Introduction to Pathology By Gandi Li Department of

Introduction to Pathology By Gandi Li Department of Pathology West China Medical School

Where there is love of medicine, there is love of humankind. -- Hippocrates (460 -377 BC)

The most common diseases in developing countries Infectious diseases (viral hepatitis, tuberculosis, bacterial pneumonia, bacterial diarrheas, AIDS, et al) Atherosclerosis and hypertension Cancer Emphysema and chronic bronchitis What happens in Nepal?

Disease could reasonably be defined as internal problems that cause pain and/or interfere with a person's ability to work, play, and/or love others. Pathology is the scientific study of disease. Now more and more people know many diseases are lifestyle-related. Pathology is a bridge between medicine and basic sciences for medical students. Pathology is also one of the most important methods to diagnose disease in clinical practice.

Pathology involves Etiology (causes of diseases, Why? ) Pathogenesis (mechanisms, How? ) Pathological changes (lesions, What? ) l l Morphological changes (anatomical pathology) Functional changes (pathophysiology) Clinical manifestations (signs and symptoms) Sequelae (healing, complications, death)

Branchs of pathology General pathology l l l cell injury tissue repair hemodynamic disorders inflammation tumor Systemic pathology l l l l the blood vessels and the heart the respiratory system the digestive system the urinary system the male and female genital system the nervous system the endocrine system

GOAL of PATHOLOGY for MEDICAL STUDENTS Be able to understand analyze the relationship between pathologic changes and clinical manifestations. Be able to take a clinical history and order tests logically. Be able to develop a correct diagnosis. Be able to communicate with professionals and patients. Does become a physician or a pathologist? Physician or surgeon mostly.

What does a PATHOLOGIST do? SURGICAL PATHOLOGY Interpret biopsies (e. g. , skin, breast, gastrointestinal tract) l Evaluate surgical resection specimens (e. g. , colectomy, nephrectomy, mastectomy) l Frozen sections (intra-operational rapid diagnosis) l

What does a PATHOLOGIST do? CYTOPATHOLOGY (e. g. , Pap smears, FNA Fine Needle Aspiration) CLINICAL PATHOLOGY l l Hematology (Peripheral blood smear, bone marrow, coagulation disorders). Chemistry (Blood, urine, cerebrospinal fluid, effusions). Microbiology. Blood bank. AUTOPSY PATHOLOGY l Final diagnosis, forensic pathology--criminal investigation

How to study pathology? Background: Basic medical sciences (anatomy, histology, physiology, biochemistry, immunology, microbiology, parasitology, et al) Medical terms (e. g. hyperplasia, et al) Clinical knowledge (physical examination, laboratory tests, X-ray, CT, et al)

How to study pathology? The key for studying pathology: Functional Changes (Pathophysiology) Characteristic morphologic lesions (lesions) Clinical manifestations Pathogenesis Etiology

How to study pathology? Approach to good result: Lectures and textbooks Laboratory practice: gross specimen and glass slides Clinicopathologic conference (CPC) Autopsy demonstration (real or video) Recommend internet web sites: http: //wwwmedlib. med. utah. edu/web. Path/webpath. html

Observation of gross specimen: a hypertrophic heart (left) and a normal heart (right)

Gross observation of a nutmeg liver and mircoscopic changes

Cancer cells in ascites of a patient with gastric carcinoma

Summary of introduction The terms l l disease lesion pathology pathologist general pathology surgical pathology The roles of pathology in medical education and clinical practice How to study pathology l l Uebung machts Master. (Practice trains master) Arbeit machts Spass! (Work brings happy!)

A famous painting about autopsy by Rhunbrant in 18 century

“As is our pathology, so is our medicine” “Ask not what disease the patient has, but rather what patient the disease has. ” Sir William Osler (Canadian Physician)

Cell Injury, Adaptation and Death Overview of cell injury Causes of cell injury Mechanisms of cell injury Cellular adaptation to injury Reversible and irreversible cell injury Programmed cell death---- apoptosis Cellular aging

Overview of cell injury Homeostasis requires functional cooperation in widely distributed cells.

