Pathology Flashcards
Definition of risk factor?
Social or individual factor which increases the risk of development of a disease
Aetiology definition?
Causative element in disease
Pathogenesis definition?
Sequence of events from healthy state to clinical disease
Sequelae definition?
Range of possible outcomes of disease process
Outcome definition?
Patient health or illness at a defined time
Necrosis requires energy. True or False?
FALSE
Requires no energy
What is necrosis? And what does it elicit?
Death of tissues
Pathological
-Elicits adjacent tissue response
Different patterns of necrosis?
- Coagulative
- Colliquative
- Caseous
- Gangrenous
- Fibrinoid
- Fat necrosis
Coagulative necrosis?
Proteins coagulate
Preservation of cell outline
-Eg MI
Colliquitive necrosis?
Necrotic material becomes softened and liquefied (PUS)
No cell structure remains
-Eg brain
Caseous necrosis?
Cheese-like
-Eg TB
Gangrenous necrosis?
Cell death by necrosis then infection on top of it
Anaerobic bacteria may grow
Fibrinoid necrosis?
Fibre deposition
-Eg damage to blood vessel in malignant hypertension
Fat necrosis example?
Eg- Acute pancreatitis
What process requires energy?
Apoptosis
What is apoptosis?
Programmed cell death
Defence against inherited injury
-Eithe physiological (normal growth) or pathological (injury, infection, chemo)
What is P53 and what can it lead to?
- Protein
- If lost it can lead to development of cancer, which is more likely resistant to treatment
Where does P53 function?
Cell cycle at G1 (like a spell checker)
-If mistakes are found cycle is paused and repair is attempted
What can occur at G1 checkpoint?
Apoptosis
If DNA is damaged
G2 checkpoint?
Mitosis will not occur if DNA is damaged or not replicated
M checkpoint?
Mitosis stops if chromosomes are not properly aligned
What happens if DNA can’t be repaired?
Then P53 stimulates and indices apoptosis
What part of the cell is involved in cell aging?
Telomere
Shortening
How do chromosomes prevent degradation and fusion?
They are capped
What does cancer reactivate?
Telomerase gets reactivated in cancer and can become immoral
What causes loss of membrane integrity?
Failure of ion pumps
Disruption of membrane
Alteration of lipids
Cross-linking of membrane proteins
What are free radicals formed by?
- Drugs
- O2 toxicity
- Reperfusion injury
- Inflammation
- Intracellular killing of bacteria
What is a metabolic disorder?
Biochemical abnormality which may itself be deleterious, but which also causes target organ damage, usually by accumulation of injurious agent
How would you inherit a metabolic disorder?
Autosomal recessive
Inherited metabolic disorder causes…?
Loss of function
What is phenylketonuria?
Due to accumulation of phenylalanine
Caused by deficiency in enzyme (phenylalanine hydroxylase) which converts phenylalanine to tryosine
Guthrie test - foot prick (PKU)
Vascular phase of inflammation?
Dilation and increased permeability of blood vessels
Exudative and cellular phase of inflammation?
Fluid and cells escape from permeable venules
What is a diagnostic feature for inflammation?
Neutrophil accumulation in extracellular space
Beneficial effects of inflammation?
- Toxin dilution
- Entry of ABs
- Fibrin formation
- Drug transport
- Oxygen and nutrient delivery
- Immune response stimulation
Harmful effects of inflammation?
- Digestion of normal tissues
- Swelling
- Inappropriate inflammatory response (Type 1 sensitivity)
What is chronic inflammation?
Subsequent and often prolonged tissue reactions
Characteristics of inflammation?
- Redness
- Heat
- Swelling
- Pain
- Loss of function
Why does redness occur in inflammation?
Due to dilation of small blood vessels
Why does heat occur in inflammation?
Increased blood flow through region
Why does swelling occur in inflammation?
Accumulation of fluid in extravascular space
Why does pain occur in inflammation?
Distortion of tissues
Why does loss of function occur in inflammation?
Inhibited by pain or swelling
What is in fluid exudate?
Proteins including immunoglobins
When does fibrinogen turn to fibrin?
On contact with ECM (Extra-cellular matric fibrin), acutely inflammed organ surfaces commonly covered in fibrin
What is margination?
