit EBV replication, but they are not indicated for acute infectious mononucleosis except in severe cases or in immunocompromised patients.

4 types of hypersensitivity

- Type I : allergy, caused by TH2 cells, IgE antibodies, and mast cells and other leukocytes - Antibody-mediated disorders (type II hypersensitivity) are caused by secreted IgG and IgM - In immune complex-mediated disorders (type III hypersensitivity), IgG and IgM antibodies bind antigens, form antigen - antibody complexes - T cell- medicated type IV hypersensitivity disorders-T lymphocytes of the TH1 and TH17 subsets produce cytokines, CD8+ CTLs also may contribute to injury by directly killing host cells.

which conditions cause stasis or turbulence?

- Ulcerated atherosclerotic plaques - Abnormal aortic and arterial dilations - Acute myocardial infarction results in focally noncontractile myocardium. - Ventricular remodeling after more remote infarction can lead to aneurysm formation. In both cases, cardiac mural thrombi are more easily formed because of the local blood stasis - Mitral valve stenosis (e.g., after rheumatic heart disease) results in left atrial dilation - Dilated atrium also produces stasis and is a prime location for the development of thrombi - Hyperviscosity syndromes polycythemia vera, increase resistance to flow and cause small vessel stasis; the deformed red cells in sickle cell anemia cause vascular occlusions, and the resultant stasis also predisposes to thrombosis.

clinical significance of any particuar hemorrhage depends on...

- Volume of blood lost - Rate of bleeding - site (cause death if in brain)

Is DNA genome longer than RNA genome of the virus and why?

- Yes DNA genome longer. because: - the viral RNA genome is reverse transcribed by RT; - a complementary, negative-strand DNA (cDNA) is produced; and the RNA template is degraded by the ribonuclease Η activity of the RT - A positive-strand DNA is generated by the DNA-dependent DNA polymerase activity of the RT - The U3 and U5 sequences from each end of the genome are duplicated and become part of the LTRs on both ends of the genome *** REMEMBER the picture

can kidney contribute Glucose to blood? does it store glycogen?

- Yes. The kidney both has the ability to synthesize glucose-6-phosphate de novo by gluconeogenesis and has glucose-6-phosphatase activity, but quantitatively, it contributes much less than the liver. - Moreover, the kidneys do NOT store glycogen.

epiretinal membrane

- a pathological membrane partially covering the surface of the retina, probably originating from the retinal pigment epithelial and glial cells. Membranes peripheral to the macula are generally asymptomatic, but those involving the macula or adjacent to it may cause reduction in vision, visual distortion, and diplopia.

Immunogenicity of molecule means? Antigenicity of a molecule means? which are the strongest immunogens? are nucleic acids good immunogens?

- ability to induce a humoral and/or cell-mediated immune response. - ability to combine specifically with the final products of the immune response (ie, antibodies and/or T-cell receptors specific for the molecule) - Proteins (pure polysaccharide and lipopolysaccharides are good too) - Nucleic acids, except when they are single stranded or associated with proteins thenthey are good

N. gonorrhoeae an aerobic or anaeobic, gram - or gram +? which test used to dx gonorrhoeae? which is the first line dx tx for gonorrhoeae

- aerobic gram-negative β-proteobacteria, - diplococci with pili (hairlike surface structures) and a marked tropism for human mucosae - replicate in warm, moist areas - resistant site: squamous epithelium - Susceptible site- transitional respiratory * in men- begins in ant urethra after sexual exposure & 2-5 day incubation period -> urethritis, urethral discharge, dysuria -> spread to epididymis -> lead to infertiity, prostate, seminal vesicles, bladder * in women- asymptomatic, incubation 5-10 days -> cervicitis - testing: 1. Gram stain (methylene blue/ gentian violet) -> gram - diplococci within neutrophils (pts with asymtmmatic or w/o purulent discharge- gram staining not accurate) 2. Cultur & nucleic acid amplification test NAAT (first line diagnostic for G) - tx: 1. single dose of ceftriaxone 250 mg intramuscularly (IM) + single dose of azithromycin 1 g orally 2. cefixime 400mg orally + azithromycin 1g orally if ceftriaxone not available

Peripheral T Cell Lymphoma.

- aggressive tumors that respond poorly to therapy - tumors of functional T cells, patients often suffer from symptoms related to tumor-derived inflammatory products, even when the tumor burden is relatively low. - tx: antibodies that block PD-1 (Hodgkin lymphoma) and drugs that antagonize BCL2 (follicular lymphoma and other B cell tumors).

- Central Tolerance

- antigen-induced deletion (death) of self-reactive T lymphocytes and B lymphocytes during their maturation in central (generative) lymphoid organs (i.e., in the thymus for T cells and in the bone marrow for B cells)

Eosinophils- major basic proteins (MBP)

- arginine-rich factor that accounts for the granule's acidophilia and constitutes up to 50% of the total granule protein -> kill parasitic worms or helminths. - triggered by allergies - abundant in CT of interstinal lining& at site of chronic inflam (lung tissue of asthma pts)

Myeloid Neoplasms types: - • In acute myeloid leukemia (AML) - • In myeloproliferative neoplasms - • In myelodysplastic syndromes (MDS)

- arise from hematopoietic progenitors and typically give rise to proliferations that involve the bone marrow and replace normal marrow elements.

Polycythemia Vera

- associated with activating point mutations in the tyrosine kinase JAK2. JAK2 normally acts in the signaling pathways downstream of the erythropoietin receptor and other growth factor receptors -> produces excessive proliferation of erythroid, granulocytic, and megakaryocytic elements (panmyelosis) - associated with low levels of serum erythropoietin, which is a reflection of the growth factor-independent growth of the neoplastic clone.

signs & symptoms of IM (Infectious Mono)

- asymptomatic when found in children - young adults are affected, about 75% are symptomatic. ***lymphadenopathy (predominantly cervical), sore throat, and malaise and fatigue. Less common manifestations include palatal petechial hemorrhage; posterior cervical, axillary, or inguinal lymphadenopathy; pharyngeal or tonsillar exudate; and cutaneous rash. Other signs and symptoms include fever, headache, decreased appetite, nausea and vomiting, myalgias (body aches), arthralgias, splenomegaly, hepatomegaly, and jaundice. Symptoms typically dissipate within 3 weeks of onset.

von Willebrand Disease

- autosomal dominant disorder - spontaneous bleeding from mucous membranes, excessive bleeding from wounds, and menorrhagia. - defects in platelet function and coagulation

some characteristics of cellular changes in HVS1 & HVS2 infections how does the virus reactivate ?

- ballooning degeneration, - intranuclear inclusion bodies - formation of multinucleated giant cells. cellular destruction comes inflammation and increasing edema, which result in formation of papules that progress to fluid-filled vesicles. These vesicles rupture, leaving an ulcerated surface that if exposed to the air will eventually crust over. - virus reactivates after exposure to trauma, sunlight, menses, intercourse, or immune suppression. The reactivated progeny migrate down the axon and can produce a recurrent infection with lesions similar to the primary infection, albeit typically less severe in nature and more localized.

integral membrane proteins includes ion channels, anion transporter called...?

- band 3 protein, and - glycophorin A

Eosinophils

- bilobed nucleus - abundance of large, acidophilic specific granules typically staining pink or red. -

Vitamin B12 (Cobalamin) Deficiency Anemia vit B12- in food and is synthesized by gut flora

- bind haptocorrin -> complex - attach intrinsic factors - attach Cubilin - transferred to Transcobalamin

How is antibody diversity generated ?

- by the rearrangement of DNA by recombinases and by RNA splicing

Sickle cell anemia

- caused by a single a.a substitution mutation in β-globin that creates sickle hemoglobin (HbS) - protective effect against Plasmodium falciparum malaria. ***On average, the normal adult red cell contains 96% HbA (α2β2), 3% HbA2 (α2δ2), and 1% fetal Hb (HbF, α2γ2). In patients with sickle cell anemia, HbA is completely replaced by HbS ***HbS differs from HbA by having a valine residue instead of a glutamate residue at the 6th amino acid position in β-globin. ***polymers distort the red cell, which assumes an elongated crescentic, or sickle, shape ***membrane distortion produced by each sickling episode leads to an influx of calcium, which causes the loss of potassium and water and also damages the membrane skeleton. With time, this cumulative damage creates irreversibly sickled cells that rapidly undergo hemolysis.

Myelophthisic Anemia

- caused by extensive infiltration of the marrow by tumors or other lesions (Infiltration is the diffusion or accumulation (in a tissue or cells) of foreign substances or in amounts in excess of the normal. The material collected in those tissues or cells is called infiltrate.) - most commonly is associated with metastatic breast, lung, or prostate cancer. - misshapen red cells, some resembling teardrops - Immature granulocytic and erythrocytic precursors also may be present (leukoerythroblastosis) along with mild leukocytosis.

Treponema pallidium causes? what type of bacteria is this? route of transmission? how to kill this bacteria?

- causes Syphilis - slender, fragile microaerobic spirochete - transmitted sexually w/ contaiminated sores may occure thru kissing, or blodborne infection , fetuses-> congenital syphilis - T pallidium is killed by heating, drying, disinfecting, soap and water - not invade completely intact skin - can invade intact mucosal epithelium-> thru hair follicle or abrasions -> spread to lymphatics, bloodstream

causes of shock types of shock

- causes: severe hemorrhage, extensive trauma or burns, myocardial infarction, pulmonary embolism, and microbial sepsis. - types: 1. cardiogenic shock- result of low CO as result of myocardial pump failure (MI, ven arrythmias, extrinsic compression cardiac tamponade), outflow obstruction (pul embolism) 2. Hypovolemic shock results from low cardiac output due to loss of blood or plasma volume (e.g., resulting from hemorrhage or fluid loss from severe burns). 3. Septic shock is triggered by microbial infections and is associated with severe systemic inflammatory response syndrome (SIRS) SIRS may be triggered by a variety of insults, including burns, trauma, and/or pancreatitis (massive outpouring of inflammatory mediators from innate and adaptive immune cells that produce arterial vasodilation, vascular leakage, and venous blood pooling.) Less commonly, shock can result from a loss of vascular tone associated with anesthesia or secondary to a spinal cord injury (neurogenic shock). Anaphylactic shock results from systemic vasodilation and increased vascular permeability that is triggered by an immunoglobulin E-mediated hypersensitivity reaction

Pathologic consequences of Sickling red cells? life span of a sickle cell? factors that enhance the tendency of red cells to sickle within microvasculature

- chronic moderately severe hemolytic anemia, produced by red cell membrane damage - vascular obstructions, which result in ischemic tissue damage and pain crises - life span 20 days - factors such as infection, inflammation, dehydration, and acidosis,

venous thrombi can cause what?

- congestion and edema in vascular beds distal to an obstruction, they are most worrisome because of their potential to embolize to the lungs and cause death

IgG4-Related Disease

- constellation of fibro-inflammatory disorders characterized by tissue infiltrates rich in IgG4 antibody-producing plasma cells and lymphocytes, particularly T cells, associated with fibrosis and obliterative phlebitis

Genital Herpes Simplex Virus Infections : - type 1- above waist (oral mucosa) - type 2- below waist (sexual transmitted, infected mom-> newborn) herpes simplx virus belong to a family of 8 human herpesviruses that includes: ....

- cytomegalovirus (CMV), - Epstein-Barr virus (EBV), - varicella-zoster virus, - human herpesvirus type 6 (HHV-6), - human herpesvirus type 7 (HHV-7), and - Kaposi sarcoma-associated herpesvirus (HHV-8) - HSV1 - HSV2

- Gas bubbles in the pulmonary vasculature cause.... - Bubbles in the central nervous system can cause

- dema, hemorrhages, and focal atelectasis or emphysema, leading to respiratory distress, the so-called "chokes". - mental impairment and even sudden onset of coma.

what are the main neurologic lesions associated with vitamin B12 deficiency?

- demyelination of the posterior and lateral columns of the spinal cord, sometimes beginning in the peripheral nerves. - severity of the neurologic manifestations is not related to the degree of anemia.

how does Genital HPV be transmitted? fetal infection common?

- direct contact during secual contact - fetal infection rare, but can lead to respiratory papiomatosis ***virus enters the epithelium or epidermis through microtears and infects the basal cell layer. When the virus is intracellular, it increases the turnover of infected cells

13. Dental management Route transmission of STDs

- direct contact with lesions, blood, or saliva, and because many affected persons may be asymptomatic

toll like receptors

- each recognize a specific "danger" molecule AND are embedded in cellular membranes. - recognize bacterial products such as lipopolysaccharide (LPS), and endosomal TLRs recognize viral and bacterial RNA and DNA - recognize and activate trsncription factors that stimulate medicators of inflam, antiviral cytokines, proteins that promote lymphocyte activation....

Role of complement system? Types of complement system?