Normal cells homeostasis Lethal Reversible Adaptative cells Reversible Cell death necrosis apoptosis atrophy, Reversible hypertrophy Lethal Reversible hyperplasia injured cells metapllasia intracellular accumulations, degeneration A summary of the relationship between normal cells, adaptative cells, reversible injured cells and cell death

The relationship between cellular function, cell death and the morphologic changes of cell injury.

Causes of cell injury Ischemia/hypoxia (e. g. heart attack) Chemical agents (toxins, acid, drugs) l Active oxygen species: free radicals, oxidants, electrophiles Infectious agents (bacterial, virus, parasite) Immunologic reactions (hypersensitivity) Genetic defects (Down’s syndrome) Nutritional imbalances (protein insufficiency) Physical agents (trauma, temperature) Aging

Mechanisms of cell injury ATP depletion Oxygen deprivation or generation of reactive oxygen species Loss of calcium homeostasis Defects in plasma membrane permeability Mitochondria damage

Mechanism of ischemic and hypoxic injury

Cell mechanisms of injury Free radicals/ reactive chemicals O Normal metabolisms 2 OH • H 2 O 2 Cell membrane Mitochondria Endo. Retic. DNA NO Detoxification SOD/Catalase Glutathiole peroxidase/GSSG Vitamin E, C

Neutralization of free radicals SOD 2 O 2 + 2 H+ H 2 O 2 + O 2 catalase 2 H 2 O 2 2 H 2 O + O 2 glutathione peroxidase 2 OH • + 2 GSH GSSH + 2 H 2 O glutathione reductase

Summary Any stimuli and stresses can result in cell injuries. The injurious consequences depend on not only the type of injury, its duration, its severity, and also the type, status, adaptability and genetic makeup of the injured cell. Cell injury can be divided into reversible and irreversible. The loss of cell function is far before the cell death, but the morphological visible changes appear far behind the cell death.

Cellular adaptation to injury Concept of Adaptation: When cells encounter physiologic stresses or pathologic stimuli from outside and inside of body, they can alter themselves to achieve a new steady state and preserve viability. All kinds of adaptation may be considered as disorders of growth and/or differentiation Cellular adaptation can be considered as a state between the normal, unstressed cell and injured, overstressed cell.

Atrophy Definition: (briefly, decrease in cell size) Shrinkage in the size of the parenchymal cells by loss of cell substances in a well developed organ or tissue is known as atrophy. Or: acquired shrinkage of cells, tissues or organs. Simple atrophy (loss of cell size only) Numerous atrophy (loss of cell size and number through apoptosis) Differentiation: aplasia, hypoplasia

Testis: Right: Atrophied Left: Normal

There are kidneys and ureters of a one-year-old boy. The right Kidney is hypoplastic and the left one with a three-ureters abnormality.

Atrophy The reasons of atrophy: l Decreased workload disuse atrophy l Loss of innervation neuropathic atrophy l Diminished blood supply ischemic atrophy press atrophy l Absence of nutrition undernourished atrophy l Loss of hormone stimuli endocrine atrophy l Aging senile atrophy

Brain atrophy in an old patient with arteriosclerosis. Note the widened sulci and narrow convolutions.

Brain atrophy in a patient with Alzheimer’s disease. The gyri are narrowed and the sulci widened toward to frontal pole.

Hydrocephalus (left) and nephrohydrosis (right) Note the dilated ventricles and thinner grey and whine matter. The renal calyces and renal pelvis are dilated too.

There are some skeletal muscle fibers. The number of cells is the same as before the atrophy occurred, but the size of some fibers is reduced. In this case, innervation of the small fibers in the center was lost. This is a trichrome stain.

Atrophy The atrophied cells, tissue and organ have l l Reduction of physiologic functions Decreased synthesis Increased catabolism—increased protein degradation through Lysosomes digest the senescent organelles (autolysis) If the number of cells decrease, there is apoptosis (cell suicide), or programmed cell death

Hypertrophy Definition: (briefly: increase in cell size) an increase in the size of parenchymal cells and consequently an increase in the size of the organ. No increase of cell number in a purified hypertrophy!

