Patho: chapter 21: Alterations of Hematologic Function

Thrombocythemia Pathophysiology

Increase in the number of platelets - platelet count over 400,000. -primary or secondary (reactive) - asymptomatic until reach RBC count of over 1 million. (Then see intravascular clots, hemorrhage, Patho Essential (primary) thrombocytopenia: myeloproliferative neoplasm characterized by increase in platelet production, increased RBC production. - leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory symptoms, itchy and risk of leukemic or bone marrow fibrotic transformations - it is an MPN, with JAK2 mutation. - RBC aggregate and adhere on endothelium so that contributes to the blockage - also the CALR or MPL mutation. Secondary thrmobocythemia: - occur after splenectomy bc platelet that normally in spleen now remain in circulation. Happens three weeks after splectomy. - reactive thrombocythemia occurs in cancer or RA.

Lymphoblastic lymphoma Pathophysiology

LL: rare variant of NHL, but 1/3 of cases in children and adolescents. - T cell origin. Patho - clone of relatively immature T cells that become malignant in the thymus.

Immune thrombocytopenia purpura

Most common cause of thrombocytopenia secondary to increase platelet destruction - acute lasts 1-2 months in children. - usually secondary to infection, SLE, H pylori. - chronic ITP form autoantibody-mediated destruction against platelet-specific

Macrocytic-normochromic anemia: name, mechanism, cause

pernicious anemia: lack of vitamin B12. - associated with end-stage type A chronic atrophic gastritis - abnormal DNA and RNA synthesis in erythroblast; premature cell death - cause: congential or acquired deficiency of intrinsic factor IF; genetic disorder of DNA synthesis Folate deficiency anemia: lack of folate; premature cell death. - cause: dietary folate deficiency.

therapeutic interventions for slowly developing anemias

treatment of underlying condition, palliation of associated symptoms, and therapies (transfusions, dietary correction, administration of supplemental vitamins or iron).

Alterations in platelet function

- qualitative alterations in platelet function: shown by increased bleeding time in the presence of normal platelet count. - acquired more common than others. Drugs, systemic inflammation conditions, and hematopoietic alterations. - asprin affects platlets bc it irreversibly inhibits cyclooxygenase function for several days NSAIDS also affect the cyclooxyegnase. Systemic disorders that affect platelet function: chronic renal disease, liver disease, cardiopulmonary bypass surgery, sevee deficiency of iron/folate and antiplatlet antibodies.

Microcytic-Hypochromic Anemias - sideroblastic anemia Pathophysiology

- ringed sideroblasts in bone marrow. These are RBCs that contain iron-laden mitochondria in a circle around 1/3 or more of the nucleus. AKA, they are RBC that contain iron granules that have not been synthesized into hemoglobin but instead are arranged in a circle around the nucleus. Also have increase tissue level of iron. Pathophysiology - altered heme synthesis in the erythorid cells in bone marrow. - acquired sideroblastic anemias (ASAs) most common: it is idiopathic or bc of other myelopathy can disorders. - reversible sideroblastic anemia: secondary to alcohol (bc folate deficiency), drug reactions,. Copper deficiency (bc inference with conversion of ferric iron to ferrous iron) , hypothermia (bc decreased heme production/incorporation into hemoglobin. - hereditary (congenital) sideroblastic anemia: rare, almost always males with recessive X-linked transmission - present in infancy and childhood but not identified until HF, diabetes from iron overload. Leading cause of primary SAS is myelodysplastic syndrome (MDS): which is a group of disorders of hematopoietic stem cells with all three stem cell lines having abnormal growth/cell characteristics. - bleeding prevalent, and most develop acute myeloblastic leukemia

clinical manifestations of anemias: others

- skin, mucous membranes, lips, nail beds, conjunctivae: pale (reduced hemoglobin concentration) OR yellow jaundice (accumulation of end-products of RBC destruction aka hemolysis -tissue hypoxemia results in impaired healing, loss of elasticity, thinning and early graying of hair - Nervous systems manifesations occur IF FROM B12 DEFICIENCY. myelination degeneration occurs so lose of nerve fibers in spinal cord, paresthesias, gait disturbances, extreme weakness, spacisity, reflex abnormalities. - GI: decreased oxygen causes abdominal pain, NV, anorexia - low grade fever less than 101 F bc of leukocyte pyrogens from ischemic tissue.

Splenomegaly Eval and treatment

- splenectomy. To alleviate the destructive effects on RBCs. - no longer mandatory bc of the overwhelming sepsis that happens after. - instead to repair and preservation. - splenectomy still done in hair cell leukemia's, Felty syndrome, agnogenic myeloid metaplaisa, thalassemia major, Gaucherie disease, hemodialysis, splenic venous thrombosis, and thrombotic thrombocytopenia purpura (TTP). - after splenectomy, RBC become thinner, broader, and wrinkled. - major complication ** overwhelming post splenectomy infection (OPSI) which can progress to septic shock and then DIC.

clinical manifestations of anemias: reduced number of RBC compensations

-reduced number of blood cells in blood --> reduced consistency and volume of blood. initial compensation: movement of interstitial fluid into the blood, causing increase in plasma volume. this maintains volume but decreases viscosity. this thinner blood flows faster and more turbulent causing a hyperdynamic circulatory state causing cardio changes like increased stroke volume and HR. that leads to cardiac dilation and valve insufficiency.

Splenomegaly Clinical manifestations

-sequestering of RBC, granulocytes, platlets. Reduction of all circulating blood cells. Up to 50% - results in anemia, - size of spleen determines how much sequestering happens.

Heparin induced thrombocytopenia Clinical manifestations

-thrombocytopenia. (Decrease in 50% of platelet count) - prothombotic state so also increase risk for venous or arterial thrombosis - DVT, and pulmonary emboli. - arterial thrombosis affects lower extremities, so tissue ischemia, CVA, MI. - bleeding uncommon.

Leukemia's : patho: acute leukemia's

ALL and AML - ALL: aggressive, fast growin leukemia with too many lymphoblasts or immature WBC found in blood and bone marrow. - AML: too many myelblasts or immature WBC that are NOT lymphoblasts in bone marrow and blood. Also called ANLL. - ALL: malignant transformation of B/C cell progenitor cells. Mostly in children in first decade of life. Children is precursor B cell transformation, and in adults it is mix of cancer of B/T cell origin so adults die more from it. -AML: most common adult leukemia. Abnormal proliferation of myeloid precursor cells, decreased apoptosis, arrest of cellular differentiation. SO leukocytosis and blast cells. As immature blast cell increase, they replace the normal, so bleeding, anemia, and infection. Hereditary cause of AML with down, Fanconi aplastic anemia, Bloom syndrome, and others.

Thromboembolic disorders.

