Session 1 Lecture Notes Flashcards
What is disease?
A pathological condition of a body part, organ or system characterised by an identifiable group of signs or symptoms
The cell is always central
What is pathology?
Study of disease and cellular dysfunction
What is the importance of a microscopic diagnosis?
It gives a definitive diagnosis
Can guide the type and extent of surgery
What is cytopathology?
Examining disaggregated cells rather than tissue
What is cytology?
Using a needle to suck a sample out
Give some examples of where serous carcinoma can be found
up to 5
Ovary Fallopian tube Uterus Cervix Peritoneum
What is an adenocarcinoma?
Tumour that has formed from glandular structures in epithelium
What does TNM stand for in cancer stages?
Tumour (graded 0-3)
Nodes (graded 0-2)
Metastasis (graded 0-X) - depends on number of places it has metastasised
What is Mohs surgery?
During Mohs surgery, thin layers of cancer-containing skin are progressively removed and examined until only cancer-free tissue remains
Name 2 types of receptors that breast cancers can have and name them
Oestrogen receptors (ER positive breast cancer) HER2 receptors (HER2 positive breast cancer)
What is tissue autolysis and how can we prevent this?
Tissue autolysis = self-digestion which begins when blood supply is cut off
Can block this using fixatives (which inactivate enzymes, denature proteins and harden tissue)
What chemical is used during fixation?
Formalin
After formalin is applied to a sample what happens?
The sample is cut up into small slices and placed in cassettes
In order to cut tissue very thin for cutting, what hardening agent is applied?
Paraffin wax Before this is applied: sample is dehydrated (water removed) using alcohol alcohol is removed using xylene xylene is replaced by paraffin wax
What is used to thinly slice tissue?
Microtome
What is the tissue stained with and what part of the cells turned what colour?
Haemotoxylin and Eosin
Haemotoxylin turns nuclei purple
Eosin turns cytoplasm and connective tissue pink
After the tissue has been hardened, sliced and stained - what is applied to the slide to preserve it?
A mounting medium and coverslip
What is immunohistology?
Looks for substance in or on cells by labelling them with specific antibodies
The antibody is joined to an enzyme that catalyses a colour producing reaction
What protein is used to identify smooth muscle cells?
Actin
What is used to identify carcinomas?
Cadherins
What are cytokeratins?
Intracellular fibrous proteins present in all epithelium
There are certain cytokines present in different types of epithelium
If a cell is positive for CK7 and negative for CK20 (types of cytokines) what does this mean?
The person has lung, breast, endometrium, ovary or thyroid cancer
If a person is negative for CK7 and positive for CK20 what does this mean?
They have colon or gastric cancer
If a patient has increase in HER2 proteins what does this mean?
Likely to indicate breast cancer
Why is MRNA expression more beneficial to look at?
You can see if the genes are being transcribed and may be able to predict behaviour of tumour
When would you use frozen sections?
In a surgical emergency when they need an urgent diagnosis before acting
What is macroscopic examination?
Looking at a sample with just your eyes
What is the most common cause of cell injury?
Hypoxia
What is ischaemia?
Decreased blood supply
What is hypoxaemic hypoxia?
When the arterial content of oxygen is low eg reduced partial pressure of oxygen at altitude
What is anaemic hypoxia?
Decreased ability of haemoglobin to carry oxygen e.g. carbon monoxide poisoning or anaemia
What is ischaemic hypoxia?
Interruption to a blood supply e.g. blockage of vessel
When is the only time you will ever see histiocytic hypoxia?
In cyanide poisoning - oxidative phosphorylation enzymes are disabled so body cannot utilise oxygen in cells
How long can a person survive hypoxia to neurones?
A few minutes
What 4 cell components are most susceptible to injury?
- cell membrane
- Nucleus
- Proteins
- Mitochondria
What happens in reversible hypoxia injury?
Reduction in oxidative phosphorylation in mitochondria = decreased function of NA, K ATPase = sodium, calcium and water influx = cellular swelling
Reduction in ATP = increased glycolysis = reduced glycogen and reduced pH
Detachment of ribosomes from ER = reduced protein synthesis = accumulation of fat in liver
What happens in irreversible hypoxia injury?
Massive influx of calcium (particularly from ER and mitochondria)
Calcium activates ATPase, phospholipase, protease and endonuclease
Leads to reduced ATP, reduced phospholipidsX disruption of membrane, chromatin (DNA) damage
What are free radicals?
A molecules with a single unpaired electron in outer orbit
What are the 3 free radicals of most significance in cells?
hydroxyl
superoxide
hydrogen peroxide
Give 5 ways in which free radicals can be produced?
- metabolic reaction eg oxidative phosphorylation
- inflammation - neutrophils use free radicals
- radiation
- contact with unbound metals in the body - iron and copper
- drugs and chemicals eg during liver metabolism by P450 enzymes
Give 3 ways in which the body controls free radicals
- Anti-oxidant system donate electrons to free radicals (vitamins A, C and E)
- metal carrier and storage proteins require iron and copper - prevent them producing free radicals
- enzymes that neutralise free radicals
What are the main target of free radicals?
Lipids in cell membranes
Lipid peroxidation
What is oxidative imbalance?
