Pathology Flashcards
What are the patterns of necrosis?
Coagulative Colliquative Caseous Gangrenous Fibrinoid Fat necrosis
2 types of metabolic disorder
Inherited
Acquired
What is phenylketonuria?
Accumulation of phenylalanine
Clinical features of phenylketonuria
Brain toxicity
Mental retardation
Fair skin, blue eyes
Guthrie test
2 types of inflammation.
Acute inflammation
Chronic inflammation
Physical characteristics of inflammation
Rubor (redness) Calor (heat) Tumor (swelling) Dolor (pain) Loss of function
2 phases of acute inflammation
Vascular phase (dilatation and increase permeability of blood vessels)
Exudative and cellular phase (fluid & cells escape from permeable venules)
What is exudate?
A fluid rich protein which oozes out of blood vessels due to inflammation
What is fibrinogen?
A soluble Ortega present in blood plasma from which fibrin is produced through the action of the enzyme thrombin
Examples of chemical mediators which increase vascular permeability?
Histamine
Bradykinin
Diagnostic feature of acute inflammation
Neutrophil accumulation in the extracellular space
Functions of neutrophils
Kill organisms Degrade necrotic tissue Ingest offending agents Produce chemical mediators Produce toxic oxygen radicals Produce tissue damaging enzymes
How do neutrophils find the site of inflammatory stimulus?
Chemotaxis
What does histamine do?
Vascular dilatation
Transient increase in vascular permeability
What is histamine release from?
Released by mast cells, eosinophils, basophils and platelets
(Stimulated by complement)
What is serotonin?
Amine present in platelets
Increases vascular permeability
What are chemokines?
Proteins
Attract leukocytos to site of inflammation
What are leukotrienes?
In neutrophils
Have vasoactive properties
Involved in type 1 hypersensitivity
What are prostaglandins?
Fatty acids
Increase vascular permeability
stimulate platelet aggregation
4 cascade systems in plasma
Complement system
The kinins
The coagulation factors
Fibrinolytic system
What are opsonins?
Bund to specific receptors on leukocytos and greatly enhance phagocytosis
(Tomato ketchup)
What is suppuration?
Formation of pus (neutrophils, bacteria, cellular debris)
What causes suppuration?
Almost always infection
What is an abscess?
A collection of pus surrounded by a membrane of sprouting capillaries, neutrophils and occasional fibroblasts
What are the beneficial effects of acute inflammation?
Dilution of toxins (can be carried away by lymphatics)
Entry of antibodies (increased vascular permeability)
Fibrin formation (impedes movement of microorganisms)
Transport of drugs (e.g. antibiotics)
Delivery of nutrient and oxygen (aided by blood flow)
Stimulation of immune response
Harmful effects of acute inflammation
Digestion of normal tissues
Swelling
Inappropriate inflammatory response (e.g. type 1 hypersensitivity)
Which factors lead to complete resolution of acute inflammation?
Minimal cell death & tissue damage
Organs regenerative capacity (e.g. liver)
Rapid destruction of causal agent
Rapid removal of fluid debris by good local vascular drainage
Why would acute inflammation progress to chronic inflammation?
Indigestible substances (result in chronic suppuration)
Deep seated suppuration inflammation
Recurrent episodes of acute inflammation
Predominant cells in chronic inflammation
Lymphocytes
Plasma cells
Macrophages
Examples of primary chronic inflammation
Resistant infective agents (e.g. TB, leprosy)
Foreign body reactions (e.g. Gout)
Specific diseases of unknown aetiology ( e.g. IBD)
Primary granulomatous diseases (e.g. sarcoidosis)
Macroscopic appearances of chronic inflammation
Chronic ulcers Chronic abscess cavity Thickening of wall by fibrous tissue Granulomatous inflammation FIBROSIS
Cell responses in acute inflammation
B lymphocytes -> plasma cells
T lymphocytes produced cytokines
Cytokines (recruit macrophages, produce inflammatory mediators, recruit other lymphocytes,maestros target cells, produce interferon)
What is a granuloma?
