Pathology Histology

what are the steps in scarring

1. Emigration of fibroblasts and the induction of fibroblast and endothelial cell proliferation. 2. Angiogenesis: Formation of new blood vessels. This is stiumulated and aided by VEGF family of growth factors (VEGF-A, -B, -C, -D, and -E), FGF family of growth factors (FGF-1 and FGF-2) and Angiopoietins (Ang1 and Ang2) The new blood vessels tend to be leaky due to the VEGF which makes them more permeable. This would be why granulated tissue has more edema 3. Granulation tissue formation: Migration and proliferation of fibroblasts and deposition of connective tissue, which, together with abundant vessels and interspersed leukocytes, has a pink, granular appearance. 4. Tissue remodeling: Maturation and reorganization of the fibrous tissue (remodeling) to produce the stable fibrous scar

Describe cellular accumulation

1. Fatty Change (Steatosis) - accumulation of triglycerides within parenchymal cells. Most often seen in the liver (involved in fat metabolism), ALSO heart, skeletal muscle, kidney. Caused by - toxins, protein malnutrition, diabetes, obesity, anoxia* ALCOHOL is the most common cause of fatty change in the liver in industrialised countries 2. Cholesterol- Atherosclerosis Smooth muscle cells and macrophages within the intimal layer of the aorta and large arteries are filled with lipid vacuoles, most of which are made up of cholesterol and cholesterol esters. 3. Exogenous Dust - most common is carbon - phagocytosed by alveolar macrophages Tattoo - amalgam Scars - matter is introduced at the time of injury 4. Endogenous Melanin - formed by melanocytes Acts as an endogenous screen against UV radiation Keratinocytes and macrophages can accumulate melanin Haemosiderin (haemosiderosis) haemoglobin derived granular pigment Represents large aggregates of Ferritin Accumulates in tissues where there is a local or systemic excess of iron Locally as a result of haemorrhage Systemic overload due to haemosiderosis

Examples of Genetic factors carcinogenics

Familial adenomatous polyposis coli : Hereditary condition in which numerous tubular adenomas develop throughout the colon with a high rate of progression to adenocarcinoma. It is caused by mutations of the adenomatous polyposis coli, or APC, gene. Numerous polyps are necessary for a diagnosis of classic FAP Neurofibromatosis type 1 : multiple neurofibromas that give rise to neurofibrosarcomas von Hippel-Lindau syndrome : angiomas of the retina and hemangioblastoma of cerebellum, with a high risk for developing renal carcinoma

Abnormal tissues descriptions

Focal segmental Multi focal Miliary - "thousands", to numerous to count Segmental Symmetrical; bilateral Diffuse Cells - normal, inflammatory, neoplastic Substances - fluid, air, pigments (melanin, haemoglobin), stroma Agents - microbial agents, Foreign bodies Cells - atrophy, hypoplasia, necrosis Substances - fluid, air, stroma Degeneration: Deterioration and loss of function in the cells of a tissue or organ Dysplasia: Abnormal development of cells Metaplasia: Transformation of tissue from one type to another Neoplasia: Pathological process that results in formation of abnormal growth of cells

various applications of frozen sections

Frozen section 1. Helps in intra-operative diagnosis by rapid sectioning 2. Immunofluorescent methodology 3. Immunohisto chemistry techniques when heat and fixation may inactivate or destroy the antigens 4. Diagnostic and research non-enzyme histo chemistry, e.g. lipids and some carbohydrates 5. Silver staining methods, particularly in neuropathology

role of H. pylori in gastrointestinal pathologies

Helicobacter pylori infection is the most common cause of chronic gastritis

Histopathology

Histopathology is the study of cellular abnormalities and disease processes in human tissues through the application of various histopathological techniques 1. Ensure adequate resection margins, 2. To determine the extent of lymphatic/vascular involvement, staging, likely outcome and prognosis, 3. Determining a cause of death, 4. Autopsies may also provide definitive data for a medical audit. 5. Determine where medical procedures have been ineffective, or may give additional data for the future treatment of other patients.

common pathologies of parathyroid gland

Hyperplasia If demand for excess parathyroid hormone persists, the gland may become markedly enlarged. These hyperplastic changes usually affect all four glands. periphery changes non normal border Adenoma Usually affect only one of the four glands. Parathyroid adenoma replaces the whole gland due to its size. Often, a fragment of normal parathyroid tissue remains at the periphery. The cellular arrangement in parathyroid adenomas is variable, with the cells arranged in sheets or in a microacinar pattern. normal border- fat tissue

Give an examples of disorders affecting cell mass

Hypertrophy: Physiological adaption: Eg: Exercise-induced skeletal muscle hypertrophy and the hyperplasia and hypertrophy of the myometrium during pregnancy Pathological adaptation: Endometrial Hyperplasia Excessive concentration of oestrogen acts on the endometrium, such as at the menopause or due to hormone replacement therapy, leading to proliferation and elongation of endometrial glands. Atrophy: Testicular atrophy in the elderly and the adrenal gland atrophy when suppressed by exogenous steroid administration Commonly, when atrophy occurs, the lost cells are replaced by either adipose or fibrous tissue, often maintaining the overall size of the organ. When adipose or fibrous replacement does not occur, the overall size of the organ is reduced.

Explain the causes of chronic inflammation

INFILTRATION WITH MONONUCLEAR CELLS, which include macrophages, lymphocytes, and plasma cells. TISSUE DESTRUCTION, induced by the persistent offending agent or by the inflammatory cells. Attempts at HEALING BY CONNECTIVE TISSUE REPLACEMENT OF DAMAGED TISSUE, accomplished by proliferation of small blood vessels (angiogenesis) and, in particular, FIBROSIS

other examples of tumours

Melanoma: tumours of melanocytes. Lymphomas: tumours of solid lymphoid tissue. Leukaemias: tumours derived from haemopoietic elements. Gliomas: tumours derived from the non-neural support tissues of the brain. Germ cell tumours: tumours derived from germ cells in the gonads. Neuroendocrine tumours: tumours derived from cells of the neuroendocrine system. Examples include phaeochromocytoma , carcinoid tumour and medullary carcinoma.

