An introduction to pathology | basis of pathology | cellular response to injury | Hypoxia | and...

 Introduction to Pathology

In the preface of the very first edition of Patho- logic Basis of Disease (1957), Stanley Robbins wrote: "The pathologist is interested not only in the recognition of structural alterations, but also in their significance, i.e., the effects of these changes on cellular and tissue function and ultimately the effect of these changes on the patient. It is not a discipline isolated from the living patient, but rather a basic approach to a better understanding of disease and there-fore a foundation of sound clinical medicine". 

The study of the origin & development of disease 

📙Pathologists investigate etiology & pathogenesis of disease by way of morphology (morphe form), using techniques of histology (histo tissue) as well as biochemistry and molecular biology with a goal of easing clinical signs and symptoms where the clinician begins.

📙Pathology means scientific study of sufferings or disease. (Pathos = suffering. Logos = study) 

📙The term pathology is used when one refers to the "scientific study of disease" or the alterations that occur when abnormal influences (bacteria, viruses, etc.) affect cells, tissues, or body systems. More specifically, pathology may be defined as the "scientific study of the molecular, cellular, tissue, or organ system response to injurious agents or adverse influences." Pathology is the study & diagnosis of disease through examination of organs, tissues, body fluids & whole bodies (autopsies).

📙Pathology has been one of the "keystones" of medicine & it serves as a "bridge" or "link" between the preclinical subjects (anatomy, physiology, etc.) & the courses in clinical medicine. Actually, pathology provides a logical means of relating the knowledge of normal structure & function (anatomy & physiology) to abnormal structure & function as encountered in a diseased person. 

It should be emphasized that pathology, as the scientific study of disease, follows the morbid process from its inception to its termination, & investigates the lesions produced. Therefore, a sound knowledge of pathology is the foundation of a solid understanding of disease as it occurs in the living patient. Pathology actually deals with etiology, pathogenesis, morphologic changes and clinical course of disease.

📙Pathology is devoted to the study of the structural, biochemical & functional changes in cells, tissues, and organs that underlie disease. By the use of molecular, microbiologic, immunologic and morphologic techniques, pathology attempts to explain the whys and wherefores of the signs and symptoms manifested by patients while providing a rational basis for clinical care and therapy. Traditionally the study of pathology is divided into general pathology and systemic pathology. The four aspects of a disease process that form the core of pathology are its cause (etiology), the biochemical and molecular mechanisms of its development (pathogenesis), the structural alterations induced in the cells and organs of the body (morphologic changes), & the functional consequences of these changes (clinical manifestations). 

📙General Pathology: General pathology is concerned with the common reactions of cells & tissues to injurious stimuli. Such reactions are often not tissue specific: thus acute inflammation in response to bacterial infections produces a very similar reaction in most tissues. General pathology is a broad and complex scientific field which seeks to understand the mechanisms of injury to cells and tissues, as well as the body's means of responding to and repairing injury. Areas of study include cellular adaptation to injury, necrosis, inflammation, wound healing and neoplasia. It forms the foundation of pathology, the application of this knowledge to diagnose diseases in humans and animals.

📙Systemic Pathology: Refers to the study of the diseases of the organ systems of the body such as the respiratory system, digestive system and nervous system. Systemic pathology examines the alterations & underlying mechanisms in organ specific diseases such as ischemic heart disease.

📙Anatomic Pathology: Anatomic pathology is a medical specialty that is concerned with the diagnosis of disease based on the gross, micro- scopic, chemical, immunologic and molecular examination of organs, tissues & whole bodies (autopsy). Anatomic pathology is itself divided in sub specialties, the main ones being surgical pathology, cytopathology & forensic pathology.

📙Clinical Pathology: Clinical pathology or Laboratory medicine, is a medical specialty that is concerned with the diagnosis of disease, based on the laboratory analysis of body fluids such as blood and urine, and tissues using the tools of chemistry, microbiology, hematology & molecular pathology. Clinical pathologists work in close collaboration with medical technologists, hospital administrations, & referring physicians to ensure the accuracy and optimal utilization of laboratory testing.

📙Forensic Pathology: Forensic pathology is a branch of pathology concerned with determining the cause of death by examination of a cadaver. The autopsy is performed by the pathologist at the request of a coroner usually during the investigation of criminal law cases and civil law cases in some jurisdictions. Forensic pathologists are also frequently asked to confirm the identity of a cadaver. 