- enhances phagocytosis, facilitates inflammation, and can directly lyse certain microorganisms. - 3 complement pathways: classical, alternative lectin pathways

in severe hemolytic anemias

- erythropoietic drive may be so pronounced that extramedullary hematopoiesis appears in the liver, spleen, and lymph nodes. (bc liver, spleen is where destructed rbcs get cleaned out)

Aspirin and blood coagulation effect

- have an inhibitory effect on platelet function and blood coagulation because they block the local prostaglandin synthesis, which is needed for platelet aggregation, contraction, and exocytosis at sites of injury -

types of hemorrhage: - Hematoma - petechiae - Purpura - Ecchymoses

- hematoma: external or accumulate within a tissue, ranges in significance from trivial (e.g., a bruise) to fatal (e.g., a massive retroperitoneal hematoma resulting from rupture of a dissecting aortic aneurysm) - Large bleeds into body cavities are described according to location—hemothorax, hemopericardium, hemoperitoneum, or hemarthrosis (in joints). Extensive hemorrhages can occasionally result in jaundice from the massive breakdown of red cells and hemoglobin. - Petechiae- minute (1 to 2 mm in diameter) hemorrhages into skin, mucous membranes, or serosal surfaces; causes include low platelet counts (thrombocytopenia), defective platelet function, and loss of vascular wall support, as in vitamin C deficiency - Purpura are slightly larger (3 to 5 mm) hemorrhages. result from the same disorders that cause petechiae, as well as trauma, vascular inflammation (vasculitis), and increased vascular fragility. - Ecchymoses are larger (1 to 2 cm) subcutaneous hematomas (colloquially called bruises). Extravasated red cells are phagocytosed and degraded by macrophages; the characteristic color changes of a bruise result from the enzymatic conversion of hemoglobin (red-blue color) to bilirubin (blue-green color) and eventually hemosiderin (golden-brown).

Warm Antibody Immunohemolytic Anemia

- hemolysis results from the binding of high-affinity autoantibodies to red cells, which are then removed from the circulation by phagocytes in the spleen and elsewhere

The fraction of iron that is absorbed is regulated by ...,

- hepcidin, a small peptide that is synthesized and secreted from the liver in an iron-dependent fashion. - hepcidin levels rise in the face of systemic inflammation because of the direct effects of inflammatory mediators such as IL-6 on hepatocytes

Mixed Connective Tissue Disease

- high titers of antibodies to U1 ribonucleoprotein. - presents with synovitis of the fingers, Raynaud phenomenon, and mild myositis. - Renal involvement is modest, and there is a favorable response to corticosteroids, at least in the short term. - Serious complications of mixed connective tissue disease include pulmonary hypertension, interstitial lung disease, and renal disease.

which protein is found on helper T lymphocytes, monocytes, and macrophages?

- highly glycosylated surface protein SU gp 120 binds to host cell surface receptor CD4

Anti-phospholipid antibodies

- in lupus patients. - directed against epitopes of various plasma proteins that are revealed when the proteins are in complex with phospholipids. Antibodies against the phospholipid-β2-glycoprotein complex also bind to cardiolipin antigen, used in syphilis serology, and therefore lupus patients may have a false-positive test result for syphilis. Because these antibodies bind to phospholipids, they may prolong the partial thromboplastin time, an in vitro clotting test that requires phospholipids. Therefore, these antibodies are sometimes referred to as lupus anti-coagulant Pathogenesis The fundamental defect in SLE is a failure of the mechanisms that maintain self-tolerance.

Inactivated bacterial vaccines consist of Some examples?

- inactivated toxins called toxoids, or protein or polysaccharide subunites of the bacs - Vibrio cholerae, Bacillus anthracis, Yersinia pestis, and Coxiella burnetii.

Thrombotic Microangiopathies: Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome

- include thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). - TTP is associated with the pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, transient neurologic deficits, and renal failure. HUS also is associated with microangiopathic hemolytic anemia and thrombocytopenia but is distinguished from TTP by the absence of neurologic symptoms, the dominance of acute renal failure, and frequent occurrence in children

Low tissue O2 levels trigger...?

- increased erythropoietin release from the kidney, which in turn stimulates the growth of erythroid elements and increased release of reticulocytes from the bone marrow. - Thus, erythroid hyperplasia and reticulocytosis are hallmarks of all hemolytic anemias

How and what conditions cause Na and H2O retention -> lead to edema?

- increasing hydrostatic pressure (expansion of intravascular volume) and reducing osmotic pressure - compromise renal function: poststreptococcal glomerulonehritis, acute renal failure -> excessive salt and water retention

CLL Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

- indolent, slowly growing tumor - BCL2 overexpression appears to be chromosomal deletions that lead to the loss of genes encoding micro-RNAs that are negative regulators of BCL2. - critical importance are signals generated by surface immunoglobulin (the so-called B cell receptor, or BCR). BCR signals flow through an intermediary called Bruton tyrosine kinase (BTK) that ultimately contributes to the expression of genes that promote the survival of CLL/SLL cells. - CLL/SLL is a neoplasm of mature B cells expressing the CD20 and surface immunoglobulins. The tumor cells also express CD5. - fatigability, weight loss, and anorexia

how to dx HIV inefction? was it symptomatic or asymptomatic initially? CD4+ T cells count in blood declined <350/ul

- initial HIV may be asymptomatic, 2-4 wks acute phase maybe - flulike or Mono like symptoms, up to 6 wks - malasie , fever, hepatospenomegaly, lymphadenopathy, rash, arthralgias. Mild aseptic meningits may be observed - After this phase, the infection may become asymptomatic or turn into ongoing generalized lymphadenopathy as a result of virus multiplication in lymph nodes. - pathogenesis of the virus i- gradual depletion of CD4+ T cells. -> immune responses controlled by T cells decline. -> opportunistic infections by fungi, herpes simplex virus, and intracellular bacteria At this stage, the CD4+ T-cell count in blood is below 350/μL, - When the CD4+ T-cell concentration falls below 200/μL and the virus load is above 75,000 RNA copies/mL, "full-blown AIDS" is manifested, with HIV wasting syndrome, neurologic symptoms, and malignancies

NK cells are lymphocytes 2 types of receptors

- innate immune cells, as they are functional without prior activation and do not express highly variable and clonally distributed receptors for antigens - Activating receptors & Inhibitory receptors - infections especially viral infection & stress r associated w/ reduced expression of class I MHC & increase expression of proteins -> NK cells are activated and infected orstressed cells are killed and eliminated - Also secrete cytokines such as interferon-γ (IFN-γ), which activates macrophages to destroy ingested microbes, and thus NK cells provide early defense against intracellular microbial infections.

Attenuated vaccines induce ... ***reducing the virulence of a pathogen, but still keeping it viable (or "live") - Viruses called low temp mutants - some are host range mutant- not replicate efficiently in human cells - obtained by growing the virus in embryonated eggs or tissue culture cells at low temperatures (25°C to 34°C), avoiding the selective pressures of the host immune response.

- innate, humoral, and cell-mediated responses that are similar to those induced by the pathogen itself - useful for eliciting an immune response against enveloped viruses that can be cleared by T-cell immune responses. - Ex: BCG vaccines against TB, effective in children but not in adults - obtained by growing the virus in embryonated eggs or tissue culture cells at low temperatures (25°C to 34°C), avoiding the selective pressures of the host immune response.

Cold Antibody Immunohemolytic Anemia

- is caused by low-affinity IgM antibodies that bind to red cell membranes only at temperatures below 30°C, such as occur in distal parts of the body (e.g., ears, hands, and toes) in cold weather. ***most cells with bound IgM pick up some C3b but are not lysed intravascularly. When these cells travel to warmer areas, the weakly bound IgM antibody is released, but the coating of C3b remains. Because C3b is an opsonin, the cells are phagocytosed by macrophages, mainly in the spleen and liver; hence, in most cases the hemolysis is mainly extravascular.

α-thalassemia mutation- α-globin genes deletion

- is caused mainly by deletions involving one or more of the α-globin genes. - delete 1 gene -> silent carrier state - delete 4 genes -> lethal in utero bc no O2 delivering capacity - loss of 3 α-globin genes is a relative excess of β-globin or (early in life) γ-globin chains. -> form stable β4 and γ4 tetramers known as HbH and Hb Bart, respectively, which cause less membrane damage than the free α-globin chains that are found in β-thalassemia; -> ineffective erythropoiesis is less pronounced in α-thalassemia. Unfortunately, both HbH and Hb Bart have an abnormally high affinity for oxygen, which renders them ineffective at delivering oxygen to the tissues.

- ischemic coagulative necrosis - liquefactive necrosis

- ischemic coagulative necrosis Coagulative necrosis is a type of accidental cell death typically caused by ischemia or infarction. In coagulative necrosis the architecture of dead tissue is preserved for at least a couple of days - liquefactive necrosis a type of necrosis which results in a transformation of the tissue into a liquid viscous mass. Often it is associated with focal bacterial or fungal infections, and can also manifest as one of the symptoms of an internal chemical burn

Inactivated vaccines, examples, how are the viruses grown, when to administer - killed version of the pathogen, - polio, inactivated influena, hepititis A, rabies vaccines - viruses are grown in embryonated eggs and then inactivated - administed soon after exposure -> post exposure prophylaxis

- killed version of the pathogen - Polio vaccine via folmaldehyde tx of poliovirus - inactivated influenza vaccine - 2 influenza A + 1 influenza B most prevalent in flu season - ahepatitis A & rabies vaccines

How is platelet adhesion mediated?

- largely via interactions with vWF, which acts as a bridge between the platelet surface receptor glycoprotein Ib (GpIb) and exposed collagen genetic deficiencies of vWF (von Willebrand disease, or GpIb (Bernard-Soulier syndrome) result in bleeding disorders, attesting to the importance of these factors. - Platelets rapidly change shape following adhesion, being converted from smooth discs to spiky "sea urchins" with greatly increased surface area. This change is accompanied by alterations in glycoprotein IIb/IIIa that increase its affinity for fibrinogen - Secretion (release reaction) of granule contents occurs along with changes in shape; these two events are often referred to together as platelet activation.

Cancer in STD chapter

- lesions diagnosed with low- or high-grade anogenital squamous intraepithelial disease or squamous cell carcinoma generally involves surgery with or without radiation therapy, chemotherapy, or targeted therapy -

on antibody, light chain is encoded by which region? (variable orjoining segment, or diversity segment) heavy chain is encoded by which segment?

- light chain - variable region V and joining segment J - heavy chain- variable segment V, Diversity segment D, and joinign segment J **κ light chain gene clusters on chromosome 2 λ light chain genes on chromosome 22, heavy chain genes (α, δ, ∊, γ, μ) on chromosome 14 encode the different components of antibodies - light chain gene is generated in a pre-B cell by combining one of 35 VLκ genes - LK - heavy chain: 100 variable segment V+ 23 H + 6 J

Arthus reaction (Local Immune Complex Disease)

- local immune complex diseases, an area of tissue necrosis appears as a result of acute immune complex vasculitis. - by injecting an antigen into the skin of a previously immunized animal with preformed antibody. - Immune complexes form as the antigen diffuses into the vascular wall at the site of injection, triggering the same inflammatory reaction and histologic appearance as in systemic immune complex disease.

treatment of Syphillis? which drugs should be used? Dental consideration? can we treat these pts?

- long-acting benzathine penicillin G 2.4 million IU IM in a single dose for primary, secondary, or early latent syphilis in adults; - 50,000 IU/kg of penicillin G should be used for children or infants Dental- still can provide dental care but with precautions unless oral esions are present

- Blood smear are stained with what?

- mixtures of acidic (eosin) and basic (methylene blue) dyes. *contain dyes called azures that are more useful in staining cytoplasmic granules containing charged proteins and proteoglycans

Anemia of Chronic Inflammation - pathogenesis of anemia of chronic disease? - clinical features?

