Pathology Flashcards
What are the clinical features in response to acute inflammation?
Rubor, calor, dolor, tumor, loss of function
What causes calor and rubor?
Increased perfusion and permeability, slow blood flow
What causes tumor?
Vascular changes
What is dolor mediated by?
Prostaglandins and bradykinin
What vascular changes occur in acute inflammation?
Vasodilation and increased permeability
What vessels does acute inflammation affect?
Arterioles first and then capillary beds
What are vascular changes in acute inflammation mediated by?
Histamine and NO
What causes white cell margination?
Because of slow blood flow and vasodilation, white blood cells move peripherally
Why is integrin/selectin binding low affinity?
So WB cells can quickly bind and unbind to stay attached the the endothelium but also roll along it to the sight of inflammation
What proteins are found on the endothelium?
Selectins and ICAMs/VCAMs
What proteins are found on WBCs?
Integrins
What increases the expression of selectins?
Histamine and thrombin
What increases the expression of ICAM/VCAMS?
TNF and IL1
What increases the affinity of ICAMS/VCAMS for Integrins?
Chemokines from the site of injury bind to protoglycans on the endothelial cell surface
How does chemotaxis work?
Cells follow a chemical gradient
What components can be involved in chemotaxis?
Complement, bacterial components, leukotrienes and cytokines
What cell characterises acute inflammation?
Neutrophil
What are the 3 stages of phagocytosis?
Recognition and attachment, engulfment and killing and degradation
What receptors (which are found on bacterial and not mammalian cells) are used for recognition?
Mannose, and sometimes scavenger receptors
What makes bacteria stand out to phagocytes?
Protein coating with antibodies and complement
What is the name for the cell arm that incapsulates the bacteria?
Pseudopod
What is the vesicles called before and after joining with a lysosome?
Phagosome, phagolysosome
What is an important molecule involved in killing and degradation?
NADPH oxidase combines with NO to form ONOO
What does the fate of an inflamed tissue depend on?
Site of injury, type/severity of injury, duration of injury
Which areas tend to have a better capacity for repair?
Those with a good vascular supply
What is resolution?
Complete restoration of tissue to normal after removal of inflammatory components
What improves chances of resolution?
Tissue with good capacity to repair, good vascular supply, injurious agent easily removed
What is supparation?
A collection of pus forming (abscess)
What forms when pus is walled off?
Empyema
What is pus described as?
A sea of neutrophils
What does pus not have and how is it treated?
No blood supply so it has to be drained
When does organisation occur?
If the injury produces a lot of necrosis or fibrin that isn’t easily cleared
What type of injury usually results in organisation?
When damage goes beyond the basement membrane
What are injuries where the basement membrane is intact known as?
Abrasions and erosions
What is the common response to inflammation in all tissues?
Formation of granulation tissue
What does scarring/fibrosis result in?
Loss of function
What do different forms of repair show on an MI autopsy?
Neutrophils (recent), granulation tissue (1-2 weeks), further scarring (6+ weeks)
What signifies acute inflammation?
Neutrophils (anything else is chronic)
What is chronic inflammation NOT related with?
no acute inflammation needed, not related to time or severity
When is chronic inflammation favoured?
Supparation, persistence of injury, infectious injury, autoimmune injury
What are granulomas?
Groups of macrophages joined together to form one big multi nucleated cells
When do granulomas usually form?
Foreign bodies, parasite/worms, eggs, mycobacterium
What do TB granulomas show?
Cheesy necrosis
What are some signs of dying cells?
Shrink, become red, nucleus shrinks and darkens, marginal contraction bands appear, also vascular changes occur
In necrosis, what are dead cells mopped up by?
Neutrophils
What are the two types of necrosis?
Caseous and liquefactive
What are neutrophils replaced by in necrosis and what does this cause?
Macrophages, a yellow appearance
In terms of adaptation and growth, what does an altered stimulus result in?
Metaplasia
In terms of adaptation and growth, what does decreased demand result in?
Atrophy
In terms of adaptation and growth, what does increased demand result in?
Hyperplasia and hypertrophy
What is hyperplasia?
Increase in number of cells
What is hypertrophy?
Increase in cell size
What other adaptations can take place when there is increased demand?
increased growth factor production, produce more growth factor receptors
What are growth factor receptors?
7 transmembrane GPCRs and receptors with or without tyrosine kinase
What are the stages of the cell cycle controlled by?
a series of CDKs that activate each other and other enzymes in a stepwise fashion
How are CDKs activated?