Pathology as a Medical Specialty

🖋 Pathologists are physicians who diagnose and characterize disease in living patients by exam- ining biopsies or body fluid. The vast majority of cancer diagnoses are made or confirmed by a pathologist. Pathologists may also conduct autopsies to investigate causes of death. Pathol- ogy is a core discipline of medical school and many pathologists are also teachers. As manag- ers of medical laboratories, pathologists play an important role in the development of laboratory information systems. 

🖋 Pathology is a unique medical specialty in that pathologists typically do not see patients directly, but rather serve as consultants to other physicians (often referred to as "clinicians" within the pathology community). 

🖋 In summary, pathology is one of several mechanisms employed to solve those problems encountered in clinical situations. Thus, the student is required to make practical use of information accumulated in the General and Special Pathology courses. The compartmental- ization & storage of knowledge for examination purposes is an exercise in futility. However, the utilization of accumulated knowledge in under- standing clinical problems is an educational reality. 

Basic Language of Pathology 

In order for a subject or course to be meaningful, one should become familiar with the basic terminology applicable to that subject. Listed below are a few basic terms used repeatedly in pathology and/or veterinary medicine. The student should become familiar with these terms and their definitions. 

Disease: A disease may be defined as a "state in which an individual exhibits an anatomical, physiological, or biochemical deviation from the normal." As generally used, the term "disease" is employed to describe a state in which there is sufficient departure from the normal for clinical signs or symptoms to be produced. 

Lesions: The term lesion is generally used to prefer to "structural or morphological altera- tions associated with a diseased state in an individual." It is the objective deviation from the normal. Lesions may be recognized with the naked-eye (gross lesions), with the aid of a light microscope (microscopic lesions), or with the aid of the electron microscope (ultrastructural lesions). Biochemical or functional lesions are recognized as changes which result from disturbed function. 

Etiology or Cause: The term "etiology" refers to a "study of the cause of a disease." An me etiologic agent is the factor (bacterium, virus, etc.) responsible for lesions or a disease state. 

Predisposing causes of disease: Refer to those factors which make an individual more suscep- tible to a disease (damp weather, poor ventila- tion, etc.) 

Exciting causes of disease: Refer to those factors which are directly responsible for a disease (bacteria, viruses, hypoxia, chemical agents, etc.). Etiologic factors can all be grouped into two classes: genetic (e.g., inherited muta- tions and disease associated gene variants, or polymorphisms) and acquired (e.g., infectious, nutritional, chemical, physical). 

Pathogenesis: Pathogenesis refers to the sequence of cellular, biochemical, and molecu- lar events that follow the exposure of cells or tissues to an injurious agent. The term "patho- genesis" refers to the "progressive development (sequence of events) of a disease from the time it is initiated to its final conclusion in recovery or death." 

Morphologic Changes: Morphologic changes refer to the structural alterations in cells or tissues that are either characteristic of a disease or diagnostic of an etiologic process. 

Pathognomonic Lesio: Refers to a change which is specifically characteristic of a disease. When one sees a pathognomonic lesion, he knows that a particular disease is present. 

Health: As generally used, the term "health" refers to the "state in which an individual is living in complete harmony with his environ- ment," it is a relative state. All body functions are performed normally even though lesions may be present in organs and/or tissues. It should be remembered that the transitional zone between health and disease is difficult to define. 

Clinical Signs : Refer to any "functional evidence of disease which can be determined objectively or by the observer" (lameness, salivation, increased respiratory efforts etc.). Remember, clinical signs are seen only in the living individual. The term clinical symptoms should be reserved for any "functional evidence of disease that can be determined subjectively or by the patient" (feeling of abdominal discomfort etc.). The end results of genetic, biochemical, and structural changes in cells and tissues are func- tional abnormalities, which lead to the clinical manifestations (symptoms & signs) of disease, as well as its progress (clinical course and outcome). Hence, clinicopathologic correlations are very important in the study of disease

The end results of genetic, biochemical, and structural changes in cells and tissues are func- tional abnormalities, which lead to the clinical manifestations (symptoms & signs) of disease, as well as its progress (clinical course and outcome). Hence, clinicopathologic correlations are very important in the study of disease

Diagnosis: The term "diagnosis" refers to the "determination of the nature of a disease expressed in a concise manner." 