Loss of intravascular fluid and increased plasma viscosity allows neutrophils into plasma (only occurs in venules)
What do neutrophils stimulate?
Inflammation
Adhesion of neutrophils increased by?
Complement C5a
Leukotriene B2
TNF
Endothelial expression of adhesion molecules increased by?
IL1
Endotoxins
TNF
What is chemotaxis?
Locomotion orientated along a chemical gradient
Examples of chemical mediators?
Histamine Seratonin Chemokines Leukotrienes Prostaglandins
What does histamine do?
-Vascular dilation
What are histamines released by?
Mast cells, eosinophils, basophils, platelets
Release of histamine is stimulated by?
C3a, C5a and lysosomal proteins (released by neutrophils)
What does seratonin cause?
Increased vascular permeability
What is another term for seratonin receptors?
5HT
Where are 5HT present in high concentration?
Platelets
What do chemokines do?
Attract various leukocytes to site of inflammation
What type of hypersensitivity are leukotrienes involved in?
Type 1
What do prostaglandins do?
Increase vascular permeability
Stimulate platelet agregation
What is necessary for recognition of microorganisms?
They must be coated with opsonin
Examples of things acting as opsonins that could coat microorganisms?
Fc fragment of IgG
C3b
Collectins
What is suppuration? What cells does it include?
Formation of pus
Neutrophils, bacteria, cellular debris
Resolution?
Complete restoration of tissues to normal after episode of acute inflammation
Cells involved in chronic inflammation?
Plasma cells
Lymphocytes
Macrophages
Macroscopic appearance of inflammation eg chronic ulcer?
Breach in mucosa
Base lined by granulation tissue
Fibrous tissue extends through muscle layers
Appearance of chronic abscess cavity?
Thickening of wall by fibrous tissue
When would something appear granulomatous?
Crohn’s
TB
On contact with____, __ Lymphocytes become _______ cells?
Antigen
B
Plasma
What cell produces cytokines?
T lymphocyte
Characteristics of reversible damage?
- Reduced aerobic respiration/increased anaerobic
- Membrane pumps fail
- Cell swelling
- Accumulation of lipids
Characteristics of irreversible damage?
- Severe damage to cell membranes and mitochondria
- Leakage of enzymes
- Nuclear changes- ATP changes, cell membrane damage
Progression of injury/damage?
Attempted repair
|
Complete= regeneration/restitution
Incomplete= repair/scarring
Labile cells. What are they? location?
Cells that multiply constantly throughout their short lives
-GI tract, Bone marrow
Stable cells. What are they? Location?
Cells that multiply only when needed
-Hepatocytes, endothelium
Permanent cells. What are they? Location?
Cells that are unable to replicate in post-natal life
-Skeletal muscle, neurones
REGENERATION of these is not possible
Stem cells. What are they?
Pluripotent cells
Can differentiate into most cell types
What becomes a fibrous scar?
Granulation tissues after it has undergone organisation
What is a granuloma and when is it normally present?
- Collection of macrophages (in response to foreign bodies eg bone, asbestos, TB, parasites, syphillis, malignancy)
- FOUND in chronic inflammation
What is differentiation?
Acquisition of specialized features
Hyperplasia?
Increase in cell number
What does amlodipine cause?
Gingival hypertrophy (overgrowth of gum tissue around teeth)
Hypertrophy?
Increase in cell size
Atrophy?
Reduction in cell size and number in an organ that was normal size
Hypoplasia?
Reduced size of an organ that never fully developed to normal size
Metaplasia?
One type of cell becomes another form of cell in response to stress
Example of metaplasia?
Barrett’s eosophagus
Meaning of neoplasia?
New growth
Neoplasia?
Abnormal mass of tissue, growth which exceeds and is uncoordinated with that of normal tissues
Describe heritage of neoplastic cells?
Monoclonal
-Derived from one single common ancestor
Benign neoplasia?
- No necrosis
- N:C nucleus to cytoplasm ration normal
- Minimal change in size/shape (pleomorphism)
- Diploid
- Adenoma
- Papilloma
Types of benign neoplasia?
Adenoma
Papilloma
Malignant neoplasia?
Necrosis common Metastatic potential Pleomorphic N:C ratio increased Aneuploid Carcinoma, carcinoma in situ, sarcoma
Carcinoma is?
