Pathological Processes Flashcards
What is pathology?
The study of disease and cellular dysfunction.
What is disease?
A pathological condition that is characterised by identifiable signs or symptoms.
What is autolysis?
Self-digestion of tissues.
What do fixatives do and what is the rate of formalin penetration?
They inactivate tissue enzymes and denature proteins to prevent bacterial growth and putrefaction. It also hardens tissues.
It penetrates at 1mm/hour, when submerged in 10x volume of fixative.
How do you remove the water from a tissue?
Dehydration using alcohol, followed by the replacement of alcohol with xylene (also removes the lipid).
What do cytokeratins show a marker of?
Epithelial differentiation, and can give information about the primary site of a carcinoma.
What does molecular pathology look for?
Mutations in DNA, RNA or proteins.
What do DNA mutations and mRNA levels show?
DNA mutations = mutations in genes.
mRNA levels = expression of genes, which can be used to predict how a tumour may behave.
What are the clinical details given in a histology report?
Age/ gender.
Past medical history.
Signs and symptoms.
Risk factors.
Endoscopic findings.
Clinical teams’ diagnoses.
What is said in the macroscopic, microscopic and conclusion sections of a histology report?
Macroscopic = details of sample received and its size.
Microscopic = description of the tissue under the microscope and differential diagnoses.
Conclusion = what the diagnosis is.
What is the hearts response to injury?
There is an initial insult, causing the myocytes to work harder.
Adaptation occurs, causing cardiac myocyte hypertrophy.
Continued insult and adaptation occurs, leading to ventricular hypertrophy.
The continuing insult increases the requirement for the heart for oxygen, leading to the second insult of hypoxia.
The insufficient oxygen supply leads to ischaemia and myocardial infarction, an irreversible cell injury and death.
What does the degree of injury depend on?
The tissue type.
The type of injury.
The severity of the injury.
The length of the injury.
What are some non-environmental cause of cell injury?
Genetic/ ageing - inborn errors in metabolism, enzyme deficiencies and dysfunctional proteins.
What are some toxins that can cause cell injury?
Alcohol.
Drugs.
Asbestos.
Poisons.
Pollutants.
Insecticides.
Herbicides.
What are the two types of immune mediated injury?
Hypersensitivity reaction - excessive immune reactions, such as anaphylaxis.
Auto-immune reactions - immune system attacks itself, causing tissue damage.
Outline some physical agents that can cause tissue injury.
Trauma.
Extreme temperatures.
Electric currents.
Radiotherapy.
What nutritional/ dietary abnormalities can cause cell injury?
Obesity.
Anorexia.
Deficiencies or excesses, particularly in fat or salt, B12, folate and vitamin D.
What can excess intracellular calcium activate?
ATPases - reducing ATP levels.
Phospholipases - breaks down the cell membrane.
Proteases - breaks down organelles.
Endonucleases - breaks down DNA.
What transport proteins control free radical formation?
Transferrin binds iron to prevent the Fenton reaction from occurring.
Ceruloplasmin binds copper to prevent free copper from being available.
What do heat shock proteins do and how do cells adapt for this?
They help re-fold damaged proteins or label them for degradation.
Cells decrease protein synthesis and increase heat shock protein synthesis.
What is pathological apoptosis caused by?
Viral infection and cells with damaged DNA.
What is fat necrosis seen in?
Acute pancreatitis and direct trauma to fatty areas.
What 3 molecules are released by injured cells and what can their effect on the body be? When would they be seen?
Potassium - is cardiotoxic and can cause heart attacks. Seen in major burns.
Enzymes - can cause a breakdown of molecules. Seen in liver disease, MI and pancreatitis.
Myoglobin - decrease in renal function and tea-coloured urine. Seen in extreme athletes and when an elderly person falls and lays on a muscle for a prolonged period of time.
What do the complications of infarction depend on?
Any alternative blood supply.
The speed of ischaemia.
The type of tissue involved.
The oxygen content of the blood.
Outline the process of how excess alcohol can cause death.
