HLSC 301 Exam 1

Atrophy

Decrease in size of the cell

Hypertrophy

Increase in size of the cell

Hyperplasia

Increase in the number of cells

Metaplasia

One cell type is replaced with another cell type

Dysplasia

Abnormal change in cellular structure, size, shape, type

Neoplasia

new growth, tumor

Liquefactive Necrosis

Tissues in the brain die, lipids and enzymes are released and start digesting the surrounding tissue. Walled-off liquefied goo.

Caseous Necrosis

In the lungs, commonly caused by TB. WBCs release enzymes to fight infection.  Pus present.  Cheese globules.

Fat Necrosis

In pancreas, breast tissue. Opaque, chalky, soupy.

Coagulative Necrosis

Due to ischemia, gelatinous, transparent.

Gangrenous Necrosis Wet and Dry

Hypoxic, due to oxygen getting cut off. Dry is coagulative, wet is liquefactive.

Gas Gangrene

Caused by a specific bacteria, clostridum

Benign Neoplasia

• Slow growing
• Well-defined Capsule
• Not invasive
• Well differentiated
• Low mitotic index
• No metastasis

Malignant Neoplasia

• Fast growing
• Not encapsulated
• Invade locally
• Poorly differentiated
• Hi mitotic index
• Able to metastasize

Inflammatory Response

• First Response to injury
• Vascular and Endothelial Reaction
• Triggered by mast cells
• Activated rapidly
• Non-specific
• No memory
• Manifestations include erythema, edema,
pain, warmth, and loss of function

Benefits of Inflammatory Response

• Prevents further infection/damage
• Checks/Balances to prevent further spread of
inflammatory response
• Interacts with adaptive immune response
• Drainage through lymphatic channels to
promote healing

Manifestations of Inflammation

• Local
– Erythema, edema, heat, pain
– Exudate
• Serous
• Purulent (suppurative)
• hemorrhagic
• Systemic
– Fever
• Pyrogens (endogenous:IL-1, exogenous)
– Leukocytosis
– Acute-phase reactants
• Chronic (can lead to granuloma formation)
– >2 weeks
– Lymphocytes and macrophages predominate

Third Line of Defense

• Adaptive (acquired) immune response
• Specific
• Develops over time
• Uses memory system
• Distinguishes self from non-self AND between
pathogens
• Can activate the innate immune response
• Includes
– T cells (cell mediated immunity)
– B cells (humoral immunity)

First Line of Defense

• Nonspecific
• No memory
• Present at birth
• Barriers
– Physical, mechanical, biochemical
• Does NOT distinguish between
pathogens

Second Line of Defense

• Responds to antigens that penetrate the
first line
– Tissue injury or Infection
• Includes:
– Inflammatory response
– Plasma Proteins
– Cellular Components

Interferons

Proteins released from
virus infected cells
• Bind to nearby
uninfected cells
• The uninfected cells
release an enzyme that
prevents viral replication
• When the virus infects
the cells they are unable
to replicate

Histamine

• Product of mast cells and basophils
• Released immediately and has instantaneous
effects
• Vasoactive
– Temporary constriction of smooth muscle and dilation
of post capillary venules
– Increased vascular permeability
• Anti-histamines block histamine from binding its
target receptors
– Benadryl, Zantac

Hypersensitivity

Inflated immune response to a foreign
substance

Type 1 Hypersensitivity

Immediate response
– Local or systemic
– Allergen activate IgE which bind to mast cells
– At next exposure, the antigen binds with the surface
IgE, releasing mediators and triggering the
complement system
– Examples:
• hay fever, food allergies, and anaphylaxis
– Treatment:
• epinephrine, antihistamines, corticosteroids, and desensitizing
injections

Type II Hypersensitivity

IgG or IgM type antibodies that react to foreign
tissue of cells
– Lysis of blood cells occurs because of the activation
of the complement
– Usually immediate responses
– Examples:
• Blood transfusion reaction and erythroblastosis fetalis
– Treatment:
• Ensuring blood compatibility, administering medication to prevent
maternal antibody development

Type III Hypersensitivity

Circulating antigen-antibody complexes accumulate
and are deposited in the tissue
– Usually immediate response
– Triggers the complement system and inflammation
– Example
• Autoimmune conditions (e.g. systemic lupus erythematosus)
– Treatment:
• is disease specific

Type IV Hypersensitivity

Cell-mediated rather than antibody-mediated
involving the T cells
– Delayed response
– Examples:
• tuberculin skin testing, transplant reactions, and contact dermatitis
– Treatment:
• is disease specific

Autoimmune Disorders

Immune system loses the ability to recognize self
• Defenses are directed against host
• Can affect any tissue
• Mechanism of triggers not clear

