<%@ Language=VBScript %> General Pathology
PDF FILES ► Course Outline PATH 201

Necrosis and Apoptosis

 

 

PATHOLOGY

  • Patho (disease, misery) and logy (study of, reasoning about).

  • Pathology is study of disease.

  • More appropriately is study of morphological, functional or biochemical changes in cells, tissues or fluids of the body.

  • From the ancient times till now there has been a mammoth increase in the knowledge about disease which has gone from macro to micro level.

  • Pathology is study of appreciating something wrong in the body which for the student is what,

  • further questions then arise that why and how this wrong has happened or developed.

  • The subject of GENERAL PATHOLOGY (a branch of pathology) revolves around the mechanisms by which tissues are injured together with the expressions of injury and the functional consequences of it,

BRANCHES OF PATHOLOGY

  • Medical Pathology deals with study of disease in man,

  • Veterinary Pathology deals with study of disease in animals.

  • Diagnostic Pathology deals with identification of nature of disease using traditionally, gross or histopathological  (microscopic pathology) tools but now a days other tools are also used in the subject.

  • Forensic Pathology deals with medicolegal issues, e.g., ruling of death of animals by poisoning in which case court or police department is involved.

  • Surgical Pathology deals with study of biopsy material (tissue taken during operation).

  • Environmetal Pathology deals with study of effects of environment in the causation of disease or impact of environment on disease 

  • Toxicological pathology deals with study of effects of different toxic substances in the causation of disease.

  • Zoo and Wild life Pathology deals with diseases in zoo and wild animals, respectively.

  • Immunopathology is a branch of pathology that deals with tissue injury produced by the involvement of immune system of the body.

  • Clinical Pathology deals with laboratory analysis of disease including haematology, cytology, serum chemistry, endocrinology, urinalysis etc.

  • Experimental Pathology deals with experimental study of diseases that may involve experimental production of disease and then study of different abnormalities produced thereto.

  • General pathology is the branch of pathology that deals with common denominators (lesions) of disease and mechanism of production of these.

  • Systemic pathology is a branch of pathology that deals with study of diseases with reference to system of involvement and is sometimes also named special pathology.

LANGUAGE OF PATHOLOGY

  • Lesion is a term used to denote an abnormality and mostly sound for any structural abnormality but rarely is used to describe the functional abnormality or biochemical lesion. The examples includes abscess, extra growth, change or missing enzyme or biochemical etc.

  • Pathognomonic is a term which means that a particular abnormality is found only in specific condition, e.g., hearing the fetal heart tone is pathognomonic of pregnancy.

  • A biopsy is tissue or peace of tissue removed from an animal during life for diagnostic purpose. This is mostly obtained to make clear a suspected cancerous from non-cancerous outgrowths

  • The autopsy  ("necropsy") is the opposite of "biopsy". It means a pathologist examines part or all of a dead body by doing postmortem. The term autopsy is used in human discipline, while necropsy is used in veterinary discipline with same meaning.

  • The Disease can simply be described by breaking the word into two, i.e., dis and ease which is self explanatory. However, disease is term used to describe clinically apparent dysfunction due to abnormalities, excesses, deficiencies, and injuries occurring at the cell and tissue level.

  • Pathogenesis is a term used to describe the mechanism of development of disease and involves step-by-step progression of disease.

  • Diagnosis means naming a disease on the basis of clinical signs, laboratory test and lesions characteristics of disease , e.g., pericarditis and perihepatitis (lesions) in poultry are very much characteristic of colibacillosis (disease).

  • Prognosis is a term used to designate the possible outcome of disease whether favourable or unfavourable or in other words good or poor.

  • Aetiology refers to cause of disease that may be due to intrinsic or extrinsic reasons, e.g., tuberculosis is caused by Mycobacterium (bacteria).

  • Clinical signs and symptoms: signs are evidence of disease discovered by the physician and are used to describe abnormal behaviour by animals as exhibited by them due to disease, e.g., higher temperature, staggering gait, yellow discolouration of eyes and mucus membranes.

  • A syndrome is a cluster of symptoms and/or signs not necessarily due to the same cause. e.g., malabsorption syndrome.