Arterial thrombo form under high blood flow and composed of platelet aggregates held by fibrin strands Veinour thmobi: low flow, composed of red cells with larger amounts of fibrin and few platlets. -thrombus events reduces/obstructs blood flow tissues or organs, such as the heart, brain, or lungs, depriving them of essential nutrients critical to survival. -anticoagulants not good fro arterial thrombosis. - IV heparin used. And oral coumarin. -spontaneous thrombi: Virchow triad: 1) injury to blood vessel endothelium, 2) abnormalities of blood flow, 3) hypercoagulability of blood. - artherosclerousis injury.

Hereditary thrombophilias(hypercoagulability

Autosomal dominant.

Infectious mononucleosis: IM

Benign, acute, self-limiting lymphoproliferative clinical syndrome characterized by acute infection of B lymph (B cells) - caused by EBV virus. Less common are CMV, HIV, hep A, influenza A, rubella, so on. - symptoms: pharyngitis, lymphadenopathy, fever. Can lead to B cell lymphoma in immunodeficiency people. If coinfected with HIV/malaria, then get EBC lymphoma like Burkitt lymphoma. (EBV also liked to Hodgkin lymphoma). - early childhood infection with EBV is normal, and results in immunity. If infected adolescence on, then results in IM. Mostly from ages 15-35 ( peak from 15-24). - transmission of EBV through saliva, close contact aka the kissing disease. Also secreted in mucosal regions. Not through coughing or sneezing though. - infection of EBV begins with widespread invasion of B lymphocytes, and then infects oropharynx, nasopharynx, salivary epithelial cells —> lymphoid tissue and B cells.

DIC Clinical manifestations

Bleeding at three or more unrelated sites. Can be eyes, mouth, needle sites, so on. Shock from loss of blood. -indicator of multisystme dysfunction include changes in level of consciousness, behavior, confusion, seizure, oliguria, hematuria, hypoxia, hypotension, hemoptysis, chest pain, tachycardia. - symmetric cyanosis of fingers and toes, nose, breasts. Gangrene Jaundice If have chronic, then subacute bleeding, diffuse thrombosis. Have compensated DIC or non-overt DIC. Here there is an increased turnover and decrease survival time of the components of hemostasis: platlets and clotting factors. T

Leukemia's : clinical manifestations: chronic leukemia's

CLL: - 70% CLL are asymptomatic at time of diagnosis. - when there are symptoms most common is LYMPHADENOPATHY. - suppression of humoral immunity, and increased infection with encapsulated bacteria. Neutrophil depressed. - 10% develop a diffuse large B-cell lymphoma. (Here you will see hypercalemia, anemia, elevated lactic dehydrogenase, low-grade fever, night sweats, weight loss, fatigue, thrombocytopenia. CML: three phases: 1) Chronic phase lasting 2-5 years. Symptoms not apparent 2) accelerated phase: 6-18 months. Primary symptoms develop. - Excessive proliferation and accumulation of malignant cells. Splenomegaly prominent and painful but no lymphadenopathy. Liver enlargement but no change in function. Hyperuricemia produces gouty arthritis. Infection, fever, and weight loss. 3) terminal blast phase (blast crisis): survival of only 3-6 months. - leukocytosis, increase basophils, then blast cells/promyelocytes predominate and have a blast crisis. Resembles acute leukemia but more prominent and painful splenomegaly.

Splenomegaly Pathophysilogy

Enlargement of the spleen. - can become overactive, with syndrome known as hypersplenism. - hypersplenism: 1) anemia, 2) leukopenia, 3) thrombocytopenia alone or in combination. Patho - inflammation/infection, congestive, infiltration (Gaucherie disease, amyloidosis, diabetic lipemia), tumor/cysts, nonmalignant hamartoma (true and false cysts) - splenic rupture if infection leads to spleen so filled with RBC that blunt trauma can rupture it. This happens in IM in males 4-21 day of acute infection. - congestive splenomegaly: ascites, portal hypertension, esophageal varicse, hepatic cirrhosis. Splenic hyperplasia - infiltration splenomegaly: engorgment by macrophages with indigestible materials associated with storage diseases. Tumors and cysts cause actual growth of spleen.

DIC Eval and treatment

Eval - clinical symptoms and confirmed by combination of lab tests. Confirm thrombocytopenia, prolongation of clotting time, presence of fibrin split products, decreased level of coagulation inhibitors, platelet count below 100,000. D-dimer test. - detection shows DIC - produced by plasmin degradation of fibrin clots. Quantified using ELISA test. Functional AT-III are low (anticoagulation ) Treatment: - eliminate underlying pathological condition (liver restore normal plasma in 24-48 hours) - continue ongoing thrombosis (heparin but only good with fetus retention, and vascular occlusion to have an organ. Contraindicated with sepsis, and postoperative bleeding, peptic ulcer, and CNS bleeding) - maintain organ function

Leukemia's : eval and treatment: chronic leukemia's

Eval: - lab analysis of peripheral blood and bone marrow. CLL: -detection of monoclonal B-cell lymphocytosis in blood. Immunophenotype of CD5+ and CD23-positive B cells at level over 5,000 cells for 4 weeks. -CLL lymph co-express B-cell antigens CD19, 20 and T-cell antigen CD5. - bone marrow has 30% lymphocytes and be normo or hypercellular. CLL treatment: observation and treatment of infection, hemorrhage, or immunologic complications. - allogenic stem cell transplant is good. - chemo not curative - anti leukemic therapy unnecessary in early disease. CML treatment: - Gleevec (imatinib mesylate): highly specific for CML and suppression of BCR-ABL kinase activity. And complete cytogenetic response in 80% of patients. There are still CML stem cells though

Malignant lymphomas: non-Hodgkin lymphoma Eval and treatment

Eval: - physical exam and history, blood test, urine, test, flow cytomegalovirus, bone marrow aspirate, biopsy, ** noncontigious lymph node involvement. Treatment: - depends on type, tumor stage, and histologic status, symptoms, age, stage of disease, aggressiveness of tumor. - not curative, so with insolent lymphoma with disseminated, observation and without treatment is best. Standard treatment: - chemo, radiation, target therapy, plasmapheresis (if blood becomes thick), biologic therapy with interferons, and watchful waiting.

Multiple myeloma Eval and treatment

Eval: - symptoms and radiographic/lab studies. Definitive diagnosis is bone marrow biopsy. - biomarkers, hypercalcemia, renal dfilaure, anemia, adn bone lesions (CRAB) Treatment: - B2-microglobulin use das indicator for prognosis or effectiveness of treatment. - chemo, radiation, plasmaphesis, stem cell transplant. - chemo: mephalan, prednisone (MP) - thalidomide inhibits angiogenesis, and increases apoptosis and G1 growth arrest.

