Blood and Lymph Pathology


What's inside blood



Blood and Lymphatic System/Disorders
Chapter 17

Blood responsible for:
Transportation – nutrients, wastes, hormones, electrolytes
Defense system – antibodies, WBCs
Homeostasis – temperature, blood pressure, clotting, buffer systems

Background/terms
Adult - 5 liters of blood – 55% water, 45% cells
Hematocrit – proportion of cells in the blood, indicates viscosity
Elevated hematocrit > dehydration
Decreased hematocrit > blood loss, anemia
Plasma – clear, yellowish fluid after cells removed
Serum – fluid, solutes after cells and fibrinogen removed
Plasma proteins – albumin, globulins, antibodies, fibrinogen

All blood cells formed in the bone marrow
Develop from stem cells – hemopoiesis

Red blood cells, biconclave, flexible, w/ hemoglobin
Erythropoitin from kidney stimulates RBC formation in response to hypoxia
RBC production needs amino acids, iron, vitamin B12, B6, and folic acid

Hemoglobin = globin made of amino acids, heme.
Each heme has a ferrous iron atom to which oxygen attaches
Heme provides red color
Oxyhemoglobin bright red saturated w/ O2
Deoxyhemoglobin – dark red, no O2
CO2 carried in different area of RBC by amino acids
Most CO2 is carried in blood as bicarbonate ion in buffer pair
Oxygen can be easily displaced by carbon monoxide
Carbon monoxide poisoning, bright cherry red coloring of victims lips and face

RBC lifespan 120 days
Then phagocytosis in liver or spleen, broken down into globin and heme
Globin put back in amino acid pool
Iron from heme returned to bone marrow and liver for hemoglobin

*Excess iron stored as ferritin or hemosiderin
Hemochromatosis – genetic- iron overload – in organs




Hemosiderosis – iron overload from increased RBC destruction

*Remainder of heme is converted to bilirubin > liver > bile
Too much RBC destruction elevated bilirubin or jaundice


How white blood cells work



Leukocytes – 1% blood volume
Leukopoiesis – production of WBCs stimulated by colony stimulating factors produced by macrophages and t lymphocytes (interleukin 3)
WBCs leave capillaries, enter tissue by diapedesis to defend

5 types of leukocytes:
Lymphocytes-30-40%, B and T cells
Neutrophils - 50-60%, polys, segs, PMNs, live 4 days,
[Band immature neutrophil - ^ in bacterial infection, shift to left (drafting younger cells)]
Basophils – leave blood enter tissue to become mast cells > histamine, heparin
Eosinophils – combat histamine, active in allergic or parasitic infections
Monocytes enter tissue to become macrophages > phagocytize

*CBC - Differential indicates the proportions of specific types of WBCs, assists in diagnosis

*Thrombocytes, platelets, not cells, essential blood clotting agents, hemostasis
Hemostasis – **
  1. Vasoconstriction, vascular spasm, decreases blood flow, platelet plug
  2. Thrombocytes adhere to tissue > platelet plug in small vessels
  3. Larger vessels require coagulation cascade
Coagulation cascade:
  1. Damaged tissue releases factors
  2. Prothrombin > thrombin
  3. Fibrinogen > fibrin
  4. Fibrin mesh forms, stops blood flow
  5. Clot shrinks, retracts bringing edges of wound together
Clotting factors are produced mainly in the liver
Vitamin K is needed for most clotting factors
Calcium ions also needed for clotting

Fibrinolysis –
Balance exists between clotting and anti-clotting
Antithrombin III, heparin
Fibrinolysis – plasminogen activator + streptokinase = Plasmin
Checks and balances

Diagnostic tests:
Complete blood count (CBC) numbers, sizes, shapes of blood components
Leukocytosis – increase in white cells – infection
Leukopenia – decrease in leukocytes virus, chemo, radiation
Increase eosinophils, allergy
Different types of anemia measured by size, shape, hemoglobin
Hematocrit – RBC - fluid and cell content,
Bone marrow function measured by reticulocyte #, immature non nucleated RBCs
Chemical analysis can measure iron, B12, B6, cholesterol, urea, bilirubin, etc
Blood clotting disorders by bleeding time, prothrombin time

