Pathology

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Pathology
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Terminology

• Pathology
• The study of the structural and functional
  changes leading to disease in
• Cell
• Tissue
• Organs
• Pathophysiology
• Is the abnormal function of organs or systems due
  to disease
• Tools
• Molecular
• Microbiological
• Immunological
• Morphological

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Terminology

• Pathology is divided
• General
• Special or systemic
• General pathology
• Basic reaction of cells and tissue to normal
  stimuli
• Specific pathology
• Specific response special organs to well defined
  stimuli

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Four aspects of disease process

• Aetiology
• Pathogenesis
• Morphological changes
• Clinical significance

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1.Aetiology(Cause )

• A) Determining cause
• Specifically known to be the soul cause of
  disease such pathogenic organism e.g. HIV
• B) Predisposing causes
• Leading indirectly to disease such as genetic
  predisposition

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2.Pathogenesis

• Is the mechanism by which a certain aetiological
  factor causes disease (In Greek pathos
  disease, genesis development).
• Some forms of pathogenesis are
• Inflammation
• Malignancy
• Tissue breakdown

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2.Pathogenesis

• The pathogenesis process leads to the formation
  of lesion
• Lesion is derived from the Latin word "laesio"
  which means "injury."
• Lesions are a result of damage to tissues. For
  example
• A cancerous tumor is an example of a lesion
• The surrounding tissue damaged by a tumour is
  also termed a lesion.

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3.Morphological changes

• Are the changes that occur in the cell tissue or
  organ as a result of the pathological process
• These changes can be Morbid
• Macroscopic appearance visible to the naked eye

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3.Morphological changes

• Are the changes that occur in the cell tissue or
  organ as a result of the pathological process
• Or Histological
• Microscopic appearance only visible under the
  microscope

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4.Clinical significance

• What impact do these changes have on the patient?

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Progression of a disease

• Complete cure
• Death
• Complication
• Additional pathological changes which may occur
  during or after the course of any disease

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Pathological investigation

• During life
• Surgical biopsy
• Fine needle aspiration biopsy (FNAB)
• Cytopathology
• Molecular techniques
• After death
• Autopsy

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Exposure to stress (irritant)

• Mild irritant A) inflammation
• Moderate B) Degeneration
• Severe irritant Necrosis

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Types of irritants

• Non-living irritant
• Physical
• Trauma, Burns, Radiation
• Chemical
• Acids, Alkalies
• Immunological
• Ag-Ab reaction
• Hypersensitivity reaction

• Living irritant
• Bacteria
• Pathogenic fungi
• Parasite
• Virus

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Inflammation

• It is the response of the living tissue to mild
  to moderate irritant
• The response is directed to defend the tissue for
  foreign irritants and to prevent further damage
• The aim is to bring more blood to the damaged
  area by acceleration of the blood stream
• It is denoted by the suffix itis

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Inflammation

• Examples of inflammation
• Tonsillitis
• Appendicitis
• Tendonitis ,etc.
• Lung?

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Inflammation
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Exudate

• An exudate is any fluid that filters from the
  circulatory system into lesions or areas of
  inflammation
• Its composition varies but generally includes
  water and the dissolved solutes of the blood,
  some or all plasma proteins, white blood cells,
  platelets and RBC

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Transudate

• A fluid that passes through a membrane which
  filters out much of the protein and cellular
  elements to yield a watery solution.
• A transudate is due to increased pressure in the
  veins and capillaries pressure forcing fluid
  through the vessel walls or low levels of protein
  the blood serum
• The transudated fluid accumulates in tissues
  outside the blood vessels and can cause edema

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Difference between exudates and transudate

• Exudate transudate
• inflammation venous congestion
• High above 4gm/m3 normal
• increased normal
• high above 1018 normal
• turbid due to pnls clear
• ve -ve

Cause Protein Fibrin SG Appearance Fibrin clot
on standing
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Types of Exudate

• Serous exudate is usually seen in mild
  inflammation, with little protein content. seen
  in certain disease states like tuberculosis
• Purulent or suppurative exudate consists of
  plasma with both active and dead neutrophils,
  fibrinogen, and necrotic parenchymal cells.
  referred to as pus.
• Fibrinous exudate is composed mainly of
  fibrinogen and fibrin. It is characteristic of
  rheumatic carditis, but is seen in all severe
  injuries such as strep throat and bacterial
  pneumonia
• Hemorrhagic exudate is seen in injury that causes
  rupture of blood vessels.
• Pleural.
• Catarrhal exudate is seen in the nose and throat
  and is characterized by a high content of mucus.