Myeloproliferative red cell disorder Polycythemia Vera eval and treatment

Eval: Thrombotic event, splenomegaly, aquagenic pruritus - absolute increase in RBC and total blood volume. - Hematocrit from 18-24 g/dl, - RBC counts: 7x10^12 - 7x10^13 -anisocytosis: (unequal size of blood cells. - JAK2 mutation confirms diagnosis. Treatment: - phelebotomy (300-500 ml at a time) and low dose aspirin. - hydroxyurea: myelosuppresion - radioactive P: (effects last 18 months. SS include anemia, leukopenia, thrombocytopenia, acute leukemia after 7 years of use - thats why more common in elderly) - with treatment, survive 10-15 years. Without treatment, die in 18 months. Can convert to acute myeloid leukemia (AML).

Leukemia's : eval and treatment : acute leukemia's

Eval: - blood test and observing the bone marrow. Treatment - chemo, blood transfusions, antibiotics, antifungals, antiviral, - allopurinol used to prevent Uric acid production and elevation. - with AML and proper treatment, 60-70 % have complete remission (CR). - Philadelphia chromosome is a bad sign. - myelosuppression: hem support for blood products and granulocyte colony stimulating facto G-CSF or GM-CSF shortens time of neutropenia and improved survival by reducing risk for infection.

Leukemia's : overview

It is a clinal malignant disorder of bone marrow and (usually but not always) blood. - uncontrolled proliferation of malignant leukocytes, causeing overcrowding of bone marrow and decreased production and function of normal hematopoietic cells. Classification based on: 1) predominant cell of origin (myeloid/lymphopid) 2) rate of progression (degree of cell differentiation when cell became malignant) so acute or chronic. Acute leukemia: undifferentiated or immature cells usually a blast cell. Abrupt and rapid onset, short survival time Chronic leukemia: predominant cell is more differentiated but doesn't function properly, slow progression. 4 types of leukemia: 1) acute lymphocytic (ALL) 2) acute myelogenous (AML) 3) chronic lymphocytic (CLL) 4) chronic myelogenous (CML) Leukemia more common in adults than children. More in females.

Alterations of Leukocyte Function Quantitative alterations in leukocytes

Leukocyctosis can be normal, like an infection, stressor, whatever Leukopenia is never Normal. An absolute blood count of 4,000 cells/uL. When neutropenia decreased to less than 1,000, risk of infection is very high, and under 500, then life threatening.

Alterations of lymphoid function: lymphadenopathy

Lymphadenopathy: enlarged lymph nodes bc increase in size and number of its germinal centered caused by proliferation of lymphocytes and monocytes (immature phagocytes) or invasion by malignant cells. Usually lymph node not palpable so this is characterized by palpable lymph, and may be painful to touch. - localized lymphadenopathy: drainage of an area associated with an inflammatory process/infection - generalized lymphadenopathy: less often, and is seen in presence of malignant or nonmalignant disease, especially in adults. Occurs with non-Hodgkins lymphoma, chronic lympcytic leukemia (CLL), histiocytosis, and lymphocytosis disorders. Results from 4 conditions: 1) neoplastic disease 2) immunologic/inflammatory conditions 3) endocrine disorders 4) lipid storage diseases. Gernalized may be caused by disease of unknown origin, autoimmune disease, drug reaction

Lymphocyte alterations

Lymphocytosis: increase in number (absolute lymphocytosis) or proportion of lymphocytes in blood. Mostly seen in acute viral infection like EBC. - Lymphocytopenia: bc of abnormalities of lymphocyte production, destruction by drugs, viruses, radiation.

Thrombocythemia Clinical manifestations

Microvasculatrue thrombosis: ischemia in finger, toes, cerebrovascular regions. Presenting conditions of this erythromyalgia (unilateral or bilateral warm, congested red hands and feet with painful burning sensations in forefoot sole and one or more toes), headache, and paresthesias. - pain initiated by standing, exercising, or warmth and relieved by elevation adn cooling. Also arterial thrombosis., involving the coronary and renal arteries.

Microcytic-Hypochromic Anemias - sideroblastic anemia Clinical manifestations

Moderate to sever symptoms -hemoglobin level from 4-10 g/dl - signs of iron overload (hemochromatosis), hepatomegaly, splenomegaly. - skin bronze tint. - growth and development impairment in children/infants

Malignant lymphomas: non-Hodgkin lymphoma Pathophysiology

NHL: WHO/REAL classifications: - B-cell neoplasms - T cell/NK cell neoplasms - different from Hodgkin bc NO RS CELLS. Patho - progressive clonal expansion of B cells, T cells, NK cells. Mostly B cell though. - oncogenes activated by chromosomal translocations or tumor suppressor loci inactivated by deletion or mutation do chromosomes. - NHL is less predictable and spreads more widely. Risk factors; -white, male, older, AND inherited immune disorder, HIV/AIDs, chemical exposure, infection with EBV, high meat diet, immunosuppressant drugs after organ transplant, H pylori infection,

Multiple myeloma Pathophysilogy

Plasma cell WBC neoplasms. - slow proliferation of malignant cells, tumor cell masses in bone marrow usually resulting in destruction of bone. - myeloma o cells reside in bone marrow, and are not usually found in the peripheral blood. Patho: - MM is plasma cell neoplasia that causes lytic bone lesions, hyerpcalcemia, renal failure, anemia, immune abnormalities. For treatment need to know the driver mutations and heterogeneity. - the myeloma cells in the bone marrow produce cytokines too. -M protein (abnormal antibody) most prominent protein in blood. Myeloma suppression of normal antibodies results in diminished or absent normal antibodies. - Bence Jones protein—> in the blood and urine —> damage the renal tubular cells.

Myeloproliferative red cell disorder Polycythemia

Polycythemia: excess red cell production. - two forms: 1) relative polycythemia (hemoconcentration of blood bc dehydration. Resolves with fluid admin 2) absolute polycythemia: 2 forms - primary and secondary. And secondary is more common (physiologic response resulting from erythropoietin secretion caused by hypoxia - the hypoxia is noted in smokers, high altitude over 10,000, COPD, CHF, abnormal types of hemoglobin that has a greater affinity for O2, inappropriate secretion of erythropoietin by certain tumors - renal, hepatoma, cerebelli hemangioblastomas)

Immune thrombocytopenia purpura Clincial manifestations

Range: from minor bleeding to major hemmorage from mucosal sites (epistaxis, hematuria, menorrhagia, bleeding gums - if prego, then kid also be thrombocytopenic - neonetal alloimune thrombocytopenia: no ITP but mom make IgG antibodies against an antigen inherited from father

Thrombocytic thrombocytopenia purpura Eval and treatment

Schizocytes (fragmented red blood cells) - high lactate dehydrogenase (LDH) and LDL also elevated. Treatment : - plasma exchange with fresh frozen plasma. - steroids Splenectomy if unresponsive to other treatment

2) Microcytic-Hypochromic Anemias

Small, abnormally shaped RBC AND reduced hemoglobin concentration (even in normal cells) Iron deficiency anemia: lack of iron for hemoglobin; insufficient hemoglobin Cause: chronic blood loss, dietary iron deficiency, disruption of iron metabolism or iron cycle Sideroblastic anemia: dysfunctional iron uptake by erythroblasts and defective prophyrin and heme synthesis Cause: Congenital dysfunction of iron metabolism in RBC, acquired deficiency of iron metabolism as results of drugs or toxins Thalassemia: impaired synthesis of alpha and beta chain of hemoglobin-A; phagocytosis of abnormal erythroblasts in marrow Cause: Congenital genetic defect of globin synthesis

Alterations of splenic function

Spleen usually 1)phagocytosis of blood cells and particulate matter (bacteria) 2) antibody production 3) hematopoiesis 4) sequesteration of formed blood elements.