Blood components



Blood types: A, B, AB and O; also Rh factors positive or negative
Blood types determined by antigens on RBCs (helmets)
Wrong blood type causes agglutination (clumping) and hemolysis
Type O lacks antigens so universal donor
Type AB universal recipient
Plasma and colloidal volume expanding can be administered due to no antigens

Blood therapies:
Whole blood, packed red cells, packed platelets severe anemia, thrombocytopenia
Plasma, colloidal volume expanding, no rx, due to no antigens
Artificial blood products – hemolink, hemopure, oxygent
Epoetin alfa (Procrit, Eprex) form of erythropoietin injection to ^ RBC production
Bone marrow or stem cell transplants – match of human leukocyte antigen needed


Blood types





*Lymphatic vessels, lymph nodes, lymphoid tissue (tonsils, spleen, thymus)


Lymph



Blood dyscrasias:

Anemias in general:
Low hemoglobin – decreased production, decreased erythrocytes

Caused by:
Deficiency of needed nutrients
Impaired bone marrow function
Blood loss
Destruction of RBCs

Symptoms:
Reduction in O2 transportation
Cell metabolism and reproduction decreased
Compensatory tachycardia, vasoconstriction
Fatigue, pallor, dyspnea
Decreased regeneration – stomatitis, cracked lips, dysphagia, brittle hair
Angina, congestive heart failure

Iron deficiency anemia
Insufficient iron = low hemoglobin = < ability to carry O2
Common – mild to severe

Etiology:
Decreased dietary intake critical times – toddlers, teens, pregnancy, breast feeding
Chronic blood loss – ulcers, menstrual cycles, cancer
Malabsorption syndromes – achlorhydria (lack of hydrochloric acid in stomach)
Severe Liver disease

Signs and Symptoms:
Mild may be asymptomatic
Vasoconstriction > pallor of skin, mucous membranes
Fatigue , lethargy, cold intolerance
Irritability
Degenerative changes – hair, nails
Stomatitis, glossitis
Menstrual irregularities
Delayed healing
Tachycardia, heart palpitations, dyspnea, syncope

Diagnostic tests:

Hgb, Hct, mean corpuscular hemoglobin, serum ferritin, serum iron

Treatment:
Iron rich foods, Iron supplements
Take with food
Take w/ straw, may stain teeth
May cause constipation


Blood disorders
























Pernicious anemia – Vitamin B12 deficiency
Megaloblastic anemia
Large, immature nucleated erythrocytes
Caused by lack of folic acid(B9), cyanocobalamin (B12)
Achlorhydria
Thrombocyte levels V
Demyelination peripheral nerves

Etiology:
Dietary insufficiency
Malabsorption - Autoimmune
Gastrectomy – removal of parietal cells

Signs and symptoms:
Tongue, enlarged, red, swollen, shiny

Causes:
Malabsorption

Aplastic anemia
Impairment or failure of bone marrow
Pancytopenia decreased numbers of erythrocytes, leukocytes, platelets

Etiology:
Temporary or permanent
Idiopathic, middle age
Myelotoxins radiation, industrial chemicals, drugs can damage bone marrow
Harvest stem cells prior to chemotherapy
Viruses, hepatitis C
Autoimmune disorders
Genetic – myelodysplastic syndrome, Fanconi’s anemia

Signs and smptoms:
Insidious onset
Anemia
Leukopenia
Thrombocytopenia petechiae, tendency to bleed
Uncontrollable hemorrhage and infection

Diagnostic tests:
Blood counts pancytopenia
Bone marrow aspiration and biopsy

Treatment:
Treatment of cause
Removal of bone marrow suppressants
Blood transfusion
Bone marrow transplant – chemo/radiation prep, harvest stem cells, reinfuse