TOOLS OF PATHOLOGY

  • Eyes and Hands
  • Light Microscope
  • Histochemical Stains — Fat - Oil red O, Best Carmine - Glycogen, Acid Fast - Mycobacterium etc.
  • Darkfield, Phase Contrast, Fluorescence microscopy
  • Electron Microscopy
    • Transmission - thin Sections
    • Scanning - Three dimensional structure
  • Photometers / Colourimeters etc.

 

NORMAL   ----   ADAPTATION   --- INJURY

NORMAL – HOMEOSTASIS

Maintenance of physicochemical activity compatible with cell survival and functions.

ADAPTATION

Establishment of new level of physicochemical activity still preserving health of itself.

INJURY

Loss of ability of cell to maintain normal of adaptive homeostatic state.

 

ADAPTATION

  • PRINCIPAL

  • Atrophy

  • Hypertrophy

  • Hyperplasia

  • Metaplasia

  • ATROPHY

    Organ Atrophy — Cell Atrophy ?

    Causes

    • reduction in work load

    • loss of innervation,

    • loss of endocrine stimulation,

    • reduced blood supply or inadequate nutrition,

    • pressure

    • aging

  • The cellular change is identical in all cells

  • Example — Leg muscles of fixed or immobilized leg in fracture.

  • The biochemical mechanism of atrophy is poorly understood, in particular the signal that triggers the process.

  • Atrophy may be numerical (number) or quantitative (cell protoplasm)

  • Catabolic processes exceed anabolic processes – autophagic vacuoles

  • There may be "residual bodies"

  • Microscopically

  • Cells may be fewer (numerical) or smaller than normal (quantitative atrophy).

  • In spleen, the trabeculae – large or too numerous

  • In kidney, the glomeruli – too numerous and closely associated

  • In atrophic muscles, – sarcoplasm narrower and disappears – leaving sarcolemma.

  • In liver, the hepatic cords – become thinner.

  • Fatty atrophy: Missing cells replaced by adipose tissue as in physiologic atrophy of the thymus

  • Fibrous atrophy: Sometimes replaced by fibrous connective tissue

  • Grossly

    • The organ or part is smaller than normal.

    • It is well appreciated in paired organs where one organ is reduced in size and weight compared with its counterpart.

     

    HYPERTROPHY

    • Increase in size of cells and thus increase in size of organ or tissue
    • Occur in tissue whose cells can not divide – STRIATED MUSCLES
    • Organ Hypertrophy – Cellular Hypertrophy (Increase in size)
    • Increase in size of most tissues and organs — hypertrophy and hyperplasia
    • Pure hypertrophy occurs in tissues whose cells cannot divide.
    • The nature of the signal to the cell is poorly understood.
    • There is an increase in total cellular proteins, including myofibril in muscle cells and organelles such as mitochondria, ER and myofilaments.
    • The anabolic processes exceed catabolic processes.
    • The metabolic activity per unit volume — close to normal cell
    • There may be hypertrophy of specific organelle system, e.g., SER.

    PHYSIOLOGICAL

  • Skeletal muscles ---- weight lifters, athletes
  • Hormonal stimulation — Uterus smooth muscles during pregnancy – oestrogen
  • PATHOLOGICAL

    • Myocardial hypertrophy — stenotic (narrowing) valvular diseases or lung diseases.

    Microscopically

    • The cells are larger than normal.
    • Cells can be compared with those of other organ from the same animal or from other animal of same age, whatsoever is suitable.

    Grossly

    • The organ/tissue appear enlarged
    • Can be compared with animal of same age and breed.
    • Seen in organs have no potential of mitotic activity

    HYPERPLASIA

    • It is the increase in size of an organ due to increase in number of its constituent cells

    • Occur in those organs/tissues whose cells can divide

    • Hyperplasia after the removal of the stimuli does not progresses.

    • Hyperplasia of connective tissue and blood vessels (together granulation tissue) in wound healing is an important response.

    PHYSIOLOGICAL

  • Increased level of a normal stimulus (hormonal),

  • In regeneration – liver regeneration after injury.

  • As a compensatory response, e.g.,

  • missing organ in paired organ,

  • partial resection

  • PATHOLOGICAL

  • Pathological hyperplasia, occur because of excessive response or due to excessive stimulation.