Excess ethanol increases the NADH/NAD+ ratio, increasing fatty acid synthesis and accumulating the fat in the liver.
The continued consumption of alcohol causes inflammation of the liver, damaging the hepatocytes.
There is then abnormal cellular accumulations, such a toxic bilirubin, leading to necrosis, fibrosis and cirrhosis.
They then have liver failure and the liver cannot carry out its normal functions, leading to death.
What are the differences between exudate and transudate?
Exudate is caused by an increase vascular permeability, whereas transudate is not.
Exudate is protein rich but transudate is not.
Exudate occurs in inflammation, but transudate occurs in heart/hepatic/renal failure.
How can leucocytes increase vascular permeability?
Enzymes and ROS are released by activated inflammatory cells and can degrade the endothelial cells, increasing vascular permeability.
What proteins delivered in the exudate can help with inflammation?
Fibrin is delivered which acts as a mesh to limit the spread of toxins.
Immunoglobulins are delivered for opsonisation.
What is the structure of a neutrophil?
It has a purple staining, trilobed nucleus.
How do neutrophils roll and adhere to endothelial cells?
They roll through selectins that are expressed on endothelial cells.
They adhere through the binding of integrins (expressed on neutrophils) to the selectins, changing the adhesion from a low to high affinity state.
How does the neutrophil change for chemotaxis?
Re-arrangement of neutrophil cytoskeleton, stimulated by chemoattractants, such as bacterial peptides, IL-1, TNF and C5a.
What is hereditary angio-oedema? What can it cause?
Autosomal dominant deficiency in C1-esterase inhibitor
Patients have itchy cutaneous oedema of the skin.
They often have intestinal oedema, causing pain and can die of sudden death due to larangyeal oedema.
What is alpha-1 antitrypsin deficiency, and what do patients develop?
Autosomal recessive resulting in low levels of alpha-1 antitrypsin. It is a protease inhibitor, meaning proteins are broken down by proteases released from neutrophils.
Patients develop emphysema due to the destruction of parenchymal tissue, and liver disease due to incorrect protein folding.
Results in liver damage and cirrhosis.
What are the characteristics of chronic inflammation?
It has a slow onset.
There is a variable duration.
It has a variable appearance.
It limits damage and initiates repair.
It can cause debilitating symptoms.
Why do macrophages in the lung appear dark red/ brown?
They have phagocytosed carbon.
What gives macrophages their foamy appearance?
Phagolysosomes - the addition of lysosomes to material that has been phagocytosed.
What are the functions of macrophages?
To phagocytose pathogens, necrosis and debris.
Antigen presenting to T-cells.
Cytokine release to accumulate immune cells at the site of damage.
Describe the appearance of plasma cells.
They are oval in shape with a large nucleus to one side that contains clumps of chromatin that lines the edge.
There is peri-nuclear clearing - a site of lighter appearance as a ‘shadow’ due to the presence of Golgi.
Where are Langhans, Touton and foreign body giant cells seen?
Langhans = tuberculosis.
Touton = fat necrosis.
Foreign body = foreign bodies present.
What are the proportion of cells seen in rheumatoid arthritis, chronic gastritis and Whipple’s disease? What is the significance of this?
Rheumatoid arthritis = mainly plasma cells.
Chronic gastritis = mainly lymphocytes.
Whipple’s disease = mainly macrophages.
The proportion of cell types can help influence a diagnosis.
What is granulomatous inflammation?
Chronic inflammation and the presence of granulomata.
What are the two different types of granuloma and what distinguishes them?
Foreign body = destruction of foreign material containing few lymphocytes.
Immune mediated = destruction and removal of pathogens with many lymphocytes. It can be idiopathic and can undergo central necrosis.
Why are mycobacterium difficult to destroy?
They have thick cell walls and mycolic acids which are resistant to macrophages.
What factors are involved in the formation of a platelet plug?
What are some causes of thrombocytopenia?
What is Li-Fraumeni syndrome, and what does it increase the risk of?
What types of cancer does smoking increase the risk of?