Example disorders affecting cell differentiation

Metaplasia In metaplasia, the basic alteration appears to occur in the stem cells of the tissue. When the stimulus is removed, the stem cells may revert to producing differentiated cells of the original type Example 1: In the bronchi the specialized columnar respiratory epithelium may be replaced by squamous epithelium under the influence of chronic irritation by cigarette smoke (squamous metaplasia). Example 2: Similarly, in response to environmental changes during the reproductive cycle, the normal columnar endocervical epithelium is replaced by a stratified squamous epithelium. In Metaplasia most commonly occurs in epithelial tissues but may also be seen in mesodermal tissues; for example, areas of fibrous tissue exposed to chronic trauma may form bone (osseous metaplasia). - Metaplasia may coexist with hyperplasia and, more importantly, dysplasia

Describe Histology of the Goitre

Microscopy: Distended thyroid glands with colloid accumulation. Fibrosis, haemorrhage and calcification are common histological features of thyroid Goitre.

what is NATA

NATA or the national Australian testing authority is the authority which accredits laboratories and is responsible for ensuring guidelines are carried out and competence and quality are maintained in the laboratory, as audited against NPAAC guidelines NATA has the responsibility of ensuring that an individual laboratory has the procedures in place to ensure all activities performed in that laboratory meet and are meeting the relevant NPAAC standards. NATA has developed a set of documents detailing how ISO/IEC standards should be applied in a laboratory under the NPAAC guidelines. These documents are known as Field Application Documents or FADs. The one which applied to medical laboraotries is NATA ISO15189 Standard application document, Medical Testing Field Application Document

what is NPAAC

NPAAC or the National Pathology Accreditation advisory council - An advisory council comprised of representative from all states and territories that ensures that pathology services in Australia are provided at the highest quality as regulated by guidelines developed and maintained by NPAAC

CNS consist of

Nerve cells (Neurons) - Glial cells (Astrocytes, oligodendrocytes, microglial cells and ependymal cells)

Briefly describe the histopathological features of tumours of the CNS

OLIGODENDROGLIOMA Adult patients A moderate cellular pleomorhism associated with microcalcifications and microcystic degeneration. • Can occur mixed with astrocyte. • Perinuclear halo with oligodendrocytes GLIOBLASTOMA MULTIFORME Malignant astrocytoma Poorly delineated tumour mass in imaging Necrosis+, vascular (endothelial cell) proliferation plus high VEGF expression causing hemorrhaging, palisading(pseudo) of tumor cells around necrotic area AVM (ARTERIOVENOUS MALFORMATION) Malformed, tortuous, dilated blood vessels Glial tissue separating blood vessel (astrocytic scar) Hyalinised blood vessel Hemorrhage

Describe oncogenes and its role in cancer

Oncogenes are cancer-inducing genes derived from normal cellular genes called proto-oncogenes. They are present in the normal cell and are under strict control. If there are mutations that remove the control, the growth of the cell will be unchecked Oncogenes are mostly genes coding for growth factors, receptors for growth factors, proteins for signal transduction and nuclear proteins. Oncogenes Proto-oncogenes can be transformed into oncogenes through four basic mechanisms: 1. Point mutation 2. Gene amplification 3. Chromosomal rearrangements 4. Insertional mutagenesis (Eg-Hepatitis virus B)

Document hirachy - precedures

Operating procedures are the second level of the document hierarchy. - The role of the procedures is to detail how the system described in the quality manual is implemented. - Procedures are specific to the organization - They will describe the correct manner of undertaking the various activities - They must be written in a way so they may be used to train staff in performing a task - They must be amended when changes are inevitably made. must include What is to be done - Who is responsible for getting it done - How when and where is is done - What resources are to be used - What records need to be kept - What checks are to be done including criteria for them, and what should be done if things are incorrect - What interfaces exist with other activities

CAUSES OF CELL INJURY

Oxygen deprivation- hypoxia, ischemia; Common cause of cell injury and cell death. Eg- Cardio respiratory failure; Anaemia; CO poisoning; Blood loss. Physical agents- Trauma, radiation, electric shock, temperature Chemical agents- Glucose and salt in hypertonic concentrations can cause cell injury directly or by deranging electrolyte balance in cells; Others include drugs, alcohol, poisons etc. Infections- Bacteria, fungi, parasites etc Immunologic reactions- Autoimmune diseases (Eg- Hepatitis; Hashimoto's thyroiditis) Genetic alterations- Congenital malformations to neoplasms Nutritional imbalances- Both excess (atherosclerosis) and deficiency (marasmus) cause cell injury.

Describe Calcification

PATHOLOGIC CALCIFICATION: It implies the abnormal deposition of calcium salts, together with smaller amounts of iron, magnesium, and other minerals. Two major types. DYSTROPHIC CALCIFICATION; Calcification happening secondary to tissue damage (cell death) and with normal calcium metabolism. Eg- Calcification in atherosclerosis; Calcification in cancer tissues METASTATIC CALCIFICATION- Calcification in normal tissues secondary to some derangement in calcium metabolism (hypercalcemia). Eg Increased secretion of parathyroid hormone Vitamin D disorders Destruction of bone Renal failure

PATHOLOGY

Pathology involves the investigationof the causes of disease and the associated changes at the levels of cells, tissues, and organs, which in turn give rise to the presenting signs and symptoms of the patient.

Examples of apoptosis

Physiological 1. Embryogenesis- Implantation, organogenesis etc. 2. Hormone dependent- Endometrial cell breakdown during menstrual cycle 3. Cell loss as part of homeostasis- During maturation of various cell populations 4. Immune response- Neutrophils and lymphocytes in inflammation Pathological 1. DNA damage- Radiation, drugs, hypoxia etc. can damage the DNA; mutations in these damaged DNA can leads to altered cellular modifications including cancer. Elimination of these cells may be a better alternative than risking mutations and malignant transformation 2. Accumulation of misfolded proteins- Due to genetic mutations 3. Infections- Viral- HIV; Viral hepatitis via cytotoxic T cells. 4. Mechanical/Physical- Atrophy of glands following obstruction (Eg- Parotid, pancreas

