Pathology

• Provisional Exam date & Time

  May 9th
• The exams will be onsite
• Collagen


  An essential structural element in the extracellular matrix of most connective tissues, including bones and cartilage
• Collagen


  • It is the most common protein in the body and grants toughness and tensile strength to bone tissue
  • It has different varieties produced by different genes
  • These varieties have different properties and happen/occur in different locations
• Collagen types


  • Type I - produces familiar eosinophilic collagen fibres of fibrous connective tissues
  • Type II - reinforces cartilage
  • Type III - forms reticular fibres and occurs in basement membranes and bones
  • Type IV - occurs in basal lamina around skeletal and smooth muscle fibres
  • Type VII - an interlinking collagen, important in forming basement membranes
• Different collagen defect disorders express different symptoms depending on the gene that was mutated
• How collagen is formed


  1. Collagen is secreted by fibroblast cells as procollagen and then is extracellularly converted into trypocollagen

  2. Trypocollagen then self assembles into visible microscopically fibres and grossly evident mechanical fibres such as tendons
• Density of collagen


  Densely packed collagen provides resistance to tearing and stretching, while loosely packed collagen provides more flexibility and allows free movement within definite limits
• Reticular fibres


  • Formed by type III collagen fibres providing a network supporting individual cells in certain organs
  • They do not show in routine H&E staining specimens, but can be demonstrated with silver salts
• Composition of bone tissue


  • 10%~ 30% Osteoid tissue (Organic matrix, majorly composed of collagen)
  • 70% Mineral matrix (Calcium phosphate and other inorganic salts provide hardness)
• Bone tissue cells


  • Fibroblasts - contribute in the synthesis and maintenance of bone tissue
  • Osteoblasts - contribute in/responsible of the formation of bones, secrete organic matrix and facilitate mineralisation
  • Osteocytes - maintain bone tissue and regulate its metabolism, contained in Lacunae spaces within the Lamellae hard intracellular matrix
  • Osteoclasts - responsible for reapsorption of bone tissue, remodelling of the bone by breaking down tissue to release minerals
• Osteons


  Each osteon consists of a central canal containing blood vessels, lymphatics and nerves surrounded by rings of hard intracellular bone matrix called lamellae in which there are spaces called Lacunae, housing osteocytes
• Pap staining


  Stains different colours reflecting the maturity of the cells
• Pap staining


  • Appropriate to determine dysplasia but not effective to determine dyskaryosis
  • Cheap to use, fast method for staining cytological preparation and usually provides consistent results
• H&E staining


  Stains the cytoplasm of the cells depending on their maturity
• H&E staining


  • Hormonal factors may affect the appearance of tissue to some extent but H&E focus more on the structure of tissues and cells rather than the specific hormonal effects
• Metaplasia


  Alternation of a mature cell tissue into another mature cell tissue more suitable for its environment due to chronic stimuli
• Metaplasia


  • A smoker's epithelium tissue in the bronchi changes into squamous epithelium tissue
• Metaplasia


  Can be reversed if the stimulus is removed/stopped
• Dysplasia


  Disordered growth or development of cells, not proper architectural structure of cells
• Dysplasia


  Can be reversed if the symptoms are mild or moderate but cannot be reversed if the severity of the symptoms are high
• Anaplasia


  Lack of differentiation in cells, cells in Anaplastic tumours lack differentiation meaning that are difficult to be distinguished from primitive or undifferentiated cells
• Characteristics of Anaplasia


  • Pleomorphism: Variation of shapes and sizes of cells within the tumour
  • Hyperchromasia: Increase of staining of cell nuclei under microscope
  • Neoplasia: Alteration of cell normal growth regulatory mechanism leading to abnormal cell growth and proliferation
• Tay-sachs


  An untreatable disorder and fatal
• Tay-sachs


  1. Accumulation of GM2 Ganglioside lipids in the membranes of nerve cells and brain

  2. Destruction of nerve cells and brain

  3. Rapid mental and physical deterioration

  4. Death in early childhood
• Enzyme Hexosaminidase (Hex-A)


  Responsible for the cutting or breaking down of specific lipids
• Tay-Sachs inheritance pattern


  Autosomal recessive
• Offspring must inherit one copy of the mutated gene from each parent to develop the disease
• Pathological feature of Tay-Sachs


  • Appearance of enlarged pale lipid-laden neurons
• Loss of HFE function due to mutation leads to loss of iron sensor capability in the iron.Also the loss of HFE function disrupts the normal signalling pathways of iron in the liver leading to continuous abnormal excessive absorption of iron from the diet.
• The excess iron can lead to tissue damage and organ failure, particularly affecting the liver, pancreas, and endocrine system.
• Symptoms may include fatigue, weakness, weight loss, joint pain, diabetes mellitus, hypogonadism, impotence, arthritis, cirrhosis, hepatocellular carcinoma, cardiomyopathy, arrhythmias, and skin pigmentation.
• Levels of iron are controlled by systematic homeostasis. But Homeostasis is controlled at the point of Iron uptake from the diet as there are no active mechanisms that remove excess Iron from the body. Hepcidin hormone regulates levels of iron uptake in the intestines. HFE helps the liver in the monitoring of circulating levels of iron. However, in haemochromatosis the capacity is lost. 
• HH (Hereditary Haemochromatosis) Hereditary haemochromatosis accumulates in mesenchymal tissues over the years leading to a gradual decline.

  Symptoms start off as mild and progressively become worse: Skin discoloration, heart irregularities, arthritis, diabetes, liver cirrhosis and eventually liver cancer.

  Hereditary haemochromatosis, HH, can be treated by Phlebotomy 
• Haemochromatosis is the disease of an iron overload. Most common type is hereditary hemochromatosis type I, due to mutations in the HFE gene which is responsible for regulating absorption of iron by interacting with transferrin receptor 1 on the surface of cells in the intestine. Mutation in the HFE gene disrupts its function leading to dysregulation of iron absorption and metabolism. HH follows an autosomal recessive inheritance pattern.
• Fabry disease


  A disease consisting of a build up of fatty material in the central nervous system, around eyes, and kidneys, a cardiovascular system leading to the blocking or slowing down of blood flow through blood vessels into reaching organs in the body
• Enzyme lacking/low levels in Fabry disease


  Alpha galactosidase-A
• Role of alpha galactosidase-A


  Responsible for the breaking down of fatty substances
• If Fabry disease is left untreated

  Individuals normally lose their life at 20 y/o due to kidney failure or 30 y/o due heart failure
• Happloinsufficiency is a genetic phenomenon in which one of the two genes is mutated or non functional and the remaining functional cannot carry normal function in the organism as it cannot make enough protein to compensate for the loss in the non functional gene.