MENNONITE COLLEGE OF NURSING

Pathophysiologic Bases of Health Deviation 437

Altered Cellular/Tissue Biology

A. Cellular adaptation

1. Atrophy

2. Hypertrophy

3. Hyperplasia

4. Dysplasia

5. Metaplasia

B. Cellular injury

1. Hypoxic

2. Chemical

3. Infectious

4. Immunologic

5. Genetic

6. Nutritional

7. Physical

C. Manifestations of cellular injury/death

1. Cellular

2. Systemic

D. Cellular Proliferation: Cancer/Alterations in cell differentiation: Neoplasia

1. Categories of cells

2. Benign vs. malignant neoplasms

3. Principles of chemotherapy

4. Invasions/metastases

5. Diagnostic methods

6. Grading and staging of tumors

Altered Cellular/Tissue Biology

Cellular adaptation

Why do cells adapt?

--to escape and protect themselves from injury

** An adapted cell is neither normal nor injured--its condition lies somewhere between these two states.

The most significant adaptive changes in cells include:

atrophy (decrease in cell size)

hypertrophy (increase in cell size)

hyperplasia (increase in cell number)

metaplasia (reversible replacement of one mature cell type by another, less mature cell type)

* Dysplasia (deranged cellular growth) is not considered a true cellular adaptation, but rather an atypical hyperplasia.

Atrophy

· decrease or shrinkage in cell size

· can affect any organ; most common in skeletal muscle, the heart, secondary sex organs, and the brain

· causes: decreases in work load, use, blood supply, nutrition,, hormonal stimulation, and nervous stimulation

· Cellular changes: less endoplasmic reticulum and fewer mitochondria and myofilaments (needed for muscle contraction)

Hypertrophy

· increase in the size of cells and thus, size of organ

· especially responsive to enlargement: heart, kidneys

· Adaptive hypertrophy: muscle thickens when resistance increases

- Left ventricular hypertrophy = increased diastolic pressure requires increased muscle --> body adapts. But the myocardial circulation and oxygen delivery don’t increase -->

- May progress to pathophysiological state

· Compensatory hypertrophy: doesn’t progress to pathophysiological state; Example: nephrectomy patient. Remaining kidney hypertrophies/compensates. Cells increase and function increases.

· Cellular changes: increased accumulation of protein in the cellular components (plasma membrane, endoplasmic reticulum, myofilaments, and mitochondria

· Cause uncertain: may be increase in rate of protein synthesis or decrease in protein degradation, or both

Hyperplasia

· increase in the number of cells resulting from an increased rate of cellular division

· Two types of normal, or physiologic, hyperplasia:

compensatory hyperplasia: an adaptive mechanism that enable certain organs to regenerate (removal of part of the liver leads to hyperplasia of the remaining liver cells (hepatocytes) to compensate for the loss.

Occurs in: epidermal and intestinal epithelia, hepatocytes, bone marrow cells, and fibroblasts

Some noted in bone, cartilage, and smooth muscle cells

Does not occur in nerve, skeletal muscle, and myocardial cells and the lens cells of the eye

hormonal hyperplasia: occurs mainly in estrogen-dependent organs, such as the uterus and breast (After ovulation, estrogen stimulates the endometrium to grow and thicken for reception of the fertilized egg. If fertilized --> uterus enlarges)

· Pathologic hyperplasia: the abnormal proliferation of normal cells, usually in response to excessive hormonal stimulation (endometriosis)

· Note: Pathologic endometrial hyperplasia, which caues excessive menstrual bleeding, is under the influence of regular growth-inhibition controls. If these controls fail, hyperplastic endometrial cells can undergo malignant transformation.

Dysplasia = abnormal changes in the size, shape, and organization (appearance) of mature cells

· not a true “adaptive process”, but is related to hyperplasia and thus called atypical hyperplasia

· occurs in epithelial tissue of the cervix and respiratory tract

· strongly associated with common neoplastic growths and often found adjacent to cancerous cells

· precancerous: * Strong predictor of breast cancer development

· if inciting stimulus is removed, dysplastic changes are often reversible

Metaplasia = the reversible replacement of one mature cell type by another, sometimes less differentiated type; in response to chronic irritation/inflammation

· NOT precancerous

· Example: replacement of normal columnar ciliated epithelial cells of the bronchial lining by stratified squamous epithelial cells. The new cells do not secrete mucus or have cilia, causing losss of a vital protective mechanism.