Common functional Adenomas in Pituitary gland

Prolactinomas: secrete prolactin and may lead to infertility and, occasionally, inappropriate breast milk production Prolactinomas are the most frequent type of hyper functioning pituitary adenoma, accounting for about 30% of all clinically recognized pituitary adenomas Corticotroph (basophils) adenomas: secrete adrenocorticotrophic hormone (ACTH) and result in Cushing's disease Somatotroph (acidifils) adenomas: secrete excess growth hormone and lead to gigantism or acromegaly

what is pus

Pus- Whitish- yellowish- brown exudate formed at the site of inflammation following secondary bacterial or fungal infection. Microscopically pus consist of RBCs, dead tissues, inflammatory cells and bacteria/fungus.

quality control and assurance

Quality control is procedures put in place to ensure results meet quality standards Quality assurance is the process of assessing the effectiveness of these procedures to do so Quality management must occur on an internal and external basis Quality management must cover the scope of the laboratory example We perform a PAS stain QC measures include - The procedure we follow which has been validated as fit for purpose - The monitor of reagents- suppliers, expiry dates - Training of staff performing the procedure - The use of control tissue with known positive result QA - Checking the control tissue to ensure staining has been effective - Assessing the competencies of staff performing testing

outline the process of healing

Regeneration: Regeneration occurs by proliferation of residual (uninjured) cells that retain the capacity to divide, and by replacement from tissue stem cells. Scarring: injured tissues are incapable of regeneration, or if the supporting structures of the tissue are severely damaged, repair occurs by the laying down of connective (fibrous) tissue.

Morphological alterations in response to cell injury

Reversible: 1. Cellular swelling Occurs when cells are incapable of maintaining ionic and fluid homeostasis and is the result of failure of energy-dependent ion pumps in the plasma membrane. 2. Fatty change Occurs as lipid vacuoles in the cytoplasm. It is seen mainly in cells involved in and dependent on fat metabolism, such as hepatocytes and myocardial cells 3. ULTRA STRUCTURAL CHANGES - Plasma membrane changesBlebbing, blunting and loss of microvilli - Mitochondrial changes- Swelling, increase in density - Dilation of endoplasmic reticulum - Nuclear changes- Disaggregation of granular and fibrillar elements.

examples of chemical carcinogenics

Smoking - polycyclic hydrocarbons Asbestos - long thin fibers and when inhaled can pass deep into the lung. -Mesothelioma-arise in the mesothelium of either the pleura or peritoneum Aromatic azo dyes : Urinary bladder cancer in workers in aniline dye industry Benzene : Leukaemia in chemical-industry workers Aflatoxin B-1 : toxin produced by Aspergillus flavus that grows on mouldy grains and peanuts; suspected as cause of liver cancer in underdeveloped countries Nickel : cancer of nasal cavity and lungs in mine workers Arsenic : skin cancer in vineyard workers

when do you write corrective action reports

The incident is critical - The incident is re-occurring

managing supplies in the workplace

The laboratory must have a process for managing stock and suppliers. All reagents must be listed with the TGA All reagents must state the necessary information in regards to - Safety precautions - Expiry date - Date opened and initials A record must be kept of all new stock coming into the laboroatory and it must be signed off as being fit for purpose

roles of macrophages in chronic inflammation

The macrophage is the dominant cellular player in chronic inflammation. Macrophages are one component of the mononuclear phagocyte system. The half-life of blood monocytes is about 1 day, whereas the life span of tissue macrophages is several months or years. When a monocyte reaches the extravascular tissue, it undergoes transformation into a larger phagocytic cell, the macrophage. Macrophages are activated by non immunologic stimuli such as endotoxin or by cytokines from immune-activated T cells (particularly IFN-γ). when macrophages are activated there is increased levels of lysosomal enzymes and reactive oxygen and nitrogen species, and production of cytokines, growth factors, and other mediators of inflammation. The role of these is that: 1. Reactive oxygen and nitrogen species are toxic to microbes and host cells. 2) Proteases are Toxic to the extracellular matrix. 3) Cytokines, chemotactic factors cause influx of other cell types. 4) Growth factors cause fibroblast proliferation, collagen deposition and angiogenesis. ROLE

use of frozen sections

The most common reason our pathologists attend a Frozen section is for skin excisions, especially in elderly patients, or sensitive areas such as the face. Frozen sections allow the surgeon to take narrow margins of a lesion and have it assessed for completeness. If a margin is involved, the surgeon can excise that margin alone until it is clear. This allows the surgery to be complete in a single procedure and generally has a better cosmetic outcome

what are some complications that can happen with healing

Wound dehiscence - inadequate formation of granulation tissue - Increase abdominal pressure Excessive tissue formation - Excessive granulation tissue formation (Hypertrophy scar and Keloid) Cicatrisation- Late reduction in the size of the scar and frequently produces great deformity

Difference between necrosis and apoptosis

apoptosis shrinkage fragmentation of nucleus intact plasma contains apoptotic bodies no adjacent inflammation physiological and pathological necrosis swelling nucleus Pyknosis-karyorrhexiskaryolysi disrupted plasma contains enzymatic digested materials frequent inflammation always pathological

Compare and contrast Benign and malignant tumours

benign grows locally encapsulated resembles cell of origin few mitosis normal or slight increase in ratio cells are uniform malignant invasive growth not encapsulated failed cellular differentiated many mitosis high ratio cells vary in shape and size

Describe Apoptosis

cell death induced by a tightly regulated intracellular programme in which cells destined to die. 1. Initiation phase- Some Caspases become catalytically active 2. Execution phase- Other caspases trigger the degradation of critical cellular components. The activation of caspases depends on a finely tuned balance between production of proapoptotic and anti-apoptotic proteins

Define Metaplasia

change in differentiation in cells

Define Atrophy

decrease in size of existing cells resulting in loss of cell substances.