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Inflammation

• Effects of inflammation
• Vascular phenomena
• Transient vasoconstriction rapidly followed
• Vasodilatation
• Stasis
• Migration of leucocytes

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Inflammation

• Effects of inflammation
• 2- Exudative stress
• Emigration of leukocytes
• Inflammation fluid exudate

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Inflammation

• Composition and function of inflammation fluid
  exudates
• Fluid exudates
• Dilution of bacterial toxins
• fibrin threads help the movement of leucocytes
  and limit the spread of infection
• Also contain antibodies

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Inflammation

• Composition and function of inflammation fluid
  exudates
• Cellular part
• Phagocytosis engulfing of and destruction of
  bacteria and necrotic tissue by phagocytes and
  PNL

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Inflammation

• Chemotaxis the movment of WBC in the area of
  inflammation towards the irritant
• Emigration of leukocytes the migration of WBC
  from within the blood vessel towards the
  inflammation site
• Diapedesis the passage and movment of RBC from
  within the blood vessel towards the inflamed area

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Cardinal signs of inflammation

• Redness
• Hotness
• Swelling (edema) due to inflammatory exudate
• Pain due to pressure of edema on nerves and
  irritation of nerve ends by metabolites
• Loss of function this is to make the inflamed
  part of tissue rest and heal.

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Types of inflammation

• Acute inflammation
• Acute non-suppurative inflammation acute without
  the formation of pus
• Acute suppurative inflammation with pus
• Localized Abscess, Furuncle, Carbuncle
• Diffused cellulitis, septic meningitis
• Chronic inflammation
• Chronic specific TB
• Chronic non-specific follows acute or chronic
  from the beginning

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Cells of inflammation

• Acute inflammation cells
• 1- RBC
• 2- PNL (leukocyte)
• Eosinophils
• Basophils
• Neutrophils
• Chronic inflammation cells
• 1- lymphocytes
• 2- Plasma cells
• 3- Histocytes

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Cells of inflammation

• Fate of acute inflammation
• 1- Regretion by resolution for example when the
  body (immunsystem) overcomes the bacterial
  infection
• 2- Progression which can lead to chronic
  inflammation and spread the bacteria overcome
  the immunsystem and can spread by
• Blood septeciemia, bacterimea, toximia
  pyaemia
• Lymphatyic lyphangitis, lyphadenites
• Direct to other surrounding tissue

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Type of cells

• Contentiously dividing cells (Labile)
  epithelium, haematopoietic (blood)
• Quiescent (Stable) hepatic, kidney and pancreas
• Non-dividing (Permanent) nerve cells and
  skeletal muscle cells

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Cell development

• Proliferation increased number
• Differentiation development through stages

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healing

• Tissue repair involves replacement of damaged
  tissue with new healthy living tissue when
  resolution cannot occur
• Types
• Usually involves two separate but coordinated
  components
• Regeneration
• healing by the same type of tissue cells from
  surrounding healthy living cells, this occurs
  with in small damages of labile cells and stable
  cells for examples liver cirrhosis and bone
  fractures
• B) Fibros (scar tissue)
• healing by granulation tissue (fibroblast with
  new capillaries formed) which mature a vascular
  fibrous tissue (scar), this occurs in the healing
  process of permanent cells and stable cells with
  high damage. for example myocardial infraction
  and wounds

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Introduction to wond healing

• Healing is a complex and dynamic process of
  restoring cellular structures and tissue layers.
• The adult wound healing process can be divided
  into 4 distinct phases
• The homeostasis phase
• the inflammatory phase
• the proliferative phase
• the remodeling phase.

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Sequence of events in healing

• Initial phase - Hemostasis
• Following vasoconstriction, platelets adhere to
  damaged endothelium and discharge adenosine
  diphosphate (ADP), promoting thrombocyte
  clumping, which dams the Wound
• The inflammatory phase is initiated by the
  release of numerous cytokines by platelets.
• Fibrinogen is cleaved into fibrin and the
  framework for completion of the coagulation
  process is formed. Fibrin provides the structural
  support for cellular constituents of
  inflammation.
• This process starts immediately after the insult
  and may continue for a few days

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Sequence of events in healing

• Second phase - Inflammation
• Within the first 6-8 hours, the next phase of the
  healing process is underway, with
  polymorphonuclear leukocytes (PMNs) or PNLs
  engorging the wound
• These cells cleanse the wound, clearing it of
  debris. The PMNs attain their maximal numbers in
  24-48 hours and commence their departure by hour
  72
• As the process continues, monocytes also exude
  from the vessels. These are termed macrophages.
  The macrophages continue the cleansing process
  and manufacture various growth factors during
  days 3-4.
• Many factors influencing the wound healing
  process are secreted by macrophages. These
  include TGFs, cytokines and interleukin-1 (IL-1),
  tumor necrosis factor (TNF)

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Sequence of events in healing