- most common form of anemia in hospitalized patients. - arises instead from the suppression of erythropoiesis by systemic inflammation: • Chronic microbial infections, such as osteomyelitis, bacterial endocarditis, and lung abscess • Chronic immune disorders, such as rheumatoid arthritis and regional enteritis • Neoplasms, such as Hodgkin lymphoma and carcinomas of the lung and breast *** path stems from high levels of plasma hepcidin, which blocks the transfer of iron to erythroid precursors by downregulating ferroportin in macrophages. The elevated hepcidin levels are caused by proinflammatory cytokines such as IL-6, which increase hepatic hepcidin synthesis. + In addition, chronic inflammation blunts erythropoietin synthesis by the kidney, lowering red cell production by the marrow *** clinical features: - low serum Fe, red cells slightly hypochromic & microcytic - but storage Fe in bone marrow & serum ferritin increase and total Fe binding capacity is reduced

septic shock

- most frequently triggered by gram-positive bacterial infections, followed by gram-negative bacteria and fungi. Watch video about pathophysiology of septic shock

Myeloproliferative Neoplasms

- mutated, constitutively activated tyrosine kinases or other acquired aberrations in signaling pathways that lead to growth factor independence

Acute Myeloid Leukemia

- mutations in genes encoding transcription factors that are required for normal myeloid cell differentiation - .....(15;17) translocation in acute promyelocytic leukemia, which results in the fusion of the retinoic acid receptor α (RARA) gene on chromosome 17 and the PML gene on chromosome 15 ................. - Most tumors express some combination of myeloid-associated antigens, such as CD13, CD14, CD15, CD64, or CD117 (KIT). CD34, a marker of hematopoietic stem cells, is often present on myeloblasts

Thalassemia - alpha - deletion - beta-

- mutations in globin genes that decrease the synthesis of α (on chromosome 16)- or β-globin (chromosome 11). -> deficiency of Hb + RBCs damage -> protect against falciparum malaria - β-thalassemia: (1) β0, in which no β-globin chains are produced; and (2) β+, in which there is reduced (but detectable) β-globin synthesis. most common mutations lead to abnormal RNA splicing

- naïve lymphocytes - effector lymphocytes - memory lymphocytes - regulatory T lymphocytes

- naïve lymphocytes express antigen receptors but have not responded to antigens and do not serve any functions - effector lymphocytes are induced by lymphocyte activation and perform the functions that eliminate microbes; - memory lymphocytes, induced during activation, survive in a functionally silent state even after the antigen is eliminated and respond rapidly upon subsequent encounters with the antigen. - T cells that function to suppress immune responses are called regulatory T lymphocytes

Acute Lymphoblastic Leukemia/Lymphoma

- neoplasms composed of immature B (pre-B) or T (pre-T) cells, which are referred to as lymphoblasts- 85% are B-ALLs, - Many chromosomal aberrations seen in ALL dysregulate the expression and function of transcription factors that are required for the normal differentiation of B and T cell progenitors. - re-B cell tumors are hyperdiploidy (more than 50 chromosomes/cell) and a (12;21) translocation involving the ETV6 and RUNX1 genes, creating a fusion gene encoding an aberrant transcription factor, whereas about 25% of adult pre-B cell tumors have a (9;22) translocation involving the ABL and BCR genes. - mutations that inactivate tumors suppressor genes such as PTEN (leading to increased pro-growth signaling) and CDKN2A, which encodes a negative regulator of the cell cycle and a positive regulator of p53.

Oral manifestations w/ IM

- palatal petechiae, enlarged tonsils, pharyngitis with tonsillar exudate, and with cervical lymphadenopathy should raise suspicion of infectious mononucleosis. - Patients with a history of infectious mononucleosis may be at risk for developing EBV-associated Hodgkin and non-Hodgkin lymphomas. -- These lymphomas may manifest as persistent cervical lymphadenopathy or oral cavity lesions.

what helps maintain platelet's shape?

- peripheral marginal bundle of microtubules and microfilaments, which helps to maintain the platelet's shape.

which drugs interfere with folate absorption? which drugs inhibit folate metabolism? site of folate absorption?

- phenytoin (dilantin) (phe fo~ lk) - methotrexate, inhibit folate metabolism. - upper 3rd of small intestine malabsorption disorders - celiac disease and tropical sprue

heme which type of bridge links 4 pyrrole ring together? heme is synthesized from____________

- porphyrin, a cyclic compound that contains four pyrrole rings linked together by methenyl bridges. - It is synthesized from glycine and succinyl-coenzyme A, which condense to form 5-aminolevulinate (5-ALA). This reaction is catalyzed by 5-ALA synthase, located in mitochondria, and is rate limiting in heme synthesis. - Subsequently, in the cytosol, two molecules of 5-ALA condense to form a molecule containing a pyrrole ring, porphobilinogen (PBG). Then four PBG molecules combine to form a linear tetrapyrrole compound, which cyclizes to yield uroporphyrinogen III and then coproporphyrinogen III. The final stages of the pathway occur again in the mitochondria, where a series of decarboxylation and oxidation of side chains in uroporphyrinogen III yield protoporphyrin IX. At the final stage, iron (Fe2+) is added by ferrochelatase to protoporphyrin IX to form heme. Heme controls the rate of its synthesis by feedback inhibition of 5-ALA synthase

75% of its blood flow is supplied by the _________, which drains blood from the intestine? - portal artery - portal vein - hepatic artery - hepatic vein *** structure of the liver

- portal vein

Monocytes

- precursor cells of macrophages, osteoclasts, microglia, and other cells of the mononuclear phagocyte system in connective tissue of nearly all organs - nuclei large, indented or C shaped - chromatin less condensed than lymphocytes, stains lighter - antigen- presenting cells - cytoplasm is basophilic , small lysosomal azurophilic granules

Chronic Myeloid Leukemia

- presence of a chimeric BCR-ABL gene derived from portions of the BCR gene on chromosome 22 and the ABL gene on chromosome 9 - The growth factor dependence of CML progenitors is greatly decreased by constitutive signals generated by BCR-ABL that mimic the effects of growth factor receptor activation. Importantly, because BCR-ABL does not inhibit differentiation

- primary immune response vs - secondary immune response which Ig produced first in primary, and which one predominantly in secondary what is Anamnestic response ?and is it in preimary or secondary

- primary immune response production of antibodies by plasma cells after a 5- to 10-day lag period produce Ig M, then Ig G -> produce memory cells - secondary immune response when antigen enters blood or tissues again memory cells respond, then Ig M, then Ig G - anamnestic responses - Ig G predominant antibody levels, measured as antibody titer , persist for a longer period compare to primary

Primary Myelofibrosis

- primary myelofibrosis is the development of obliterative marrow fibrosis, which reduces bone marrow hematopoiesis and leads to cytopenias and extensive extramedullary hematopoiesis - JAK-STAT signaling seems to be the underlying driver in almost all cases. - characteristic marrow fibrosis is caused by the inappropriate release of fibrogenic factors from neoplastic megakaryocytes. Two factors synthesized by megakaryocytes have been implicated: platelet-derived growth factor and TGF-β. - platelet-derived growth factor and TGF-β are fibroblast mitogens. In addition, TGF-β promotes collagen deposition and causes angiogenesis, both of which are observed in myelofibrosis.

Diffuse Large B Cell Lymphoma

- rearrangements of the BCL6 gene, located on 3q27, and an even higher fraction of tumors have activating point mutations in the BCL6 promoter. - tumors express the B cell antigen CD20. Many also express surface IgM and/or IgG. Other antigens (e.g., CD10, BCL2) are variably expressed.

NOD-Like Receptors and the Inflammasome - C-type lectin receptors (CLRs) - G protein-coupled receptor - Mannose receptor - cytosolic receptors,

- recognize a wide variety of substances, including products of necrotic cells (e.g., uric acid and released ATP), ion disturbances (e.g., loss of K+), and some microbial products - C-type lectin receptors (CLRs) expressed on the plasma membrane of macrophages and DCs detect fungal glycans and elicit inflammatory reactions to fungi. - G protein-coupled receptors on neutrophils, macrophages, and most other types of leukocytes recognize short bacterial peptides containing N-formylmethionyl residues. Because all bacterial proteins and few mammalian proteins (only those synthesized within mitochondria) are initiated by N-formylmethionine, this receptor enables neutrophils to detect bacterial proteins and stimulates chemotactic responses. - Mannose receptors recognize microbial sugars (which often contain terminal mannose residues, unlike mammalian glycoproteins) and induce phagocytosis of the microbes - RIG-I and the other called cytosolic DNA sensors, recognize microbial RNA and DNA, respectively.

Red cell disorders= Anemia

- reduction in the oxygen-transporting capacity of blood, resulting from a decrease in the red cell mass to subnormal levels. - from bleeding, increased red cell destruction, or decreased red cell production.

Chronic serum sickness

- results from repeated or prolonged exposure to an antigen. - occurs in several diseases, such as systemic lupus erythematosus (SLE), which is associated with persistent antibody responses to autoantigens.

Cat-Scratch Disease

- self-limited lymphadenitis caused by the bacterium Bartonella henselae - regional lymphadenopathy, most frequently in the axilla and the neck.- feline scratch or, less commonly, after a splinter or thorn injury.

Chronic Discoid Lupus Erythematosus

- skin manifestations may mimic SLE, but systemic manifestations are rare - presence of skin plaques, most often on the face and scalp, showing varying degrees of edema, erythema, scaliness, follicular plugging, and skin atrophy surrounded by an elevated erythematous border - subacute cutaneous lupus erythematosus refers to a group intermediate between SLE and lupus erythematosus localized only to skin. The skin rash in this disease tends to be widespread and superficial - strong association with antibodies to the SS-A antigen and with the HLA-DR3 genotype.

Aplastic anemia clinical features Do not cause Splenomegaly

- slowly preessive anemia - weakness, pallor, and dyspnea - Thrombocytopenia often manifests with petechiae and ecchymoses. - Neutropenia may set the stage for serious infections.

Genital warts and human papillomavirus infections

- small, double-stranded, nonenveloped DNA viruses that infect and replicate in mucosal and cutaneous sites - Subtypes of HPV have been classified as "high-risk" or "low-risk" types *** Low-risk HPVs (>90% of subtypes are HPV-6 and -11) cause benign lesions (involving genital and other nongenital skin and mucosal sites) *** High-risk HPV types (predominantly HPV-16 and -18) are strongly associated with intraepithelial lesions and carcinoma of the cervix, vagina, and anus. HPV-16 is also strongly associated with oropharyngeal cancer (base of tongue and tonsils).

Specific secondary granules

- smaller and less dense, stain faintly pink, and have diverse functions, including secretion of various ECM-degrading enzymes such as collagenases, delivery of additional bactericidal proteins to phagolysosomes, and insertion of new cell membrane components.

Megaloblastic anemias: 1. Folate deficiency 2. Vit B12 deficiency both of these requried for DNA synthesis and the effects on hematopoieses Roles of folate & Vit 12

- stems from metabolic defects that lead to inadequate biosynthesis of thymidine, one of the building blocks of DNA - roles: essential factors for the synthesis of thymidylate, which is required for DNA replication -Deficiency of thymidine causes: abnormalities in rapidly dividing cells throughout the body, but the hematopoietic marrow is most severely affected. -> hematopoietic precursors show nuclear-cytoplasmic asynchrony - Many red cell progenitors are so defective in DNA synthesis that they undergo apoptosis in the marrow (ineffective hematopoiesis) - Granulocyte and platelet precursors also are affected (although not as severely) and most patients present with pancytopenia (anemia, thrombocytopenia, and granulocytopenia).

Disseminated Intravascular Coagulation (DIC)

- systemic activation of coagulation and results in the formation of thrombi throughout the microcirculation. - DIC usually is triggered by either (1) the release of tissue factor or thromboplastic substances into the circulation or (2) widespread endothelial cell damage - DIC is most often associated with sepsis, obstetric complications, malignancy, and major trauma (especially to the brain) - Severe endothelial cell injury can initiate DIC by causing the release of tissue factor and by exposing subendothelial collagen and vWF.

what happens once virus enters the cytoplasm? - change from RNA -> cDNA (ribonuclease H degrade RNA template) - DNA- dependent DNA polymerase generates positive strand DNA on RT - U3 & U5 sequences from each end of genome duplicate -> become part of the LTRs on both end of genome *** LTRs- RNA sequences that comprise promoter and enhancer gene sequences that bind transcription factors.

- the viral RNA genome is reverse transcribed by RT; - a complementary, negative-strand DNA (cDNA) is produced; and the RNA template is degraded by the ribonuclease Η activity of the RT - A positive-strand DNA is generated by the DNA-dependent DNA polymerase activity of the RT - The U3 and U5 sequences from each end of the genome are duplicated and become part of the LTRs on both ends of the genome -> the DNA genome is longer than the RNA genome of the virus. Reverse transcription does not faithfully transcribe the viral genome, introducing mutations -> leading to the emergence of new strains and allowing the virus to escape immune recognition.

- hemostasis involved... ? - thrombosis - thrombus

- thrombosis: formation of blood clot - thrombus- blood clot within non-traumatized, intact vessels. Hemostasis is a process involving platelets, clotting factors, and endothelium that occurs at the site of vascular injury and culminates in the formation of a blood clot, which serves to prevent or limit the extent of bleeding

Neutrophils (Polymorphonuclear Leukocytes)

- two to five lobes linked by thin nuclear extensions - Females, inactive X chromosome may appear as a drumstick-like appendage on one of the lobes of the nucleus - Inactive & spherical while circulating but bc amoeboid & active during diapedesis, adhere to ECM substrates collagen- 1st to arrive at sites of infection using CHEMOTAXIS. - Azurophilic primary granules or lysosomes are large, dense vesicles with a major role in both killing and degrading engulfed microorganisms. - contain glycogen, which is broken down into glucose to yield energy via the glycolytic pathway. - contain proteases and antibacterial proteins, including the following: *Myeloperoxidase (MPO), which generates hypochlorite and other agents toxic to bacteria Lysozyme, which degrades components of bacterial cell walls Defensins, small cysteine-rich proteins that bind and disrupt the cell membranes of many types of bacteria and other microorganisms.