Hemolytic anemias:
Excessive destruction of RBCs, hemolysis
Causes – genetic defects, immune rx, infections

Sickle Cell Anemia
Hemoglobinopathy, abnormal hemoglobin S
When deoxygenated crystallizes, sickles, damaged cell membrane, hemolysis, 20 day
Initially oxygen can reverse sickling, but then irreversible
Can transport O2, sickling = obstruction, thrombus, infarctions all over
Crisis due to dehydration, lung infection
Increased hemolysis = hyperbilirubinemia, jaundice

Etiology:
Genetic, recessive, sickle cell trait, not as many symptoms b/c only ½ blood affected
Sickle cell = decreased incidence of malaria
African or Middle East heritage

Signs and symptoms:
Symptoms don’t appear until child is 6-12 months old and Hgb F replaced
Proportion of Hgb S = number of symptoms
Anemia… so what are the symptoms?
Hyperbilirubinemia …why , symptoms?
Splenomegaly – congestion, scaring, fibrotic
Vascular occlusions – painful, damaging
Chest syndrome
Hand-foot syndrome
Growth/development impacted, delayed dentition
Congestive heart failure
Infections, damaged spleen cannot filter blood, hypoxia, congestion = poor healing

Diagnostic tests:
NB testing, Hemoglobin electrophresis (blood test)

Treatment:
Hydroxyurea (Hydrea)
Dietary folic acid (folate)
Avoid strenuous exercise, dehydration, high altitudes, cold, infection
Immunizations
Penicillin



Thalassemia:
Genetic defect affects Asians, Mediteraneans, AA
Interference with hemoglobin synthesis, RBCs produced
2 alpha globins and 2 beta globins normally
Thalassemia alpha lacks alpha chains, beta lacks beta chains
Lack of alpha or beta chains missing, extra globins damage cell membranes
Damaged cell membrane leads to hemolysis and anemia
Hemolysis leads to splenomegaly, hepatomegaly, hyperbilirubinemia,
Hyeractive bone marrow

Etiology:
Most common genetic disorder in the world
Cooley’s anemia

Signs and symptoms
Anemia
Increased hemolysis
Growth and development impaired by hypoxia, fatigue, inactivity
Hyperactive bone marrow
Heart failure increased workload

Diagnostic tests:
Microcytic, hypochromic
Increased erythropoietin levels
Iron overload

Treatment:
Blood transfusions every 3 weeks
Iron chelation therapy - desferal, xjade
Administration of folate
Bone marrow transplant


Polycythemias
Primary – polycythemia vera
Increased erythrocytes, granulocytes, thrombocytes
Increased blood volume and viscosity
Distended blood vessels, sluggish, leading to thromboses, infartions
High blood pressure
Hypertrophied heart
Hemorrhage
Liver, spleen, congested, enlarged
Neoplastic disorder, serum erythropoietin levels low

Secondary
Erythrocytosis
Increase RBCs in response to hypoxia, increased erythropoietin secretion
Compensatory mechanism to increase O2 w/ lung or heart disease or erythropoietin-secreting tumor


Sometimes bone marrow becomes fibrotic, hematopoiesis develops in the spleen and anemia ensues
AML may develop

Etiology:
Neoplastic disorder noted between 40 – 60 years old

Signs and symptoms:
Plethoric, cyanotic
Hepatomegaly (enlarged liver)
Splenomegaly
Increased blood pressure, pulse full
Pruritis
Dyspnea
Headaches, visual disturbances
Thromboses, infarctions
Congestive heart failure
High levels of uric acid – joint pain

Diagnostic tests:
Cell counts increased, Hgb ^, Hct ^
Erythrocyte is the malignant cell
Bone marrow hypercellular
Hyperuricemia due to ^ cell destruction rate

Treatment:
Drugs/radiation to v activity of the bone marrow
Periodic phlebotomy, removal of blood