Thrombocytic thrombocytopenia purpura

TTP: multisystem disorder characterized by thrombotic microangiopathy (TMA) aggregation from this cause increased platelet consumption and ischemic tissue damage. - can be drug induced: found quinine, cyclosporine, and tacrolimus 2 types of TTP: familial and acquired idiopathic. - Familial is more rare, and typically seen in children. Recurring episodes every 3 weeks. - microthrombic formation throughout entire vascular system. - IgG autoantibody.

Myeloproliferative red cell disorder Polycythemia Vera overview

This is primary polycythemia. - stem cell disorder with hyperplastic and neoplasticism bone marrow alterations. - Abnormal uncontrolled proliferation of RBC, (accompanied by proliferation of WBC aka leukocytosis and thrombocytosis) - increased blood volume and viscosity - part of myeloproliferative neoplasms (MPNs). Which all are abnormal regulation of the hematopoietic stem cells - mutation of Janus kinase 2 gene (JAK2 gene), resulting in overproduction of blood cells. - common features: 1) increased proliferation drive in bone marrow cells, 2) hematopoesis of neoplasticism stem cells to secondary hematopoietic organs, 3) marrow fibrosis and peripheral Deficiencies in blood cells (cytopenias), 4) variable transformations to acute leukemia

Myeloproliferative red cell disorder Polycythemia Vera Clincial manifestations

Uncommon and occurs insidiously. - increased red cell mass and hematocrit Increase in blood volume, more viscous blood, so hypercoaguable state, clogging and occulusion, tissue ishemia, infarction. (Directly related to hematocrit levels. (Also increased thrombocytes and dysfunctional platlets lead to this state). - plethora (red color to face) - engorgement of retinal and cerebral veins - headache, drowsy, delirious, mania, psychotic depression, chorea, visual disturbances. Enlarged spleen. Death from cerebral thrombosis more common. cardio function mostly fine ** development of intense, painful itching that appears to be intensified by heat or exposure to water (aquagenic pruritus) so avoid warm water when showering. Not responsive to antihistamines.

Leukemia's : patho: chronic leukemia's

CML and CLL - CML (also known as CGL. Many forms of CML depending on line of granulocytes. Slow progressing with too many blood cells in blood. A myeloproliferative disorder. -CLL is too many immature leukocytes in blood and bone marrow. Cancer cells may be found in lymphoid tissue, (small lymphocytic lymphoma SLL. Aka CLL/SLL. Aka non-Hodgkin lymphoma) Patho: CML: chimeric (genetically distinct cells) BCR-ABL fusion (22/9) aka the Philadelphia chromosome. Causes abnormal cell signaling resulting in pro-growth and prosurvival pathways of the leukemic cells. - only known cause is ionizing radiation CLL: transformation and progressive accumulation of monoclonal B lymphocytes (rarely T cell). - can predict outcome based on IGHV gene mutation status. There are 5 epigenetic markers of CLL. - NOTCH1 gene mutation. -cause unknown.

DIC Pathophysiology

Coagulopathy in small and midsize vessels leading to ischemic necrosis. - simultaneous widespread clotting and bleeding bc fibrinolytic activation happens too. - not a diseas,e but secondary to something - excessive and widespread exposure to TF. - TF binds to clotting factor 7 —> prothrombin to thrombin —> formation of thrombin clots. - anticoagulation pathways inhibited (protein C, antithrombin III, TF inhibitor) -fibrinolytic activity of plasmin causes bleeding and produces fibrin split products FSPs which are powerful anticoagulants - low level of fibronectin is bad. Means FSPs are not removed so more bleeding. - DIC can also be activated by proteolytic activation of factor 10 (thrombin mimicry).

Lymphoblastic lymphoma Eval and treatment

Combined chemo. Bulky tumor treated with radiation therapy

Consumptive Thrombohemorrhagic Disorders: DIC

DIC: acquired clinical syndrome characterized by widespread activation of coagulation resulting in formation of fibrin clots in medium and small vessels or microvascular throughout the body. - widespread clotting: blockage of blood flow to organs, so Multiple organ failure. - tendency to bleed despite the clotting. - can be acute or chronic. Systemic thrombohemorrhagic disorder with laboratory evidence of 1) clotting activation, 2) fibrinolytic activation, 3) coagulation inhibitor consumption, 4) biochemical evidence of end-organ damage/failure. Sepsis is most commonly associated with DIC. Gram negative bacteria so can cause DIC. Cancer wise, DIC can be caused by lung, pancreas, colon, stomach cancer. Direct tissue damage and the TF can cause DIC.

Disorder of Coagulation : impaired hemostasis

Deficit of deficiency of one or more of the clotting factors. - vasculitis (inflammation of vessels) along with vessel damage activates platelets Impaired hemostasis: inability to promote coagulation and the development of a stable fibrin clot associated with liver dysfunction caused by liver disorder of lack of vitamin K. Vitamin K deficiency: needed for the synthesis and regulation of prothrombin, pro Coagulation factors 7, 9, 10, and anticoagulation factors in the liver (proteins C and S.) - vitamin K in leafy greens - most common cause of vitamin K deficiency is parenteral nutrition in combination with antibiotics that destroy normal gut flora. - treat with IV vitamin K, and resulting correction in 8-12 hours. Fresh frozen plasma for life threatening hemorrhage. Liver disease: Decreased production of factor VII (7). With advance destruction see Decrease in favor 9. - also site of thrombopoetin so if diminished then leads to thrombocytopenia, but aggregated platlets. Looks like DIC. -treatment: FFP

Immune thrombocytopenia purpura Eval and treatment

eval: - history of bleeding, and associated symptoms like weigh loss, fever, headache. - CBC, peripheral blood smear - usually no evidence of splenectomy Treatement: Acute will resolve without major clincial consequences but the chronic form is variable. - treatment is palliative not curative, focusing on prevention of platelet destruction - initially treatment with glucocorticoids (prednisone) to suppress immune response. -IV immunoglobulin used to prevent major bleeding. -RhoGAM used with limited success to treat individuals who are Rh negative - if platelet count not better, then splenectomy considered.

