Pathology Flashcards
How does the World Health Organisation define health?
Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.
How does the World Health Organisation define illness?
Illness is a state in which a person’s physical, intellectual, emotional, social or spiritual functioning is diminished or impaired in comparison with the previous experience.
Define a syndrome
A syndrome is a set of signs and symptoms that occur together. May have a well-defined cause (eg. Down syndrome) or multiple etiologies (eg. acute respiratory distress syndrome).
Pathology
Study of diseases
What are the different approaches to disease?
- History and epidemiology of the disease
- Etiology (the why, causes)
- Pathogenesis (the how, mechanism of the disease)
- Pathological alterations (macroscopic, microscopic)
- Pathophysiology (how pathologic changes alter function on different levels of organisation)
- Clinical manifestations
- Imaging and laboratory data
- Diagnosis
- Complication of a disease
When the etiology of a disease is unknown, we say it is…
idiopathic
When the etiology of a disease is known, it can be either… (3)
genetic, acquired, multifactorial
What is a differential diagnosis?
Method of analysis that distinguishes a given disease from others that present similar signs and symptoms.
What are predictive factors?
Factors that predict potential response to a specific therapy or treatment (drug, biological compound).
What are prognostic factors?
Factors that provide information about the likely outcomes and course of a disease, regardless of the treatment received - patient’s survival.
Example of a prognostic factor
In cancers, higher stages are associated with poorer prognosis
Example of predictive factor
In breast cancer, patients who are ER positive are more likely to respond to hormone therapy.
Etiology
Causes, “why” of a disease
Pathogenesis
Mechanism, “how” of a disease
Pathophysiology
How the structural pathologic changes (pathology) affect the function of the cells and tissues of a patient
Hospital diagnostic pathology can be divided into …(2)
- Anatomic (diagnostic) pathology
- Clinical pathology
Diagnostic (anatomic) pathology encompasses… (4)
- Autopsy pathology
- Surgical pathology
- Cytopathology
- Specialty labs
Diagnostic (anatomic) pathology is related to the field of …
diagnostic imaging (radiology)
Autopsy pathology
Examination of a body after death to determine the causes of death and evaluate any injury or disease present.
There is a decline in autopsies being done in patients. However, autopsy pathology is still important for… (3)
- Quality assurance or improvement
- Patient concern with personalized medicine and hereditary conditions
- Helping families get the facts, grieve and find closure
Surgical pathology
Study and diagnosis of disease through the examination of tissues removed from the body during surgery.
Surgical pathology is … than autopsy pathology.
a) much more common
b) much less common
a) much more common
Surgical pathology is the main practice of pathologists.
Name the 5 surgical procedures used in surgical pathology.
- Core (needle) biopsies
- Incisional biopsies
- Excisional biopsies
- Resection
- Exenteration
Core (needle) biopsy)
Uses a long, hollow tube to obtain a sample of tissue.
Incisional biopsy
Surgical procedure during which a cut is made in the skin to remove a sample of abnormal tissue (e.g. of a large mass).
Excisional biopsy
Surgical procedure during which an entire lump or suspicious area is removed (e.g. lymph node, breast mass). Purpose is diagnostic examination.
Resection
Removal of a larger area of tissue (tumor, organ, part of an organ) for therapeutic purposes. The lesion removed is usually larger than in excisional biopsy.
Exenteration
Surgery for treating cancer of reproductive organs. Entire pelvic contents are removed (e.g. uterus, cervix, vagina).
Tissue preparation in autopsy and surgical pathology aims to produce a …
thin translucent section with stains to differentiate cell and tissue components
Name the 9 steps of slide preparation before they are analyzed by a pathologist
- Gross (macroscopic) examination
- Tissue fixation
- Tissue processing
- Tissue embedding
- Microtomy (sectioning)
- Staining
- Mounting
- Labeling
- Microscopic review
- Gross (macroscopic) examination
Inspection of the specimen and selection of most appropriate sections.
If the biopsy is already a small piece, it can be fixed directly. If we have a larger specimen, we must first sample and cut representative sections.
- Tissue fixation
Purpose: To preserve tissue structure and prevent degradation.
Tissue sample is placed in a fixative solution (10% formalin) almost immediately after removal. The faster a tissue is fixed the better. It takes longer for the fixative to penetrate the entire tissue if it is a larger sample.
- Tissue processing
Purpose: To dehydrate and embed the samples in a solid medium that can be cut into very thin sections.
- Graded alcohol baths to dehydrate the tissue
- Placed in xylene or other clearing agents to remove the alcohol + increase transluscency
- Infiltrated with paraffin wax (provides firm matrix, allowing thin slicing).
- Tissue embedding
Tissue is placed in a mold and surrounded by liquid paraffin wax which hardens as it cools. This makes it easier to cut the tissue into thin sections.
- Microtomy (sectioning)
Cutting the tissue into extremely thin slices (3-5 microns thick) for microscopic examination using a microtome.