Hairy Cell Leukemia.

- uncommon, indolent B cell neoplasm characterized by the presence of fine, hairlike cytoplasmic projections. The tumor cells express B cell markers (CD20), surface immunoglobulin, and CD11c and CD103; the latter two antigens are not present on most other B cell tumors, making them diagnostically useful - all cases are associated with activating mutations in the serine/threonine kinase BRAF - mainly in older males, infiltration of bone marrow and spleen. Splenomegaly, often massive, is the most common and sometimes only physical finding. Pancytopenia, resulting from marrow infiltration and splenic sequestration, is seen in more than half of cases. -- extremely sensitive to chemotherapeutic agents, particularly purine nucleoside

Platelets (thrombocytes)

- very small non nucleated, membrane bound cell fragment - originate by separation from ends of cytoplasmic processes extending from giant polyploid bone marrow cells = Megakaryocytes - life span 10 days - normal platelet counts range from 150,000 to 400,000/μL (mm3) of blood - in blood smear- discoid, hyalomere- very lightly stained peripheral zone granulomere = darker staining central zone rich in granules

Coagulation Disorders

- vitamin K is required for the synthesis of prothrombin and clotting factors VII, IX, and X, and its deficiency causes a severe coagulation defect. The liver synthesizes several coagulation factors and also removes many activated coagulation factors from the circulation; thus, hepatic parenchymal diseases are common causes of complex hemorrhagic diatheses - DIC also may lead to multiple concomitant factor deficiencies. Rarely, autoantibodies may cause acquired deficiencies limited to a single factor. - Hemophilia A (a deficiency of factor VIII) and hemophilia B (Christmas disease, a deficiency of factor IX) are X-linked traits, whereas other deficiencies are autosomal recessive disorders. Of the inherited deficiencies, only von Willebrand disease, hemophilia A, and hemophilia B are sufficiently common to warrant further consideration

what is provirus? in formed in which phase? (latent, dormant reproductive, or growth phase?)

- when the cell is in a growth phase, the complex is integrated into the host chromosome via the action of the viral integrase, forming the provirus. - The provirus may stay dormant or enter a productive cycle. In the latter case, the viral genome is transcribed into a full-length RNA by the RNA polymerase II of the host cell.

dx test for IM

- white blood cell count demonstrating lymphocytosis (>50%) with blood smears revealing more than 10% atypical "reactive" lymphocytes is highly predictive - nonspecific heterophile antibody test, specific enzyme immunoassay antibody tests, and PCR. - Heterophile antibodies are IgM antibodies that bind (agglutinate) to erythrocytes from nonhuman species such as sheep and horses. This process forms the basis for the inexpensive rapid latex agglutination test (Monospot test).

SLE

- • Most of the systemic lesions are caused by immune complexes (type III hypersensitivity). DNA-anti-DNA complexes can be detected in the glomeruli and small blood vessels. - • Autoantibodies of different specificities contribute to the pathology and clinical manifestations of SLE (type II hypersensitivity). Autoantibodies specific for red blood cells, white blood cells, and platelets opsonize these cells and promote their phagocytosis, resulting in cytopenias. - • Anti-phospholipid antibody syndrome. Patients with anti-phospholipid antibodies may develop venous and arterial thromboses, which may be associated with recurrent spontaneous miscarriages and focal cerebral or ocular ischemia. - • The neuropsychiatric manifestations of SLE have been attributed to antibodies that cross the blood-brain barrier and react with neurons or receptors for various neurotransmitters.

Do you as a dentist treat pts w/ IM comes in bc of oral sign and symptom? how about routine dental tx

-> refer to physician for eval and tx - routine dental tx should be delayed for about 4 wks until the pt has recovered

Lymphoplasmacytic Lymphoma

-B cell neoplasm of older adults - associated with acquired mutations in MYD88. -MYD88 gene encodes an adaptor protein that participates in signaling events that activate NF-κB and also augment signals downstream of the BCR (Ig) complex, both of which may promote the growth and survival of the tumor cells. -lymphoid component expresses B cell markers such as CD20 and surface immunoglobulin- IgM -weakness, fatigue, and weight loss.

1. Leukopenia - Neutropenia/ Agranulocytosis

-Leukopenia results most commonly from a decrease in granulocytes, the most numerous circulating white cells. - • Decreased granulocyte production. Clinically important reductions in granulopoiesis are most often caused by marrow hypoplasia. caused by certain drugs or by neoplastic proliferations of cytotoxic T cells and natural killer (NK) cells (so-called "large granular lymphocytic leukemia"). - • Increased granulocyte destruction. This can be encountered with immune-mediated injury (triggered in some cases by drugs) or in overwhelming bacterial, fungal, or rickettsial infections resulting from increased peripheral use. Splenomegaly also can lead to the sequestration and accelerated removal of neutrophils. ***ulcerating, necrotizing lesions of the gingiva, floor of the mouth, buccal mucosa, pharynx, or other sites within the oral cavity (agranulocytic angina). Owing to the lack of leukocytes

an acute event... caused by sudden decrease in red cell production

aplastic crisis

Hodgkin Lymphoma subtypes: (1) nodular sclerosis, (2) mixed cellularity, (3) lymphocyte rich, (4) lymphocyte depletion, and (5) lymphocyte predominant. In the first four subtypes the RS cells share certain morphologic and immunophenotypic features (described later), leading some researchers to lump together these entities under the rubric classical Hodgkin lymphoma

-encompasses a distinctive group of neoplasms that are characterized by the presence of a tumor giant cell, the RS cell. - arise in a single lymph node or chain of lymph nodes and typically spread in a stepwise fashion to anatomically contiguous nodes. - Hodgkin lymphoma is a neoplasm that arises from germinal center B cells. - Another clue into the etiology of Hodgkin lymphoma stems from the frequent involvement of EBV. -The characteristic nonneoplastic, inflammatory cell infiltrate is generated by a number of cytokines -

Aplastic anemia - pathogenesis

-multipotent myeloid stem cells are suppressed, leading to bone marrow failure and pancytopenia (it is not the same as pure red cell aplasia, which only erythroid progenitors are affected) - pathogenesis: *extrinsic, immune-mediated suppression of marrow progenitors *intrinsic abnormality of stem cells

Path chapter 4- Hemodynamic disorder

1. Edema 2. Hemorrhage 3. Hemostasis & thrombosis 4. Embolism 5. Infarction 6. Shock

2 major types of abundant cytoplasmic granules of GRANULOCYTES

1. Lysosome (aka azurophilic granules in blood cells) 2. Specific granules- bind neutral, basic, or acidic stains *** granulocytes have POLYmorphic nuclei (>2 lobes) - short life span - Golgi and rough ER poorly developed - few mitochondria -> depend largely on glycolysis for energy - undergo apoptosis in CT -> removed by macrophages *** agranulocytes- no specific granulees - do contain some azurophilic granules (lysosomes) - lymphocytes & monocytes

Fate of the thrombus. 4 processes:

1. Propagation- thrombus enlarge 2. Embolization- part or all thrombus 's dislodged & transport 3. Dissolution- if thrombus is newly form -> rapid shrinkage & complete dissolution. Old thrombus -> need therapeutic administration fo fibrinolytic agents like t-PA withing few hrs of thrombus formation 4. Organization & recaralization- thrombus become vascularized mass of CT -> incoporrated itto wall of remodeled vessle

Sequence of events leading to hemostasis - in orders

1. arterior vasoconstriction- secretion of endothelin 2. primary hemostasis- formation of platelet plug, wWF & collagen promote platelet adherence, platelet aggregation to form primary hemostatic plug 3. secondary hemostasis- deposition of fibrin. tissue factors bind & activate factor VII -> thrombin generation. Thrombin cleaves fibrinogen -> insoluble fibrin cause fibrin meshwork -> additional platelet aggregation 4. CLot stabilization & resorption- fibrin + platelet aggregate -> solid, permanent plug

monomeric antibody molecule consists of many polypeptide chains?

4 polypeptide chains: - 2 light chains, - 2 heavy chain

Caison disease

A more chronic form of decompression sickness is called caisson disease (named for pressurized underwater vessels used during bridge construction), in which recurrent or persistent gas emboli in the bones lead to multifocal ischemic necrosis; the heads of the femurs, tibiae, and humeri are most commonly affected.

which pathway is this? C3b binds components of the microbial cell surface (endotoxin or polysaccharides). Factor D (a serine protease) cleaves factor Β (also a serine protease) bound to C3b, forming Bb (and Ba). The complexation of C3b and Bb forms C3 convertase, which produces C3b. C3b then binds to the membrane-bound C3b/Bb complex, resulting in the formation of C5 convertase

Alternative pathway

which is toxic: ammonia or ammonium? which part of the body/ organ mostly affected? how is it detoxified?

Ammonia toxic Central nervous sytem - Most ammonia is detoxified at its site of formation, by amidation of glutamate to glutamine, which is mainly derived from muscle and is used as an energy source by the enterocytes. - The remaining nitrogen enters the portal vein either as ammonia or as alanine, both of which are used by the liver for the synthesis of urea

what is mycotic aneurysm?

An aneurysm caused by bacteria. Called mycotic aneurysm since the bacteria look like mushrooms. If bacterial seeding occurs, the contents of degraded thrombi serve as an ideal culture medium, and the resulting infection may weaken the vessel wall, leading to the formation of a mycotic aneurysm

Embolism emboli are composed of...?

An embolus is a detached intravascular solid, liquid, or gaseous mass that is carried by the blood from its point of origin to a distant site, where it often causes tissue dysfunction or infarction. vast majority of emboli derive from a dislodged thrombus—hence the term thromboembolism emboli are composed of : - part of thrombus - fat droplets, - bubbles of air or nitrogen atherosclerotic debris (cholesterol emboli - tumor fragment - bits of bone marrow - amniotic fluid.

Reactive Leukocytosis

An increase in the number of white cells in the blood -

Infarction which organs are primarily affected by infarction?

An infarct is an area of ischemic necrosis caused by occlusion of the vascular supply to the affected tissue. - heart and the brain is a common • Infarcts are areas of ischemic necrosis most commonly caused by arterial occlusion (typically resulting from thrombosis or embolization); venous outflow obstruction is a less frequent cause. • Whether or not vascular occlusion causes tissue infarction is influenced by collateral blood supplies, the rate at which an obstruction develops, intrinsic tissue susceptibility to ischemic injury, and blood oxygenation.

what types of vaccines are measles, mumps, and rubella (MMR) vaccine and the varicella zoster vaccine and how are they administered?

Attenuated vaccines administered after a child reaches 1 year of age, when a robust T-cell response can be elicited. A live attenuated influenza vaccine is administered intranasally to individuals in the age range 2 to 49 years, inducing T-cell and B-cell responses and mucosal immunity

Plasma Cell Neoplasms and Related Entities

B cell proliferations contain neoplastic plasma cells that virtually always secrete a monoclonal immunoglobulin or immunoglobulin fragment, which serve as tumor markers and often have pathologic consequences - A monoclonal immunoglobulin = M protein,

which is the key elements in fat metabolism? and where is it synthesized? roles?

Bile acids Bile acids are synthesized in the hepatocytes roles- - solubilizing biliary lipids and emulsifying dietary fat to facilitate its digestion - Biliary excretion is also the only route by which cholesterol can be eliminated from the body.

what are inflmmatory mediators?

C3a & C5a - C3b acts as an opsonin, coating microbial surfaces and facilitating phagocytosis. - C5b initiates the formation of the membrane attack complex.

how does CD4- cells get infected

CD4-negative cells such as renal and gastrointestinal cells and astrocytes in the brain may also be infected, possibly via alternative receptors or via cell-cell fusion.

CD8+ T Cell-Mediated Cytotoxicity

CD8+ T Cell-Mediated Cytotoxicity In this type of T cell-mediated reaction, CD8+ CTLs kill antigen-expressing target cells.

HIV establishes latency in memory T cells, which do not express the virus. There is an extended period of clinical latency, without apparent evidence of disease. However, HIV still replicates in lymph nodes and is trapped by follicular dendritic cells that are located in germinal centers. These cells trap microorganisms, including HIV, as Β cells initiate their response after recognizing antigens of the trapped pathogen. During periods of undetectable virus in the blood (usually less than 50 RNA copies/mL), large numbers of HIV accumulate in the lymph nodes. CD4+ T cells in the germinal centers and their vicinity become activated by cytokines secreted by other immune cells in the lymphoid tissue; this enables productive infection of the CD4+ cells by HIV and increases virus production by infected cells.

