Cell And Tissue Pathology Flashcards Preview

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Flashcards in Cell And Tissue Pathology Deck (149):
1

Which types of cells are present in granulomatus inflammation?

Macrophages, T cells, epitheloid cells (large macrophages) and giant cells (fused macrophages)

2

What are the two types of granulomas?

Foreign body granules and immune granules

3

What is an epitheloid cell?

A macrophage with an abundant cytoplasm

4

What is a giant cell?

A multinucleated cell formed by fusion of active macrophages

5

What are the inciting agents of immune granulomas?

Persistent microbe or self antigen

6

How do immune granulomas form?

Macrophages activate T cells, which produce IL-2, which activate more T cells, which produce IFN-gamma which activates more macrophages. IL-4 or IFN-gamma transform macrophages into epitheloid and giant cells

7

What causes crohns disease?

Intestinal bacteria and possibly self antigens

8

What is the tissue reaction in crohns disease?

Occasional noncaseating granulomas form in the intestine wall

9

What are the 4 characteristics of inflammation?

Calor
Rubour
Dolor
Tumour

10

What are the 4 stages of inflammation?

Vascular response
Inflammation
Cell proliferation
Remodelling

11

What are 3 types of inflammatory muscle disease?

Temporal arteritis
Dermatomyositis
Polymyositis

12

Which arteries are affected by giant cell arteritis?

Temporal arteries
Opthalmic arteries
Vertebral arteries
Aorta

13

What is the pathogenesis of temporal arteritis?

T cell mediated immune response against vessel wall antigens
Cytokine production
Anti-endothelial cell antibodies and anti-smooth muscle cell antibodies - causative or consequence of?

14

What is the morphology of temporal arteritis?

Intimal thickening that reduces laminal diameter

Granulomas form on internal elastic lamina causing elastic lamina fragmentation

Inflammatory lesions are focally distributed

15

What are the symptoms of temporal arteritis?

Headache, fever, fatigue, weight loss, ocular symptoms

16

What is the pathogenesis of dermatomyositis?

Components of the MAC are found in the capillary beds in muscle and skin

17

What are the symptoms of dermatomyositis?

Rash
Proximal muscle weakness
Myalgia
Dysphagia
Elevated serum creatine kinase levels
Interstitial lung disease

18

What is the pathogenesis of polymyositis?

CD8+ cytotoxic T cells infiltrate muscle cells

Vascular injury has no major role

19

What are the symptoms of polymyositis?

Proximal muscle weakness
No cutaneous features

20

What are the 2 types of inflammatory bowl disease? What are the differences between them?

Ulcerative colitis and crohns disease. Ulcerative colitis is characterised by continuous lesions of the bowl whereas crohns is characterised by skip lesions and mouth ulcers

21

Which diseases are associated with inflammatory bowl disease?

Ankylosing spondylitis and uveitis

22

Ulcerative colitis increases the risk of which two diseases?

Anaemia and bowel carcinoma

23

What causes gastric ulceration?

Excess stomach acid

24

Which bacteria is associated with gastric ulceration?

H. Pylori

25

How is gastric ulceration treated?

Proton pump inhibitors and antibiotics if have H. Pylori infection

26

Which tracts are affected by cystic fibrosis?

Respiratory tract
GI tract
Reproductive tract

27

What are the symptoms of CF?

Finger clubbing

Cough

Recurrent lung infections

Reduced FEV1

28

Where is the CFTR gene found?

7q31.2

29

What is the most common CFTR mutation?

DeltaF508 (60 %)

30

What inheritance is associated with Cystic fibrosis?

Autosomal recessive

31

How common is cystic fibrosis?

1 in 2000 have CF
1 in 20 are carriers
(In caucasian population)

32

What is the CFTR structure?

2 transmembrane domains (containing 6 alpha helices)
2 nucleotide binding domains
R domain (has protein kinase A and C phosphorylation sites)

33

How does the CFTR channel work?

Agonist binds epithelial cells
Increase in cAMP
Activates protein kinase A
Phosphorylates R domain using ATP
Channel opens
Cl out of cell

34

What are ENaC channels responsible for?

Na uptake into cells

35

What is the relationship between CFTR protein and ENaC protein in most parts of the body?

Normally functioning CFTR inhibits ENaC uptake of Na into cells

36

Which tissue is the exception in terms of CFTR and ENaC?

Sweat glands. CFTR pumps Cl into cells. In cystic fibrosis patients Cl is not pumped into cells and neither is Na, leading to salty sweat

37

What is a class 1 CFTR mutation?

No CFTR is trafficked to cell surface

38

What is a class 2 CFTR mutation?

DeltaF508 mutation
Some CFTR is trafficked to the cell membrane but none is functional

39

What is a class 3 CFTR mutation?

Normal amount of CFTR at cell surface
None is functional

40

What is a class 4 CFTR mutation?

Normal no of CFTR at cell surface
Some is functional

41

What is a class 5 CFTR mutation?