These sections are then carefully placed on glass slides.
- Staining
Purpose: To enhance tissue contrast and highlight cellular structures. The most common stain is hematoxilin and eosin (H&E).
- Mounting
A coverslip is placed over the stained tissue section using resin to help preserve the sample and ensure a clear view under the microscope
- Labeling
Slide is labeled with relevant patient info for the pathologist and for identification.
- Microscopic review
Pathologist reviews the slides under the microscope and examines the tissue for abnormalities (cancer, necrosis, inflammation).
Hematoxilin is a…
a) blue/purple stain
b) red/pink stain
It binds to…
a) acidophilic substances
b) basophilic substances
Hematoxilin is a BLUE/PURPLE stain that binds to BASOPHILIC substances.
What is a synonym for basophilic? Name examples of basophilic substances bound by hematoxylin
Basophilic = acidic
DNA and RNA in nucleus (stained blue/purple)
Eosin is a…
a) blue/purple stain
b) pink/red stain
It binds to…
a) acidophilic substances
b) basophilic substances
Eosin is a PINK/RED stain that binds to ACIDOPHILIC substances
Synonym of acidophilic. Names examples of acidophilic substances bound by eosin.
Acidophilic = basic
Proteins (with lysine, arginine) in the cytoplasm
The normal slide preparation process takes time. What do we do when a patient is on the operating table and an urgent diagnosis is needed?
- Pathologist does an OR consultation
- Tissue is frozen and cut on a cryostat at -20•C, then stained with H&E
Name the advantages and disadvantages of “frozen sections” when an urgent diagnosis is needed.
Advantages: fast, pathologist can make a diagnosis in 5-15 min
Disadvantages: not all specimens can be frozen; creates a small diagnostic error rate
Nuclear staining (hematoxilin) reflects…
DNA, genetic material, the regulator if proliferation and metabolic activity (genotype of the cell)
Cytoplasmic staining reflects…
Effector proteins (enzymes, contractile elements, mitochondria) and the phenotype of the cell (is it a hepatocyte , myocyte, etc)
When a tissue is more intensely stained with eosin than usual, we say it is…
This is usually an indication of…
highly eosinophilic
usually an indication of necrosis or apoptosis
Prussian blue stain targets…
ferric iron deposits in tissues (stains blue)
Compare a normal liver section to a section of a liver with hemochromatosis when stained with Prussian blue.
Normal liver: cells appear pink (we only see background eosin)
Liver with hemachromatosis: hemachromatosis causes you to absorb too much iron from the food you eat - excess iron is stored in liver and other organs - the section will apear purplish blue, strongly stained by Prussian blue
Masson trichrome stain is used for tissues with fibrosis and stains different tissue components in different colors.
Collagen: blue
Muscle: red
Cytoplasm: light red or pink
Nuclei: dark blue
Name two stains for microorganisms
- Ziehl-Neelsen
- Grocott
Zhiel-Neelsen
Stains lipid coat of acid-fast bacilli (eg. M. tuberculosis)
Grocott
Stains fungal organisms (silver stain reacts with carbohydrate capsule) (eg. aspergillus infection in lung transplant patient). Fungi are stained black.
Describe the principle of Ag-Ab binding used in immunohistochemistry
In the body, antibodies bind specifically to corresponding antigens (viruses, etc) to eliminate them. Immunohistochemistry utilizes this binding to identify specific cellular macromolecules
How are antibodies used in immunochemistry made?
- Protein of interest is injected in an animal, which will generate a specific antibody for that protein
- Antibody is purified
- Antibody is applied to histologic sections to detect the presence of the protein of interest
Antibodies are applied to histologic slides along with a chromogen like peroxidase-diaminobenzidine, producing a … color
brown color
Define the cluster of differentiation (CD)
CD number is assigned to antibodies that recognize a given cell surface molecule (e.g. anti-CD20 ani body will recognize cells expressing CD20 on their surface).
How can we recognize the epithelium?
By doing a keratin stain using antibodies for keratin.
Immunofluorescence is usually done on… and mainly used in … pathology
Immuofluorescence is usually done on FROZEN SECTIONS and mainly used in RENAL PATHOLOGY.
Immunofluorescence usually looks for…
IgA, IgM, IgG
Electron microscopy is a very imprecise tool, nowadays used mostly only in…
renal pathology
In electron microscopy we need ultra-thin sections, so the samples are embedded in epoxy resin and cut on…
diamond knives
Cytopathology examines…
whole cells or sheets of cells (rather than sections of pieces of tissue)
Cytopathology is divided into (2)
- gynecologic cytopathology (PAP smears)
- non-gynecologic cytopathology
How do procedures, sampling methods and fixation in cytopathology differ from surgical pathology?
Cytopathology uses smears, cytocentrifuge, etc. However, if there is enough tissue, we can make “cell blocks” that are processed similar to surgical pathology samples
What is the overall goal in the future of pathology?