Macrocytic-normochromic anemia

large, abnormally shaped RBC. normal hemoglobin concentrations from large stem cell megaloblasts. they are macrocytic: unusually large in size, thickness, and volume. - are the result of ineffective erythrocyte DNA synthesis commonly casued by deficiency in B12 (cobalamin) or folate (folic acid). - causes RBC growth and development to happen at different rates with DNA synthesis or cell division blocked or delayed. -RNA replication and hemoglobin synthesis is normal though so overproduction of hemoglobin thus large RBC with small nucleus. - they die prematurely, and so cause anemia. - - premature death of damaged erythrocytes is eryptosis. common in peple with anemia secondary to deficiency of iron, infection, chronic disease, genetic disease, and myelodysplastic syndrome.

clinical manifestations of anemias

main thing: reduced oxygen-carrying capacity of blood leading to tissue hypoxia. -ss: vary depending on body ability to compensate for reduced oxyegn-carrying capacity (EXAMPLE: if the onset of the anemia is mild and gradual then it is easier to compensate and only causes issue during physical exersion). -compensation: involves cardiovascular, respiratory, and hematologic systems (ie involves heart, lungs, and blood.)

anemia

reduced number of RBC OR decrease in the quality or quantity of hemoglobin. result from 1) impaired erythrocyte production 2) blood loss (acute or chronic) 3) increased erythrocyte destruction 4) combination of these three factors classified by: 1) causes or 2) shit that affects size, shape, or substance of erythrocyte. - most common though is anemia based on changes that affect cell size and hemoglobin content - end with "cytic": cell size - end with "chromic": hemoblobin content - anisocytosis: assuming various sizes - poikilocytosis: assuming various shapes

clinical manifestations of anemias: hypoxemia

reduced oxygen in blood --> dilation of arterioles, cappilaries, and venules --> increased flow through them --> increased HR +stoke colume --> heart failure. -also effects pulmo and hematologic systems. - pulmo: lungs increase breathing rate and depth to increase oxygen and increased release of oxygen from hemoglobin. compensations result in dyspnea, dizziness, rapid pounding heart, fatigue.

Morphologic Classifications of anemias

1) Macrocytic-normochromic anemia 2) Microcytic-hypochromic anemia 3) Normocytic-normochromic anemia

Malignant lymphomas: Hodgkin lymphoma Clinical manifestations

- cytokines from the RS cells. So get enlarged, PAINLESS, lymph node in the neck (first sign of HL). - also can see an asymptomatic mediastinal mass on chest x-ray. - cervical, axillary, inguinal, and retroperitoneal lymph nodes affected in HL. - local symptoms: pressure and obstruction of lymph notes from lymphadenopathy Systemic effects: - intermittent fever, drenching night sweats, itchy skin, fatigue. Bad sign if also have weight loss. Displaced ureters, spinal cords involvement in dorsal lumbar regions, - pericardial friction rub, engorgemnt of vein on neck. - in mixed cellular and lymph depleted, see spleen involvement.

Acquired hypercoaguability

- deficiency in protein C, S, and AT-III. APS: autoimmune syndrome characterized by autoantibodies against plasma membrane of phospholipids and phospholipid binding proteins. Eval with lupus anticoagulant, and specific ELISA for antibodies against phospholids. For obstetric complication, use heparin. And low does asprin.

Macrocytic-normochromic : Pernicious anemia

- Pernicious anemia (PA) most common macrocytic anemia. lack of vitamin B12. - associated with end-stage type A chronic atrophic gastritis - common affetcs pple over 30, European

Heparin induced thrombocytopenia Eval and treatment

- dropping platelet count after 5 days on heparin. - platelet count may reach 60,000. - many post-surgery, so need to rule out infection or other drug reactions Tests: anti-heparin-platelet factor for 4 antibodies. Very sensitive but not specific, so false positive (dialysis). Treatment: Withdrawal of heparin, and use of alternative anticoagulant.

Lymphoblastic lymphoma Clinical manifestations

- painless lymphadenopathy in the neck. - peripheral lymph nodes in chest involved in 70% of people. - very aggressive, usually stage IV in people. Unique mediastinal mass bc of origin in thymus resulting in dyspnea, chest pain, compression of bronchi, or superior vena cava. - type B symptoms (fever, night sweats, weight loss)

Leukemia's : patho

- driven by genetically abnormal stem-like cancer cells (SLCCs). - abnormal immature WBC called blasts, fill the bone marrow and spill into the blood. It crowds out the marrow and causes cellular proliferation of the other cell lines to cease. - pancytopenia. -Philadelphia chromosome: 95 % of CML, and 30% of ALL. 9/22 chromosome, and increases rate of cellular division, inhibition of DNA repaire, and other dysregulations of cell growth. - ALL risk factors: x-rays, radiation chemo, Down syndrome, NF1, Schwachman syndrome, Bloom syndrome, ataxia telangiectasia. -ALL developes at different rates in different t regions.

Thrombocythemia Eval and treatment

- 2/3 of cases diagnosed through CBC - WHO: 4 criteria 1) sustained platelet count of at least 450 x 10^9/L 2) bone marrow biopsy showing proliferation of enlarged mature megakarocytes and no increase of granulocytes or erythrocytes precursors. 3) failure to meet criteria of polycythemia Vera, myelofibrosis, CML, or other myelodysplastic syndromes 4) presence of JAK2 Treatment: - preventing thrombosis or hemorrhage - hydroxyurea HU is a nonaklkatyting myelosuppressive agent. And it suppresses platelet production - interferon IFN Anagrelide interferes with platelet Maturation, not production. Low does asprin to alleviate the erthromyalgia

Normocytic-Normochromic Anermias

- Aplastic anemia: insufficient erythropoiesis —> depressed stem cell proliferation - post hemorrhagic anemia: blood loss —> increased erythropoesis; iron depletion - hemolytic anemia: premature destruction (lysis) of mature erythrocytes in circulation —> increased fragility of RBC - sickle cell anemia: abnormal hemoglobin synthesis, abnormal cell shape with susceptibility to damage, lysis, phagocytosis —> congenital dysfunction of hemoglobin synthesis - anemia of chronic inflammation: abnormally increased demand for new erythrocytes—> chronic infection of inflammation; malignancy.

Burkitt lymphoma Pathophysiology.

- B-cell tumor. - usually Africa - classification of Burkitt: 1) African endemic Burkitt lymphoma, 2) sporadic non endemic Burkitt lymphoma, 3) subset of aggressive lymphoma with HIV infected pple. - fast growing, often appearing in jaw. And sometimes abdomin. Pathophysilogy: - enedemic Burkitt: EBV infected. - B-cell chromosomal translocation, and overexpression of c-MYC protooncogene thus loss of control of cell growth. T8;14 translocation. - Warburg effect: aerobic glycolysis

Leukemia's : clinical manifestations : acute leukemia's

- Days/weeks: abrupt stormy onset, especially in ALL. - Clincial manifestations: anemia, bleeding (purpura, petechaie, ecchymosis, hemorrhage), infection, weight loss, bone pain, liver/spleen/lymph node enlargement, elevated Uric acid level (normal is 300-500 but in leukemia it becomes 50 times more). - spleen, liver enlargement more common in ALL. - neuromanifestatinos from leukemic infilatration or cerebral bleeding.