Document Hirachey - Test methods

details how a laboratory performs its testing, and or calibrating To Ensure tests are done correctly and give valid, reproducible results, it is necessary that: - All methods are documented, validated and or verified - All methods are up to date and readily available to all staff - Staff need to have their competency established before performing testing unsupervised - Staff are aware of updates to versions and familiarize themselves with such When implementing any new procedure in a laboratory it needs to be verified and or validated. Validation is needed when a method is altered from recommendations and or developed solely by the individual laboratory. It must detail how the procedure was worked up and how it was verified to be fit for purpose Verification is needed when a procedure is implemented as per recommendations and details that it was perfomed and achieved required results in the laboratory

what are some tumours of the connective tissue

fibrous tissue - fibroma- fibrosarcoma bone- osteoma - osteosarcoma cartilage - chrondroma - chrondrosarcoma adipose - lipoma - liposarcoma smooth muscle - leiomyoma - leiomyosarcoma blood vessels - haemangioma - haemangiosarcoma

Define Hypertrophy

increase in the size of existing cells resulting in increase in the size of the organ.

outline tumor suppressor genes and their role in cancer

p53 : Inactivation of this tumour suppressor gene on chromosome 17 is found in many common malignant tumours, such as carcinoma of the large intestine, lung, and breast. APC : This gene, identified in familial adenomatous polyposis coli, is inactivated in tumours that develop in large bowel cancer NF1 : It is inactivated in neurofibromatosis type 1. NF2 : It is inactivated in people who have bilateral acoustic schwannomas. WT-1 : It is inactivated in Wilms tumours of the kidney. VHL : It is inactivated in renal cell tumours that develop in the von Hippel- Lindau syndrome but also in renal cancers unrelated to this syndrome. Rb: is a tumour suppressor gene found on chromosome 13

what are some tumours of the epithelium

surface epithelium - adenoma- carcinoma squamous - squamous cell papilloma - squamous cell carcinoma glandular (villous or tubular)- adenoma- adenocarcinoma transitional - transitional cell papilloma - transitional cell carcinoma solid glandular (liver, kidney, thyroid) - adenoma- adenicarcinma

causes of neoplasms

CHEMICAL CARCINOGENESIS IRRADIATION VIRUSES & OTHER ORGANISMS DEMOGRAPHIC FACTORS (AGE) GENETIC FACTORS ETHNIC, GEOGRAPHIC AND SOCIAL ASSOCIATIONS DRUGS and HORMONES IMMUNOLOGICAL FACTORS

identify the special stains specific to connective tissue components

COLLAGEN FIBRES are the dominantfibre type in most connective tissues. The primary function is to add strength to the connective tissue. RETICULAR FIBRES: Gordon & Sweets Silver Stain for Reticulin or Reticulin stain). Reticular fibres give support to individual cells, for example, in muscle and adipose tissue. ELASTIC FIBRES: Verhoeff's Van Gieson Stain for elastin.

histological responses of CNS tissues towards injury

Chromatolysis: Is a process in which neurons may undergo reversible cell damage which is recognizable histologically by swelling of the cell body associated with loss of Nissl substance. This process is particularly seen in the cell body of a neuron after damage to the axonal process. Necrosis of brain tissue usually results in liquefaction, leaving a fluid-filled space. Due to lack of fibroblasts, healing through granulation tissue and fibrous scarring following an injury or necrosis is an uncommon event in the CNS. As a initial response to injury, there will be an exudative response with activation of local microglia and recruitment of phagocytic monocytes to phagocytose dead tissue. This is followed by proliferation of astrocytes to form an astrocytic scar. This process is generally termed gliosis and is (astrocytic scar) a common end product of damage to the specialized structures of the CNS. The

what is chronic inflammation

Chronic inflammation is inflammation of prolonged duration (weeks or months) in which inflammation, tissue injury, and attempts at repair coexist, in varying combinations In chronic inflammation, different stimuli may cause variations in the morphological appearances, but overall, the lymphocytes, macrophages and plasma cells predominate, in contrast to acute inflammation where the major cell type is the neutrophil.

Types of necrosis

Coagulated Necrosis: The affected tissues exhibit a firm texture. The injury denatures not only structural proteins but also enzymes (proteolytic enzymes) and so blocks the proteolysis of the dead cells; as a result, eosinophilic, anucleate cells may persist for days or weeks. Ischemia caused by obstruction in a vessel may lead to coagulative necrosis of the supplied tissue in all organs except the brain. eg- myocardial infarction LIQUEFACTIVE NECROSIS Enzymatic digestion of the dead cells, resulting in transformation of the tissue into a liquid viscous mass. Seen in focal bacterial or fungal infections in Brain Microbes stimulate the accumulation of leukocytes and the liberation of enzymes from these cells. The necrotic material is frequently creamy yellow because of the presence of dead leukocytes and is called pus CASEOUS NECROSIS Most often in tuberculous infection. "caseous" (cheeselike) or friable white appearance on the area of necrosis (Macroscopic). Microscopic: necrotic area appears as a structureless collection of fragmented and amorphous granular debris enclosed within a distinctive inflammatory border. - granuloma. GANGRENOUS NECROSIS Generally necrosis presents with typical features of coagulative necrosis involving multiple tissue planes- Dry Gangrene When bacterial infection occurs liquefactive necrosis comes in because of the actions of degradative enzymes in the bacteria and the attracted leukocytes- Wet gangrene

How does Irradiation cause cancer

UV light causes mutations in skin epithelial cells A DNA repair gene, p53, attempts to correct the errors in genetic code (mutation) If p53 is mutated, DNA errors begin to accumulate in skin cells Cells become cancerous and begin to proliferate uncontrollably

what are the three major components, pathological sequence of events and outcomes of acute inflammation

VASCULAR DILATATION : Relaxation of vascular smooth muscle leads to engorgement of tissue with blood (hyperaemia). This result is increased blood flow, which is the cause of heat and redness (erythema) at the site of inflammation. (induced by histamine and nitric oxide). ENDOTHELIAL ACTIVATION : Increased endothelial permeability allows plasma proteins to pass into tissues. Expression of adhesion molecules on the endothelial surface mediates neutrophils adherence. Production of factors that cause vascular dilatation. NEUTROPHIL ACTIVATION AND MIGRATION : Expression of adhesion molecules causes neutrophils to adhere to endothelium. Increased motility allows neutrophil emigration from vessels into surrounding tissues. Increased capacity for bacterial killing

common vascular lesions of CNS. Briefly go through their clinical and histopathological characteristics

VASCULAR LESIONS Haemorrhage Ischemia Ischaemic necrosis Infarction or stroke - Cerebral Infarction Common causes: - Thrombosis of a cerebral artery (due to atheroma). Occlusion of a vessel by embolus Haemorrhagic or 'anaemic' (pale). The haemorrhagic pattern is thought to be a result of reperfusion of capillaries damaged by the initial ischaemic episode Infarction of the cerebellum: Histological manifestations involve neurons, which become shrunken, eosinophilic and exhibit nuclear pyknosis. The infarcted area on the left exhibits loss of basophilia because of necrosis N of the small neurons of the granular layer and extravasation of erythrocytes E. DEGENERATIVE DISEASES Alzheimer's disease Parkinson's disease Lewy body dementia DEMYELINATING DISEASES Multiple sclerosis INFECTIONS Meninges- Meningitis CNS parenchyma- Encephalitis Spinal cord - Myelitis Mixed-eg: Encephalomyelitis