· Converted/newly created cells are more able to tolerate noxious stimuli

· Reversible if the inducing stimulus (such as cigarette smoking) is removed

· With prolonged exposure to the inducing stimulus, however, cancerous transformation can occur

Cellular injury - occurs when the need to adapt is overwhelmed

Free radical injury - when enter cells, cause intracellular destruction (unmatched electron)

· radiation

· tobacco smoke

· pesticides

· hyperoxic environments (oxygen toxicity in sustained prolonged O2 therapy)

· chemical poisons (those with free radical)

1. Hypoxic (diabetes indirectly: atherosclerosis --> decreased circulation --> hypoxia)

2. Chemical

3. Infectious (toxins into cell; bacteria, virus, parasites: alter cellular permeability and cellular metabolism

4. Immunologic

5. Genetic

6. Nutritional (excesses and deficiencies)

7. Physical (extremes of cold and hot, electricity)

Manifestations of cellular injury/death (cellular dissolution = necrosis)

Cellular:

· accumulations of water due to failure of transport mechanisms (sign of many types of cellular injury)

· accumulations of organic substances (lipids, carbohydrates, glycogen, proteins, pigments, hemosiderin (storage of iron), bilirubin) due to either cellular uptake of the substance exceeds the cell’s capacity to catabolize (digest) or use it OR cellular anabolism (synthesis) of the substance exceeds the cell’s capacity to use or secrete it.

· Accumulation of calcium salts (dystorphic calcification) is always a sign of pathologic change because it only occurs in injury or dead cells. Metastatic calcification, however, can occur in uninjured cells in individuals with hypercalcemia.

· Disturbances in urate metabolism can result in hyperuricemia and deposition of sodium urate crystals in tissue (gout).

Systemic:

· fever

· fatigue and malaise

· loss of well-being

· altered appetite

· leukocytosis

· increased heart rate

· pain

· presence of cellular enzymes in extracellular fluid (LDH, CK, AST/SGOT, ALT/SGPT, ALP, amylase, aldolase)

Cellular proliferation: Cancer

Cellular proliferation: process by which cells divide

· “cell sex”; have offspring

Cellular differentiation: process whereby cells are transformed into different and more specialized cells

· takes place as they divide and bear offspring

· cellular maturation

Categories of cells

1. Stable cells:

· cannot reproduce

· Generally: the higher specialized the cellular activity, the less the cells are able to reproduce...Examples of stable cells: neural cells (higherly differentiated) and cardiac cells

2. Progenator cells:

· less differentiated

· divide throughout life

· Examples: blood cells, skin cells, liver cells

3. Stem cells:

· Undifferentiated

· bone marrow (RBCs, WBCs, platelets produced)

· with decrease in certain type of cell, stem cells differentiate to needed type

· Bone marrow transplants: new bone marrow with disease-free stem cells --> reestablish normal differentiation patterns

Tumor:

· suffix = “-oma” = tumor (benign)

- attach parenchymal substance to suffix to get name (osteoma = benign tumor of bone)

- glial tissue (white matter/support tissue of brain) “glioma”

· suffix = “-coma” = malignant tumor

- osteosarcoma = malignant tumor of bone

Characteristics of Benign Neoplasms

· well encapsulated (usually); growth occurs evenly, usually well-defined border

· cells more cohensive than those of malignant neoplasms (“stick together”)

· slow growth rate; usually limited to one area

· blood supply is less profuse than that of a malignant neoplasm

· won’t infiltrate other tissues

· well-differentiated cells; look much like parent cell

· does not metastasize

· primarily localized S/S depending on location (non-systemic); produce their effects from obstruction, pressure, and secretion

· usually not fatal, but can have a benign tumor that is dangerous due to location (brain, spinal cord)

Characteristics of Malignant Neoplasms

· very poorly differentiated

· infiltrate and destroy surrounding tissues ratehr than pushing them aside

· rate of growth is variable; greater blood supply than normal tissue

· cells are not cohesive; metastasizes to other organs (route/pathway = blood system, lymph system)

· systemic S/S: weight loss (cancer cells use nutrients; hypermetabolic state); fatigue, pain (not encapsulated, release of chemical mediators, so tissue becomes ischemic)

· “hogs” blood supply, so able to get nutrients and grow; eventually slows as outgrows its blood supply

· S/S vary with location/expandibility of cavity

Principles of chemotherapy:

· Cancer chemotherapy is most effective against small tumors because they usually have an efficient blood supply and therefore drug delivery is increased. Also, small tumors generally have a higher percentage of proliferating cells so that a higher cell-kill factor is possible.