Systemic Lupus Erythematosus (SLE

Chronic inflammatory condition
• Remission and exacerbations
– stressors tend to trigger
• May affect connective tissue of any body organ
• Disease progression varies from mild to severe
• More common in females (20-40 y.o.)
• Blacks most common
• Cause is unclear, but thought that B cells are activated to
produce autoantibodies to self antigens (nucleic acids, RBC’s, coag
proteins, phospholipids, lymphocytes, platelets) that combine to form
circulating immune complexes, which attack the body’s own
tissues
– Type III reaction
• Type II reaction
– Complement lysis due to Ab binding

Diagnostic Criteria for Lupus Erythematosus

(four or more of the following)
1. Malar (butterfly) rash over the cheeks
2. Discoid rash patchy redness, scaling & possible
scarring
3. Photosensitivity
4. Mucous membrane ulcers
5. Arthritis (@ least 2 peripheral joints)
6. Serositis (Pleuritis or pericarditis)
7. Renal disorders
8. Neurologic disorders
9. Hematologic disorders
10. Immunologic disorders
11. Antinuclear antibody

Diagnosis of Systemic Lupus Erythematosus

H&P using 11 criteria, X-rays, Labs: routine, Ab presence,
elevated sedimentation rate (ESR), C-reactive protein (CRP),
blood clotting times, Urine tests, Tissue Biopsies

Treatment of Systemic Lupus Erythematosus

No Cure
• Control symptoms & prevent further damage
– Stress management and health promotion behaviors
– Pharmacological
• NSAIDs, antimalarials, corticosteroids, and immunosuppressants,
anticoagulants, monoclonal Ab’s, corticotropin injection
– Plasmapheresis – if not responding and have hemolytic anemia
– Autologous stem cell transplantation

Immunodeficiency

Diminished or absent immune response
• Renders the person susceptible to disease
normally prevented

Primary Immunodeficiency

B cells
– Bruton agammaglobulinemia
– Selective IgA deficiency
• T cells
– DiGeorge syndrome
• Combined immune deficiency
– SCIDs (severe combined immunodeficiency)
• Complement Deficiency
– C3 deficiency
• Phagocyte Deficiency
– Severe congenital neutropenia
– Chronic granulomatous disease

Secondary Immune Deficiencies

Common
• Normal physiologic condition, stress, dietary
deficiencies, malignancies, trauma, iatrogenic
(medical treatments), other diseases:
– Diabetes
– Alcoholic cirrhosis
– Sickle cell disease
– SLE
– Chromosome abnormalities (i.e. trisomy 21)
– HIV

HIV/AIDS Treatment

• No cure
• Combination therapy works best
– Highly Active Antiretroviral Therapy
• May have to change regimen d/t viral adaptation
• Other meds and vaccines will be used to prevent
opportunistic infections as needed
• Vaccinations
• Transmission prevention

Human Immunodeficiency Virus

Retrovirus that infects CD4 & macrophages upon entry
• Overtime reduces the # of CD4 cells

Physiological Response to Stress

Fight-or-flight response
• activation of the sympathetic and the endocrine
systems
• Includes:
• Increased:
• heart rate, respirations, diaphoresis, blood flow to muscles,
muscle strength, mental alertness, increased fat and protein
mobilization, glucose availability
• decreased inflammation

Stages of General Adaptation Syndrome

1. Alarm
– Initial reaction
– Sympathetic nervous system
2. Resistance
– Adaptation
– Limit stressor
3. Exhaustion
– Adaptation failing
– Disease develops

Local Adaptation Syndrome

• Local version of the general adaptation
syndrome
• Body’s attempt to minimize the damage of the
stress to a small location

Anemia

not disease state but group of
disorders with decreased oxygen carrying
capacity (RBC and Hgb)

Iron-Deficiency Anemia

Very common
• Iron is necessary for hemoglobin production
• Causes:
– decreased iron consumption or iron absorption
– increased bleeding

Diagnosis of Iron-Deficiency Anemia

complete blood count (low hemoglobin, hematocrit, MCV, and
MCHC), serum ferritin, serum iron, and transferrin saturation

Treatment of Iron-Deficiency Anemia

Identify and treat cause, increase dietary intake, and iron
supplements

Megaloblastic Anemia

Folate and Vit B12 are required for DNA synthesis
– Leads to decreased maturation & cell division
– Become anemic – large red cells
• Decreased intake from diet
– Stores in body vary (folate few months, B12 few years)
• In Vit B12 deficiency may be caused by a lack of intrinsic
factor (binds to Vit B12 and enables the ileum to absorb)