A morphologic or anatomic diagnosis is based on the location and nature of the lesion (hemorrhagic enteritis, etc.). Etiologic diagnosis is made on the basis of the cause (dirofilariasis, etc.). Definitive diagnosis is made on the basis of the specific disease entity involved (canine distemper, animal disease etc.). A clinical diag- nosis is made on the basis of clinical signs observed in the living animal. 

Biopsy: Removal or collection of tissue or specimen obtained from the living body for examination is known as biopsy.

Necrosis: Refers to the morphological changes caused by the progressive degradative action of enzymes on the lethally injured cell within the living body. After a cell dies, lysosomes rupture and their hydrolytic enzymes are released. The release and activation of these lysosomal enzymes are responsible for cell necrosis. Remember, necrotic cells are dead cells, but dead cells are not necessarily necrotic. 

Postmortem change: Refer to cell death which accompanies or occurs after death of the entire body (somatic death), whereas antemortem changes refer to those alterations that occur in cells, tissues, organs, etc. prior to somatic death or in the living individual. It is important to differentiate postmortem changes from ante- mortem changes in order to interpret correctly those lesions encountered at necropsy. 

Gross Pathology (macroscopic pathology, patho- logical anatomy, morbid anatomy): Refers to the study of disease in which tissues and organs are examined with the unaided eye. 

Cellular Pathology (microscopic pathology, histopathology): Refers to the study of diseased tissues & organs with the aid of a micro-scope. 

Surgical Pathology: Refers to the study of tissues removed at the time of surgery

Clinical Pathology: Refers to the study of disease by examination of blood, urine, feces, skin scrapings, etc. 

Immunopathology: Refers to the study of diseases associated with abnormalities of the immune mechanisms of the body. 

Chemical Pathology: Refers to the study of chemical changes in the fluids and tissues of the body as the result of disease. This branch of pathology is merely a portion of clinical pathology. 

Morphologic Terminologies

• Follicular pattern: Forming follicle-like structure. 
• Diffuse pattern: Distributed diffusely.
• Glandular pattern: Arranged in a gland like structure.
• Acinar pattern: Cells arranged in gland having lumen.
• Tubular pattern: Arranged in tubule like structure.
• Villous pattern: Forming villi-like structure
• Papillary pattern: Arranged in finger like structure.
• Stag-horn or antler-horn pattern: Arranged in tight clusters or monolayered sheets of cells taking the pattern of antler horn
• Cyst: - Abnormal closed sac like structure containing liquid or semi solid substances. lined by epithelium.
• Pseudocyst: Abnormal closed sac containing fluid covered by fibrocollagenous tissue
• Adenoma: Benign epithelial neoplasms forming glands or formed from the glands (but not necessarily exhibiting gland pattern).
• Papilloma: Benign epithelial neoplasm growing on any surface that produce micro- scopic or macroscopic finger-like projections. 
• Polyp: A mass that projects above a muco- sal surface to form a macroscopically visible structure. 
• Abscess: Collection of pus lined by pyogenic membrane.
• Ulcer: Ulcer is a local defect or excavation of the surface of an organ or tissue that is produced by the sloughing (shedding) of inflamed necrotic tissue (breech in the tissue continuum) e.g. Peptic ulcer, Typhoid ulcer. 

Cellular response to stress

Cells are the basic unit of tissues, which form organs and systems in human body.Normal cell is in a steady state "Homeostasis". Change in Homeostasis due to stimuli "Injury". When a cell is exposed to an injurious agent, it achieves a new steady state to survive is called cellular adaptation. If the adaptive capability is exceeded or if the external stress is inherently harmful or excessive, adaptation fails and thus cell injury develops. 

When stimuli or stress is mild to moderate the injured cell may recover or revert to normal (reversible cell injury). When stimuli or stress is persistent or severe the injured cell cannot recover or revert to normal (irreversible cell injury or cell death). The effects of reversible cell injury may persist in the cell as evidence of cell injury at subcellular level (subcellular alteration). Various metabolites may accumulate within the cells (intracellular accumulation). 

The effects of injury depend on : 

a. Type, duration and severity of injury.

b. Type of injured tissue, its adaptability and genetic makeup. 

■Brain tissue is very sensitive to hypoxia (3-4 min). 

■ Myocardial tissue is also sensitive to hypoxia (20-30 min).

■ Skeletal muscles can adapt hypoxia for 2-6 hours. 

■Reversibility depends on the type, severity and duration of injury. 

■Cell death is the result of irreversible injury. 