Some CFTR is trafficked to cell surface
All is functional

42

What is the chaperone protein that tried to fold CFTR?

HSP40

43

What are the treatments for CF symptoms?

Antibiotics
Bronchodilators
Physiotherapy
DNAse
High calorie diet
Insulin
Lung transplant

44

What is VX-809

A corrector. It increases the no of CFTR molecules which get to the cell surface

45

What is ivacaftor?

Potentiator. Increases CFTR channel opening

46

What is ataluren?

Ribosomal skipping agent. Allows stop codons to be skipped

47

What treatments are available to address Cl transport?

VX-809
Ivacaftor
Ataluren

48

What is a sarcoma?

Tumour of connective tissue or its mesenchymal precursor

49

What is atrophy?

Degeneration

50

What is dysplasia?

Cells that look abnormal but are not cancerous

51

What is metaplasia?

Reversible change where one cell type is replaced by another

52

What is pleomorphism?

Unusual nuclei

53

What is an adenoma?

Benign tumour in the glandular epithelia

54

What 2 component tissues are all tumours made up of?

Parenchyma and stroma

55

What is a papilloma?

Benign epithelial tumour which forms a finger-like or warty projection

56

What is a cystadenoma?

Benign epithelial tumour which forms hollow masses

57

What is a papillary cystadenoma?

Papillary pattern protrudes into a cyst-like space

58

What is the difference between a fibroma and a fibrosarcoma?

A fibroma is a benign fibroblast tumour. A fibrosarcoma is a malignant fibroblast tumour.

59

What is neoplasia?

Uncontrolled cell growth

60

What is anaplasia?

Lack of differentiation

61

What do the T N and M stand for in TNM staging?

T = extent of the primary tumour
N = is there any regional lymph node metastasis
M = is there distant metastasis

62

What is karyolysis?

Loss of dna

63

What is pyknosis?

Nuclear shrinkage

64

What is karyohexis?

Nuclear fragmentation and disappearance

65

What are common causes of panceatitis?

Alcohol
Gallstones
Infection
Genetic

66

What are rare causes of pancreatitis?

Trauma
Corticosteroids
Hyperlipidaemia

67

How does alcohol causes pancreatitis?

It destroys acinar cells

68

How do gallstones causes pancreatitis?

If they move into the pancreas

69

What is a symptom of gallstones?

Elevated AST levels

70

How are gallstones treated?

By removal of the gallbladder

71

What are complications associated with pancreatitis?

Infection
Pancreatic necrosis
Pancreatic cysts

72

How is pancreatitis treated?

Pain relief, IV fluids, nil by mouth. Treat the complications antibiotics for infection, operative resection for pancreatic necrosis, drainage of pancreatic cysts

73

What genes are responsible for hereditary pancreatitis?

PRSS1 a cationic trypsin gene
SPINK1 a pancreatic trypsin inhibitor
CTRC a chymotrypsin c gene
CASR a g protein coupled receptor
CFTR a chloride ion channel gene

74

Why does the PRSS1 mutation cause pancreatitis?

Trypsin is overactive and causes autodigestion

75

What is trypsin?

A protease

76

How do SPINK1 and CTRC mutations causes pancreatitis?

Disrupt trypsin inhibition leading to autodigestion

77

What does cathepsin B do in the pancreas?

Turns trypsinogen into trypsin

78

What is CASR?

An extracellular calcium sensing receptor

79

What role does calcium play in the pancreas?

It prevents premature zymogen activation

80

How do CFTR mutations cause pancreatitis?

Distuption in bicarbonate transport (not chloride)

81

What are symptoms of pancreatitis?

Elevated amylase levels
Abdominal pain
Fever
Nausea
Diarrhoea

82

What causes gallstones?

An imbalance of bile salts and cholesterol

83

What do acinar cells do?

Store, synthesise, secrete digestive enzymes (exocrine pancreas)

84

What cells make up the islets of langerhans?

Alpha, beta, delta and pp cells

85

What do alpha cells secrete?

Glucagon

86

What does glucagon do?

Converts glycogen to glucose

87

What do beta cells do?

Secrete insulin and amylin

88

What does insulin do?

Promotes uptake of glucose by liver, fat and muscle cells and converts glucose to glycogen

89

What does amylin do?

Promotes satiety

90

What do delta cells secrete?

Somatostatin

91

What does somatostatin do?

Inhibits release of growth hormone

92

What do pp cells secrete?

Pancreatic polypeptide

93

What does pancreatic polypeptide do?

Regulates pancreas secretions

94

What is type 1 diabetes?

Where T cells attack beta cells in the pancreas

95

What is type 2 diabetes?

Reduced levels of insulin are produced or insulin receptors on fat, liver and muscle cells do not work properly so these cells do not take up enough glucose

96

How is insulin synthesised?

As pre pro insulin

97

How many amino acids make up insulin?

51

98

What chains make up insulin?

A B C

99

What happens to the C chain on insulin?