Describe the differentiation of neoplasms

Well differentiated malignancy: Malignant cells will closely resembles with the tissue of origin. Poorly differentiated malignancy: Malignant cells may bear little resemblance to the tissue of origin. Anaplastic: Malignant cells will exhibit no evidence of differentiation with its tissue of origin.

compare and contrast between acute and chronic inflammation

Acute 1. Is the immediate and early response to injury 2. Relatively short duration (minutes - days) 3. Characterised by fluid and plasma protein exudation and a predominantly neutrophilic infiltrate 4. Resolves with out any scarring Chronic 1. Late response to injury 2. Is of longer duration (days years) 3. Characterised by influx of lymphocytes and macrophages 4. Associated vascular proliferation and scarring

Outline equipment control with the workplace

All equipment in a laboratory must be validated and then maintained in good working order It must be verified to: - Be suitable for the task - Be accurate - Comply with specifications for performing that test - Maintained and have records of such maintenance, internally and externally - Uniquely identified There needs to be procedures for the use of equipment Staff need to be trained to use the equipment Operating instructions must be readily available Responsibility for management of the equipment needs to be assigned There needs to be a procedure for identifying the equipment when its Records in relation to the equipment must be kept for the lifespan of the equipment Equipment responsible for performing measurements must be calibrated against set standards on a regular basis to ensure results are accurate

important degenerative and demyelinating diseases of the CNS

Alzheimer's disease Histological features in Alzheimer's disease: Plaques, neurofibrillary tangles and neuronal loss are identified. Plaques (P) are accumulations of a peptide (amyloid β) and appear as amorphous, pink masses in the cortex which may be revealed with immunocytochemistry Neurofibrillary tangles: are aggregates of hyperphosphorylated tau protein that are most commonly known as a primary marker of Alzheimer's Disease. It can be demonstrated by using immunocytochemical techniques Multiple sclerosis The pale-staining demyelinated area D is easily distinguished from the normal-staining white matter W. Micrograph (b)- the increase in cellularity in these regions is a result of macrophages and reactive astrocytes. Another typical feature is cuffing of small blood vessels by lymphocytes L. Micrographs (c) and (d)Normal myelin stains dark blue, with areas of demyelination D appearing pale-stained.

Describe Necrosis

Cytoplasmic changes : - increased eosinophilia due to loss of cytoplasmic DNA and denaturation of cytoplasmic proteins (*Breakdown of plasma membrane and leakage of contents) - Glassy homogenous appearance (denaturation) - Vaculations (enzyme digestion) Nuclear changes : Breakdown of DNA Pyknosis, karyorrhexis and karyolysis

Mechanism of Genetic derangement

Deficiency of functional proteins, such as enzyme defects in inborn errors of metabolism, or accumulation of damaged DNA or misfolded proteins DNA sequence variants that are common in human populations (polymorphisms) can also influence the susceptibility of cells to injury by chemicals and other environmental insults.

Chromosomal abnormalities and their role in cancer

Deletions (e.g., deletion of a segment of the long arm of chromosome 13 in retinoblastoma) Translocations (e.g., translocations in Burkitt lymphoma and CML) Amplifications of chromosomal regions (e.g., in neuroblastoma)

what are the types of chronic inflammation

Diseases with Granulomatous inflammation: Tuberculosis, Leprosy, Syphilis, Cat-scratch disease, Sarcoidosis and Crohn's disease. There are two types of Granulomatous Inflammation 1. Foreign body granulomas are incited by relatively inert foreign bodies. These granulomas form when material such as talc (associated with intravenous drug abuse), sutures, or other fibers are large enough to prevent phagocytosis by a single macrophage and do not incite any specific inflammatory or immune response. foreign body GC placed haphazardness 2. Immune granulomas are caused by insoluble particles, typically microbes, that are capable of inducing a cell-mediated immune response. In these responses, macrophages engulf the foreign material and process and present some of it to appropriate T lymphocytes, causing them to become activated and transform into epithelioid cells and multinucleated giant cells. Langhans GC placed in a necklace shape

What is atypia

Due to the defects in the cell maturation, a population of cells may appear structurally abnormal. Due to incomplete maturation, there may be lack of specialized structures which are normally seen in that cell type, such as mucin vacuoles or surface cilia. This is called failure of differentiation and the cells are called cellular atypia.

Name the common infections of the CNS.

Encephalitis & Myelitis Encephalitis and myelitis are usually caused by viral infections (HSV/HIV), some having a particular propensity to affect specific types of neuron. In viral encephalitis or myelitis, there are three main histological features: 1.Focal neuronal loss and phagocytosis as a direct result of viral infection 2.Lymphocytic 'cuffing (surrounding) of vessels with increase in microglial cells; this is because of a local immune response 3.Astrocytic reaction with increase in number and size of astrocytes in response to loss of neurons. Meningitis Encephalitis Myelitis

Describe Carcinoma in situ

Epithelial tissue shows the cytological and histological features of carcinoma, but there is no evidence that the basement membrane bounding the abnormal epithelial tissue has been breached and there is no encroachment of atypical cells into the underlying stroma

characteristics of Granulomatous Inflammation

Epithelioid" macrophages +/- Langhans GCs +/- central necrosis T cell "halo

pathological significance of Carcinoma of the oesophagus

Esophageal adenocarcinoma typically arises in a background of Barrett esophagus and long-standing GERD. Progression of Barrett esophagus to adenocarcinoma occurs over an extended period through the stepwise acquisition of genetic and epigenetic changes. Chromosomal abnormalities and TP53 mutation are often present at early stages of esophageal adenocarcinoma. Additional genetic changes and inflammation also are thought to contribute to neoplastic progression. Adenocarcinoma usually occurs distally and, as in this case, often involves the gastric cardia Sqarmous cell carcinoma Use of alcohol and tobacco, nutritional deficiencies, fungus-contaminated foods, have been considered as possible risk factors. HPV infection also has been implicated in esophageal squamous cell carcinoma in high-risk. The molecular pathogenesis of esophageal squamous cell carcinoma remains incompletely defined. The countries with highest incidences are Iran, central China, Hong Kong, Argentina, Brazil, and South Africa. Squamous cell carcinoma most frequently is found in the midesophagus, where it commonly causes strictures. Squamous cell carcinoma is composed of nests of malignant cells that partially recapitulate the stratified organization of squamous epithelium.

