Pathology Flashcards
(163 cards)
1
Q
What are the clinical features in response to acute inflammation?
A
Rubor, calor, dolor, tumor, loss of function
2
Q
What causes calor and rubor?
A
Increased perfusion and permeability, slow blood flow
3
Q
What causes tumor?
A
Vascular changes
4
Q
What is dolor mediated by?
A
Prostaglandins and bradykinin
5
Q
What vascular changes occur in acute inflammation?
A
Vasodilation and increased permeability
6
Q
What vessels does acute inflammation affect?
A
Arterioles first and then capillary beds
7
Q
What are vascular changes in acute inflammation mediated by?
A
Histamine and NO
8
Q
What causes white cell margination?
A
Because of slow blood flow and vasodilation, white blood cells move peripherally
9
Q
Why is integrin/selectin binding low affinity?
A
So WB cells can quickly bind and unbind to stay attached the the endothelium but also roll along it to the sight of inflammation
10
Q
What proteins are found on the endothelium?
A
Selectins and ICAMs/VCAMs
11
Q
What proteins are found on WBCs?
A
Integrins
12
Q
What increases the expression of selectins?
A
Histamine and thrombin
13
Q
What increases the expression of ICAM/VCAMS?
A
TNF and IL1
14
Q
What increases the affinity of ICAMS/VCAMS for Integrins?
A
Chemokines from the site of injury bind to protoglycans on the endothelial cell surface
15
Q
How does chemotaxis work?
A
Cells follow a chemical gradient
16
Q
What components can be involved in chemotaxis?
A
Complement, bacterial components, leukotrienes and cytokines
17
Q
What cell characterises acute inflammation?
A
Neutrophil
18
Q
What are the 3 stages of phagocytosis?
A
Recognition and attachment, engulfment and killing and degradation
19
Q
What receptors (which are found on bacterial and not mammalian cells) are used for recognition?
A
Mannose, and sometimes scavenger receptors
20
Q
What makes bacteria stand out to phagocytes?
A
Protein coating with antibodies and complement
21
Q
What is the name for the cell arm that incapsulates the bacteria?
A
Pseudopod
22
Q
What is the vesicles called before and after joining with a lysosome?
A
Phagosome, phagolysosome
23
Q
What is an important molecule involved in killing and degradation?
A
NADPH oxidase combines with NO to form ONOO
24
Q
What does the fate of an inflamed tissue depend on?
A
Site of injury, type/severity of injury, duration of injury
25
Which areas tend to have a better capacity for repair?
Those with a good vascular supply
26
What is resolution?
Complete restoration of tissue to normal after removal of inflammatory components
27
What improves chances of resolution?
Tissue with good capacity to repair, good vascular supply, injurious agent easily removed
28
What is supparation?
A collection of pus forming (abscess)
29
What forms when pus is walled off?
Empyema
30
What is pus described as?
A sea of neutrophils
31
What does pus not have and how is it treated?
No blood supply so it has to be drained
32
When does organisation occur?
If the injury produces a lot of necrosis or fibrin that isn't easily cleared
33
What type of injury usually results in organisation?
When damage goes beyond the basement membrane
34
What are injuries where the basement membrane is intact known as?
Abrasions and erosions
35
What is the common response to inflammation in all tissues?
Formation of granulation tissue
36
What does scarring/fibrosis result in?
Loss of function
37
What do different forms of repair show on an MI autopsy?
Neutrophils (recent), granulation tissue (1-2 weeks), further scarring (6+ weeks)
38
What signifies acute inflammation?
Neutrophils (anything else is chronic)
39
What is chronic inflammation NOT related with?
no acute inflammation needed, not related to time or severity
40
When is chronic inflammation favoured?
Supparation, persistence of injury, infectious injury, autoimmune injury
41
What are granulomas?
Groups of macrophages joined together to form one big multi nucleated cells
42
When do granulomas usually form?
Foreign bodies, parasite/worms, eggs, mycobacterium
43
What do TB granulomas show?
Cheesy necrosis
44
What are some signs of dying cells?
Shrink, become red, nucleus shrinks and darkens, marginal contraction bands appear, also vascular changes occur
45
In necrosis, what are dead cells mopped up by?
Neutrophils
46
What are the two types of necrosis?
Caseous and liquefactive
47
What are neutrophils replaced by in necrosis and what does this cause?
Macrophages, a yellow appearance
48
In terms of adaptation and growth, what does an altered stimulus result in?
Metaplasia
49
In terms of adaptation and growth, what does decreased demand result in?