Malignant lymphomas: Hodgkin lymphoma Pathophysiology

- HL: progresses from one group of lymph nodes to another ,including the development of systemic symptoms and prescience of B cells called *Reed-Sternberg RS cells*. Usually these RS cells are infected with EBV virus. - peaks during the 2/3 decade and then the 6/7 decade. Patho: - RS cell is the malignant transformed lymphocyte. - RS release cytokines, hence the systemic effects. There is classical Hodgkin and nodular lymphocyte-predominant Hodgkin. - classical: 1) nodular sclerosis HL, 2) lymphocyte-rich classic HL, 3) Mixed celluarity HL, 4) Lymphocyte-depleted HL. Therese are based on the morphology of RS cells and the characteristics of the inflammatory cell inflitrate in the tumor. - nodular lymphocyte-predominant Hodgkin: earlier stages, longer survival, fever treatment failures, than classic. Can transform to large B-cell lymphoma by 10 years.

Microcytic-Hypochromic Anemias - iron deficiency anemia Pathophysiology

- IDA: most common type. Most in poverty, women of childbearing age, and children. Children bc of chronic infections that result in blood and iron loss greater than intake. Also people with lead poisoning that get treatment have decreased iron levels. Increased iron deficiency in overweight people. Pathophysiology - 2 etiologies: inadequate dietary intake OR chronic blood loss - also metabolic disorders where cannot use the iron that you have. - blood loss of 2-4 ml/day can cause IDA. -So heavy period flow can cause IDA in women. Males can get IDA from bleeding of ulcers, hernia, esophageal varices, cirrhosis, hemorrhoids, ulcerative colitis, cancer. Also medications that cause GI bleed, surgery, eating disorders like pica, H pylori infection Stages: 1) body iron stores for red cell production and hemoglobin synthesis are depleted. RBC production is normal with hemoglobin content of red cells also normal. 2) insufficient amounts of iron are transported to the marrow and the iron-deficient RBC production begins. 3) hemoglobin deficient red cells enter the circulation to replace normal, aged RBC. Manifestations of IDA happens here insufficient iron supply and diminished hemoglobin synthesis.

Myeloproliferative red cell disorder Polycythemia Vera pathophysiology

- cells have normal receptors, but proliferation of erythrocytes progenitors -JAK2 mutaiton increases activity of erythropoietin receptor

Macrocytic-normochromic : Pernicious anemia clinical manifestations

- develops slowly over 20-30 years so when seek treatment usually severe. - early symptoms nonspecific - once hemoglobin reach 7-8 g/dl —> classic signs of PA: weakness, fatigue, paresthesias of feet and fingers, difficulty walking, loss of appetite, abdominal pain, weight loss, sore tongue that is smooth and beefy red. Skin becomes lemon yellow (sallow) bc of combo of pallor and jaundice. Hepatomegaly indicated right sided heart failure and splenomegaly. - neuro manifestations from neuronal demyelination causes neuron death. Loss of position, vibration, ataxia, spasticity. They are NOT reversible. B12 deficiency in Alzheimer's.

Burkitt lymphoma Eval and treatment

- distributions of tumors and biopsies of enlargened lymph nodes/bone marrow with malignant B cells are usually indicative of Burkitt. One of the most aggressive and quickly growing malignancies

Multiple myeloma Clinical manifestations

- elevated calcium levels - Renal failure - Bone lesions. Lytic lesions (punched out) - Destruction of bone tissue causes pain, and pathological fractures. - Vertebrae—> ribs —> skull —> pelvis —> femur —> clavicle —> scapula. - spinal cord compression. - Amyloidosis: antibody proteins increase and stick together in peripheral nerves and organs like kidney and heart. The SS of this is fatigue, purple spots on skin, enlarged tongue, diahhrea, edema, and numbness/tingle of feet. -proteinuria in 90% - renal failure second to hypercalcemia and the Bence Jones protein. - Anemia: (normo though) bc of inhibited erythropoiesis cause by tumor cell infiltration of the bone marrow. - High concentration of paraproteins lead to hypereviscocity syndrome, - some neuro shit - infection bc of suppressed humoral response. Preceded by monoclonal gammopathy of undertermined significance (MGUS). Diagnosed through presence of M protein in blood/urine without additional evidence of MM. MGUS—> asymptomatic MM (smoldering myeloma/indolent myeloma bc no end-organ damage) —> symptomatic MM.

Myeloproliferative red cell disorder Iron overload - Hereditary hemochromatosis HH eval and treatment

- elevated iron levels, transferrin saturation, and ferritin levels. - check blood with phlebotomy or liver for iron. Treatment: - phlebotomy of 550 mL of whole blood aka 200-250 mg of iron. This needs to continue until ferritin level is between 20-50 ng/mL. So continue weekly until ferritin level there. Then continue ever 2-3 months. - do not take iron and vitamin C supplements or consume raw shellfish. - alcohol in moderation

Myeloproliferative red cell disorder Iron overload - Hereditary hemochromatosis HH clincial manifestations

- fatigue, malaise, abdominal pain, arthraglasias, impotence. - hepatomegaly, abnormal liver enzymes, bronzed skin, diabetes, cardiomegaly. - diagnosis: serum iron

Macrocytic-normochromic : folate deficiency anemia's Overview

- folate (folic acid): essential vitamin for RNA and DNA synthesis for maturing RBC. Also needed for synthesis of thymine, purines (A and G) and conversion of homocysteine to methionine. - deficiency in thymine —> affects cells undergoing rapid division. - dependent on dietary intake of 50-200 mg/day. - folate absorped from upper small intestines, and doesnt need anything to facilitate absorption. - stored in liver - more common that B12 deficiency especially with alcoholics and pple with chronic malnourishment. Clinical manifestation: - similar to the malnourished appearance of individuals with PA. - cheilosis (scales and tissues on mouth), stomatitis (inflammation of mouth), painful ulcerations of the check and tongue (burning mouth syndrome). Also dysphasia, farting, watery diarrhea, sprue (chronic absorption disorder). - undiagnosed inflammatory bowel (Crohn/ulcerative colitis) underlying cause of folate deficiency. - decreased folate stops proliferation of intestinal mucosa, and results in GI damage. - Neuro manifestations from thiamine deficiency Eval: - blood test, measurement of serum folate levels, and clinical manifestations - treatment: administration of oral folate until adequate blood levels are obtained and manifestations are reduced/eliminated. - long term therapy NOT needed if appropriate dietary adjustments made. - after treatment, Manifestations of anemia disappears after 1-2 weeks.