CD8+ cytotoxic T lymphocytes (CTLs) recognize and kill actively infected cells that are producing virions CTLs secrete chemokines such as RANTES, MIP-1α, and MIP-1β that bind the chemokine co-receptors for HIV, thereby restricting HIV entry and replication. CTLs have to be activated by helper T cells; thus, when the number of CD4+ T cells declines, CTL numbers also decline, contributing to disease progression One explanation may be that HIV develops the ability to use co-receptors in addition to CCR5 (eg, CXCR4).

which cytochrome P 450 gene responsible for most of phase I drug metabolism

CYP1, CYP2, and CYP3

Which complement pathway is this? - 2 IgG antibody or 1 IgM bound to surface of microorganisms activates 1st component of complement , protein C1 C1 -> C2 : C2a & C2b ; C4 : C4a & C4b C4b + C2b -> C3 convertase -> C3a + C3b C3a- inflammatory mediator - facilitates chemotaxis & histamine release C3b- participates in the formation of C5 convertase -> C5a + C5b C5a- causes chemotaxis & histamine release C5b- + C6, C7, C8, C9 -> form pore = membrane attack complex (Neisseria species, cell lysis)

Classic pathway

Hutchin incisors, peg shaped permanent central incisors w/ notching of incisal edge, multiple supernumerray cusps (mulberry MLs), skin fissure- are oral manifestation of which STD infection

Congenital syphillis

Capsular polysaccharides vaccine from Streptococcus pneumoniae, four major serotypes (A, C, Y, and W-135) of Neisseria meningitidis, and for Haemophilis influenzae B. Are what type of vaccine?

Conjugated vaccine- subunit vaccines immunogenicity can be improved by conjugation to a protein carrier, such as diphtheria toxoid or Ν meningitidis outer membrane protei

Case 3- Coville "tired all the time" - bruise easily - anemic- absent Fe stores, hemocult negative, anemia w/ normal cell count - fatigue - occasional bleeding when brushing and flossing - Past- GI bleeding 2ndary to angiodysplasia of colon -> corrected by cautery - Past - stroke CVA - chronic open angle glaucoma - hypertension 30 yrs - compensated congestive heart failure - acute pancreatitis of undetermined etiology - gout & joint pain - right cataract extraction w/ intraocular lens implant -> complicated by epiretinal membrane - early cataract formation in left eye - Acute gastritis - Cholecystectomy & appendectomy

Coville's dx tests: - CBC high bands, low lymphocytes, platelets high (see below) - Liver function test: Uric acid high - bc of gout CRP high - indicates inflammation

Dendritic cells (DCs)

Dendritic cells (DCs) are the most important antigen-presenting cells for initiating T-cell responses against protein antigens. - Langerhans cellson skin within epidermis - One subset of DCs is called plasmacytoid DCs because of their resemblance to plasma cell

Drug-Induced Lupus Erythematosus

Drug-Induced Lupus Erythematosus - An SLE-like syndrome may develop in patients receiving a variety of drugs, including hydralazine, procainamide, isoniazid, and D-penicillamine. - anti-TNF therapy, which is effective in rheumatoid arthritis and other autoimmune diseases, also can cause drug-induced lupus. - associated with the development of ANAs, especially antibodies specific for histones

dx of HIV

ELISA - dx by the presence of antibodies against viral components - results is confirmed by Western blot (detect protein) - antibodies can be detected in blood or oral fluid - viral RNA is reverse transcribed into cDNA, which is then amplified with the polymerase chain reaction - number of viral RNA copies per milliliter of plasma is termed the viral load.

Hematocrit

Erythrocytes comprise the sedimented material, and their volume, normally about 44% of the total blood volume in healthy adults, is called the hematocrit. - A tube of blood after centrifugation (center) has nearly half of its volume represented by erythrocytes in the bottom half of the tube, a volume called the hematocrit.

how is excess edema fluid removed ?

Excess edema fluid is removed by lymphatic drainage and is returned to the bloodstream by way of the thoracic duct *** know the picture

which herpes drugs are safe for pregnant women?

Famciclovir and Valacyclovir Cat B, B

cerebral malaria falciparum malaria is becoming more difficult to treat due to the emergence of drug-resistant strains Blackwater fever is a complication of malaria infection in which red blood cells burst in the bloodstream (hemolysis), releasing hemoglobin directly into the blood vessels and into the urine, frequently leading to kidney failure (hemolysis, hemoglobinemia, hemoglobinuria, and jaundice.)

Fatal falciparum malaria often involves the small vessels of the brain, a complication known as cerebral malaria. - Normally, rbcs negatively charged surface (-) interact poorly w/ endo cells - infected RBCs -> + charged surface knobs containing parasite- encoded proteins -> bidn to adhesion molecules expressed on activated endothelium ICAM-1 (endo cell adhesion molecules) -> trap RBCs in post cap venules - showers of new morozoites are released from rbcs at 24 hours for P. knowlesi, 48 hours for P. vivax, P. ovale, and P. falciparum, and 72 hours for P. malariae. (24, 48, 72 k-vof-m) -Episodic shaking, chills, and fever - falciparum malaria more - often pursues a chronic course that may be punctuated at any time by blackwater fever.

Most common nutritional deficiency in the world that is related to Anemia

Fe

fat embolism

Freely floating fat globule in the blood stream, which can obstruct blood circulation to vital organs (e.g., heart, brain). Usually caused by injury to subcutaneous tissue or a bone fracture that allows fat release. Clinical signs and symptoms appear 1 to 3 days after injury as the sudden onset of tachypnea, dyspnea, tachycardia, irritability, and restlessness, which can progress rapidly to delirium or coma Thrombocytopenia is attributed to platelet adhesion to fat globules and subsequent aggregation or splenic sequestration; anemia can result from similar red cell aggregation and/or hemolysis. A diffuse petechial rash (seen in 20%-50% of cases) is related to rapid onset of thrombocytopenia and can be a useful diagnostic feature. - pathogenesis of fat emboli syndrome involves both mechanical obstruction and biochemical injury. -> Fat microemboli occlude pulmonary and cerebral microvasculature, both directly and by triggering platelet aggregation. ***fatty acid release from lipid globules, which causes local toxic endothelial injury. Platelet activation and granulocyte recruitment (with free radical, protease, and eicosanoid release)

In infected individual, mutations in gp.... occur over time? and what does it do

Gp 120 , preventing the immune system from completely clearing the virus , and make it difficult for vaccine to work

which gp mediates virus- cell & cell-cell fusion

Gp120 is attached noncovalently to the transmembrane glycoprotein (TM) gp41

which type of hemoglobin is found 95% in adult human, and what is the globin subunit composition? - which hemoglobin is eleavted in β-thalassemia - what is the fetal Hb?

HbA, with the α2β2 globin subunit composition. think A as adult - HbA2 is elevated in β-thalassemia, a disease characterized by a deficiency in β-globin biosynthesis. - HbF, α-globin and γ-globin. < 1% of adult Hb Gene switching on chromosome 11 causes HbF to decrease shortly after birth. Functional difference between HbF and HbA is its decreased sensitivity to 2,3-BPG. interaction of 2,3-BPG with HbF is weaker, resulting in an increased affinity for O2 -> hence babies breath faster greater stabilization of the oxygenated R state. The direct benefit of this structural and functional change in the HbF isoform is a more efficient transfer of O2 from maternal HbA to fetal Hb

how does heme control its rate of synthesis? PICTURE

Heme controls the rate of its synthesis by feedback inhibition of 5-ALA synthase

Deficiencies of Factor VIII-von Willebrand Factor Complex

Hemophilia A and von Willebrand disease are caused by qualitative or quantitative defects involving the factor VIII-vWF complex - factor VIII is an essential cofactor for factor IX, which activates factor X in the intrinsic coagulation pathway. Circulating factor VIII binds noncovalently to vWF, - When endothelial cells are stripped away by trauma or injury, subendothelial vWF is exposed and binds platelets, mainly through glycoprotein Ib and to a lesser degree through glycoprotein IIb/IIIa ( Fig. 12.31). The most important function of vWF is to facilitate the adhesion of platelets to damaged blood vessel walls, a crucial early event in the formation of a hemostatic plug. Inadequate platelet adhesion is believed to underlie the bleeding tendency in von Willebrand disease. In addition to its role in platelet adhesion, vWF also stabilizes factor VIII; thus, vWF deficiency leads to a secondary deficiency of factor VIII. vWF function is assessed using the ristocetin platelet agglutination test. Ristocetin somehow "activates" the bivalent binding of vWF and platelet membrane glycoprotein Ib, creating interplatelet "bridges" that cause platelets to clump (agglutination), an event that can be measured easily. Thus, ristocetin-dependent platelet agglutination serves as a useful bioassay for vWF.

Heparin-Induced Thrombocytopenia

Heparin causes a decrease in platelet count because of the formation of a complex with platelet factor 4, IgG antibodies against platelet-heparin complex that the spleen proceeds to destroy - The risk of this complication is lowered (but not prevented entirely) by use of low-molecular-weight heparin preparations.

general roles of Hepcidin role of Hepcidin in Fe deficiency

Hepcidin circulates to the duodenum, where it binds ferroportin and induces its internalization and degradation Hep - liver Ferro- Fe In iron deficiency, the suppression of hepcidin is beneficial as it serves to help to correct the deficiency, but inappropriately low levels of hepcidin, as in primary hemochromatosis, eventually lead to systemic iron overload.

what are Herpetic whitlow Herpetic paronychia

Herpetic whitlow- infection of nails Herpetic paronychia- infection of fingers

which proinflammatory cytokine increase hepatic hepcidin synthesis?

IL6

conjugated bilirubin (in gut) -> stercobilinogen (colorless) -> stercobilin (feces's color) -> some may be reabsordded from gut and then reexcreted bu liver or kidneys

If the biliary excretion of conjugated bilirubin is impaired by a disease that obstructs the flow of bile into the intestine (obstructive jaundice), no stercoblinogen/stercobilin is formed, and the feces is pale in color.

which antibodies are found on B cell membranes w/ Ig m and function as antigen receptors and activate B cell growth?

Ig D Remember MD

which Ig present at low conc and are involved in type I hypersensitivity by bidning to...cells? -> cause ... secretion ->... allergy symptoms -> protect against ... infections

Ig E - bind to basophils & mast cells - histamine secretion - allergy symptoms - protect against parasitic infections

Penicillin allergies are mediated by recognition by what type of antibodies as well as by ... cells.

Ig E & T cells

most abundant Ig in blood?

Ig G (so many girls) antibody - dependent celular cutotoxicity, where a cell coated with specific antibodies is killed by natural cytotoxic cells (also known as natural killer cells Can cross the placenta IgG constitutes between 75% and 85% of antibodies in blood and has the longest half-life (23 days) among the immunoglobulins

what is open angle glaucoma?

In open-angle glaucoma, the trabecular meshwork offers increased resistance to fluid outflow. This causes the pressure to build up inside your eye. In closed-angle glaucoma, both the uveoscleral drain and the trabecular meshwork become blocked. Typically, this is caused by a damaged iris (colored part of the eye) blocking the outlet

Innate lymphoid cells (ILCs)

Innate lymphoid cells (ILCs) are populations of lymphocytes that lack TCRs but produce cytokines similar to those that are made by T cells. They are classified into three groups, which produce IFN-γ, IL-5, or IL-17, cytokines that are characteristic of TH1, TH2, and TH17 subsets of T cells, respectively (described later). NK cells are related to group 1ILCs based on their production of IFN-γ, a cytokine also made by TH1 cells. Because ILCs mostly reside in tissues, they are thought to provide early defense against infections in the tissues, before T cells are activated and can migrate into tissues. ILCs also may be early participants in inflammatory diseases.

what excess bilirubin causes? what is bilirubin

Jaundice - Bilirubin is the catabolic product of heme. - About 75% of all bilirubin is derived from the breakdown of hemoglobin from senescent red blood cells, which are phagocytosed by mononuclear cells of the spleen, bone marrow, and liver (reticulo-endothelial cells). The ring structure of heme is oxidatively cleaved to biliverdin by heme oxygenase, a P-450 cytochrome Biliverdin is, in turn, enzymatically reduced to bilirubin Bilirubin imparts a yellow color to the skin and conjunctivae known clinically as jaundice, or icterus. Jaundice is a clinically important sign to the presence of significant liver disease.

