Applied Pathophysiology: Altered Cell Growth

Applied Pathophysiology: A Conceptual Approach to the Mechanisms of Disease

• The lecture material is adapted from 2022 Wolters Kluwer Health, Lippincott Williams & Wilkins.
• The book is titled "Applied Pathophysiology: A Conceptual Approach to the Mechanisms of Disease".
• The fourth edition of the book is mentioned.
• The lecture series is MPAT12001 Medical Pathophysiology Lecture Series.
• The lecture is given by Dr. Romeo Batacan Jr.

Altered Cell Proliferation and Differentiation

• Normal cell proliferation and differentiation are controlled by genes.
• Neoplastic cells ignore genetic controls, leading to:
  • Autonomy: Unregulated cellular proliferation
  • Anaplasia: Loss of cellular differentiation, resulting in loss of cell function.
  • The degree of anaplasia correlates with the aggressiveness or malignancy of the tumor.

Altered Cell Proliferation and Differentiation: Further details

• Loss of cell-to-cell communication leads to unrestricted tumor growth.
• Increased energy expenditure by tumor cells deprives unaffected cells of nutrients.
• Increased motility and loss of cohesion/adhesion promote tumor movement to other locations.
• Rapid angiogenesis provides extensive blood flow to the tumor.
• Substance secretion alters metabolism and degrades surrounding unaffected cells.
• Foreign antigens presented on the cancer cell surface trigger an immune response.

Benign versus Malignant Tumors

• Benign tumors remain localized and resemble the tissue of origin.

• While benign tumors overproliferate, they are differentiated. They can be dangerous if they impact nearby structures or obstruct vital functions.

• Malignant tumors are invasive, destructive, and rapidly proliferate. They promote ischemia and necrosis.

• Cancer is malignant neoplasm.

• Benign tumors are characterized by:

  • Near normal cell structure
  • Orderly tissue structure
  • Growth rate usually above normal
  • Invasive growth is uncommon
  • Metastasis is absent
  • Typical capsule
  • Minimal anaplasia
  • Good prognosis

• Malignant tumors are characterized by:

  • Abnormal shapes and larger cells/nucleolus
  • Disordered/irregular tissue structure
  • Rapid growth rate
  • Typical invasive growth
  • Typical metastasis
  • Rare/incomplete capsule
  • Typical anaplasia
  • Poor prognosis

Cancer Spread

• Local spread: proliferation within the original tissue of origin.
• Direct extension: tumor cells move into adjacent tissues and organs.
• Seeding: direct extension, with tumor cell implantation in body cavities.
• Metastasis: spread to distant sites
  • Main mechanism is metastasis via embolism.
  • Metastasis can also occur via body cavities.
  • Iatrogenic metastasis is due to medical intervention.
  • Neoplasms tend to have predictable tropism (a preferred location) due to environmental suitability, adherence molecule compatibility, and location relative to blood flow paths.

Cancer Classification: TNM Staging

• This system classifies the extent and spread of the neoplasm.
• Usually for solid tumors.
• Includes tumor size, lymph node involvement, and location of metastasis.
• Higher numbers indicate more extensive tumor size and involvement.

Cancer Classifications: Grading

• Grading refers to the degree of anaplasia (loss of cell differentiation) in the tumor.
• Staging (numeric) indicates a higher number indicates a greater tumor size and invasion (local to distant).
• Grade I tumors are well-differentiated, resembling the original tissue.
• Grade IV tumors are highly undifferentiated.

Cancer Prognosis

• Many factors affect cancer outcome and course, including type of cancer, location, stage, patient age, and overall health.
• Some factors that influence prognosis are the response to treatment, a 5-year survival rate (rate if people are living after 5 years with cancer, and cancer-free), remission, and living with cancer.

Clinical Manifestations of Cancer

• Early general symptoms can be vague.
• Major manifestations are related to:
  • Systemic inflammatory and immune responses.
  • Increased metabolic rate induced by tumors.
  • Systemic effects of neoplasm, including paraneoplastic syndromes.
  • Local effects of tumor encroachment.
  • Effects on blood.

Paraneoplastic Syndromes

• These are hormonal, neurologic, hematologic, or chemical disturbances unrelated to the primary tumor's invasion.
• They cause a wide range of clinical manifestations and are common characteristics of neoplasms.
• These neoplasms have the ability to produce and secrete ectopic (or inappropriate) hormones.
• These neoplasm mimic hormone functions, which leads to clinical manifestations.
• These neoplasms may also disturb neurologic function.

Diagnostic Tests

• History taking and physical examination
• Imaging studies (X-rays, endoscopy, CT, MRI, ultrasound)
• Direct visualization of masses.
• Biopsy and cytology studies
• Tumor markers: used to observe cancer course, screen for cancer risk, and aid in diagnosis. (Most cancer is only diagnosed by microscopic tumor cell examination)

Cancer Treatment

• Treatment strategies include:
  • Completely eradicating neoplasms.
  • Controlling continued growth.
  • Reducing symptoms without curing the cancer using surgery, chemo, radiation, hormones, or immunotherapy.
• Treatment of cancer frequently involves comprehensive care including psychsocial aspects of treatment and care.

Adverse Effects of Cancer Treatment

• Adverse effects can include surgery-related issues, chemotherapy side effects, radiation-related side effects, biologic response modifier side effects, and/or hormonal side effects.

Cancer Prevention

• Awareness of known carcinogens (the "hateful 13").
• Avoiding known risk factors can sometimes help prevent some types of cancer
• Awareness of factors that increase risk .

Cancer Screening

• Regular screening can lead to early detection, which reduces cancer incidence.
  • Breast cancer (mammography)
  • Cervical cancer (Pap smear)
  • Colorectal cancer (rectal examination, fecal occult blood test, colonoscopy)
  • Prostate cancer (PSA testing, transrectal ultrasonography)
  • Melanoma (self-examination)

Explore the concepts of altered cell proliferation and differentiation as introduced in the fourth edition of 'Applied Pathophysiology: A Conceptual Approach to the Mechanisms of Disease.' This quiz focuses on how neoplastic cells bypass genetic controls, leading to autonomy and anaplasia, and the implications on tumor aggressiveness.