Hypertrophy Compensatory hypertrophy l l l Mechanical stimuli---skeletal muscle of a sportsman Increased workload---left ventricle hypertrophy of systemic hypertension Decompensation---heart failure Endocrine hypertrophy l Hormonal stimuli---pregnant uterus ---Cushing’s syndrome

Hypertrophy of left ventricle (centripetal hypertrophy) in a patient with essential hypertension. Note the marked thickened wall of ventricle.

a. Hypertrophy of the left ventricle b. Normal myocardial fibers c. Hypertrophic myocardial fibers

A pregnant uterus (right) and normal uterus (left)

Physiologic hypertrophy of the uterus during pregnancy. Left: gross appearance of a normal uterus and a gravid uterus. Middle: small spindle-shaped uterine smooth muscle cells from A normal uterus. Right: large, plump hypertrophied smooth muscle cells from a gravid uterus.

Cushing’s syndrome resulted from adenoma of adrenal cortex

Hypertrophy Hypertrophic cells and organ with Increased function l Increased synthesis of structural protein l Induced by two types of signals l Mechanical triggers----stretch l Trophic triggers----activation of alphaadrenergic receptors l Differentiate from hyperplasia, pseudohypertrophy

Hyperplasia Definition: (briefly, increase in cell number) An increase in the number of parenchymal cells in an organ or tissue. Hyperplasia can occur with hypertrophy in various tissue except muscles. Hyperplasia can be divided into l l Physiologic hyperplasia l Hormonal: breast glandular epithelium at pregnancy Pathologic hyperplasia l Compensatory: liver after partial resection

Hyperplasia of endometrium in an adult woman with menorrhagia

Examples of hyperplasia: Red bone marrow of blood donor

Examples of hyperplasia: Hyperadrenalism

Examples of hyperplasia: Goiter (absence of iodine)

Note the prostate is nodular enlarged Hyperplasia of prostatic gland

Hyperplasia is induced by stimulation of hormonal or growth factors, cytokines and chemokines through the signal transduction pathway Hyperplasia can turn off when the organ restores or the stimulus stops Continuous pathologic hyperplasia constitutes a fertile soil for cancerous proliferation

Metaplasia Definition: (briefly: change in cell type) A reversible change in which one adult cell type is replaced by another adult cell type. This replacement is through hyperplasia of “stem cell” or “undifferentiated cell”, so metaplasia is actually an abnormal hyperplasia. The significances of metaplasia are l l To be able to withstand the stress better To be able to transform into a cancerous proliferation

Squamous metaplasia in bronchus in a heavy smoker

Squamous metaplasia of laryngeal respiratory epithelium in a heavy smoker

Columnar to squamous metaplasia: Barrett metaplasia in lower part of esophagus

Intestinal metaplasia in a patient with chronic atrophic gastritis Note the goblet cells

This is dysplasia. The normal squamous epithelium at the left transforms to a disorderly growth pattern at the right. This is farther down the road toward neoplasia.

Summary of adaptation Enlargement of an organ can result from l l l l Hypertrophy Hyperplasia Hypertrophy with hyperplasia Pseudohypertrophy (actual atrophy) Edema Tumor Congestion Inflammation

Summary of adaptation Shrinkage of an organ can result from l l Atrophy Aplasia and hypoplasia Hyperplasia persists only for so long as the stimulus is applied. When it is removed, the hyperplastic tissue tends to revert to its normal size. Hyperplasia must be distinguished from dysplasia and neoplastic proliferation.

Summary of adaptation Metaplasia is an abnormal hyperplasia. It can become a malignant neoplasm. All kind of adaptation can be considered as abnormal growth and/or differentiation Adaptation is the result of long time persisted, but mild stimuli Most adaptations are reversible when the stimulus is removed

Dysplasia Malignant tumor Normal cells adaptation Simple atrophy Numerous atrophy Hyperplasia Summary of abnormal growth Metaplasia

Learn words Greek derivation: dysbad, abnormal hyperabove, excessive hypobelow, deficient metabeyond, between -plasia a forming -trophe nourishment

Requirements The overview of cell injuries The main mechanisms of cell injury l Ischemia/hypoxia free radicals Concepts and recognition of lesions l l Adaptation Hyperplasia Atrophy Metaplasia Hypertrophy Give samples of various forms of adaptation and understand their significances

Thank you for your attention!