Langerhans Cell Histiocytoses

Langerhans cells are immature dendritic cells found in the epidermis; similar cells are found in many other organs, and they function to capture antigens and display them to T cells. - proliferating Langerhans cells express MHC class II antigens, CD1a, and langerin. Langerin is a transmembrane protein found in Birbeck granules, cytoplasmic pentalaminar rodlike tubular structures that in electron micrographs have a characteristic periodicity and sometimes a dilated terminal end ("tennis racket" appearance). abundant, often vacuolated cytoplasm and vesicular nuclei, an appearance more akin to that of tissue macrophages - 2 types: PIC - different clinical forms are frequently associated with an acquired mutation in the serine/threonine kinase BRAF, that leads to hyperactivity of the kinase. BRAF is a component of the RAS signaling pathway that drives cellular proliferation and survival, effects that likely contribute to the growth of neoplastic Langerhans cells.

which pathway is this? the host's mannose-binding protein (MBP), also known as mannose-binding lectin, binds to various sugar residues on bacterial surfaces. This binding activates MBP-associated serine protease, which then cleaves C4 and C2 to form C3 convertase (composed of C4b and C2b)

Lectin pathway

which organ is the lasrgest organ in the body and has a substantial reserve metabolic capacity?

Liver Structure of the liver facilitates exchange of metabolites between hepatocytes and plasma

manigestations of syphilis can mimic which condition?

Malignant neoplasms

Mantle cell lymphoma

Mantle cell lymphoma is composed of cells resembling the naive B cells found in the mantle zones of normal lymphoid follicles. - Almost all tumors have an (11;14) translocation that fuses the cyclin D1 gene to the IgH locus -> overexpression of cyclin D1- promoting the progression of cells from the G1 phase to the S phase of the cell cycle - tumor cells express surface IgM and IgD, the B cell antigen CD20, and CD5, and they contain high levels of cyclin D1 protein.

schistocytosis Sch-> Sh-> Shear red cells

Mechanical fragmentation of red cells -> "burr cells," "helmet cells," and "triangle cells" in peripheral blood smears

Systemic thromboembolism

Most systemic emboli (80%) arise from intracardiac mural thrombi; two-thirds of these are associated with left ventricular infarcts

Venous thrombosis(Phlebothrombosis) think of phlebotomist draw blood from vein -> venous Picture of thrombosis SUMMARY

Most venous thrombi occur in the superficial or the deep veins of the leg arise in the saphenous system, particularly in the setting of varicosities; rarely emboli but can be painful, congesting, swelling - DVTs- deep venous thrombese in larger leg veins at or above knee joint- more serious bc prone to emboli, usually asymtompmatic and only recognized after they have embolized to lungs

Neutrophils contain which protease and antibacterial proteins?

Myeloperoxidase (MPO), which generates hypochlorite and other agents toxic to bacteria Lysozyme, which degrades components of bacterial cell walls Defensins, small cysteine-rich proteins that bind and disrupt the cell membranes of many types of bacteria and other microorganisms.

MI and rheumatic heart disease

Myocardial infarction can predispose to cardiac mural thrombi by causing dyskinetic myocardial contraction and endocardial injury and rheumatic heart disease may engender atrial mural thrombi by causing atrial dilation and fibrillation. Both cardiac and aortic mural thrombi are prone to embolization.

which gas is released in response to hypoxia or on conversion to the T state

NO is released from Hb in response to hypoxia or on conversion to the T state, for example, in venous capillaries, where it induces vasodilation and increased blood flow.

Gonorrhea is caused by which bacteria?

Neisseria gonorrhoeae. - Humans are the only natural hosts for this disease gonorrhea is transmitted almost exclusively via sexual contact, whether genital-genital, oral-genital, or rectal-genital. - Gonorrhea primarily infects the urethra, cervix, rectum, and oropharynx, although it also can infect other sites such as the conjunctiva.

Are antibodies the primary cause of gastric pathology?

No. Autoantibodies are of diagnostic use, but they are not thought to be the primary cause of the gastric pathology; rather, it seems that an autoreactive T cell response initiates gastric mucosal injury and triggers the formation of autoantibodies

does folate administration prevent certain neurologic symptoms that are specific to vitamin B12 deficiency?

No. it does not and in facr worsen cetain neurologic symptoms of Vit B12 deficiency

platelet open canalicular system

Open canalicular system of vesicles is connected to invaginations of the plasma membrane, which may facilitate platelets' uptake of factors from plasma. A much less prominent set of irregular tubular vesicles comprising the dense tubular system is derived from the ER and stores Ca2+ ions -> extremely rapid exocytosis of proteins from platelets (degranulation) upon adhesion to collagen or other substrates outside the vascular endothelium.

what is cell adhesion protein that appears on the endothelial cells' luminal surfaces following exocytosis from cytoplasmic Weibel-Palade bodies.

P-selectin surfaces of neutrophils and other leukocytes display glycosylated ligands for P-selectin, and their interactions cause cells flowing through the affected venules to slow down, like rolling tennis balls arriving at a patch of velcro.

Biochem ch34- role of liver in metabolism

PICTURE impairment of hepatic liver cells -> what to find in blood - increase bilirubin- heme catabolism ->jaundice - low glucose - low albumin - high ammonia, low urea - protein catabolism - high triglycerides, high cholesterol - fat - lipid metabolism - alter half time of drug - drug metabolism - high bile acids

anticoagulant (normal endothelium, no clotting) vs procoagulant (clotting) activities of endothelium

PICTURE: Anti-coagulant properties of normal endothelium (top) and procoagulant properties of injured or activated endothelium (bottom)

most prequent cause Vit B12 deficiency?

Pernicious anemia- result from an autoimmune attack on the gastric mucosa that suppresses the production of intrinsic factor

2 phases of drug metabolism? phase 1- polar group - oxidation/ hydroxylation, cytochrome P450 oxidases phase 2- conjugation- cytoplasmicE + funtional group of phase I by glucuronidation / sufation, acetylation & methylation

Phase I is the addition of a polar group: the polarity increased by its oxidation or hydroxylation, catalyzed by a family of microsomal enzymes known collectively as cytochrome P-450 oxidases. Phase II is conjugation: cytoplasmic enzymes conjugate the functional groups introduced in the first-phase reactions, most often by glucuronidation or sulfation but also by acetylation and methylation.

First opportunistic infections recognized early in the HIV epidemic was _____________

Pneumocystis carinii pneumonia The organism has been recently renamed Pneumocystis jirovecii

Polyarteritis nodosa

Polyarteritis nodosa - necrotizing inflammation of the walls of blood vessels that show strong evidence of an immunologic basis. Any type of vessel may be involved—arteries, arterioles, veins, or capillarie

ubiquitin-proteasome system

Protein degradation by the ubiquitin-proteasome system

Bohr effect

Protons, through the Bohr effect, and CO2 promote the release of oxygen from hemoglobin in peripheral tissue. 2,3-Bisphosphoglycerate is also an important allosteric effector of Hb, decreasing the oxygen affinity of hemoglobin; this is an important adaptation to high altitude and in pulmonary disease.

Pulmonary thromboembolism

Pulmonary emboli originate from deep venous thromboses and are responsible for the most common form of thromboembolic disease usually pass through the right side of the heart before arresting in the pulmonary vasculature. Most pulmonary emboli (60%-80%) are small and clinically silent

which enzyme of host cells transcribe viral genome into a full length RNA ? - RNA polymeras I - RNA polymerase II - DNA polymerase I - DNA polymerase II

RNA polymerase II of host cells

12. path hematopoietic

Red Cell Disorders 442 Anemia of Blood Loss: Hemorrhage 443 Hemolytic Anemia 443 Hereditary Spherocytosis 444 Sickle Cell Anemia 445 Thalassemia 447 Glucose-6-Phosphate Dehydrogenase Deficiency 450 Paroxysmal Nocturnal Hemoglobinuria 450 Immunohemolytic Anemia 451 Hemolytic Anemia Resulting From Mechanical Trauma to Red Cells 451 Malaria 452 Anemia of Diminished Erythropoiesis 453 Iron Deficiency Anemia 453 Anemia of Chronic Inflammation 455 Megaloblastic Anemias 456 Aplastic Anemia 458 Myelophthisic Anemia 458 Polycythemia 459 White Cell Disorders 459 Nonneoplastic Disorders of White Cells 459 Leukopenia 459 Reactive Leukocytosis 460 Reactive Lymphadenitis 461 Neoplastic Proliferations of White Cells 463 Lymphoid Neoplasms 463 Myeloid Neoplasms 478 Histiocytic Neoplasms 484 Bleeding Disorders 485 Disseminated Intravascular Coagulation (DIC) 486 Thrombocytopenia 488 Immune Thrombocytopenic Purpura 488 Heparin-Induced Thrombocytopenia 488 Thrombotic Microangiopathies: Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome 489 Coagulation Disorders 489 Deficiencies of Factor VIII-von Willebrand Factor Complex 489 Complications of Transfusion 491 Allergic Reactions 491 Hemolytic Reactions 491 Transfusion-Related Acute Lung Injury 492 Infectious Complications 492 Disorders of the Spleen and Thymus 492 Splenomegaly 492 Disorders of the Thymus 493 Thymic Hyperplasia 493 Thymoma 493

Glucose-6-Phosphate Dehydrogenase Deficiency G6PD gene is on the X chromosome (female affected) Heinz bodies bite cells - are trapped on recirculation to the spleen & ar destroyed by phagocytes (extravascular hemolysis)

Red cells are constantly exposed to both endogenous and exogenous oxidants, which are normally inactivated by reduced glutathione (GSH) G6PD deficiency is associated with transient episodes of intravascular hemolysis caused by exposure to an environmental factor (usually infectious agents or drugs) that produces oxidant stress Abnormalities affecting enzymes responsible for the synthesis of GSH leave red cells vulnerable to oxidative injury and hemolysis drugs include drugs include anti-malarials (e.g., primaquine), sulfonamides, nitrofurantoin, phenacetin, aspirin (in large doses), and vitamin K derivatives. oxidants, such as hydrogen peroxide, are normally sopped up by GSH, which is converted to oxidized GSH in the process Because regeneration of GSH is impaired in G6PD-deficient cells, oxidants are free to "attack" other red cell components including globin chains. Oxidized hemoglobin denatures and precipitates, forming intracellular inclusions called Heinz bodies, which can damage the red cell membrane so severely that intravascular hemolysis results. Other cells with lesser damage lose their deformability and suffer further injury when splenic phagocytes attempt to "pluck out" the Heinz bodies, creating bite cells ( Fig. 12.6). Such cells become trapped on recirculation to the spleen and are destroyed by phagocytes (extravascular hemolysis).

Paroxysmal Nocturnal Hemoglobinuria - mutations in PIGA, gene for synthesis of PIG (membrane anchor for many proteins) - X- linked

Red urine in the morning, fragile RBCs - hemolytic anemia that stems from acquired mutations in PIGA, a gene required for the synthesis of phosphatidylinositol glycan (PIG), which serves as a membrane anchor for many proteins. - normal cells have only 1 active PIGA gene -> sufficient to cause PIGA deficiency ***most feared complication of PNH is thrombosis, which often occurs within abdominal vessels such as the portal vein and the hepatic vein. -, antibody that binds C5 and inhibits the assembly of the C5b-C9 membrane attack complex - Loss of C5b-C9 activity in patients receiving Eculizimab poses a risk for Neisseria infections, particularly meningococcal sepsis;

- Hyperemia and Congestion - Cyanosis

Refer to an increase in blood volume within a tissue, but have different underlying mechanisms. - Hyperemia - active process- arteriolar dilation and increased blood inflow, as occurs at sites of inflammation or in exercising skeletal muscle. - Congestion - passive process resulting from impaired outflow of venous blood from a tissue. It can occur systemically, as in cardiac failure, or locally as a consequence of an isolated venous obstruction.

what is important in amino acid metabolism

Removal of nitrogen The urea cycle is essential for the removal of nitrogen generated by amino acid metabolism Catabolism of amino acids generates ammonia (NH3) and ammonium ions (NH4+). Ammonia is toxic, particularly to the central nervous system (CNS). Most ammonia is detoxified at its site of formation, by amidation of glutamate to glutamine, which is mainly derived from muscle and is used as an energy source by the enterocytes. The remaining nitrogen enters the portal vein either as ammonia or as alanine, both of which are used by the liver for the synthesis of urea

T Cell-Mediated Diseases (Type IV Hypersensitivity)

Several autoimmune disorders, as well as pathologic reactions to environmental chemicals and persistent microbes, are now known to be caused by T cells

Peripheral Tolerance

Several mechanisms silence potentially autoreactive T cells and B cells in peripheral tissues; these are best defined for T cells. Mechanisms: - Anergy: functional inactivation (rather than death) of lymphocytes that is induced by encounter with antigens under certain conditions -Suppression by regulatory T cells. A population of T cells called regulatory T cells functions to prevent immune reactions against self antigens. Regulatory T cells develop mainly in the thymus, but they also may be induced in peripheral lymphoid tissues - Deletion by apoptosis. T cells that recognize self antigens may receive signals that promote their death by apoptosis. -Some self antigens are hidden (sequestered) from the immune system, because the tissues in which these antigens are located do not communicate with the blood and lymph. -• Genome-wide association (GWAS) studies and linkage studies in families are revealing many genetic polymorphisms that are associated with different autoimmune diseases Most autoimmune diseases are complex multigenic disorders - • Autoimmune diseases have a tendency to run in families, and there is a greater incidence of the same disease in monozygotic than in dizygotic twins. - • Several autoimmune diseases are linked to the HLA locus, especially class II alleles (HLA-DR, HLA-DQ).