Personalized medicine
The cell works like a factory that makes proteins. Name the 6 key organelles involved in this process and briefly summarize their role.
- Ribosome (makes proteins)
- Endoplasmic reticulum (makes proteins and lipids)
- Mitochondria (makes energy)
- Lysosome (gets rid of unwanted waste and debris)
- Nucleus (stores genetic material)
- Golgi apparatus (sorts proteins)
When a cell undergoes an irreversible injury, it will die by…
necrosis or apoptosis
What are the different possible types of cell injury (VICTORIAN)?
V: Vascular
I: Infectious
C: Chemical
T: Trauma and temperature
O: Ospital (iatrogenic)
R: Radiation
I: Inherited
A: Autoimmune
N: Nutritional
The cellular response to injury depends on the… (2)
- Severity, intensity and duration of the injurious agent
- The nature and genetic background of the cell
Reversible injury
Temporary change in function and cellular morphology in response to an injurious agent (cell returns to normal after the agent is removed).
Macroscopic morphologic features of reversible cell injury (2)
- Increased organ weight
- Pale with increased turgor (swollen)
Light microscopic morphologic features of reversible cell injury (4)
- Cellular swelling
- Blebbing (bubbling) of cell membrane
- Hydronic change/vacuolar degeneration (bubbly appearance)
- Fatty change
Ultrastructural (i.e. electron microscopy) morphologic features of reversible cell injury (4)
- Plasma membrane damage
- Mitochondrial swelling
- Dilation of endoplasmic reticulum
- Detachment of ribosomes
Fatty change is also known as…
steatosis
Define fatty change and name two causes
Fatty change (steatosis) is the abnormal accumulation of lipids in the cellular cytoplasm. It can occur due to alcohol-related liver disease OR in metabolic dysfunction-associated fatty liver disease.
Is fatty change due to alcohol-related liver disease reversible?
Yes, if the individual stops drinking alcohol!
Necrosis
Pathologic, uncontrollable cell death in response to severe or persistent injury
5 macroscopic (gross) patterns of necrosis
- Coagulative necrosis
- Liquefactive necrosis
- Caseous necrosis
- Fat necrosis
- Fibrinoid necrosis
Coagulative necrosis features (3)
- Cellular outline is maintained
- Protein degradation
- Inflammatory response is sparse
Liquefactive necrosis features (2)
- Loss of cellular outlines/structural integrity
- Enzymatic digestion of necrotic tissue (leading to its liquefaction) and inflammation (pus)
Coagulative necrosis is often due to…
hypoxia/ischemia
Caseous necrosis features (2)
- Special type of necrosis in mycobacterial infection (tuberculosis)
- Amorphous granular debris surrounded by granulomatous inflammation
In caseous necrosis, a mix of different types of inflammatory cells including … and … surround a center necrotic debris.
macrophages and giant cell macrophages
Pathologists will usually perform special stains to look for … when caseous necrosis is seen.
mycobacterial or fungal organisms
Caseous necrosis is often seen in…
children
Fat necrosis features (2)
Fat necrosis = death of fat tissue
- Fat destroyed through action of lipases on adipocytes
- Grossly appears as chalky white areas (lipids are broken down into fatty acids which react with calcium in a process call saponification)
Fat necrosis is often observed in the …
pancreas
(due to release of pancreatic enzymes that digest fat)
Fibrinoid necrosis features (2)
- Autoimmune diseases (like vasculitis) lead to deposition of immune complexes (antigen-antibody complexes) in blood vessel walls leading to damage and leakage of the immune complexes and plasma proteins from the injured vessels.
- Fibrinogen (a plasma protein) can leak out of the damaged vessels into the surrounding tissue and combines with other debris to creat a fibrinoid appearance under the microscope (appears bright pink - highly eosinophilic - and amorphous).
Fibrinoid necrosis is often seen in … (2)
vasculitis (group of disorders that destroy blood vessels by inflammation) and transplant rejection
In what type of necrosis do the tissue and cells remain recognizable?
Coagulative necrosis, because cell outline is maintained.
*Note however that nuclei are missing because the cells are dead!
Necrosis - light microscopy cytoplasmic changes (4)
- Increased eosinophilia (stains bright pink due to accumulation of eosinophils)
- Hyaline change (glassy pink appearance due to glycogen loss in cytosol)
- Vacuolation (bubbly appearance due to loss of organelles)
- Calcification (calcium buildup in necrotic or dying tissues)
Necrosis - light microscopy nuclear changes (4)
- Pyknosis
- Karyorrhexis
- Karyolysis
- Complete loss of nucleus
Pyknosis
Irreversible condensation of chromatin in the nucleus of a dying cell (nucleus shrinks and becomes darkly-stained under microscope).
Karyorrhexis
Destructive fragmentation of the nucleus of a dying cell.
Karyolysis
Complete dissolution of the chromatin and nucleus of a dying cell.