Atrophy
50
In terms of adaptation and growth, what does increased demand result in?
Hyperplasia and hypertrophy
51
What is hyperplasia?
Increase in number of cells
52
What is hypertrophy?
Increase in cell size
53
What other adaptations can take place when there is increased demand?
increased growth factor production, produce more growth factor receptors
54
What are growth factor receptors?
7 transmembrane GPCRs and receptors with or without tyrosine kinase
55
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
56
How are CDKs activated?
By a specific cyclin
57
What happens in G1?
Protein synthesis and growth
58
What CDK is activated in G1 and how?
CDK4 by cyclin D
59
What does CDK4 do?
Phosphorylates the Rb protein
60
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
61
What does phosphorylation of Rb do?
It no longer binds to E2F so cell division can occur
62
What happens in the S phase?
DNA replication
63
What does E2F do in the S phase?
Initiates DNA replication and increases cyclin A
64
What is activated in the S phase and how?
CDK2 by cyclin A
65
What does CDK2 do?
Promotes DNA replication
66
What should cells have by the end of the S phase?
2 copies of the genome
67
What happens in G2?
More growth and protein synthesis
68
What happens at the end of G2?
The main checkpoint involving p53
69
What are telomeres?
Chromosomes are capped to provide protection and stop chromosome ends from degradation and fusing. This consists of TTAGGG repeats
70
What must there be for hyperplasia to occur?
An external stimulus, hyperplasia will regress with withdrawal of this
71
What are some physiological causes of hyperplasia?
Puberty, pregnancy, compensatory after loss of tissue
72
What are pathological causes of hyperplasia?
Hormonally induced or infection (lymph nodes)
73
What is hyperplasia tissue at risk for?
CANCER- particularly endometrial
74
What are physiological causes of atrophy?
Hormonal, uterus, embryological structures
75
How do cells atrophy?
Protein degradation and digested in lysosome
76
What hormones oppose atrophy?
insulin
77
what hormones promote atrophy?
glucocorticoids and thyroid hormones
78
What are pathological causes of atrophy?
Pressure, blocked blood supply, inadequate nutrition, loss of innervation, decreased workload
79
What does hypertrophy often occur in response to?
Mechanical stress
80
Can necrosis ever be good?
No- it is always pathological
81
Does necrosis require energy?
No
82
What are some features of coagulative necrosis?
Preserved cell outline and dead cells enzymatically consumed
83
What type of necrosis is most common?
Coagulative
84
When is coagulative necrosis seen a lot
In the heart post MI
85
What are some features of liquefactive necrosis?
Liquid viscous mass with no cell structure, pus
86
What is liquefactive necrosis associated with?
Bacterial and fungal infections
87
What is the only type of necrosis in the brain?
Liquefactive
88
What is caseous necrosis?
Granulomas out inflammation with necrosis?
89
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
90
What is apoptosis?
Programmed cell death in response to specific signals. Requires ATP.
91
What are some physiological causes of apoptosis?
Growth, we need cells to die off, removal of self reactive lymphocytes
92
What are pathological causes of apoptosis?
Response to injury, radiation, chemotherapy, viral infections or cancer, transplant rejection
93
What do all mechanisms of apoptosis rely on?
Activating caspases
94
What initiates the extrinsic pathway?
Death receptors e.g. TNF or Fas
95
When is Fas used in apoptosis?
Self recognition and apoptosis in lymphocytes
96
When is TNF used in apoptosis?
Indices apoptosis in inflammatory conditions
97
What type of pathway is the intrinsic pathway?
A mitochondrial pathway involving a balance between anti and pro apoptotic proteins
98
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
99
What does increased permeability of the mitochondrial membrane result in in the intrinsic apoptotic pathway?
Release of cytochrome c to stimulate caspases
100
What can too much apoptosis cause?
Neurodegenerative diseases
101
What can too little apoptosis result in?
Cancers and autoimmune disease
102
What is the morphology of apoptosis?
Cells shrink, chromatin condenses the nucleus, cytoplasm breaks up and macrophages digest the debris
103
What is cancer?
Uncontrolled cell proliferation and growth that can invade other tissues
104
What is a tumour?
a descriptive term- can be benign or malignant, inflammatory or a foreign body
105
What is a neoplasm?
New growth not in response to a stimulus
106
Where can neoplasms come from?
Any cell or organ (common in epithelium)
107
What do malignant tumours have?
Metastatic potential
108
What is classed as metastases in epithelial cells?
Once the mass has passed the basement membrane
109
What is metaplasia?
A reversible change from one mature cell type to another
110
What can metaplasia be in response to?