Sjögren syndrome

Sjögren syndrome is a chronic disease characterized by dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) resulting from immunologically mediated destruction of the lacrimal and salivary glands - occurs as an isolated disorder (primary form), also known as the sicca syndrome - lacrimal and salivary glands characteristically show dense lymphocytic infiltration consisting mainly of activated CD4+ helper T cells and some B cells, including plasma cells - Antibodies against two ribonucleoprotein antigens, SS-A (Ro) and SS-B (La) - albeit weak, with HLA alleles, all point to activation of autoreactive T cells and B cells - initiating trigger may be a viral infection of the salivary glands, which causes local cell death and release of tissue self antigens - CD4+ T cells and B cells specific for these self antigens may escape tolerance and participate in immune reactions that lead to tissue damage and, eventually, fibrosis. Keratoconjunctivitis produces blurred vision, burning, and itching, and thick secretions that accumulate in the conjunctival sac. Xerostomia results in difficulty in swallowing solid foods, a decrease in taste, cracks and fissures in the mouth, and dryness of the buccal mucosa. Parotid gland enlargement is present in half the patients; dryness of the nasal mucosa, epistaxis, recurrent bronchitis, and pneumonitis are other symptoms

what is haptens?

Small molecules like penicillin are antigenic, but they are incapable of inducing a specific immune response by themselves; they become immunogenic if they are bound to peptides or proteins.

Smoking

Smoking is a risk factor for RA, perhaps because it leads to chemical modification of self antigens. Local tissue injury for any reason may lead to the release of self antigens and autoimmune responses.

why Subcutaneous edema is important to recognize primarily? what are other types of edema?

Subcutaneous edema is important to recognize primarily because it signals potential underlying cardiac or renal disease - Pulmonary edema is a common clinical problem. It is seen most frequently in the setting of left ventricular failure, but also may occur in renal failure, acute respiratory distress syndrome), and inflammatory and infectious disorders of the lung. - Brain edema is life threatening; if the swelling is severe, the brain can herniate (extrude) through the foramen magnum. With increased intracranial pressure, the brain stem vascular supply can be compressed, leading to death due to injury to the medullary centers controlling respiration and other vital functions

Systemic Sclerosis (Scleroderma)

Systemic Sclerosis (Scleroderma) is an immunologic disorder characterized by excessive fibrosis in multiple tissues, obliterative vascular disease, and evidence of autoimmunity, mainly the production of multiple autoantibodies. - Disease limited to the skin is also called localized scleroderma. - disease likely results from three interrelated processes—autoimmune responses, vascular damage, and collagen deposition Systemic sclerosis is classified into two groups on the basis of its course: • Diffuse systemic sclerosis, characterized by initial widespread skin involvement, with rapid progression and early visceral involvement • Limited systemic sclerosis, with relatively mild skin involvement, often confined to the fingers and face. Involvement of the viscera occurs late, so the disease generally follows a fairly benign course. This presentation also is called CREST syndrome because of its frequent features of calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia.

_________are involved by stimulating the breakdown of specific intracellular proteins by the ubiquitin-proteasome system

TNF and IL-1, are involved by stimulating the breakdown of specific intracellular proteins by the ubiquitin-proteasome system

Accessory gene aka auxiliary proteins that regulate HIV gene which one are synthesized from fully spliced mRNA? TRN (RN nurse)

Tat is a transcriptional activator that acts at a site (TAR) near the onset of mRNA transcription by recruiting cellular proteins to the RNA polymerase and enabling the complete transcription of the HIV genome. Rev promotes the transport of unspliced mRNA into the cytoplasm. Only Rev, Tat, and Nef are synthesized from fully spliced mRNA. The RNAs encoding the other genes are not spliced and hence would not normally be transported into the cytoplasm. Thus, Rev plays a crucial role in the production of viral proteins by binding to the Rev-responsive element in the env region of the viral RNA and transporting the latter into the cytoplasm. Nef down regulates cellular CD4 and MHC class I proteins. Vif (virion infectivity factor) increases the ability of HIV to infect primary T cells and some nonpermissive cells in culture. Vif inhibits APOBEC-3G, a cellular RNA-editing enzyme that hypermutates the HIV genome. Vpu complexes with CD4 in the endoplasmic reticulum to enable the newly synthesized gp120 to reach the plasma membrane and mediates the release of the virus at the plasma membrane. Vpr is essential for virus replication in nondividing cells like macrophages and enables the viral DNA to reach the nucleus.

P 450 cytochrome

The ring structure of heme is oxidatively cleaved to biliverdin by heme oxygenase, a P-450 cytochrome

emboli

Thrombi are significant because they cause obstruction of arteries and veins and may give rise to emboli - Arterial thrombi can embolize and cause tissue infarction, their tendency to obstruct vessels (e.g., in coronary and cerebral vessels)

Edema 1- 1. what causes increased in hydrostatic pressure?- heart failure 2. what causes reduced plasma osmotic pressure? - protein malnutrition, - decreased hepatic synthesis (cirrhosis , liver dont make enough albumin), - nephrotic syndrome (most common cause of albumin loss from blood, glomerular become leaky-> leak out albumin in urine) what causes edema - increase capillary hydrostatic pressure - decrease osmotic pressure - increase blood vol (decrease renal blood flow caused by HF)

aused by disorders that impair venous return - remmember hydrostatic pressure is at aterior - Increased capillary hydrostatic pressure (as occurs when venous pressures become elevated by gravitational forces, volume expanded states, in heart failure or with venous obstruction) *** caused by Deep venous thrombosis in lower extremity -> edema restricted to Distal portion of affected leg Systemic edema: *** heart failure -> increase capillary hydrostatic pressure, *** decrease renal blood flow -> increase blood vol by renin angiotensin aldosterone system to retent water -> increase blood vol *** malnutrition, decrease hepatic synthesis, nephrotic syndrome -> decrease albumin -> decrease osmotic pressure - nephrotic syndrom- glomerular become leaky -> loss of albumin in urine

Rheumatoid Arthritis

autoimmune disease that affects primarily the joints but also may involve extraarticular tissues such as the skin, blood vessels, lungs, and heart.

which drugs to use to lower risk of transmission from mom to fetus?

azidothymidine (zidovudine) + antiretroviral drugs However, the virus may also be transmitted via breastfeeding, and thus affordable alternatives to breastfeeding are needed.

Antibody consists of 1 light chain & 1 heavy chain which region (variable or constant) of heavy chain recognize epitope on antigen

Variable region of heavy chain

coumadin

Vitamin K enzymatic reactions that produce γ-carboxylated glutamic acid use vitamin K as a cofactor and are antagonized by drugs such as Coumadin, a widely used anti-coagulant.

do HbH and Hb Bart have an abnormally high affinity for oxygen?

Yes

does lymphatic obstruction cause edema?

Yes. lymphatic obstruction caused by inflammatory or neoplastic condition -> compromise resorption of fluid from interstitial spaces *** breast cancer -> infiltrate & obstruct superficial lymphatics -> cause edema of overlying skin = peau d'orange (orange peel)- big orange = breast cancer - edema

Shock

a state in which - diminished cardiac output or - reduced effective circulating blood volume impairs tissue perfusion and leads to cellular hypoxia - outset, the cellular injury is reversible; however, prolonged shock eventually leads to irreversible tissue injury and is often fatal.

feature of both intravascular and extravascular hemolysis is decreased serum levels of...? a. hemoglobin b. metaglobin c. haptoglobin d. seroglobin

c. haptoglobin a plasma protein that binds free hemoglobin and is then removed from the circulation. Apparently macrophages "regurgitate" sufficient hemoglobin during consumption of red cells to cause haptoglobin levels to fall, even when hemolysis is entirely extravascular.

Infectious mononucleosis

caused by Epstein-Barr virus (EBV), a member of the herpesvirus family. The infection is characterized by (1) fever, sore throat, and generalized lymphadenitis and (2) a lymphocytosis of activated, CD8+ T cells. - direct oral contact- tranmission - virus initially infects oropharyngeal epithelial cells and then spreads to underlying lymphoid tissue (tonsils and adenoids), where mature B cells are infected. - B cells that are latently infected with EBV become "activated" and proliferate as a result of the action of several viral proteins - impaired T cell immunity places patients at high risk for EBV-driven B cell proliferations.

Immunohemolytic Anemia - caused by antibodies drugs, chemicals - Dx: use direct Coombs test - 2 types: warm antibody... Cold antibody...

caused by antibodies that bind to determinants on red cell membranes. These antibodies may arise spontaneously or be induced by exogenous agents such as drugs or chemicals - dx depends on detection of antibodies &/or complement on Red cells. done by direct Coombs test

Essential thrombocythemia

condition characterized by an increased number of platelets (thrombocythemia). Platelets (thrombocytes) are blood cell fragments involved in blood clotting. While some people with this condition have no symptoms, others develop problems associated with the excess platelets. Abnormal blood clotting (thrombosis) is common in people with essential thrombocythemia and causes many signs and symptoms of this condition. Clots that block blood flow to the brain can cause strokes or temporary stroke-like episodes known as transient ischemic attacks. Thrombosis in the legs can cause leg pain, swelling, or both. In addition, clots can travel to the lungs (pulmonary embolism), blocking blood flow in the lungs and causing chest pain and difficulty breathing (dyspnea). Another problem in essential thrombocythemia is abnormal bleeding, which occurs more often in people with a very high number of platelets. Affected people may have nosebleeds, bleeding gums, or bleeding in the gastrointestinal tract. It is thought that bleeding occurs because a specific protein in the blood that helps with clotting is reduced, although why the protein is reduced is unclear. Other signs and symptoms of essential thrombocythemia include an enlarged spleen (splenomegaly); weakness; headaches; or sensation in the skin of burning, tingling, or prickling. Some people with essential thrombocythemia have episodes of severe pain, redness, and swelling (erythromelalgia), which commonly occur in the hands and feet.

platelet electron-dense delta granules (δG)

contain ADP, ATP, and serotonin (5-hydroxytryptamine) taken up from plasma

MHC restriction

each person, T cells recognize only peptides displayed by that person's MHC molecules, which, of course, are the only MHC molecules that the T cells normally encounter. This phenomenon is called MHC restriction.

- hydrothorax - hydropericardium - ascites= hydroperitoneum

effusion pleural cavity (hydrothorax), the pericardial cavity (hydropericardium), or the peritoneal cavity (hydroperitoneum, or ascites)

what is endothelium-derived relaxing factor (EDRF)?

endothelium-derived relaxing factor (EDRF), is synthesized in endothelial cells and participates in normal vascular physiology, including vasodilation (smooth muscle), hemostasis (platelet), and adhesion molecule expression (endothelial cell).

in hereditary spherocytosis, this usually is triggered by the infection of...

erythroblasts by parvovirus B19 and, although severe, is self-limited.

major cause of liver disease?

excess of alcohol (ethyl alcohol- ethanol) -> cause excessive fat deposition in the liver (alcoholic steatosis), and this may progress to hepatitis and finally fibrosis (known as cirrhosis), which in turn leads to liver failure.

Hemolytic Anemia Resulting From Mechanical Trauma to Red Cells

exposure to abnormal mechanical forces: - traumatic hemolysis is sometimes produced by defective cardiac valve prostheses -> create sifficiently turbulent blood flow to shear red cells - Microangiopathic hemolytic anemia - small vessels become partially obstructed or narrowed by lesions that predispose passing red cells to mechanical damage. -> vessels are narrowed by the intravascular deposition of fibrin.

liver & protein metabolism - production of coagulation factors __________ what do they bind to ?

factors II, VII, IX, and X All the coagulation factors undergo posttranslational γ-carboxylation of specific glutamyl residues, allowing them to bind calcium

The replication cycle of HIV-1 begins with binding of ______ *** PICTURE from book

gp120 to CD4 (via a constant region on gp120) and to a secondary receptor (via the variable V3 loop region on gp120)

which cells make cytokines?

helper T cells - cytokines - soluble protein mediators -> activate phagocytes to kill ingested microbes.

Heme is a constituent of ________________

hemoglobin, myoglobin, and cytochromes

P 02 shift right when increase or / decrease temp, 2-3 DPG, [H+]?

increase , shift right lowering O2 affinity

Except emia caused by chronic renal failure or chronic inflammation (described later), the decrease in tissue oxygen tension that accompanies anemia triggers what?

increased production of the growth factor erythropoietin from specialized cells in the kidney. This in turn drives a compensatory hyperplasia of erythroid precursors in the bone marrow

what is the compensation of deficiency of O2 carrying capacity in slow onset?

increases in cardiac output, respiratory rate, and red cell 2,3-diphosphoglycerate (DPG), a glycolytic pathway intermediate that enhances the release of O2 from hemoglobin.