By a specific cyclin
What happens in G1?
Protein synthesis and growth
What CDK is activated in G1 and how?
CDK4 by cyclin D
What does CDK4 do?
Phosphorylates the Rb protein
What is the Rb protein normally bound to and what does this do?
Normally bound to E2F which kicks off cell division but Rb blocks it so there is no cell division
What does phosphorylation of Rb do?
It no longer binds to E2F so cell division can occur
What happens in the S phase?
DNA replication
What does E2F do in the S phase?
Initiates DNA replication and increases cyclin A
What is activated in the S phase and how?
CDK2 by cyclin A
What does CDK2 do?
Promotes DNA replication
What should cells have by the end of the S phase?
2 copies of the genome
What happens in G2?
More growth and protein synthesis
What happens at the end of G2?
The main checkpoint involving p53
What are telomeres?
Chromosomes are capped to provide protection and stop chromosome ends from degradation and fusing. This consists of TTAGGG repeats
What must there be for hyperplasia to occur?
An external stimulus, hyperplasia will regress with withdrawal of this
What are some physiological causes of hyperplasia?
Puberty, pregnancy, compensatory after loss of tissue
What are pathological causes of hyperplasia?
Hormonally induced or infection (lymph nodes)
What is hyperplasia tissue at risk for?
CANCER- particularly endometrial
What are physiological causes of atrophy?
Hormonal, uterus, embryological structures
How do cells atrophy?
Protein degradation and digested in lysosome
What hormones oppose atrophy?
insulin
what hormones promote atrophy?
glucocorticoids and thyroid hormones
What are pathological causes of atrophy?
Pressure, blocked blood supply, inadequate nutrition, loss of innervation, decreased workload
What does hypertrophy often occur in response to?
Mechanical stress
Can necrosis ever be good?
No- it is always pathological
Does necrosis require energy?
No
What are some features of coagulative necrosis?
Preserved cell outline and dead cells enzymatically consumed
What type of necrosis is most common?
Coagulative
When is coagulative necrosis seen a lot
In the heart post MI
What are some features of liquefactive necrosis?
Liquid viscous mass with no cell structure, pus
What is liquefactive necrosis associated with?
Bacterial and fungal infections
What is the only type of necrosis in the brain?
Liquefactive
What is caseous necrosis?
Granulomas out inflammation with necrosis?
When there is caseous necrosis and granulomas what could this be and what should you do?
Probably TB- ask for culture, PCR, Zeihl neilson stain
What is apoptosis?
Programmed cell death in response to specific signals. Requires ATP.
What are some physiological causes of apoptosis?
Growth, we need cells to die off, removal of self reactive lymphocytes
What are pathological causes of apoptosis?
Response to injury, radiation, chemotherapy, viral infections or cancer, transplant rejection
What do all mechanisms of apoptosis rely on?
Activating caspases
What initiates the extrinsic pathway?
Death receptors e.g. TNF or Fas
When is Fas used in apoptosis?
Self recognition and apoptosis in lymphocytes
When is TNF used in apoptosis?
Indices apoptosis in inflammatory conditions
What type of pathway is the intrinsic pathway?
A mitochondrial pathway involving a balance between anti and pro apoptotic proteins
What blocks anti-apoptotic pathways and what does this cause?
Bac/Bax- causes pro apoptotic proteins to punch holes in the mitochondrial membrane to increase permeability
What does increased permeability of the mitochondrial membrane result in in the intrinsic apoptotic pathway?
Release of cytochrome c to stimulate caspases
What can too much apoptosis cause?
Neurodegenerative diseases
What can too little apoptosis result in?
Cancers and autoimmune disease
What is the morphology of apoptosis?
Cells shrink, chromatin condenses the nucleus, cytoplasm breaks up and macrophages digest the debris
What is cancer?
Uncontrolled cell proliferation and growth that can invade other tissues
What is a tumour?
a descriptive term- can be benign or malignant, inflammatory or a foreign body
What is a neoplasm?
New growth not in response to a stimulus
Where can neoplasms come from?
Any cell or organ (common in epithelium)
What do malignant tumours have?
Metastatic potential
What is classed as metastases in epithelial cells?
Once the mass has passed the basement membrane
What is metaplasia?
A reversible change from one mature cell type to another
What can metaplasia be in response to?