Aggregate of epithelial histiocytes
Histiocytes = macrophage present in connective tissue (secretory function)
Causes of granulomatous inflammation
Specific infections Foreign bodies (endogenous, exogenous) Specific chemicals Drugs Unknown
Properties of mycobacteria
Slow growing in culture
Acid/alcohol fast on microscopic staining
Resistant to many antimicrobials (e.g. Penicillin)
Induce granulomatous reactions in tissue
Intracellular pathogens able to survive and replicate within neutrophils and macrophages
What is hyperplasia?m
Increase in cell number
Where does hyperplasia occur?
Hormonally sensitive organs
- endometrium
- breath
- thyroid
Example of hyperplasia
Enlargement of gingival tissuesn
Hyper plastic responses within spit helium & underlying connective tissue
Various causes including certain drugs
What is hypertrophy?
Increase in cell size
What tissue does hypertrophy affect?
Muscle
- skeletal
- cardiac
What is atrophy?
Reduction in cell size and number in an organ that was of normal size
Causes of atrophy
Ageing
Lack of use
- mechanical
- functional
What is hypoplasia?
Reduced sized of an organ that was never fully developed
A developmental defect
What is metaplasia?
An acquired form of altered differentiation.
One fully formed cell type to another fully formed cell type
Can be part of an adaptive response to stress
Example of metaplasia?
Barrett’s oesophagus
Squamous epithelial cells -> columnar epithelial cells
Is metaplasia a neoplasticism disorder?
No.
Environmental changes lead to metaplasia and may if persistent lead to further changes that can manifest as dysplasia and progress to malignancy
What is the Hayflick limit?
Number of times a cell can divide
What is senescene?
Process of aging
What are the 3 processes involved in regulation of cell number?
Proliferation
Senescene
Cell death
What are labile cells?
Continuously dividing cells
e.g. surface epithelia, haematopoetic cells
What are stable cells?
Cells with low level of replicative activity
May divide rapidly if stimulated
e.g. hepatocytes, fibroblasts, endothelium
What are permanent cells
Non-dividing cells
Not able to renter cell cycle
e.g. neurones, skeletal & cardiac muscle
In what types of diseases is there increased apoptosis?
AIDS
Neurodegenerative disorders
Reperfusion injury
In what diseases is there decreased apoptosis?
Neoplasia
Autoimmune disease
What is neoplasia?
Abnormal growth
How is neoplasia classified?
Behavioural
- benign
- malignant
Histogenetic
Description of benign neoplasms
Resemble Norma, tissue No invasion Encapsulated No necrosis Minimal pleomorphism Diploid DO NOT METASTASISE
Features of malignant neoplasms
Invasive growth pattern Not encapsulated Necrosis common Pleomorphic Abnormal mitosis figures Aneuploid MAY METASTASIISE
Are neoplastic cells monoclonal?
Yes
What is dysplasia?
A premalignant process
e.g. In Squamous or glandular epithelia
What is desmoplasia?
The proliferation of fibroblast to produce fibrous stroma in response to malignant tumour
What is angiogenesis?
Formation of new blood vessels
Control is lost in tumours - forms abnormal vessels
Do tumour require less or more oxygen than normal cells?
Less
What is metastasis?
Spread of a mi,grant tumour from its original site of origin
Common sites of metastasis
Regional lymph nodes Liver Lung Bone Brain Adrenal gland Skin
Routes of metastasis?
Lymphatic (carcinoma)
Haematogenous (sarcoma)
Across body cavities
Direct implantation
Role of immune system in cancer
May target tumour cells
Can regress some cancers (melanoma)
Immunodeficiencies - increased risk
Main stages of cancer development?