Name three morphological types of acute inflammation

FIBRINOUS INFLAMMATION Acute inflammation where the acute inflammatory exudate has a high plasma protein content. Fibrinogen, derived from plasma, is converted to fibrin, which is deposited in tissues. Eg: Inflammation of pleura, pericardium and peritoneum. SEROUS INFLAMMATION Acute inflammation where the main tissue response is an accumulation of fluid with a low plasma protein and cell content (transudate). commonly seen in the skin in response to a burn. Abscess- Enclosed collection of pus with in the body tissue

what is inflammation

Many causes of tissue damage provoke an acute inflammatory response but some types of insult may bring about a typical chronic inflammatory reaction from the outset (e.g. viral infections, foreign body reactions and fungal infections). Acute

Document Hirachey - documentation

Any completed documentation becomes a record. ISO 15189 details the timeframe in which records must be kept, relevant to the type of information stored Records include such things as Paraffin blocks and slides Patient request forms Pathology reports All completed documents in a laboratory All documents must be document controlled and give the following information (this is a requirement of ISO) The following information must be included in document control: Who the document was authorized by and the date Who the document was approved by Who the document was reviewed by (in subsequent versions) and the date of review If it is current (controlled) or Obsolete The version of the document The location of the document (if digital copies exist) Page numbers The purpose of document control is to ensure that all procedures are performed in the same way each time rendering results consistently valid and reproducible All staff are following the same version of the document

pathological significance of Barrett's oesophagus

Barrett esophagus is a complication of chronic GERD that is characterized by intestinal metaplasia within the esophageal squamous mucosa. It occur in as many as 10% of persons with symptomatic GERD

common special stains in Histopathology

Masson's Trichrome: This stain is intended for use in histological observation of collagenousconnective tissue fibers in tissue specimens. It is used to assist in differentiating collagen and smooth muscle in tumors and assists in the detection of diseases or changes in connective/muscle tissue. such as leiomyoma (uterine fibroid), cirrhosis, Verhoeff's' Van Gieson Verhoeff's Van Gieson stain is useful in demonstrating atrophy of elastic tissue in cases of emphysema, and the thinning and loss of elastic fibres in arteriosclerosis, and other vascular diseases. Periodic Acid Schiff (PAS) Stain PAS staining is mainly used for staining structures containing a high proportion of carbohydrates such as glycogen, glycoproteins, proteoglycans typically found in connective tissues, mucus and basement membranes Perls' Prussian Blue This stain is used to detect and identify ferric (Fe3+) iron in tissue preparations, blood smears, or bone marrow smears. Minute amounts of ferric iron (haemosiderin) are commonly found in bone marrow and in the spleen. Ziehl Neelsen Stain: This stain is used to detect and identify acid fast bacilli in tissue by penetrating their waxy cell wal. . § Bacilli are rod-shaped bacterial organisms. § A primary function of this stain is to identify tuberculosis in lung tissue. Differentitation treatment with both acid and alcohol removes the basic fuchsin from all structures except the organisms under investigation. Alcian Blue: Alcian Blue is normally prepared at pH 2.5 and is used to identify acid mucopolysaccharides and acidic mucins. § Toluidine blue: It is a metachromatic dye. It has the ability to modify the absorption characteristics of a dye molecule upon chemical reaction while maining the structural integrity of the dye. This is due to the PH, concentration and temperature. This dye stains mast cellsa red/purple. Helps in diagnosing cancers, inflammatory responses, IBS. Gordens and sweets stain: Stains reticulin fibres. Unstable silver salt and a reducing agent such as formalin causes a black metallic silver that settles on the reticulin fibres. The metallic fibre is then toned and converted to metallic gold to give better contrast. Giemsa: permits differentiation of cells such as nuclear, cytoplasm morphology of platelets, RBC, WBC, and parasites such as H.Pylori. Oil red demonstrates fats or lipids in fresh tissue sections. this fat can be from a fatty embolism or from a bone fracture where the inuries has occurred in a fatty area. Diff Quik Rapidly stainand differentiate a variety of smears, commonly blood and non-gynecological smears, including those of fine needle aspirates CRESYL FAST VIOLET STAIN Detects Nissl substance. Nissl substance is lost after cell injury and if the axon degenerates, the myelin covering also breaks down. LUXOL FAST BLUE STAIN Staining of myelin/myelinated axons ALCIAN BLUE Alcian blue stain should be positive for the acidic mucin present in the goblet cells. CONGO RED STAIN Stains amyloids Amyloidosis is a rare condition where abnormal proteins accumulate in patient's organs and tissues. PERL'S PRUSSIAN BLUE STAIN demonstrate both hemosiderin and ferric ions and to distinguish it from other brown pigments and extracellular material.

Genes affected by carcinogenics

1. Genes encoding growth factors and Activation of growth promoting oncogenes receptors, and signalling proteins involved in various steps of cell division (Hyperplasia) such as TGF-B, EGF etc 2. Oncogenes: Transform normal cell to a malignant phenotype and direct them on carcinogenic pathway such as Kras, BRAF) 3. Genes regulating apoptosis such as Bcl-2, p53 4. Genes belonging to the family of tumour suppressors and Inactivation of growth inhibitory genes (tumour suppressor genes) such as P53 5. Genes encoding DNA repair enzymes and Subtype of tumour suppressor genes involved in maintaining genomic integrity/DNA repair (caretaker genes) such as BRCA 6. Cell cycle regulators: Eg- Cyclins and Cyclin dependant Kinase (CDK). Regulate cell proliferation via adjusting the cell cycle phases. 7. Angiogenesis: Formation of new blood vessels and enrich oxygen and nutrients to growing tumours. E.g. VEGF 8. Gate keepers: Genes that prevent growth of potential cancer cells and prevent accumulation of mutations that directly lead to increased cellular division and cell death. (E.g.- APC) 9. MicroRNAs (miRNA)s: Non-coding RNAs that mediate posttranslational gene silencing. They negatively regulate the expression of an oncogene or tumour suppressor gene.