Cytokines, but usually in response to an injurious or noxious stimulus
111
What type of cell is commonly changed in response to injury?
Squamous epithelium
112
What is the relationship between metaplastic tissue and cancer?
Metaplastic tissue is an at risk site for cancer but doesn't always become cancer
113
What is dysplasia?
Disordered growth in abnormal cells not in response to a stimulus
114
How is dysplasia graded?
From low to high (risk of becoming cancer)
115
What is carcinoma in situ?
The very last stage before dysplasia crosses the epithelium and becomes cancer i.e. high grade dysplasia
116
What do oncogenes do?
Promote growth of cancer cells
117
What do tumour suppressors do?
Turn off any inhibition to grow
118
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
119
What are some examples of chemicals which increase risk of cancer?
Smoking, fungus, chemical dye, food preservatives, arsenic
120
How does radiation increase risk of cancer?
Causes the formation of pyramidine dimers in DNA- with repeated exposure this cannot be repaired
121
What other factors can increase risk of cancer?
Viruses (HPV), chronic inflammation, constant catheterisation, obesity
122
What are the Weinberg hallmarks of cancer?
Increased growth signals, removed growth suppression, avoiding apoptosis, achieve immortality, become invasive, have own blood supply
123
What are common sites of metastases in general?
Liver and local lymph nodes
124
What is angiogenesis?
Tumours successfully developing their own blood supply
125
As well as oncogenes and tumour suppressors, what other factors can contribute to cancer?
Apoptosis (stopping cell death) and breaking spell checker
126
What does breaking the spell checker do?
Allows progression through the cell cycle even with mistakes
127
What is the first mutation in cancer known as?
Initiation
128
What is needed for cells to proliferate and become cancer?
At least another mutation after the first one
129
What is the further accumulation of mutations, resulting in a pre-malignant phase known as?
Promotion
130
What is lots of accumulation of cells to become malignant known as?
Progression
131
What is cachexia?
Weight loss in cancer
132
What are features of benign tumours?
Organised, smooth edges and surface, all looks the same, slow growing
133
What are features of malignant tumours?
Not natural looking, irregular, infiltrating and destructive
134
What are epithelial tumours known as?
Carcinomas
135
What are benign and malignant glandular tumours known as?
Adenoma and adenocarcinoma
136
What are benign and malignant squamous cell tumours known as?
Papillomas and squamous cell carcinomas
137
What are transitional/uroepithelial cell carcinomas?
Bladder tumours
138
What is mesenchyme?
Benign tumour of connective tissue
139
What are malignant tumours of connective tissue known as?
Sarcomas
140
What are benign and malignant tumours in fat connective tissue?
Lipoma and liposarcoma
141
What are benign and malignant tumours in bone connective tissue?
Osteoma and osteosarcoma
142
Who and where do osteosarcomas occur in?
Rare- in long bones of children
143
What are benign and malignant tumours in cartilage connective tissue?
Endroma and chondrosarcoma
144
What is leiomyoma?
Benign tumour of the smooth muscle- one of the commonest tumours in the body
145
What is a leiomyosarcoma?
Malignant tumour of the smooth muscle- very rare
146
What are benign and malignant tumours in blood vessel connective tissue?
Haemangioma and angiosarcoma
147
What is melanoma?
Malignant skin tumour
148
What are blood tumours and what are examples?
Always malignant e.g. lymphomas or leukaemia
149
What does the stage of a tumour describe?
How far it has grown- often depends on the site
150
What does Tis stand for?
Tumour in situ- within the lamina propria and not broken through the muscularis mucosae
151
What does T1 mean?
Invaded the submucosa but not the muscularis externa
152
What does T2 mean?
Invaded the muscularis propria but not beyond it
153
What does T3 mean?
Invaded beyond the muscularis propria and into subserosa
154
What does T4 mean?
Directly invaded other organs or perforated the visceral peritoneum
155
What does NX mean?
Lymph nodes cannot be assessed
156
What does N0 mean?
No regional lymph node metastases
157
What does N1 mean?
Metastases to 1-3 nearby lymph nodes
158
What does N2 mean?
Metastases to 4+ nearby lymph nodes
159
What does M0 mean?
No metastases to distant tissues
160
What does M1 mean?
Metastases to distal tissues including distal lymph nodes
161
What does the grade of a tumour convey?
Concept of differentiation
162
What suggests low grade tumours?
Well differentiated- looks like it should
163
What suggests high grade tumours?
Poorly differentiated- difficult to tell what type of cell it came from