Hereditary Spherocytosis name of the membrane protein which organ play a role in this condition? and how? - characteristic features

inherited (intrinsic) defects in the red cell membrane that lead to the formation of spherocytes, nondeformable cells that are highly vulnerable to sequestration and destruction in the spleen. * major membrane protein= spectrin - bind short actin - mutation involve ankyrin, band 3, or spectrin. - they weaken vertical interactions between the membrane skeleton and intrinsic red cell membrane proteins - spleen, splenomegaly. Red cells must undergo extreme degrees of deformation to pass through the splenic cords. The floppy discoid shape of normal red cells allows considerable latitude for shape changes. they are destroyed by macrophages ***characteristic features are anemia, splenomegaly, and jaundice.

where is Vit B12 stored?

liver

low/ or high substrate specificity of some hepatic enzymes produces a wide-ranging capability for drug metabolism? where are most drugs metabolized? excreted?

low metabolized in liver, excreted by kidneys or bile some drugs are inactive when administered but are converted to their active forms as a result of liver metabolism (pro-drugs).

microbiome

microbiome (the diverse collection of commensal microbes that live with us in a symbiotic relationship)

which cells/ where synthesize heme in the body? - kiney cells - liver cells - bone marrow - spleen - blood where inside the cell is heme synthesized? - cytoplasm - mitochondria - nucleus - golgi

most cells of the body. But liver is the main erythrocyte source of its synthesis - Mitochondria

Hemophilia A—Factor VIII Deficiency

most common hereditary cause of serious bleeding. It is an X-linked recessive disorder caused by reduced factor VIII activity. It primarily affects males. - . Severe hemophilia A is observed in people with marked deficiencies of factor VIII - easy bruising and massive hemorrhage after trauma or operative procedures. In addition, "spontaneous" hemorrhages frequently are encountered in tissues that normally are subject to mechanical stress, particularly the joints, where recurrent bleeds (hemarthroses) lead to progressive deformities that can be crippling. Petechiae are characteristically absent.

tx/ drugs used to treat Herpes? In case of severe or complicated infections and may be required for immune suppressed pts -> which durgs to use to treat herpes?

oral - acyclovir, famciclovir, or valacyclovir. Cat C, B, B (fam and val are safe for pregnant women) All three are nucleoside analogue drugs that act as DNA chain terminators during virus replication in infected cells. - severe or complicated infections and may be required for immune suppressed pts -> IV antiviral agents (acyclovir, cidofovir, and foscarnet)

which protein make up of the HIV viral capsid? What does the capsid contain

p24 protein capsid contains: p24 protein, RT, intergrase, and protease

what are these: spectrin, ankyrin

peripheral proteins are associated with the inner surface of the membrane, including spectrin, dimers of which form a lattice bound to underlying actin filaments, and ankyrin, which anchors the spectrin lattice to the glycophorins and band 3 proteins. -> role: maintain cell shape, provide cell elasticity required for passage thru capillaries

Food folates are predominantly in which form?

polyglutamate form and must be split into monoglutamates for absorption, a conversion that is inhibited by acidic foods and substances found in beans and other legumes.

How much blood loss would impact a healthy adult?

rapid loss of up to 20%. more than 20% -> hemorrhagic (hypovolemic) shock

yellow pigmentation of the skin (jaundice); ready bruising and profuse bleeding, commonly from varicosities of the esophageal vasculature due to increased pressure in the portal circulation; abdominal distension due to the accumulation of fluid (ascites); and an altered consciousness level (hepatic encephalopathy; are characteristics of which disease?

severe liver disease

Transfusion-Related Acute Lung Injury

severe, frequently fatal complication in which factors in a transfused blood product trigger the activation of neutrophils in the lung microvasculature - most common antibodies associated with TRALI are those that bind major histocompatibility complex (MHC) class I antigens. These antibodies are often found in multiparous women, in whom they are generated in response to foreign MHC antigens expressed by the fetu

Anasarca - Types of edema

severe, generalized edema- swelling of subcutaneous tissues and accumulation of fluid in body cavities

which of the following is responsible for the color fo feces? - bilirubin - urobilinogen - stercobilinogen - stercobilin

stercobilin is mainly responsible for the color of feces - stercobilinogen - colorless - stercobilin- color

gluconeogenesis

synthesize glucose/ produce glucose- in liver Body protein catabolizes -> a.a -> synthesize glucose ( can not synthesize from Lipid)

what is junctional diversity?

terminal deoxyribonucleotidyl transferase, an enzyme that adds or removes nucleotides between the different gene segments to create...that increases the specificity of the variable region up to 1010

Diapedesis

the passage of blood cells through the intact walls of the capillaries, typically accompanying inflammation .

Membrane fusion and viral entry is dependent on __________

the secondary receptor, which is a G-protein-coupled chemokine receptor

clinical features of β-Thalassemia trait and α-thalassemia trait

typically asymptomatic - usually only a mild microcytic hypochromic anemia; generally, these patients have a normal life

ultraviolet (UV) radiation

ultraviolet (UV) radiation causes cell death and may lead to the exposure of nuclear antigens, which elicit pathologic immune responses in lupus; this mechanism is the proposed explanation for the association of lupus flares with exposure to sunlight.

what does post exposure prophylaxis mean

vaccine can be administered soon after exposure, in a procedure called post-exposure prophylaxis, because the disease develops slowly and the elicited antibodies are protective.

2 cell types in the sinusoid (connect Portal vein & Central hepatic vein)

vascular endothelial cells, which are loosely connected one with another, leaving numerous gaps. There is no basement membrane between the endothelial cells and the hepatocytes. Kupffer cells, the second type of sinusoidal cells, are mononuclear phagocytes; they are generally found in the gaps between endothelial cells.

how Fluid movement between the vascular and interstitial spaces How does fluid get to interstitial space and causes edema?

vascular hydrostatic pressure and the colloid osmotic pressure produced by plasma proteins - increased hydrostatic pressure or diminished colloid osmotic pressure causes increased movement of water into the interstitium

Hemophagocytic Lymphohistiocytosis (HLH)

viral infection or other proinflammatory exposures trigger activation of macrophages throughout the body, leading to phagocytosis of blood cells and their precursors, cytopenias, and symptoms related to systemic inflammation and organ dysfunction.

Disseminated Intravascular Coagulation (DIC)

widespread thrombosis within the microcirculation that may be of sudden or insidious onset - microvascular thrombosis consumes platelets and coagulation proteins - excessive clotting and bleeding may co-exist in the same patient.

binding of O2 to heme is an exothermic process? if so is the O2 affinity increase of decrease with increasing temp?

yes decrease. the O2 affinity of Hb decreases with increasing temperature. (too hot- decrease O2 binding)

Does Lower-extremity DVTs are associated with stasis and hypercoagulable states

yes common predisposing factors include congestive heart failure, bed rest, and immobilization

Stages of shock

• An initial nonprogressive stage during which reflex compensatory mechanisms are activated and vital organ perfusion is maintained, • A progressive stage characterized by tissue hypoperfusion and onset of worsening circulatory and metabolic derangement, including acidosis, • An irreversible stage in which cellular and tissue injury is so severe that even if the hemodynamic defects are corrected, survival is not possible.

summary of lymphoid neoplasms

• Classification is based on cell of origin and stage of differentiation • Most common types in children are ALLs/lymphoblastic lymphomas derived from precursor B and T cells • Most common types in adults are non-Hodgkin lymphomas derived from germinal center B cells Acute Lymphoblastic Leukemia/Lymphoma • Highly aggressive tumors that manifest with signs and symptoms of bone marrow failure, or as rapidly growing masses • Tumor cells contain genetic lesions that block differentiation, leading to the accumulation of immature, nonfunctional blasts Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia • Mature B cell tumor that usually manifests with bone marrow and lymph node involvement • Indolent course, commonly associated with immune abnormalities, including an increased susceptibility to infection and autoimmune disorders Follicular Lymphoma • Tumor cells recapitulate the growth pattern of normal germinal center B cells; most cases are associated with a (14;18) translocation that results in the overexpression of BCL2 478 Mantle Cell Lymphoma • Mature B cell tumor that usually manifests with advanced disease involving lymph nodes, bone marrow, and extranodal sites such as the gut • Associated with an (11;14) translocation that results in overexpression of cyclin D1, a regulator of cell cycle progression Extranodal Marginal Zone Lymphoma • Mature B cell tumor arising at extranodal sites involved by chronic inflammation resulting from autoimmunity or infection (e.g., H. pylori) • Remains localized for long periods and may regress if the inflammatory stimulus is removed Diffuse Large B Cell Lymphoma • Heterogeneous group of mature B cell tumors that shares large cell morphology and aggressive clinical behavior and is the most common type of lymphoma • Rearrangements or mutations of BCL6 gene are recognized associations; one-third carry a (14;18) translocation involving BCL2 Burkitt Lymphoma • Very aggressive mature B tumor that usually arises at extranodal sites • Nearly always associated with translocations involving the MYC protooncogene • Tumor cells often are latently infected by EBV Multiple Myeloma • Plasma cell tumor often manifesting with multiple lytic bone lesions associated with pathologic fractures and hypercalcemia • Neoplastic plasma cells suppress normal humoral immunity and secrete partial immunoglobulins that are nephrotoxic (Bence Jones proteins) Hodgkin Lymphoma • Unusual B cell tumor consisting mostly of reactive lymphocytes, macrophages, and stromal cells • Malignant RS cells make up a minor part of the tumor mass.

Mycosis Fungoides and Sézary Syndrome. mycosis fungo - fungus -> on skin

• Different manifestations of a CD4+ T cell tumor that home to skin. - Mycosis fungoides usually manifests as a nonspecific erythrodermic rash (1) a generalized exfoliative erythroderma (2) tumor cells (Sézary cells) in the peripheral blood

Multiple myeloma has a number of untoward effects on the skeleton, the immune system, and the kidney, all of which contribute to morbidity and mortality:

• Factors produced by neoplastic plasma cells mediate bone destruction, the major pathologic feature of mul • Myeloma causes defects in humoral immunity • Renal dysfunction

Anemia classification based on RBCs morphology

• Mean cell volume (MCV): the average volume per red cell, expressed in femtoliters (cubic microns) • Mean cell hemoglobin (MCH): the average mass of hemoglobin per red cell, expressed in picograms • Mean cell hemoglobin concentration (MCHC): the average concentration of hemoglobin in a given volume of packed red cells, expressed in grams per deciliter • Red cell distribution width (RDW): the coefficient of variation of red cell volume

destruction of CD4+ T cells is caused by a number of factors.

• The budding of a large number of virions from the cell surface may compromise the integrity of the plasma membrane. The large amounts of viral proteins and nucleic acids produced in the cell may affect the proper functioning of cellular processes. • When HIV proteins distort cellular regulation, or when nonintegrated circular viral DNA accumulates in nonpermissive (nonactivated) CD4 T cells, the cells may undergo programmed cell death (apoptosis). The HIV envelope alone, or that bound to antibodies, may impart an inappropriate signal to CD4+ cells, forcing them to initiate apoptosis. • Uninfected cells ("innocent bystanders") may be killed by cytotoxic T cells that recognize HIV bound to the surface of the cell in a process known as antibody-dependent cellular cytotoxicity. Cytotoxic T cells may also destroy uninfected cells that have taken up HIV particles and present viral fragments on their surface. • CD4+ T cells may be unable to respond to immune stimulation when they are "deactivated" by signals from HIV, resulting in a state known as anergy. • HIV can kill hematopoietic precursor cells and damage the microenvironment needed for the differentiation of these cells in the bone marrow and thymus. These tissues may not be able to regenerate, thus adversely affecting the immune system. • Chronic activation of helper T cells in response to the large amounts of HIV antigen produced may lead to the terminal differentiation and death of the cells.

Carvedilol

○ an alpha-/beta-adrenergic blocker. ■ INDICATIONS: It is used to treat congestive heart failure and essential hypertension, either alone or in combination with other antihypertensives. ■ CONTRAINDICATIONS: Known hypersensitivity to this drug, bronchial asthma, class IV decompensated cardiac failure, second- or third-degree heart block, cardiogenic shock, or severe bradycardia and pulmonary edema prohibits the use of carvedilol. ■ ADVERSE EFFECTS: Life-threatening effects of this drug include atrioventricular block, bradycardia, congestive heart failure, pulmonary edema, and thrombocytopenia. Other serious adverse effects include somnolence, depression, ataxia, diarrhea, dependent edema, peripheral edema, extrasystoles, hypertension, hypotension, palpitations, peripheral ischemia, urinary tract infection, viral infection, and hypertriglyceridemia.