When the number of free radicals overwhelms the anti-oxidant system
What do heat shock proteins do? Give an example of one
They aim to mend misfolded proteins
eg ubiquitin
In hypoxia what do injured cells look like?
Swollen and pink cytoplasm
What is karyorrhexis?
Where the nucleus of dead cells break apart into small pieces (during hypoxia)
What is karyolysis?
Where the nucleus of dead cells break disappear (during hypoxia)
What do cells look like under microscope during reversible hypoxia injury?
Blebs appear as cytoskeleton begins to break apart
Swelling of cell
Dispersion of ribosomes
What does the cell look like under a microscope in irreversible cell injury from hypoxia?
Nucleus pyknosis, karyolysis or karyorrhexis
Myelin figures appear - fat collects under disrupted cell membrane
What is oncosis?
Cell death with swelling (the process)
What is necrosis?
The changes that occur after a cell has been dead some time
What are the 2 main types of cell necrosis?
Coagulative
Colliquitive (liquefactive)
When will you see coagulative necrosis?
During ischaemia of solid organs (where there is lots of CT)
When will you see liquefactive necrosis?
During ischaemia of loose tissues and presence of many neutrophils (little CT)
When is the only time you will see caseous necrosis and what is it?
When a person has tuberculosis
You see broken down debris of cells with no structure (looked like cottage cheese)
What is fat necrosis and what does it looks like?
When digestive enzymes eg lipase begin to attack fatty acids
Gives the appearance of wax drops
What is gangrene?
Necrosis visible to the naked eye
What is an infarction?
Necrosis caused by a reduction in arterial blood flow
What is dry gangrene? Give an example
Necrosis modified by exposure to air
eg umbilical cord in babies
What is wet gangrene?
Necrosis modified by infection
What is gas gangrene?
Wet gangrene where the infection is from anaerobic bacteria that produce gas
What is the most common cause of infarction?
Blood clot (thrombus) in a coronary artery
What is a thrombosis?
Where a clot occurs within an intact blood vessel
What is an embolism?
Where a clot breaks off and travels in the artery to the brain - blocking the blood supply
When does an infarct appear white?
In coagulative necrosis (solid organ with CT) - no blood
When does an infarct appear red?
In liquefactive necrosis (loose organs with less CT) - blood vessels may haemorrhage
The tissue may also have a dual blood supply
What is ischaemia reperfusion injury?
What can cause damage in this condition?
If blood flow is returned to damaged but not yet necrotic tissue damage can be worse
Damage from:
increased production of free radicals
increased number of neutrophils = increased inflammation and tissue injury
complement proteins = activate complement pathway
Name 3 key things that can leak out of a membrane
- Potassium
- Enzymes eg troponin released after myocardial infarction
- Myoglobin - after damage to skeletal muscle
What is apoptosis?
Cell death with shrinkage - cell activates enzymes to degrade its own DNA and proteins
Do you see inflammation in apoptosis?
No
Cell membrane is maintained
When might apoptosis occur physiologically?
To maintain a steady state (new cells coming in via mitosis)
Embryogenesis (cells between digits apoptose)
When does apoptosis occur pathologically?
When cells are damaged
When a graft acts against a host eg WBCs from graft recognise host cells as foreign and attack
What does apoptosis look like?
Apoptic bodies appear - acellular breaks up into fragments
What are the 3 phases of apoptosis?
- initiation
- execution
- degradation and phagocytosis
What are caspases and what do they do?
Enzymes that are activated during apoptosis and cause cleavage of DNA and proteins of cytoskeleton
What is the intrinsic pathway of apoptosis? What key protein is activated and what does it release?
When the signal is initiated from within the cell
p53 protein is activated which causes outer mitochondrial membrane to become leaky
It causes cytochrome C to be released from mitochondria which causes activation of caspases
What is the extrinsic pathway of apoptosis? What does it secrete and what is the result?
Initiated by extracellular signals eg. when cells have become a danger
One of the signals is TNFa (secreted by T killer cells which binds to cell membrane death receptor)
Results in activation of caspases
When can fluid enter/accumulate in cells?
During hypoxia NA, K ATPase no longer functions and sodium calcium and water enter the cell
What is steatosis and what does it look like?
Accumulation of triglycerides (often seen in liver)
Organ swells and takes on yellow appearance
Fat pushes nucleus to edge of cell
Where does cholesterol accumulate?
In smooth muscle cells and macrophages in atherosclerotic plaques (cells with bubbled appearance)
Name 2 conditions where proteins accumulate in the cell
Alcoholic liver disease
a-1 antitrypsin deficiency
When do pigments accumulate in cell?
Through air pollution or tattooing
Pigments are inhaled and phagocytosed by macrophages remaining in dermis
Some will travel to lymph nodes
What is haemosiderin and when does it form?
An iron storage molecule derived from haemoglobin
Forms when there is an excess of iron
What is hereditary haemochromatosis? What is the treatment?
Genetically inherited disorder resulting in increased intestinal absorption of iron
Treatment = repeated bleeding
What accumulates in jaundice?
Bilirubin (breakdown product of heme)
What 2 methods cause hypercalcaemia?
Increased secretion of parathyroid hormone (PTH) resulting in bone resorption
Destruction of bone tissue
What determines length of cell life?
Length of telomeres
Why can germ cells and stem cells live indefinitely?
They contain an enzyme called telomerase which maintains original length of telomerase