  • Hyperplasia of thyroid gland (goiter) — iodine deficiency

  • Hyperplasia of bronchial epithelium — chronic irritation

  • Hormonal Stimulation – uterine – abnormally high oestrogen

  • Excessive growth factor stimulation — warts – papillomaviruses

  •  

    Microscopically

    • The cells are more numerous than normal number.

    • Some cells may have mitotic activity (can confuse with neoplasia)

    • Cell are highly differentiated

    • Cells can be compared with those of other organ from the same animal or from other animal of same age, whatsoever is suitable.

    Grossly

    • The organ/tissue appear enlarged

    • Can be compared with animal of same age and breed.

    • Seen in organs/tissue have potential of mitosis

    METAPLASIA

  • Mature differentiated (highly specialized) cell type is replaced by another differentiated cell (less specialized ) type.

  • Change occurs as a response to better withstand the adverse environment

  • The change is thought to occur due to genetic reprogramming of the epithelial stem cells or of undifferentiated mesenchymal cells.

  • Occurs mostly due to chronic irritation, including inflammation.

  • Change of columnar epithelium of trachea, bronchi and bronchioles into stratified squamous epithelium in cigarette smokers is an example of metaplasia.

  • Vitamin-A deficiency results in wide spread squamous metaplasia in the body.

  • In most of the cases, metaplasia depends on proliferation of germinal cells or stem cells whose progeny undergo modified differentiation.

  • In fewer cases, direct transformation of differentiated cells takes place.

  • Microscopically

  • In mesenchymal metaplasia, the fibrous tissue may get replaced by bone or cartilage.

  • Osseous metaplasia occurs as an ageing process in cartilage, e.g., the costal and thyroid cartilages.

  • Osseous metaplasia is also seen in soft tissues, as in scars and in areas of dystrophic calcification.

  • There is change in differentiated cell type from that present in routine in a tissue.

  • Grossly

    • Difficult to appreciate grossly

     

    DYSPLASIA

    • Is abnormal development of tissue or disorderly growth, or malformation of tissue.

    • The term is more often used to describe a proliferative response (non-neoplastic) accompanied by loss of regular differentiation.

    • The change is considered as preneoplastic.

    Microscopically

    • There is cell atypia and disorderliness.

    • It is loss of uniformity of the individual cells and loss of architectural orientation.

    • Cellular atypia is characterized by pleomorphism and hyperchromasia

    • Mitotic figures are seen in abundant cells.

    Grossly

    • No much can be appreciated grossly

     

    APLASIA

    • The term refers to failure to grow of an organ and there may be presence of a rudimentary organ.

    • This is abnormality in growth which may be genetic.

    • Haematologist use the term where the bone marrow undergoes destruction

    • And there is no regeneration and no new cell formation

    Grossly

    • Absence of or rudimentary organ

     

    HYPOPLASIA

    • The term is used to refer to failure of an organ to reach its normal full adult size.

    • It is arrested growth.

    • Examples include renal hypoplasia and hypoplasia of the testis.

    • The causes include, (1) genetic mutations (hereditary), and (2) deletion of critical cell population during development, may be in utero, due to certain viruses, toxins and irradiation.

    • Congenital cerebellar hypoplasia in young animals can occur due to viral infection during pregnancy.

    • Hypoplasia of kidney, pituitary and pancreas can occur spontaneously and is hereditary.

    Microscopically

    • Fewer cells than normal

    • Size of cells may also be small

    Grossly

    • Smaller than normal organ

     

    NEOPLASIA

    • The term is used to refer to new growth, i.e., an excessive and persistent tissue growth which is not under the growth control mechanism of the body

    • The growth continues even after the cessation or removal of the stimulus.

    • Both benign and malignant tumors are clonal overgrowths of cells bearing multiple genetic injuries.

    • Tumor cells typically have failure of division control, failure of senescence ("immortalization"), and failure of proper apoptosis.

    • Cancer cells can be characterized as antisocial, fairly autonomous units that appear to be indifferent to the constraints and regulatory signals imposed on normal cells.

    • For further detail, the reader is referred to chapter on neoplasia.