· The removal of large, localized tumors by surgery reduces the tumor cell burdena dn thus contributes to the success of adjuvant chemotherapy. The major use of adjuvant chemotherapy is to help eradicate the micrometastases of cancer after surgery or radiation.

· In general, combination cancer chemotherapeutic agents have a higher cancer cell-kill than treatment with a single drug agent. (for example: Mustargen 20% response rate, Oncovin < 10%, procarbazine <10%, and prednisone < 5%. against Hodgkin’s disease. However, when all 4 drugs are used (MOPP) in combination, the complete response rate is 80%0.

Invasions/Metastases

· Direct invasion or extension: localized metastases; crab-like extensions; makes surgical removal very difficult

· Seeding: tumors erode into another body cavity (ovarian cancer seeds into peritoneum; lung seeds into pleural space)

· Metastasis: the spread of cancer cells from a primary site of origin to a distant site

The process of metastasis involves a series of sequential steps:

1. extension or local invasion of the surrounding tissue

2. penetration into blood vessels or lymphatics, or both, and into body cavities

3. release into the lymph or blood circulation

4. transport to a secondary site

5. arrest, adherence, and proliferation of cells at the secondary site

S/S of metastasis:

By lymph channels: starts with slightly enlarged lymph node (tumor draining into lymph nodes) --> dumps into venous system

By blood: liver metastases - high blood flow (500 cc of blood in liver at all times)

All blood from GI, pancreas, lower body --> portal artery --> detox --> hepatic vein

Cancer in situ

- malignant, but caught before metastasized or spread

- 100% curable

Clinical manifestations of cancer:

· cachexia (wasting)

· pain

· weakness

· coagulation abnormalities and hormonal abnormalities (many tumors secrete hormones or coagulation factors)

· with bone involvement: hypercalcemia

· effusions

Diagnostic methods:

· exfoliative cytology (Pap smear)

· biopsy (needle, bronchoscopy, endoscopy, cytoscopy)

· tumor cell markers (substances produced by cancer cells that are found on tumor plasma membranes or in the blood, spinal fluid, or urine. Include hormones, enzymes, genes, antigens, and antibodies.) Can be used in 3 ways:

1. to screen and identify individuals at high risk for cancer

2. to help diagnose the specific type of tumor in individuals with clinical manifestations related to cancer

3. to follow the clinical course of cancer

Example: PSA (prostate specific antigen)

Grading and Staging of Tumors:

grading: according to the histologic or cellular characteristics of the tumor

More poorly differentiated, more malignant:

Grade I: well differentiated

Grade II: moderately diff.

Grade III: poorly to very poorly diff.

Grade IV: very poorly differentiated

staging: according to the clinical spread of the disease (TNM system)

T stands for the extent of the primary tumor

N refers to the involvement of the regional lymph nodes

M describes the extent of the metastatic involvement

The higher the number in each category, the worse the prognosis.

Pathophysiologic Bases of Health Deviation 437

Altered Cellular/Tissue Biology

Fill in the following chart using the letters of the listed descriptions.

Concept Definition Example

Atrophy _____ _____

Hypertrophy _____ _____

Hyperplasia _____ _____

Metaplasia _____ _____

Dysplasia _____ _____

Descriptions

A. increased size of remaining kidney after nephrectomy

B. deranged/atypical cellular growth

C. stratified squamous epithelial cells of bronchial lining

D. skeletal muscles of fractured leg

E. atypical cells in cervix

F. shrinkage in cell size

G. increased number of cells

H. increase in organ size

I. replacement of one mature cell type by another

J. thickening of endometrium after ovulation

For each of the following, circle the end of the continuum indicating the more malignant type of situation:

Cell differentiation:

Poorly differentiated <----------------------------------> Well-differentiated

Grading:

Grade I <-------------------------------------------------------------> Grade IV

Staging:

T0,N0,M0 <---------------------------------------------------------> T3,N2,M1