Hemorrhagic disorders and alterations of platlets and coagulations

- hemostatis: arrest of bleeding. - purpuric disorders: when deficiency of normal platlets necessary to plug damaged vessels or prevent leakage from tiny tear in capillaries. - thromboembolic disease: spontaneous clotting - hypercoagulability (thrombophilia): predisposes clotting to blood or thrombosis.

Burkitt lymphoma Clinical manifestations

- in children or young adults. - most tumors in extranodal locations. - enemdic: mass on jaw (mandible), and involves abdominal viscera. Sporadic Burkitt: mass in ileocecum and peritoneum - type B symptoms.

Infectious mononucleosis: IM Eval and treatment

- increased WBC count with atypical forms. Diagnosis: - 1) increase in lymphocytes based on the Hoagland criteria of at least 50% lymphocytes and at least 10% atypical lymphocyte in blood 2) positive heterophile antibody reaction ( mono spot test) 3) rising titles of specific antibody for EBV antigens. Heterophilic antibodies are IgM antibodies that are agglutinins against nonhuman RBC and are detected by qualitative - monospot - or quantitative - heterophile antibody test. Monospots yield a lot of false positives bc a lot of viruses produce heterphilic antibodies. Treatment: - supportive. Rest and alleviation of symptoms with analgesics and antipyretic - no aspirin with children bc of Reye syndrome. - streptococcal is treated with penicillin or erythromycin ( NOT AMPICILLIN bc rash) - Steroids used when airway obstruction, or organ involvement/CNS manifestations, thrombocytopenic purpura, myocarditis, pericarditis. - Acyclovir in immunocompressed pple. - if splenic rupture, then removal of spleen.

Infectious mononucleosis: IM Clincial manifestations

- incubation is 30 - 50 days with - first few days: early flu like symptoms, headache, malaise, joint pain - at diagnosis: fever, sore throat (pharyngitis), cervical lymph node enlargement, and fatigue. The pharyngitis is diffuse with white/grey/green thick exudate. - as progresses: generalized lymphadenopathy, enlarged spleen, atypical activated T cells. - self-limiting, recover in few weeks. Fatigue lasts 1-2 months after though. - splenomegaly - splenic rupture is most common cause of death related to IM, as well as hepatic failure, extensive bacterial infection, viral myocarditis. Other: Gillian-Barre, Bell palsy, so on. Eye you have orbital edema, keratitis, uveitis, conjunctivitis. - Reye syndrome in children with EBV infection.

Myeloproliferative red cell disorder Iron overload - Hereditary hemochromatosis HH pathophysiology

- iron absorption regulated by erythropoietin, tissue oxygenation, iron stores. - HH is excessive iron absorption. - it is autosomal recessive disorder of iron metabolisms, increased GI iron absorption, and iron tissue deposition. -excess iron first deposited in liver, and pancreas, then heart, joints, and endocrine glands. - causes tissue damage, cirrhosis, diabetes, heart failure, arthropathies, impotence. - homozygosity of C282Y mutation on the HFE gene chromosome 6 - Hepcidin lowers plasma iron levels, so deficiency caused by the genetic mutation in it caused iron accumulation. - Cirrhosis is late-stage development of HH, and it is a risk factor so want to prevent it in HH.

Malignant lymphomas: non-Hodgkin lymphoma Clincial manifestations

- localized or generalized lymphadenopathy like in HL. Painless swelling. - Retroperitonneal and abdominal masses, back pain, ascites, skin arch, itchy skin, fatigue, fever of unknown origin, drenching night sweats, leg swelling - lymphoma classified as low, intermediate, or high grade. Low grade is indolent. Painless, peripheral adenopathy. Spontaneous regression of the nodes can happen, mimicking infection. Cytopenia reflects bone marrow involvement. Hepatomegaly

Macrocytic-normochromic : Pernicious anemia pathophysiology

-absence of IF (intrinsic factor) from congenital or autoimmune cause. IF needed for gastric absorption of B12 - congenital is autosomal recessive - autoimmune also has geneitc component, with 20-30% of people related to someone with it have it as well. females have gastric autoantibodies. - also associated with autoimmune polyendocrinopathy which is cluster of autoimmune thyroditis (Hashimoto), type I diabetes, Addisons, primary hypothyroidism, Graves, and myasthenia gravis. - usually caused by type A gastritis. - commonly PA patients have autoantibodies against gastric H+K+ ATPase. gastric mucosal atrophy from deficiency of all secretions of stomach. - autoantibodies against IF --> prevent B12-IF complex. -Caused by infection from H. pylori - environmental factors: chronic gastritis from excessive alcohol or hot tea ingestion and smoking. - complete or partial removal of stomach causes IF deficiency - PPIs can decrease B12 absorption -PA is begnin but if have type A chronic gastritis --> get gastric adenocarcinoma, gastric cacinoid type I.

Thrombocytic thrombocytopenia purpura Clincial manifestations

-chronic relapsing TTP: rare familial form in children - acute idiopathic TTP: more common and more severe: - fatal within 90 days. Acute idiopathic TTP: - pentad of symptoms: extreme thrombocytopenia (20,000) - intravscular hemolytic anemia - ischemic signs and symptoms with CNS memory - kidney failure - fever

Disorders of platelets: Thrombocytopenia Pathophysiology

-decrease in the number of circulating platlets - less than 150,000 platelets but not significant until 100,000. - hemorrhage with minor trauma under 50,000 platelets - spontaneous bleeding without trauma is 10,000-15,000. Skin manifestations (petechiae, ecchumoses, larger purpuric spots, frank bleeding - less than 10,000 is fatal, GI respiratory tract, respiratory tract, central nervous system. - before diagnosis need to rule out pseudothrombocytopenia where agglutinate platets from a preservative called EDTA makes it look like there is thrombocytopenia. - also dilution effect of massive transfusion when more than 10 units of blood transfused in 24 hours. - sequestering by spleen and hypothermia also show false thrombocytopenia. Patho - decreased platelet production, increased consumption or both. - Congenital or acquired, primary or secondary. - secondary to Congenital condition: TAR syndrome, Wiskott-Aldrich syndrome, may-haggling anomaly, x-linked thrombocytopenia. - more common is secondary to viral infections, nutritional deficiency, chronicle renal failure, bone marrow hypoplasia, radiation therapy, bone marrow infiltration by cancer. - most common: increased platelet consumption Heparin induced thrombocytopenia, idiopathic (immune) thrombocytopenia purpura, thrombotic thrombocytopenia purpura, and DIC

Malignant lymphoma

-diverse group of neoplasms that develop from proliferation of malignant lymphocytes in lymphoid system. - now REAL classification. WHO modified this, and now three major categories: 1) B-cell neoplasms 2) T-cell/NK cell neoplasms 3_ Hodgkin lymphomas. - two basic lymphomas are Hodgkin and non-Hodgkin lymphoma. Nonhodgkin: cancer that have indolent course or aggressive course. - happen bc of genetic mutation or viral infection.

