Session 1 ILOs - Introduction to pathology, Cell injury and death Flashcards
Describe and classify the different branches of pathology
Pathology is the study of suffering (disease and cellular dysfunction)
- Chemical pathology
- Haematology
- Cellular pathology (histology nad cytopathology)
- Immunology
- Medical microbiology (virology and bateriology)
Explain why examination of tissue microscopically is important and what information can be obtained from such examination
Able to identify abnormal strctures, if it’s inflammatory or neoplastic, benign or malignant or if it’s a primary tumour or metastatic tumour
Also able to say: - Type of cancer - Grade of cancer - Completeness of excision - Sage of cancer - Efficacy of further treatments (aspect of subjectiveness)
Describe the processes involved in producing slides for microscopy
- Fixation
- Cutting/trimming
- Embedding
- Blocking
- Microtomy
- Staining
- Mounthing
- Microscopy and diagnosis = histopathology report
Briefly outline the principals behind immunohistochemistry and how it aids diagnosis
Immunohistochemistry is used to label substances in/on cells that are antigenic with specific antibodies (enzyme attached which generates light forming reaction)
Can be used to see if receptors are present (e.g. ER and Her2 receptors in breast cancer) to see if treatments are likely to work
Recognise the principals behind molecular biology
Sequencing of DNA - can show if mutation is present in a particular gene
mRNA expression profiling can predict how a tumour is likely to behave
Explain what a frozen section is, giving examples of when then may be indicated
Type of urgent histopathology - for use during operations to influence the course of the operation
- Only takes 5-15 mins as it bypasses the fixation and embedding processes
- Tissue is rapidly frozen
- However it is less accurate (96% accurate) as it’s vulnerable to misinterpretation
Describe the common causes (aetiology) of cell injury
Environmental:
- Hypoxia (oxygen depravation)
- Toxins (drugs etc.)
- Physical agents (physical trauma, temp extremes etc.)
- Radiation
- Microorganisms
- Immune mechanisms
- Nutritional/deficiency
Genetic and ageing process
Explain the different mechanisms of cell injury:
- Reversible hypoxia
- Irreversible hypoxia
- Free radicles
Hypoxia (4 types) / ischaemia:
Reversible cell injury:
- Reduced oxygen supply causes a reduction in oxidative phosphorylation = reduced ATP
- Influx of calcium, Na+ (and water) leads to cell swelling
- Increased glycolysis leads to more lactic acid production and more acidic pH
- Also , detachment of ribosomes so less protein synthesis and lipid deposition occurs
Irreversible cell injury:
- Not fully understood but thought to occur due to influx of calcium due to increased calcium permeability with a series of consequences
Radiation / free radicals
- Most likely to damage lipids, proteins and DNA
- Damage by stealing electrons in a chain reaction
Describe and interpret the appearance of injured cells by light and electron microscopy (i.e. cytoplasmic changes, nuclear changes, intracellular accumulations)
Injured cells by light microscopy:
(Reversible)
- Cytoplasmic changes (reduced staining of cytoplasm due to H2O)
- Nuclear changes where chromatin clumps together
- Abnormal cellular accumulations
(Irreversible / cell death)
- Pyknosis = shrinkage of nucleus/chromatin
- Karyorrhexis = fragmentation of the nucleus
- Karyolysis = complete loss of nucleus
Injured cells by electron microscopy:
(Reversible)
- Blebs
- Clumping of nuclear chromatin
- Detachment of ribosomes
- Generalised swelling (incl. mitochondria)
(Irreversible / cell death)
- Lysis of endoplasmic reticulum
- Defects in cell membrane (no longer blebbing)
- See Pyknosis, Karyorrhexis or Karyolysis at the nucleus
Define and explain the clinical terms often associated with cell death (i.e. types of gangrene, infarction etc)
Gangrene = visible necrosis of a tissue
Dry - due to restricted blood supply and exposure to air which dries it out (coagulative necrosis)
Wet - due to infection and can cause sepsis (liquefactive necrosis)
Gas - due to infection with anaerobic bacteria which produce gas bubbles (mainly from trauma/RTA)
Infarction = necrosis caused by a reduction in arterial blood flow
- Coagulative (mainly solid organs)
- Liquefactive (mainly loose organs)
(then can be red or white, usually red for liquefactive and vice versa)
Infarct = AREA of necrotic tissue caused by a reduction in arterial blood flow
Describe, with examples, the different types of abnormal cellular accumulations that can occur in cells secondary to cell injury
Accumulation occurs when the cell is injured and isn’t able to metabolise something, could be normal cell components, abnormal components or pigment:
Fluid/water:
- Na+ and water enter due to cellular disturbance
- Oncosis
Lipids / triglycerides:
- Accumulation of cholesterol in the liver, stored in intracellular vesicles if it can’t be eliminated
- Can cause atherosclerosis, xanthoma or inflammation/necrosis
Proteins:
- Can accumulate in the liver = alcoholic liver disease or alpha-1-antitrypsin deficiency disease
Pigment:
- Can be exogenous (e.g. soot/dirt and tattooing) where it’s phagocytosed by macrophages and it remains there
- Can be endogenous (e.g. haemosiderin) which is in iron storage molecule and there is a build up in haemolytic anaemias for example
- Jaundice is another example from the build up of unconjugated bilirubin
Recognize the most common molecules released by injured cells and how they may affect the cell/body processed
Potassium:
- Normally high in cells, can be released into the interstitium
- Important for ‘Tumour lysis syndrome’, if someone has chemotherapy then need to make sure we can mop up potassium if lots of necrosis
- Mainly affects the heart!
Enzymes:
- Used clinically to determine which organ has been damaged
Myoglobin:
- Released from dead myocardium and striated muscle (rhabdomyolysis if severe)
- Can result in acute renal failure/injury
- Appears in the urine as dark brown urine
Discuss the effects of chronic excessive alcohol misuse and obesity on the liver (i.e. fatty change, acute alcoholic hepatitis and cirrhosis)
Acute effects:
- Acute liver failure
- Hepatitis
- Steatohepatitis
Long term effects:
- Cirrhosis
- Liver failure
Explain the different types of pathological calcifications (dystrophic and metastatic)
Pathological calcifications = abnormal deposition of calcium salts within tissues (2 types)
Dystrophic / localised:
- Tend to get in dead/dying tissues but occurs with normal levels of body calcium
- Common in atherosclerosis
Metastatic / generalised:
- Deposition of hydroxyapatite crystals in normal tissues throughout the body, but occurs when there are disturbances to calcium metabolism
- Usually asymptomatic but can be lethal
Explain how cell injury targets the different components of the cell (cell membrane, nucleus, proteins and mitochondria)
Cell components most susceptible to cell injury:
- Cell membranes (plasma membrane or organelle membranes)
- Nucleus (DNA)
- Proteins (enzymes or structural)
- Mitocondria (oxidative phosphorylation)