     

    ATRESIA

    • It is the complete failure of the lumen, or a portion of the length of the lumen to form

    • The condition is congenital and the animal is born with the defect.

    • The most common occurrence is atresia-ani, i.e., there is no anal opening right from the birth.

    • It is a non-neoplastic narrowing of a lumen.

    • It may be a birth defect, or acquired.

    • Occlusion is the complete obstruction of lumen that was once open.

    • Atherosclerosis (narrowing of lumen of blood vessels), the disease results when phagocytic cells in the intimal layers of large arteries become engorged with cholesterol and its esters.

    • The cholesterol (esters) in tissue sections can be recognized by the "needle-shaped" clear spaces left behind as it is removed in processing ( Cholesterol crystals are really flat rectangles in cross section).

     

    CELL INJURY

    Cell Injury: Mechanism of cell injury by interfering with energy production, Hypoxic injury

     

    SCHEMATIC DIAGRAM OF CELL SWELLING AND COAGULATIVE NECROSIS -LIVER

     

     

    CAUSES OF CELL INJURY

    HYPOXIA (lack of oxygen),

    Ischaemia

    • Occlusion of the blood vessels

    • Failure of the heart to pump enough blood

    Hypoxaemia:

    Too little oxygen in the blood

    • Too little oxygen in the air

    • Failure to properly ventilate the lungs

    • Failure of the lungs to properly oxygenate the blood

    • Failure of the heart to pump enough blood through the lungs

    • Tremendously increased dead space (i.e., pulmonary thromboembolus)

    Haemoglobin problems ("anaemic hypoxia")

    • Inadequate circulating red cell mass ("anaemia")

    • Inability of haemoglobin to carry the oxygen (carbon monoxide poisoning, methaemoglobinemia)

    • High affinity haemoglobins that will not give up their oxygen to the tissues

    Failure of the cytochromes ("histotoxic hypoxia")

    • Cyanide poisoning

    • Rotenone poisoning

    • Dinitrophenol poisoning

    LACK OF NERVE SUPPLY

  • Horses used unprepared for heavy work load

  • CHEMICALS AND DRUGS

  • Direct reacting Cyanide, heavy metals

  • Indirect reacting Carbon tetrachloride

  • Acids and alkalies

  • PHYSICAL AGENTS

  • Mechanical injury (crush injury, fractures, lacerations, haemorrhage)

  • Extremes of heat or cold

  • Radiation - (x-rays, radioactive elements, ultraviolet radiation)

  • Electric shock

  • Sudden changes in atmospheric pressure (blast injury, decompression injury in divers)

  • Noise trauma.

  • GENETIC DEFECTS

  • Congenital malformations.

  • Genetic factors can produce diseases directly or influence its outcome.

  • Inherited diseases

  • Patent ductus arteriosus (dog),

  • lysosomal storage disease,

  • combined immunodeficiency (horse)

  • Genetic influence on susceptibility to disease

  • Canine distemper, a disease of young pups

  • BIOLOGIC AGENTS

    • Bacteria, Viruses, Prion, Mycoplasma, Chlamydia etc.

    NUTRIONAL IMBALANCES

    • Deficiencies Se, Vitamin E, Protein, Carbohydrate etc.

    • Excesses Fat – cholesterol

    IMMUNE MECHANISM

    • Allergic anaphylactic reactions mediated by IgE antibodies

    • Cytotoxic reactions during which complement is activated

    • Autoimmune reactions

    USEFUL

    http://www.brisbio.ac.uk/

    http://155.37.5.42/NAV/Title.HTM

    http://www.med.uiuc.edu/PathAtlasf/titlePage.html

    http://www.uniud.it/drmm/anpat/pathgallery/

    http://www.pathguy.com/~lulo/gallery.htm

     LINKS

    http://alf3.urz.unibas.ch/pathopic/e/intro.htm

    http://erl.pathology.iupui.edu/c603/

    http://www.path.uiowa.edu/virtualslidebox/

    http://www.palms.med.usyd.edu.au/pathology_museum/

    http://www.whfreeman.com/kuby/content/anm/cell-deathv06.swf

    Hosted by www.Geocities.ws

    1