Blood clotting disorders:
Has many causes:
Thrombocytopenia due to viral infection, autoimmune rx.
Chemotherapy, radiation, cancers reduce platelets
Defective platelet associated uremia (end stage)
Ingestion of ASA, NSAIDS can interfere with platelet adhesion
Vitamin K deficiency decrease in prothrombin and fibrinogen
Liver disease reduces protein and vitamin K
Inherited diseases
Hemorrhagic fever viruses such as Ebola
Anticoagulation drugs

Hemophilia A
Defect of clotting factor VIII
X linked recessive trait

Hemophilia B (Christmas disease)
Deficit of clotting factor IX

Hemophilia C (Rosenthal’s)
Deficit of clotting factor XI
Milder

Signs and symptoms:
Bleeding from minor tissue trauma
Hemarthrosis hemorrhage into the joints
Blood in urine, feces, from bleeding in kidneys or digestive tract
What is an area that may bleed undetected?

Diagnostic tests:
Bleeding time, PT normal
PTT, APTT and coagulation prolonged
Serum levels of factors low

Treatment:
Desmopressin raise clotting factors



Von Willebrand’s
Type I, 2 and 3 with I the most common, mildest
Can be acquired – Wilm’s tumor, SLE, hypothyroidism
Manifestations are abnormal bleeding
Bleeding studies and factor VIII assessed
Desmopressin, cryoprecipitate
Teaching

Disseminated intravascular coagulation (DIC)
Clotting factors become abnormally active
In short clotting factors are used up and hemorrhage
Triggers include blood transfusion rx, cancer, infection, pregnancy complications, recent surgery, sepsis, liver disease, poisonous snake bites

Signs:
Ischemia of organs
Dyspnea
Abnormal bleeding – epistaxis, bleeding gums, petechiae, hematuria

Diagnostics:
CBC
Bleeding studies
Treatment – stop clots and stop bleeding

Idiopathic Thrombocytopenic Purpura

Leukemias
Characterized by large numbers of immature white cells in bone marrow and circulation
Leukemias are differentiated depending on the cell involved

ALL - acute lymphocytic leukemia (precursors to B lymphocytes involved)
AML – acute myelogenous leukemia (all types of blood cells)

Proliferation of leukemic cells suppresses production of other cells, crowding
This leads to anemia, thrombocytopenia
Crowding leads to bone pain
Lymphadenopathy

Etiology
Radiation, benzene, chemicals, radiation, viruses
Chromosomal disorders

Signs
Infection
Hemorrhage – thrombocytopenia
Bone pain
Weight loss, fatigue
Fever
Enlarged lymph nodes

Treatment: chemotheraphy

Lymphomas
Hodgkins lymphoma ‘hogs’ the lymph nodes

Signs:
Lymph node, nontender, in the neck and spreads to others in an orderly fashion
Later other lymph nodes
Weight loss, low grade fever, night sweats
Pruritis
Recurrent infection

Staged I-IV
Treatment:
Radiation
Chemotheraphy
Surgery

Nonhodgkins – differences
Involve B lymphocytes
Multi node involvement
Scattered, nonorganized
Less favorable prognosis







References:

Gould, B. E., & Dyer, R. M. (2011). Pathophysiology for the health professions (4 ed.). St. Louis, Missouri: Saunders Elsevier.


Story, L. (2012). Pathophysiology: A practical approach. Sudbury, MA: Jones & Bartlett Learning .


Videos:

What's inside blood
http://youtu.be/5MOn8X-tyFw

Hemachromatosis
http://youtu.be/At8WBn4-FHc

How white blood cells work
http://youtu.be/0TvTyj5FAaQ

Blood components
http://youtu.be/YMTtS2BbehI

Blood types
http://youtu.be/G_-9_CF02qI

Lymph
http://youtu.be/pTSiuTQ1nwE

Blood disorders
http://youtu.be/p14tLl8rORE

Aplastic anemia
http://youtu.be/w8-jx1dtg0U

Sickle cell
http://youtu.be/9AHFHleYwdU

Hemophilia
http://youtu.be/oExbzAJP7t4