Clin Med: hematology/oncology - Block 4 Q1

When does high hemoglobin most commmonly occur?

When body requires increased oxygen-carrying capacity

What factors would cause an increased hemoglobin level?

Smoking, COPD, CHF

Living at high altitude

Congenital heart disease in adults

Polycythemia vera

Tumors producing EPO

What meds can cause increased hemoglobin?

Testosterone

Anabolic steroids

what causes low hemoglobin- decreased production?

Nutritional deficiency

Thalassemia

Primary or secondary bone marrow disorders

CKD

What causes low hemoglobin destruction?

Hemolysis

Sickle cell/thalassemia

Enlarged spleen

Blood loss

What causes high hematocrit?

Severe dehydration

Polycythemia Vera

Lung or heart disease

severe dehydration results in _________ fluid volume. HCT percentage appears to be ________ due to the reduced plasma concentration.

reduced; elevated

What causes low hematocrit?

fewer RBC

anemia

bone marrow disorders

pregnancy

RBC cell structure

Oval biconcave disc

What is the protein in the RBC responsible for carrying oxygen throughout body?

Hemoglobin

RBC functions

Most abundant cell

Transport O2 and CO2

Where is RBC formed?

Bone marrow, and released as reticulocytes

what is a reticulocyte

an immature RBC

What is the normal life span of RBC's?

100-120 days

where does RBC breakdown occur?

Spleen

Bone marrow

Liver

What is the major breakdown product of heme?

Bilirubin

What is the function of the vascular wall physiology?

Keep lumen patent

Adequate size/flow control

Prevent leakage/hemostasis

When does endothelium become prothrombitic?

When stimulated

What are small, colorless, non-nucleated cells

Platelets

Where are platelets formed?

Bone marrow, released form megakaryocyte

What is the normal life span for platelets?

7-10 days

Where are platelets mainly eliminated?

By tissue macrophage system in spleen

How many receptors does a single platelet have?

1000

What is platelet adhesion?

Vessel wall injury exposes connective tissue molecules and platelets adhere to collagen via von Willebrand factor (vWF)

What is platelet activation?

Adhesion triggers release platelet granules which contain chemicals that induce changes in metabolism, shape, and surface proteins of platelets

What is platelet aggregation?

Additional platelets from circulation come to injury site and forms occlusive platelet thrombus

Plug is anchored and stabilized by development of fibrin mesh

platelet aggregation is a ___________-__________ interaction

"platelet-platelet interaction"

What defines Leukocytosis?

WBC count >11,000

What commonly causes Leukocytosis?

Benign disease:

Infection

Inflammation

Stress

Meds

Trauma

What is the goal for Leukocytosis?

Distinguish a primary hematologic malignancy from a secondary (reactive) Leukocytosis

What is the WBC count of leukemoid reaction?

50,000-100,000

Where does leukemoid reaction occur?

Outside the bone marrow

What is usually a relatively benign process?

Leukemoid reaction

Some non-hematologic malignancies secrete G-CSF as an

Ectopic hematopoietic growth factor

What almost always causes leukemias or myeloproliferative disorders?

Leukocytosis >100,000

What can happen as a result of Leukocytosis?

Weight loss

Bleeding/bruising

Hepatomegaly

Splenomegaly

Lymphadenopathy

Immunosuppression increase suspicion

What is the most common type of Leukocytosis?

neutrophilia

What is "left shift"?

Refers to presence of immature neutrophils

other labs to consider for Leukocytosis

Liver function

cultures

mono, EBV, CMV titer

Uric acid and lactate dehydrogenase

serologic studies

Imaging - CXR, CT, PET

treatment of leukocystosis

repeat lab (in 4-6wks)

treat underlying disorder

if persistent, hematology

evaluation of leukocytosis

peripheral smear and bone marrow biopsy

What defines leukopenia?

WBC count

What is synonymous with neutropenia?

Leukopenia

What frequently causes leukopenia?

Benign and self-limited conditions

Primary hemostasis

When platelet plug gets formed

What are important factors of leukopenia?

Acuity, severity, age, presence of infection

aspects of a through H&P w/ leukopenia

hx of recurrent infections

lymphadenopathy

hepatosplenomegaly

pallor

bleeding/bruising/petechiae

fatigue

fever, chills, nights sweats

unexplained weight loss

autoimmune symptoms

Medication history for leukopenia

Antidepressants

Antibiotics

Antimalarials

Anticonvulsants

Cardiovascular drugs

Antihistamines

Diuretics

NSAIDs

What tests are done for leukopenia?

CBC w/ differential

Vitamin B12, folate levels

Liver function tests

ESR and CRP

If patient with leukopenia is asymptomatic, when should you repeat CBC?

2-4 weeks

When should you refer patient with leukopenia to hematology?

Leukemic blasts

ANC

What are characteristics of cancer?

Abnormal cell proliferation

Lack of controlled growth and cell division leads to tumors

Ability to spread

Ability to involve any tissue in body

Evasion of natural cell death

How does cancer develop?

Spontaneously

Exposure to chemical or physical carcinogens- asbestos, radiation, tobacco, arsenic, agent orange

Genetic alterations

Exposure to viruses

What is a must for cancer diagnosis?

Tissue sampling

what is a FNA?

Fine need aspiration

Minimally invasive biopsy for cancer diagnosis

Negative results CANNOT rule out tumor

What are ways to biopsy tissue for cancer?