• Third phase - Granulation
• This phase consists of different subphases.
  These subphases do not happen in discrete time
  frames but constitute an overall and ongoing
  process. The subphases are
• fibroplasia
• matrix deposition
• angiogenesis
• and re-epithelialization
• In days 5-7, fibroblasts have migrated into the
  wound, laying down new collagen of the subtypes I
  and III
• The wound is suffused with GAGs and fibronectin
  that are bonded covalently to a protein core and
  contribute to matrix deposition
• Angiogenesis is the product of parent vessel
  offshoots. The formation of new vasculature
  requires extracellular matrix and basement
  membrane degradation followed by migration,
  mitosis, and maturation of endothelial cells
• Re-epithelization occurs with the migration of
  cells from the periphery of the wound and adnexal
  structures. This process commences with the
  spreading of cells within 24 hours. Division of
  peripheral cells occurs in hours 48-72, resulting
  in a thin epithelial cell layer, which bridges
  the wound.
• This succession of subphases can last up to 4
  weeks in the clean and uncontaminated wound.

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Sequence of events in healing

• Fourth phase - Remodeling
• After the third week, the wound undergoes
  constant alterations, known as remodeling,
• This can last for years after the initial injury
  occurred. Collagen is degraded and deposited in
  an equilibrium-producing fashion
• The collagen deposition in normal wound healing
  reaches a peak by the third week after the wound
  is created.
• Contraction of the wound is an ongoing process
  resulting in part from the proliferation of the
  specialized fibroblasts termed myofibroblasts,
  which resemble contractile smooth muscle cells.

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Types of healing
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Types of healing
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Types of healing
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Complications of the healing process

• This process can go wrong and produce an increase
  of fibroblastic proliferation with a resultant
  hypertrophic scar
• Further exuberance can result in keloid formation
  where scar production extends beyond the area of
  the original insult. Conversely, insufficient
  healing can result in atrophic scar formation.

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Complications of the healing process

• Week scar this may lead to hernia
• Cicatrisation contracture of the size of the
  scar
• Implantation epidermiod cyst
• Stump neuroma following amputation causing a
  painful coiled mass of nerves
• Sinus is a track of septic granulation tissue
  connecting a cavity to the outside and has one
  blind end e.g. pilonidal sinus
• Fistula is a tract of septic granulation tissue
  connecting 2 epithelial surfaces
• Infection leading to delayed healing
• Rarely scars may develop squamous cell carcinoma
• Ulcers discontinuity of cover epithelium or
  muscle membrane

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Bone Introduction

• Bone is a dynamic tissue
• Osteoblasts - osteoid (type 1 collagen)
• Calcium and phosphate (calcium hydroxyapatite)
• Osteoclasts are multi-nucleated cells which
  resorb bone (PTH).

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Osteogenic cells
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Bone Anatomy

• Diaphysis
• Metaphysis
• Epiphysis Prox/Dist
• Epiphyseal line
• Periosteum
• Compact cortical bone
• Spongy bone
• Articular Cartilage
• Medullary cavity
• Marrow
• Nutrient artery

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The Histologic Types

• Compact bone
• Spongy bone
• Lamellar bone
• Woven bone
• Osteoid
• Callus

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The matrix of bone

• Contains inorganic salt Calcium Hydroxyapatite in
  collagen framework.
• Osteoblasts - Calcification - Mineralization
• Minerals ? hardness
• Collagen fibres ? Tensile strength.
• Collagen is necessary for Calcification.

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Fractures

• Break in the bone.
• Simple / Compound infection.
• Single - Horizontal, oblique, spiral,
• Comminuted multiple.
• Greenstick partial children.
• Torus compression of cortex children.

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Types of Fracture
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Bone Remodeling

• 5-10 bone / year.

• Vitamin D
• Nutrition
• Physical activity
• Age, hormones
• PTH, PHRP
• IL1, TNF,TGF-ß

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Stages of wound healing
Resolution/ Remodeling
Vessel regression, Collagen remodeling
Proliferation
Reepithelialization, Angiogenesis, Fibrogenesis,
Inflammation
PMNs, Macrophages, Lymphocytes
Hemostasis
Fibrin clot, platelet deposition
1D 3D 1wk
6wk 8wk
Time after injury
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Healing in Bone

• 1D - Hematoma formation (fibrin mesh)
• 3D - Inflammation
• 1W - Soft callus granulation, matrix.
• 3-6W - Callus ossification, woven bone
• 8W - Re-modeling absorb/deposit, strength,
  lamellate.

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Healing in Bone
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Healing in Bone
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Healing in Bone
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Healing in Bone
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Healing in Bone
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Factors affecting Healing

• Systemic Local factors
• Immobilization
• Improper reduction abnormal position
• Infection. Debris, dead tissue in wound
• Joint involvement

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Complications

• Delayed healing.
• Non healing.
• Joint involvement - ankylosis
• Abnormal position arthritis.
• Bone necrosis nutrient artery
• Involucrum formation.
• Pseudoarthrosis