Cytokines, but usually in response to an injurious or noxious stimulus
What type of cell is commonly changed in response to injury?
Squamous epithelium
What is the relationship between metaplastic tissue and cancer?
Metaplastic tissue is an at risk site for cancer but doesn’t always become cancer
What is dysplasia?
Disordered growth in abnormal cells not in response to a stimulus
How is dysplasia graded?
From low to high (risk of becoming cancer)
What is carcinoma in situ?
The very last stage before dysplasia crosses the epithelium and becomes cancer i.e. high grade dysplasia
What do oncogenes do?
Promote growth of cancer cells
What do tumour suppressors do?
Turn off any inhibition to grow
What are examples of an inherited predisposition to cancer?
BRCA gene (one copy needed to increase risk), Rb mutation in children increases chance of retinoblastoma and familial adenomatous polyposis causes bowel cancer before 50
What are some examples of chemicals which increase risk of cancer?
Smoking, fungus, chemical dye, food preservatives, arsenic
How does radiation increase risk of cancer?
Causes the formation of pyramidine dimers in DNA- with repeated exposure this cannot be repaired
What other factors can increase risk of cancer?
Viruses (HPV), chronic inflammation, constant catheterisation, obesity
What are the Weinberg hallmarks of cancer?
Increased growth signals, removed growth suppression, avoiding apoptosis, achieve immortality, become invasive, have own blood supply
What are common sites of metastases in general?
Liver and local lymph nodes
What is angiogenesis?
Tumours successfully developing their own blood supply
As well as oncogenes and tumour suppressors, what other factors can contribute to cancer?
Apoptosis (stopping cell death) and breaking spell checker
What does breaking the spell checker do?
Allows progression through the cell cycle even with mistakes
What is the first mutation in cancer known as?
Initiation
What is needed for cells to proliferate and become cancer?
At least another mutation after the first one
What is the further accumulation of mutations, resulting in a pre-malignant phase known as?
Promotion
What is lots of accumulation of cells to become malignant known as?
Progression
What is cachexia?
Weight loss in cancer
What are features of benign tumours?
Organised, smooth edges and surface, all looks the same, slow growing
What are features of malignant tumours?
Not natural looking, irregular, infiltrating and destructive
What are epithelial tumours known as?
Carcinomas
What are benign and malignant glandular tumours known as?
Adenoma and adenocarcinoma
What are benign and malignant squamous cell tumours known as?
Papillomas and squamous cell carcinomas
What are transitional/uroepithelial cell carcinomas?
Bladder tumours
What is mesenchyme?
Benign tumour of connective tissue
What are malignant tumours of connective tissue known as?
Sarcomas
What are benign and malignant tumours in fat connective tissue?
Lipoma and liposarcoma
What are benign and malignant tumours in bone connective tissue?
Osteoma and osteosarcoma
Who and where do osteosarcomas occur in?
Rare- in long bones of children
What are benign and malignant tumours in cartilage connective tissue?
Endroma and chondrosarcoma
What is leiomyoma?
Benign tumour of the smooth muscle- one of the commonest tumours in the body
What is a leiomyosarcoma?
Malignant tumour of the smooth muscle- very rare
What are benign and malignant tumours in blood vessel connective tissue?
Haemangioma and angiosarcoma
What is melanoma?
Malignant skin tumour
What are blood tumours and what are examples?
Always malignant e.g. lymphomas or leukaemia
What does the stage of a tumour describe?
How far it has grown- often depends on the site
What does Tis stand for?
Tumour in situ- within the lamina propria and not broken through the muscularis mucosae
What does T1 mean?
Invaded the submucosa but not the muscularis externa
What does T2 mean?
Invaded the muscularis propria but not beyond it
What does T3 mean?
Invaded beyond the muscularis propria and into subserosa
What does T4 mean?
Directly invaded other organs or perforated the visceral peritoneum
What does NX mean?
Lymph nodes cannot be assessed
What does N0 mean?
No regional lymph node metastases
What does N1 mean?
Metastases to 1-3 nearby lymph nodes
What does N2 mean?
Metastases to 4+ nearby lymph nodes
What does M0 mean?
No metastases to distant tissues
What does M1 mean?
Metastases to distal tissues including distal lymph nodes
What does the grade of a tumour convey?
Concept of differentiation
What suggests low grade tumours?
Well differentiated- looks like it should
What suggests high grade tumours?
Poorly differentiated- difficult to tell what type of cell it came from