Microcytic-Hypochromic Anemias - sideroblastic anemia Eval and treatment

Eval: - can be mistaken for deficiency of stem cells in the marrow (hypoplastic anemia) or iron deficiency anemia. - The diagnosis of SA is established by bone marrow biopsy (to see presence of siberoblasts and confirm diagnosis Treatment: Initial: indenting causative agent. - treatment is supportive, so tranfusion is primary thing - then oral pyridoxine (100 mg/day) (if from alcohol abuse or pyridoxine antagonist then complete recovery form this) - hereditary SA: pyridoxine therapy (50-200 mg/day) good for 1/3 of people. Good response to this is reticulocytis with blood hemoglobin levels and low free erythrocytes proptoprphyrin level normal in 1-2 months. (Structural abnormalities like microcytosis do not disappear) - of no response to pyridoxine then need blood transfusions - if iron overload then need iron deflection therapy to prevent or minimize organ damage. - phlebotomy used if have mild-moderate anemia and no other complications. Have maintaince phlebotomies too. - when severely anemic, the transfusions cause severe iron overload, so need to use deferoxamine (iron-cheating agent) - recent advancements in treatment: prolonged administration of erythropoietin, stem cell transplants. Best response in refractory anemia MDS. - death from SA rare, mostly from complications like infection, bone marrow failure, liver failure, HF, arrhythmia or both.

Microcytic-Hypochromic Anemias - iron deficiency anemia Eval and treatment

Eval: - iron stores measured directly through bone marrow biopsy, indirectly through serum ferritin level, transferrin saturation, or total iron-binding capacity. Also FEP level in RBC. Treatment: - eliminate blood loss - iron replacement therapy. Initials 150-200 mg/day until serum ferritin reaches 50 mg/L. Within first month, see a decrease in fatigue and shit. Treatment for 6-12 months after bleeding stop (but can last 24 months. Menstruating women may need daily iron intake.

Malignant lymphomas: Hodgkin lymphoma Eval and treatment

Eval: - sedimentation rate, lymph biopsy, RS cell, disease markers. Staging used CT and PET scans. - staging laparotomy is NO longer recommended. No in chemo patients. - adult Hodgkin lymphoma can be cured. Staging: 1) one lymph node, one organ 2) 2 or more lymph nodes on same side of diaphragm , involvement of one extralymphatic organ 3) lymph nodes on both sides of diaphragm, spleen, and other organ involvement 4) disseminated involvement of extralymphatic organs, with or without associated lymph node involvement. Distal nodal involvemtent. Treatment: - prego women: observation and steroid therapy. - chemo, radiation, stem cell transplantation, monoclonal antibody therapy. The chemo and radiation can increase risk fro a second cancer.

Macrocytic-normochromic : Pernicious anemia Eval and treatment

Eval: blood tests, bone marrow aspiration, ecological studies, gastric biopsy, clinical manifestation. - Schilling test: indirectly measures B12 absorption through admin of radioactive B12 and measuring excretion in urine. LOW urinary secretion —> PA. - this test replaced with serological studies measure methylmalonic acid and homocysteine levels (elevated in early PA) —> this test more sensitive. - presence of circulating autoantibodies for parietal cells and intrinsic factor also useful in diagnosis. These decrease abortion of B12 cpbalamin. - H. Pylori infection - gastric biopsy total achlorhydria (no hydrochloric acid) is also diagnostic for PA Treatment: replacement of B12. - injection of B12 weekly until deficiency corrected. Then monthly injections for remainder of life. - effectiveness determined through rising reticulocyte count. Should return to normal within 5-6 weeks. - not curable, so maintain therapy is lifelong. - untreated PA is fatal bc of heart failure.

Microcytic-Hypochromic Anemias - iron deficiency anemia Clinical Manifestations

Gradual onset. Don't seek attention until hemoglobin 7-8 g/dl. - early symptoms: fatigue, weakness, shortness of breath, pale earlobes, palms, and conjunctivae - later symptoms: severe, structural and functional changes occur in epithelial tissue. Finger nails are brittle and spoon-shaped (Koilonychia), tongue papillae atrophy. These go away after 1-2 weeks of replacement therapy. - other symptoms: corners of mouth become dry and sore (angular stomatitis), difficult swallowing bc of web in throat. IDA: have gastritis, neuromuscular changes, irritability, headache, numbness, tingling, and vasomotor disturbances. In elderly, mental confusion, memory loss, disorientation.

Quantitative alterations in leukocytes Granulocyte and monocyte

Granulocytosis/neutrophilia: increase in granulocyte (neutrophils, eosinophils, basophils - early stages of infection, when absolute count exceeds 7,500. - shift to the left (leukemoid reaction): premature release of the immature cells, so see microscopic detection of disproportionate number of immature leukocytes in peripheral blood smears. Also seen in leukemia which is why also called leukemoid reaction. Return to normal is shift to the right. - Neutropenia: neutrophil count less than 2,000. Primary is Congenital (Kostmann, Barth syndrome, Diamond stuff) or acquired like with leukemia or anemia, starvation, so on. Secondary is with neutrophil survival, sequestering, and so on. - Granulcytopenia/agranulocytosis: severe neutropenia, less than 500, or none at all. Get severe infection, septicemia, general malaise, fever, tachycardia - Eosomphilia: > 450. Allergic disorders. -eosinopenia: caused by migration of eosinophils into inflammatory sites.Cushings, stress (surgery, shock, burn, trauma) - Basophilia: increase. Rare. Response to inflammation, immediate hypersensitivity. Seen in chronic myeloid leukemia, myeloid metaplasia. - Basopenia: basophils leukopenia. Seen in hyperthyroidism, acute infection, ovulation, pregnancy,. With endocrine, it is associated with Graves. - Monocytosis: > 800. Transient. Late stage, recovery in infection. Chronic infection like TB, SBE, so on. - monocytopenia: rare. Seen in hairy cell leukemia, prednisone therapy.

clinical manifestations of anemias: ACUTE

Hemorrhage: initial compensation is peripheral blood vessel contriction, diverting blood flow to essential vital organs. -decreased blood flow to kidney --> renin-angiotensin response --> salt and water retention in an attempt to increase blood volume.

Heparin induced thrombocytopenia

Heparin is most common cause of drug-induced thrombocytopenia (HIT) - HIT is immune mediated, adverse drug reaction caused bu IgG antibodies against heparin-platelet factor 4 complex leadin to platelet activation. Then thrombin activation leads to increased platelet consumption, and decrease in platelet count beginning 5-10 days after admin of heparin.