FNA

Core needle biopsy

Incisional biopsy

Excisional biopsy

What is preferred biopsy method for cancer diagnosis?

Excisional biopsy

How are tumors graded?

Based on cell differentiation

Well differentiated cells =

Low grade

Grow and spread slowly, better prognosis

Poorly differentiated cells=

More aggressive

Grow and spread rapidly

May need stain to determine primary tumor

Grading parameters depend on tumor ________

Type

Progression of epithelial neoplasm

Carcinoma

Hyperplasia

Increase in the number of normal cells

What is dysplasia?

Disorganized cell growth

Abnormal mitosis

What is In situ carcinoma?

Dysplasia throughout full thickness of epithelium without invasion

What is invasive carcinoma?

Tumor cells invade through basic membrane

What is metastatic carcinoma?

Spread to distant organs

What are pre-neoplastic?

Hyperplasia

Dysplasia

In situ carcinoma

Why do we use cancer staging?

To determine extent of disease, prognosis, plan treatment

Clinical cancer staging is based on what?

Physical exam and imaging (CT and PET most common, MRI)

Pathological cancer staging is based on what?

Histology

Gross intra-operative findings

What is the classification of solid tumors?

TMN

T- size of primary tumor lesion (1-4)

N- presence of lymph node involvement (0-4)

M- presence of metastatic disease (0 or 1)

Further broken down into stages I-IV

What are the goals of cancer therapy?

Cure

Control- treatment

Palliation- reduce symtpoms (surgery, chemo, radiation)

Neoajuvant therapy= shrink tumor

Adjuvant therapy- target disease after primary tx modality

Conditioning or preparation therapy- myeloablation

What teams converge for cancer treatment planning?

Medical oncology

Surgical oncology

Hematologist

Radiation oncologist

Interventional radiologist

Pharmacist

Dietician

Social work

Local treatment of cancer: surgery

Remove portion or all of tumor

May be curative

Debunking for palliation

Preservation of organ function

Staging info

Resection of draining lymph nodes, tumor size

May be preceded by XRT or systemic tx to control size or undetected metastatic disease (Neoadjuvant therapy)

What is the local treatment of cancer that uses radiation?

Radiation therapy (XRT)

What is a key characteristic of cancer cells that radiation therapy exploits?

Cancer cells' inability to repair DNA damage

What are the three factors that define radiation therapy treatment?

Total absorbed dose, number of fractions, time of treatment

Systemic treatment for cancer: chemotherapy

Smaller molecules targeting DNA during mitosis

Single agent or combo

limited by toxic effects on normal tissues

tumor cell populations are

heterogenous

Systemic treatment for cancer: hormonal therapy

Target biochemical pathways involving estrogen and androgen function

(Breast, prostate, uterus, ovarian)

Targeted therapy of systemic treatment target

Specific receptors or molecular targets on tumor cells associated with various cancers

Side effects and toxicities are different than chemo

Systemic treatment for cancer: immunotherapy

Stimulate immune system to work harder and smarter

Give immune system components, like man-made immune system proteins

Checkpoint inhibitors

Vaccine therapy

Factors that affect cancer treatment response

Pretreatment comorbidities

Heavily pretreated

Tumor type

Tumor burden- inverse relationship between the # of cells & response

Rate of tumor growth

Drug resistance

Impaired metabolism

What is a prognostic indicator related to physiologic reserve?

Performance status

What is tolerance of physiologic stress imposed by disease and treatment?

Performance status

Major side effects of chemotherapy: myelosuppresion

Reduced bone marrow function

Major side effects of chemotherapy: cytopenias

Reduction one or more of the cell lines

(WBC, RBC, platelets)

neutropenia due to chemo would cause

neutropenia fever

fungal infection

sepsis

anemia due to chemo would cause

fatigue

dyspnea

risk of cardiac events

thrombocytopenia due to chemo would cause

bleeding

epistaxis

purpura

Major side effects of chemotherapy: pancytopenia

All three cell lines reduced (WBC, RBC, and platelets)

What causes complication due to chemo?

Missing cells function

What is a management tactic for cytocpenia?

granulocyte colony stimulating factor

- filgrastim, pegfilgrastim

Abx and anti fungal prophylaxis

- fluconazole, FQ, TMP/SMX

Transfusions as needed

What is the most common side effect of chemo?

Nausea

How to manage chemotherapy related nausea?

Pre-tx prophylaxis

Other anti-emetics given scheduled or PRN throughout tx

Combo from different classes is most effective

N/V patterns of emesis with chemo: anticipatory

- conditioned response occurs prior to tx

- usually begins 2-3 cycles of therapy

- 20-60% of patients

- more common in females

NV patterns of emesis with chemo: acute

- within minutes or hours after tx

- influenced by type, dose, route of chemo

- incidence determined by emetogenicity of agent used

- risk factors: females over 50 yo, susceptibility to GI distress, nausea during pregnancy

- heavy alcohol use decreases risk

NV patterns of emesis with chemo: delayed

Occurs at least 24 hours after chemo

Metabolites thought to exert ongoing effect on CNS and GI

Highest incidence occurs with cistplatin (60-90%)

Can last up to 6 days

Risk factors: cisplastin-containing regiments, high dose chemo, anthracyclines, history of poorly controlled N/V with previous cycles

What are complications with N/V due to chemo?

Discomfort, decreased QOL

Delay of tx

Dehydration, metabolic disturbances

Anorexia, weight loss, malnutrition

Aspiration