common histopathological lesions of thyroid gland

1. Graves disease The three most common causes of thyrotoxicosis are 1. Diffuse hyperplasia of the thyroid (approximately 85% of cases) 2. Hyperfunctional multinodular goiter 3. Hyperfunctional thyroid adenoma Normal Physiology: Thyroid function is normally under the control of the hypothalamicpituitary axis via the release of thyroid-stimulating hormone (TSH) from the pituitary which stimulates thyroid acinar cells to liberate thyroxine. The resulting level of circulating thyroxine then regulates TSH production by a negative feedback mechanism. Pathogenesis is Characterized by the production of autoantibodies against multiple thyroid proteins, most importantly the TSH receptor. A variety of antibodies that can either stimulate or block the TSH receptor are detected in the circulation. The most common antibody subtype, known as thyroid-stimulating immunoglobulin (TSI), is observed in approximately 90% of patients with Graves disease. This binds to TSH receptors on thyroid acinar cells, mimicking the effects of TSH and resulting in excess secretion of thyroxine. The hyperplastic acinar cells may crowd up on one side of the acini, projecting into the lumen as papillary structures (P). The colloid in hyperplastic follicles shows peripheral scalloping S, reflecting the increased utilisation of stored thyroid colloid to produce thyroxine by the hyperactive thyroid acinar cells. 2. Hashimoto's thyroiditis Histopathology: Small darkly staining lymphocytes aggregate to form typical lymphoid follicles, often with germinal centres. - In the early stages of the disease, the extensive lymphoid infiltrate produces a diffusely enlarged, firm thyroid gland with a pale cut surface, resembling a lymph node (macroscopically). When almost all thyroid acini are destroyed, the lymphoid infiltrate becomes less obvious (late stage) and fibrosis supervenes, with progressive reduction in size of the gland. - Hurthle cell change (oxyphilic metaplasia) 3. Thyroid Carcinoma- Papillary type Papillary thyroid carcinoma is the most common thyroid cancer (75 to 85% of all thyroid cancers). It is associated with radiation exposure. Most papillary carcinoma grows slowly and maybe an incidental finding. It can spread by local infiltration and lymphatic spread. Microscopy: Ground glass nuclei, nuclear grooves and intranuclear inclusions; Laminated calcified bodies (psammoma bodies). (calcification)

Examples of viral carcinogenics

1. Human papilloma virus (HPV) subtypes 16 and 18 are related with carcinoma of the cervix and the lower female genital tract. 2. Epstein-Barr virus has been associated with Burkitt lymphoma and nasopharyngeal carcinoma. 3. Hepatitis virus B and C chronic liver disease has been associated with an increased incidence of hepatocellular carcinoma. 4. Herpes virus 8 has been isolated from cells of Kaposi sarcoma. 5. Helicobacter pylori - gastric lymphoma 6. RNA retrovirus (HTLV-1) causing human T-cell leukemia/ lymphoma.

ECM role in healing

1. It provides mechanical support to tissues; this is the role of collagens and elastin. 2. It acts as a substrate for cell growth and the formation of tissue microenvironments. 3. It regulates cell proliferation and differentiation; proteoglycans bind growth factors and display them at high concentration, and fibronectin and laminin stimulate cells through cellular integrin receptors.

what do macropages release to help with inflammation

1. Reactive oxygen and nitrogen species are toxic to microbes and host cells. 2) Proteases are Toxic to the extracellular matrix. 3) Cytokines, chemotactic factors cause influx of other cell types. 4) Growth factors cause fibroblast proliferation, collagen deposition and angiogenesis. ROLE

outline People management within the workplace

A laboratory must have: - Sufficient staff to adequately carry out necessary tasks - Senior staff with authority and resources - Arrangements to ensure staff are not exposed to inappropriate pressures which may affect their quality of work - Policies for confidentiality - Policies to protect the labs integrity A laboratory needs to have procedures and documentation for the training of all staff in the laboratory Staff also need to be assessed for their competency in each area they are trained These procedures should take into consideration - Skills - Knowledge - Attitudes Staff require assessment against tasks they perform as per detailed in their job description and in which they have been trained. This requires assessment at least annually Action must be taken if staff do not meet competency requirements - This includes identifying reasons why a staff may not be meeting this competency and making changes to ensure they are able to reach that competency

Describe INTERNAL AUDITS

ISO 15189 requires an organization to perform internal audits on its management system. An internal audit program is required to have the following 1) A procedure for how the audits are scheduled, how the audit process is conducted, and how any findings are recorded and reported 2) A document detailing the audit schedule. Must include horizontal (procedure based) and vertical (systems based) 3) Trained auditors whose aim is to improve the system and not to place blame 4) Documents to record findings which outline how those results are attined 5) Records of the audits and their outcomes Audits must demonstrate that the pre examination, examination and post examination processes are being conducted and meeting requirements of the quality management system and ISO15189. They should aim to continually improve the quality management system. Audits should assess individual systems (horizontal audits) and the entire process (vertical audits) The laboratory needs to develop quality indicators to be audited against- ie- number of acceptable errors at data entry. The results of these audits need to form part of the annual management meeting If results do not meet quality indicators management must initiate corrective action.

difference between routine and special staining.

In histopathology laboratory, "routine staining" refers to the H&E stain and it is used "routinely" with all tissue specimens to reveal the underlying tissue structure and conditions. The term "special stains" refer to a large number of alternative staining techniques that are used when the H&E does not provide all the information the pathologist or researcher needs.