Injurious Stimulus / Stress factors (Causes of cell injury) 

The causes of cell injury range from gross physical trauma (such as after a motor vehicle accident) to a single gene defect (results in a nonfunctional enzyme in metabolic disease). 

Most injurious stimuli can be grouped into the following categories: 

1. Oxygen Deprivation: 

• Hypoxia (deficiency of oxygen in tissue level). 
• Hypoxemia (deficiency of oxygen in arterial blood). 
• Ischemia (loss of blood supply).
• Anoxia (complete lack of oxygen).

2. Physical agents: 

•  Mechanical trauma.
• Extremes of temperature (burn or deep cold). 
• Sudden change in atmospheric pressure.
• Radiation.
• Electric shock. 

3. Chemical agents & drugs: 

• Glucose or salt in high concentration. 
• High concentration of oxygen.
• Trace amounts of poisons (e.g. Arsenic, cyanide, mercuric salt).
• Environmental and air pollution.
• Insecticides and herbicides.
• Industrial & occupational hazards (e.g. asbestos).
• Alcohol. 

4. Infectious/microbiological agent: 

• Virus.
• Bacteria.
• Fungi.
• Protozoa. 
• Parasites. 

5. Immunologic reactions (several autoimmune diseases discuss in lesson 20). 

6. Genetic defects (discuss in lesson 19) 

7. Nutritional imbalance (discuss in lesson 22A). 

8. Free radical damage (discuss in lesson 2C). 

9. Reperfusion injury. 

Hypoxia

Definition: 

Hypoxia is a condition in which the body or a region of the body is deprived of adequate oxygen supply at the tissue level. 

There are Four Types of Hypoxia : 

1. Hypoxic hypoxia: Due to low oxygen in arterial blood. 
2. Anemic hypoxia: Due to low level of hemo-globin in blood. 
3. Stagnant hypoxia: Due to inadequate blood supply.
4. Histotoxic hypoxia: Low oxygen uptake due to cellular toxicity. 

Clinical Manifestations: 

1. Cyanosis (bluish discoloration of skin and mucous membrane) 
2. Confusion / disorientation / hallucinations / behavioral change, 
3. Dyspnea (Breathlessness) 
4. Lethargy. 

Hypoxemia

Definition: 

Hypoxemia is defined as reduced partial pressure of oxygen (mmHg) in arterial blood. Hypoxemia can cause hypoxia (hypoxemic hypoxia), but hypoxia can also occur via other mechanisms, such as anemia. 

■It can be estimated by measuring the oxygen saturation of blood using a pulse oximeter, a small device that clips to a finger. 

■Normal pulse oximeter readings usually range from 95 to 100 percent. 

■Values under 90 percent are considered low. Normal arterial oxygen is approximately 75 to 100 millimeters of mercury (mm Hg). 

■Values under 60 mm Hg usually indicate the need for supplemental oxygen.

Causes: 

1. Decrease concentration of oxygen in air. 
2. Respiratory acidosis. 
3. Ventilation defect 
4. Perfusion defect 
5. Hemoglobin related abnormalities e.g. anemia. 

Ischemia 

Definition: 

Ischemia is a decrease in blood supply to tissues, causing a shortage of oxygen and glucose needed for cellular metabolism. 

Causes : Coronary artery atherosclerosis, decreased cardiac output, Thrombosis. 

Consequences: 

1. Atrophy 
2. Infarction of tissue 
3. Organ dysfunction 

Clinical manifestations are acute limb ischemia include pain, pallor, pulseless, paresthesia, paralysis. 

Major structural targets for cell damage: 

• Cell membranes : 

• Plasma membrane 
• Organelle membranes 

• DNA. 

•Structural protein 

• Enzymes 

• Mitochondria: 

• Oxidative phosphorylation 

Cellular responses to Injury 

1. Cellular adaptation: 

• Atrophy. 
• Hypertrophy. 
• Hyperplasia. 
• Metaplasia. 

2. Cell injury: 

• Reversible (Cellular swelling, Fatty change). 
• Irreversible (Necrosis, Apoptosis). 

3. Subcellular alterations- in sublethal & chronic injury. 

4. Intracellular accumulations. 

5. Pathologic calcification. 

6. Cell aging. 

Cellular response to injurious stimuli

Reference: -

🖎Text book of pathology by Harsh Mohan

🖎 Pathology tutorial by Mohammad Zillur Rahman