Pernicious Anemia

Autoimmune:
– anti-IF or anti-parietal cell antibodies

Manifestations of Pernicious Anemia

bleeding gums, diarrhea, impaired smell, loss of deep
tendon reflexes, anorexia, personality or memory changes,
positive Babinski’s sign, stomatitis, paresthesia, and
unsteady gait

Diagnosis of Pernicious Anemia

CBC, serum B12 levels, Antibody presence, gastric
analysis, folate
– (Schilling’s test, bone marrow biopsy)

Treatment for Pernicious Anemia

Treatment: injectable B12
– Bypass GI tract absorption

Aplastic Anemia

Pancytopenia:
– Bone marrow depression of all blood cells – damage to PSC

Causes of Aplastic Anemia

insidious, other anemias, autoimmune, medications, medical
treatments, viruses, cancer, and genetic

Manifestations of Aplastic Anemia

Anemia (e.g., weakness, pallor, dyspnea)
– Leukocytopenia (e.g., recurrent infections)
– Thrombocytopenia (e.g., bleeding)

Diagnosis of Aplastic Anemia

complete blood count and bone marrow biopsy

Treatment of Aplastic Anemia

identify and manage underlying cause, oxygen therapy, infection
control & treatment, bleeding precautions, blood transfusions, and
bone marrow transplants

Hemolytic Anemia

Excessive erythrocyte destruction
• Reticulocyte production index is high

Causes of Hemolytic Anemia

idiopathic, autoimmune, genetics, infections, blood
transfusion reactions, and blood incompatibility in the
neonate

Sickle Cell Anemia

Autosomal recessive inheritance
– Abnormal Hemoglobin “S” (one AA substitution)
– Trait is both Hgb S and Hgb A (normal)
– Disease/Anemia is homozygous SS
• Hgb S causes the RBC to become abnormally
shaped/sickled under low oxygen conditions
– Abnormal RBC’s carry less oxygen and clog vessels
– Causing tissue hypoxia and ischemia

Manifestations of Sickle Cell Anemia

Appear as early as 6 months of age
– Sickle cell crisis
• Painful episodes that can last for hours to days
• Pain is caused by tissue ischemia and necrosis
• Triggered by dehydration, stress, infection, high altitudes, and
fever

Include: abdominal pain, bone pain, dyspnea, delayed
growth and development, fatigue, fever, jaundice, pallor,
tachycardia, skin ulcers, angina, excessive thirst,
frequent urination, priapism, and vision impairment

Diagnosis of SIckle Cell Anemia

CBC, sickle solubility (screen), hemoglobin electrophoresis,
CMP

Treatment of Sickle Cell Anemia

No cure, palliative
• EXCEPTION: Stem cell or bone marrow transplant
• Gene therapy under research
– Avoid triggers
– Medications (e.g., Hydrea [hydroxyurea])
– Other strategies: oxygen therapy, hydration, pain
management, infection control, vaccinations, blood
transfusions, bone marrow transplants, genetic counseling

Polycythemia Vera

Chronic clonal overproduction of erythrocytes
– Outside of regulatory mechanism
• Low erythropoietin

Manifestations of Polycythemia Vera

Plethoric skin, pruritus with heat or water exposure,
high blood pressure, tachycardia, dyspnea,
headaches, visual abnormalities, psychological
changes (mania or depression)

Diagnosis of Polycythemia Vera

CBC, bone marrow biopsy, Iron studies, and uric acid levels

Treatment of Polycythemia Vera

Phlebotomy, chemotherapy, radiation, and managing clotting
disorders

Neutropenia

Low levels of Neutrophils

Manifestations of Neutropenia

Depends on severity
and cause
– Infections and
ulcerations especially of
the respiratory tract,
skin, vagina, and
gastrointestinal tract
– Signs and symptoms of
infection
• fever, malaise, and chills

Diagnosis of Neutropenia

CBC and differential (neutrophil level) and bone
marrow biopsy

Treatment of Neutropenia

Antibiotic therapy and hematopoietic growth
factors

Infectious Mononucleosis

“Kissing Disease”-oral transmission
• Self-limiting
• Most prevalent in adolescents and young adults
• Caused by Epstein-Barr virus in the herpes family
– EBV infects the B cells by killing the cell or being incorporated into
its genome
– Those B cells incorporated with EBV produce heterophile
antibodies

Manifestations of Infectious Mononucleosis

Insidious onset
– Incubation = 4 to 8 weeks
– Initially see anorexia, malaise, and chills
– Manifestations intensify to include leukocytosis,
fever, chills, sore throat, and lymphadenopathy
– Acute illness usually last 2-3 weeks; may not fully
recover for 2-3 months