What is dysplasia and give examples

In some occasions, the atypical cells remain persistent and in these cases the population of atypical cells may eventually be the focus from which invasive cancer develops. dysplasia is a morphological feature characterized by increased cellular proliferation with incomplete maturation of cells. It occurs most commonly at the uterine cervix and in the skin. Example: Solar Keratosis.

components of a matured scar

Inactivated fibroblasts dense collagen elastic tissue

Define Hyperplasia

Increase in cell number

what is an example of an benign tumour

Lipoma- is made up of mature fat cells laden with cytoplasmic lipid vacuoles

How can tumours spread

Local invasion: The most common pattern of spread of malignant tumors is by direct growth into adjacent tissues. Lymphatic spread. Tumor cells frequently spread via draining lymphatic vessels and are conducted to local lymph nodes. Vascular spread. Tumor cells can spread via the veins draining the primary lesion. Gastrointestinal tumors are frequently conducted via the portal vein, giving rise to metastases in the liver. Tumor cells that enter systemic veins most frequently form metastases in the lung, bone marrow, brain and adrenal glands. Transcelomic spread. Primary tumors in the abdominal cavity or the thorax can spread directly across celomic spaces, e.g. the peritoneal or pleural cavities.

Describe changes in anaplastic cells

Malignant neoplasms are characterized by a wide range of cell differentiation, from surprisingly well differentiated to completely undifferentiated. Malignant neoplasms that are composed of undifferentiated cells are said to be anaplastic. Anaplastic cells display marked 1. Pleomorphism (i.e., variation in size and shape). 2. Hyperchromatic (dark-staining) nuclei. 3. Large sized nuclei resulting in an increased nuclear-to-cytoplasmic ratio. 4. Variable and bizarre shaped nuclei. 5. Numerous and distinctly atypical mitosis.

what is Management review

Management reviews must occur annually and must assess the effectiveness of the management systems with reference to whether currently the system is: - Helping meet the laboratories goals - Helping control the laboratories operations - Improving its efficiency and reducing errors - Satisfying customers It must determine if - Any changes are required to documents and practices - There are additional resource or training needs - If there are any patterns or trends to non-conformities - Corrective actions have been performed where there was a need identified - New business opportunities or threats to the organization Any changes then require planning and implementing

Quality policies

The most important document for a laboratory to have and maintain is the QUALITY MANUAL. The quality manual describes how the laboratory meets every aspect of NPAAC guidelines relevant to its Scope of testing. It also includes information about other aspects that affect the running of the lab- eg employment contracts, health and safety, waste management It is somewhat the master document of every process that happens in a laboratory It must be maintained, reviewed and updated annually The Quality manual is required to include a policy statement which details the "overall intentions and directions of an organization related to quality as formally expressed by Top management" (ISO 9000) ISO15189 requires a quality policy to contain - The laboratories intentions to the standard of service it will provide - Quality objectives, which must be measurable- ie quantifiable targets which are measured to show the effectiveness of the quality management system. - A statement of the requirement that all staff read the quality manual and follow its procedures. - The laboratories commitment to . Good professional practice . Compliance with standards . Continual improvement to the effectiveness of the management system.

what is the SCOPE OF ACCREDITATION

The scope of accreditation is the detailed areas in which a laboratory performs testing to which they seek accreditation by NATA. This scope will influence how a laboratory develops procedures and documents etc and which elements of NPAAC apply to that laboratory

Function of a telomere and its involvement in cancer

The telomeres are disposable buffers at the ends of chromosomes which are truncated during cell division. Over time, due to each cell division, the telomere ends become shorter. They are replenished by an enzyme, telomerase reverse transcriptase. In cancer Telomerase act to promote tumorigenesis by mechanisms that do not depend on telomere length. Telomerase activity and maintenance of telomere length are essential for the maintenance of replicative potential in cancer cells.

Describe neoplasm and give examples

The term neoplasia (from the Greek for 'new growth') describes a state of autonomous cell division and the abnormal mass of cells that results is termed a neoplasm. In a neoplasm, cellular proliferation and growth occur in the absence of any continuing external stimulus Benign neoplasms: grow slowly and remain localised to the site of origin Malignant neoplasms: grow rapidly and may spread widely.

what is ISO stands

This standard was developed from "ISO/IEC 17025: General requirements for the competence of testing and calibration laboratories" to be more specific to the medical field and take into consideration the effect the laboratory environment has on patient care

what are the 4 Tiers of NPAAC guidelines

Tier 1: THE PRINCIPLES: Health insurance (accredited pathology laboratories- approvals) Principles, 2017 Describes the terms and conditions on which NPAAC may accredit a pathology testing laboratory including categories of accreditation Tier 2: OVERARCHING STANDARDS FOR ALL PATHOLOGY LABORATORIES: Requirements for medical pathology services (second edition 2018): Sets out requirements of best practice to ensure safe and reliable test results - This tier includes guidelines applicable to all pathology labs including those relating to Risk management Ethics Personnel Equipment Tier 3: A- Supervisory requirements for pathology laboratories B- Technical and specific detailed Requirements for good medical practice in all pathology services details the supervisory requirements, by a medical practitioner and the conditions of such relevant to the category of the medical testing laboratory. The 4 categories are GX or GY (general), S (specialized), M (medical) or B (Branch). It details - the requirements that laboratories only perform testing within their scope of accreditation - Supervisors and their delegates requirements to meet CPD - The requirements of a document risk management and incident reporting system Comprises of multiple documents which outline requirements which ensure good pathology practice. They cover - Measurement of uncertainty - Transport of pathology specimens - Need to participate in external quality assessment programs - Requirements for quality control, quality assurance and method testing internally - Requirments for retention of records and diagnostic material - Requirements for communication - Requirements for development and use of in house IVDs - Guidelines for approved collection centres Tier 4: Technical publications for specific areas of pathologyAnatomical Pathology Technical publications for specific areas of pathology - ANATOMICAL PATHOLOGY Documents including - Requirements to perform anatomical pathology cutup - Requirements for the facilities and operations of mortuaries - Performance measures for Australian laboratories reporting cervical cytology (third edition 2015) - Requirements for gynaecological (cervical) cytology (third edition 2017) - Requirements for laboratories reporting tests for the national cervical screening program (first edition 2017) Genetic Pathology

How do you attain Accreditation

To do this we must submit an application to NATA which includes a QUALITY MANUAL, details of other management systems and details of technical procedures NATA will then organize and advisory visit to examine these procedure and advise the laboratory on what they need to do to meet standards When a laboratory feels they have established all the necessary procedures and documentation necessary to display they are meeting criteria for accreditation NATA will return for an assessment visit In an assessment visit NATA will thoroughly examine the following : Management system Staffing, training of staff and supervision Methods Proficiency Validation/verification Equipment and its calibration Reporting of test results The environment in which the laboratory is established