Cancer of epithelial cell
Carcinoma in situ is?
Not invading other tissues, confined to site of origin
Sarcoma is?
Cancer of mesenchymal cell
What is meaning of dysplasia?
Disordered growth
What is dysplasia?
Pre-malignant process
Abnormal cell changes
Angiogenesis?
Formation of new abnormal blood vessels
Successfully growing tumors will develop ability to create own blood supply
Metastasis?
Formation of tumour implants that are discontinuous with the primary lesion
Roues of mets?
- Carcinoma?
- Sarcoma?
Lymphatic= carcinoma Sarcoma= haematogenous
Stepwise progression of cancer?
Initiation- 1st mutation
Promotion- more mutations
Persistence - Malignant?
What is involved in initiation?
Oncogenes
Tumour suppresors
DNA repair
Evasion of apoptosis
What is involved in promotion?
Further accumulation of mutations
What is involved in persistence?
Unregulated abnormal growth, can become malignant
What do classical oncogenes do?
Stimulate cell proliferation (turn up genes that promote growth)
Inhibition
Dominant
Examples of oncogenes affected by mutations?
RAS - colon, lung, bladder, melanoma, pancreatic
BRAF -
Myc -Lymphoma. neuroblastoma, small cell carcinoma of lung
P13K - Haematological malignancies
What do tumour suppressors do?
Turn of genes that slow growth
- Inhibit cell proliferation
- Stimulate cell death
- Recessive
Examples of tumour suppressors affected by mutations?
P53 protein
What is P53? What is is activated by?
Transcription factor
Activated by cell stress
Dna repair genes affected by mutations?
BRCA 1 and BRCA2
What malignant cells look like?
Usually rough and nasty
What benign cells look like?
Usually smooth and round
Epithelium cancer?
Carcinomas
Glandular cancers?
Adenoma vs adenocarcinoma
Squamous cancers?
Papilloma vs squamous cell carcinoma
Sarcoma is malignant. True or false?
TRUE
Paraneoplastic syndromes?
Clinical syndromes involving non-metastatic systemic effects that accompany malignant disease. They are rare disorders
Example of an acquired metabolic disorder?
Diabetes
Which diabetes is insulin dependant?
Type 1
What is type 2 diabetes?
Non-insulin dependent
Biochemical complications of diabetes?
Ketoacidosis
Non-enzymatic glycosylation
Hypoglycaemia
Lactic acidosis
Other issues associated with diabetes?
Macroangiopathy
Diabetic nephropathy
Diabetic retinopathy
Cataracts
Peripheral obesity?
Around around arms and thighs
Pathogenesis of atheroma?
- Fatty streak
- Fibrofatty plaque
- Proliferative atheroma
- Complicated atheroma
Aetiology of atheroma?
Endothelial injury
- Response to injury
- Macrophages + platelets
- Lipid accumulation
- Smooth muscle proliferation
Complications of atheroma?
Thrombosis Aneurysm Dissection Embolism Ischaemia
How hypertension and the heart works?
- Left ventricular hypertrophy
- Increased LV load
- Poor perfusion
- Interstitial fibrosis
- Micro-infarcts
- Diastolic dysfunction
Thrombus definition?
Solid mass of blood constituents, formed within blood vessels
3 parts of Virchow’s triad?
Vessel wall
Blood flow
Blood constituents
Vessel wall in Virchow’s triad?
Loss of endothelial tissues
Inflammation
Blood flow in Virchow’s triad?
Stasis
Turbulence
Blood constituents in Virchow’s triad?
Platelets
Coagulation proteins
Viscosity
What are platelets?
Anucleated cell fragments
What constitutes of platelets?
Adherance properties
Procoagulant contents
Growth factors
Embolism?
Mass of material in vascular system moving form its site of origin to lodge in the vessels in a distant site
DVT possible causes?
Post-op Bed bound Travel Involves= Unilateral leg swelling Oedema Pain
What is a PTE and it’s symptoms/risk factors?
Pulmonary thromboembolism
- Sudden onset
- Haemoptysis
- Breathlessness
- CV collapse and shock
- Cardiac arrest
What is the pathology of an MI?
Zonal necrosis due to sudden occlusion of blood supply
-Due to lack of nutrients and oxygen
How long does it take neurons in brain to die without oxygen?
3 mins