Treatment for Infectious Mononucleosis

symptomatic and supportive

Leukemia

Cancer of the leukocytes

Acute Lymphoblastic Leukemia

Affects primarily children
– Responds well to therapy
– Good prognosis

Acute Myeloid Leukemia

Affects primarily adults
– Responds fairly well to treatment
– Prognosis somewhat worse than that of
acute lymphoblastic leukemia

Chronic Lymphoid Leukemia

Affects primarily adults (usually >60
y.o.)
– Responds poorly to therapy, yet
most patients live many years after
diagnosis

Chronic Myeloid Leukemia

Affects primarily adults
– Responds poorly to
chemotherapy, but the prognosis
is improved with allogenic bone
marrow transplant

Manifestations of Leukemia

leukopenia, leukocytosis, anemia,
thrombocytopenia, lymphadenopathy, joint swelling,
bone pain, weight loss, anorexia, hepatomegaly,
splenomegaly, and central nervous system
dysfunction

Diagnosis of Leukemia

H&P , CBC with a peripheral blood smear, and
bone marrow biopsy

Treatment of Leukemia

chemotherapy and bone marrow transplant

Multiple Myeloma

B-cell cancer (plasma cell proliferation)
• Cells aggregate in the bone marrow and
skeleton
– Often do not see plasma cells in circulation
– Crowds the normal cells
– Secrete excessive light chain immunoglobulins
(Bence-Jones proteins) that are excreted in the
urine
• Bone destruction leads to hypercalcemia
and pathologic fractures
• Often well advanced upon diagnosis
– Insidious onset

Manifestations of Multiple Myeloma

Anemia, thrombocytopenia, leukopenia,
decreased bone density, bone pain,
hypercalcemia, and renal impairment

Diagnosis of Multiple Myeloma

CBC, serum and urine protein levels, protein
electrophoresis, IgG/IgM & IgA levels,
calcium levels, renal function tests, biopsy, X-
rays, CT-scan and MRI

Lymphomas

Cancers originate in lymphatic system
– Affects WBC’s as well
• Most common hematologic cancer in the
US

Hodgkin Lymphoma

Solid tumors with the presence
of Reed-Sternberg cells
• Typically originate in the lymph
nodes of the upper body
• Several subtypes
• Amenable to cure

Manifestations of Hodgkin Lymphoma

painless enlarged lymph nodes,
weight loss, fever, night sweats,
pruritus, coughing, difficulty
breathing, chest pain, recurrent

Diagnosis of Hodgkin Lymphoma

Physical examination, presence of Reed-Sternberg cells in a lymph node
biopsy, CBC, chest X-rays, CT-scan, MRI, PET scan, and bone marrow
biopsy

Treatment of Hodgkin Lymphoma

chemotherapy, radiation, and surgery

Non-Hodgkin Lymphoma

More common
• Poor prognosis
• Many different types
• Similar to Hodgkin
manifestations, staging, and
treatment
• Different in the spread and
diagnosis
• Can originate in the T or B cells
• No Reed-Sternberg cells

Immune Thrombocytopenia Purpura

Quantitative problem resulting in hypo-coagulation
from destruction of platelet

Manifestations of Immune Thrombocytopenia Purpura

bleeding or indications of bleeding
• bruising, petechia, purpura

Diagnosis of Immune Thrombocytopenia Purpura

H&P, CBC (platelet levels < 20,000) and bleeding studies

Treatment of Immune Thrombocytopenia Purpura

Remove underlying cause
• Glucocorticoids, immunoglobulins (IVIg)

Causes of Immune Thrombocytopenia Purpura

Idiopathic, autoimmune diseases, immunodeficiency
disorders, and viral infections

Hemophilia A

X-linked recessive bleeding
disorder
• Deficiency or abnormality of
clotting factor VIII
• Varies in severity

Manifestations of Hemophilia A

bleeding or indications of bleeding

Diagnosis of Hemophilia A

lotting studies (PT,
PTT)
– serum factor VIII
levels

Treatment of Hemophilia A

lotting factor
transfusions
– recombinant clotting
factors
– desmopressin
(DDAVP)
– bleeding
precautions

Von Willebrand Disease

Most common hereditary bleeding
disorder
– Autosomal dominant or recessive
(chromosome 12)
– Missing or defective von Willebrand factor
(VWF)
• Decreased platelet adhesion and
aggregation
– Affects primary and secondary hemostasis
– 4 types

Diagnosis of Von Willebrand Disease

H & P, bleeding studies, VWF antigen levels (can fluctuate
with stress, estrogen levels, exercise), and factor VIII levels

Treatment of Von Willebrand Disease

Mild cases usually do not require treatment
– Desmopressin (DDAVP)
• Stimulates release of VWF
• Injectable or nasal spray
– Cryoprecipitate infusions
– Recombinant VWF medication (new)
– Bleeding precautions
– Measures to control bleeding