Self sufficient growth signals Escape from senescene Evasion of apoptosis Limitless replicative potential Angiogenesis Invasion & metastasis
What is a carcinogen?
A substance that can lead to the development of cancer
Can genetic predisposition have a role in cancer?
Yes
What viruses can predispose to cancer?
SV40
HBV
HPV
Example of RNA tumour virus
RSV (Rous Sarcoma Virus)
Examples of classical oncogenes
PDGF EGFR ras Src myc
4 ways of activating Proto-oncogenes
Amplification
Translocation
Point mutation
Insertional mutagenesis
Examples of tumour suppressor genes
p53
pRB
ALC
BRCA-1
What are classical oncogenes?
Stimulate cell proliferation
Inhibit cell death
Are dominant
What are tumour suppressors?
Inhibit cell proliferation
Stimulate cell death
Are recessive
Vague symptoms that present with cancers
Fatigue
Weight loss
Anorexia
Fever
Clinical presentation of cancer if it’s an ulceration with bleeding
Chronic blood loss - anaemia (eg colorectal cancer)
Acute blood loss - haematemesis, haemoptysis
Clinical presentation of cancer if it’s caused a narrowing of lumen
Dysphagia Abdominal pain Renal failures Jaundice Infection behind an obstructing lesion (e.g. pneumonia, cholangitis)
Clinical presentation of cancer which has caused pressure or damage to adjacent structures
Pain, nerve palsied (e.g. mediastinal tumours) Bone destruction (e.g. local invasion or primary bone tumours) A endocrine glands (e.g. Pituitary adenomas) Raised intracranial pressure (CNS tumours)
Clinical presentation of cancer if it has elicited an effusion
Breathlessness (pleural effusion) Abdominal distension (peritoneal effusion)
Presentation if cancer has metastasised to bone
Pain and patholigical feature
Presentation if cancer has metastasised to brain
Raised intracranial pressure, epilepsy, CVA (stroke)
Presentation if cancer has metastasised to liver
Jaundice
Presentation if cancer has metastasised to adrenal glands
Addisons disease
What is paraneoplastic syndrome?
Symptoms/syndromes in cancer patients not directly associated with local or distant spread of tumours
What underlying cancer presents with venous thrombosis?
Pancreatic carcinoma
What is a tumour grade?
A histological assessment of how well differentiated tumour cells are
Well differentiated tumours tend to have a better prognosis
What is the dukes stage grade of colorectal cancer?
A - confined to wall, no lymph node metastasis
B - penetrates wall, no lymph node metastasis
C - lymph node metastasis
D - metastatic disease
TNM classification of cancer
T STAGE (size of tumour)
- Tx - primary tumour cannot be assessed
- T0 - no evidence of primary tumour
- Tis - carcinoma in situ
- T1-4 - size and or extent of tumour
N STAGE (lymph node involvement)
- Nx - nodes cannot be assessed
- N0 - no node involvement
- N-3 - regional node metastasis
M STAGE (metastasis)
- M0 - no distant spread
- M1 - distant metastasis
Treatment of HER2 breast cancer
Trastuzumab (herceptin) which is a monoclonal antibody
Characteristics of IDDM
Onset young Weight normal Reduced insulin levels Anti-islet antibodies Ketoacidosis HLA linked
Characteristics of NIDDM
Onset > 30 Overweight Normal or decreased insulin No islet antibodies No ketoacidosis No HLA linkage
Complications of diabetes
Ketoacidosis Lactic acidosis Macroangiopathy Diabetic neuropathy Diabetic retinopathy - cataracts
What is Virchows triad?
Hypercoagulability
Haemodynamic changes
Endothelial injury
What are platelets?
Anucleated cell fragments
Adherence properties
Procoagulant contents
Growth factors
What is an embolism?
A mass of magi weak in the vascular system moving from its site of origin to lodge in the vessels in a distant site
What is infarction?
Zonal necrosis due to sudden occlusion of blood supply