Removed in the golgi

100

Name two types of type 1 diabetes

Familial hyper pro insulinaemia
Permanent neonatal diabetes mellitus

101

Why do diabetics get foot ulcers?

Neuropathy

Impairment of wound healing - blood vessels narrow due to high blood glucose levels

Infection (compromised immune system)

102

What gene is linked to ankylosing spondylitis?

HLA-B27*05

103

Is ankylosing spondylitis more common in men or women?

Men

104

Are autoimmune diseases more common in men or women?

Women

105

What is the median age of onset for ankylosing spondylitis?

23

106

What causes the bamboo spine seen in akylosing spondylitis?

Damage to the sacro-ileal joint

107

Which type of MHC is HLA-B27 a variant of?

MHC 1

108

What is the function of MHC 1?

To present cytosolic peptides to CD8+ T cells

109

What is the median age of onset for ankylosing spondylitis?

23

110

What causes the bamboo spine seen in akylosing spondylitis?

Damage to the sacro-ileal joint

111

Which type of MHC is HLA-B27 a variant of?

MHC 1

112

What is the function of MHC 1?

To present cytosolic peptides to CD8+ T cells

113

What complications are associated with ankylosing spodylitis?

Uveitis
Enthesitis
IBD

114

What are the 4 explanations for why HLA-B27 is linked to AS?

Molecular mimicry

Unfolded protein response (misfolding of B27 heavy chain)

Inappropriate B27 homodimers forming on the cell surface

Deposition of Beta 2 m in joints following disassociation from HLA-B27

115

What suggests HLA-B27 may not be the sole factor in AS?

5% of AS patients do not have the HLA-B27 gene

HLA-B27*05 is associated with AS but HLA-B27*09 is not

HLA-B27 is expressed on all nucleated cells but AS has specific tissue involvement

116

What other genes are linked to AS?

ERAP (antigen processing enzyme)

IL23R (cytokine receptor which causes CD4+ t cells to differentiate into inflammatory TH17 cells

117

Which gene is associated with rheumatoid arthritis?

HLA-DR4

118

On which chromosome are MHC genes found?

Chromosome 6

119

What job do MHC class 2 molecules have?

The present exogenous peptides to CD4+ helper T cells

120

What are the tests for rheumatoid arthritis?

X ray
Blood tests

121

What are the blood tests for rheumatoid arthritis?

Anaemia
Elevated ESR
Elevated gamma globulin
Elevated C reactive protein
High titre rheumatoid factor

122

What are the treatments for rheumatoid arthritis?

NSAIDs
DMARDs (methotrexate targets rapidly dividing cells)
Corticosteroids (prednisolonr inhibit NFkb)
Monoclonal antibodies (against IL1 (anakinra) and TNF alpha)

123

Which molecules help WBC leave blood vessels?

Selectins

124

What are the 4 stages of a WBC leaving a blood vessel?

Tethering and rolling
Activation
Firm adhesion
Transmigration

125

What is aneuploidy?

Unusual chromosome number

126

What does euploid mean?

Has normal numbers of chromosomes

127

What are the stages of the cell cycle?

G1, S, G2, M

128

Where are the checkpoints in the cell cycle?

G1 check (entering S phase, is environment okay)
G2 check (entering m phase, is dna replicated, is environment okay)
Metaphase check (exit m, are chromosomes attached to spindle)

129

What controls the cell cycle?

Cyclins

130

When in the cell cycle do cyclin A levels rise?

During the s phase

131

When in the cell cycle do cyclin b levels rise?

During the m phase

132

When in the cell cycle do cyclin E levels rise?

After the r point and collapse during the s phase

133

When do cyclin D levels rise?

During the G1 phase

134

What is anoikis?

Apoptosis due to incorrect cell/ECM attachment

135

Why is epithelial to mesenchymal transition required for metastasis?

Epithelial cells cannot migrate
Mesenchymal cells can migrate

136

What are the local affects of interleukin 1B?

Endothelium activation (expresses e-selectin and ICAM1)
Leukocyte activation
Destroys local tissue

137

What are the local affects of TNF-alpha?

Activates endothelium and makes endothelium more permeable. This causes migration of immune cells, IgG, complement. Also allows fluid drainage to lymph nodes

138

What are the local affects of interleukin 6?

Activates lymphocytes
Increases antibody production

139

What is the role of CXCL8?

Chemotactic. Recruits neutrophils, basophils and T cells

140

What is the role of IL-12?

Activates NK cells
Induces differentiation of CD4 T cells to TH1 cells

141

What is expressed on activated endothelium?

E-selectin
ICAM-1

142

How do leukocytes bind to e-selectin?

S-LEX

143

How do leukocytes bind to ICAM-1?

LFA-1

144

What is the function of histamine?

Dilates blood vessels

145

How is histamine synthesised?

From histidine via histidine decarboxylase

146

Where is histamine found?

In secretory vesicles bound to proteoglycan

147

How is CFTR activated?

Adrenergic receptor activity

148

How is CFTR inhibited?

LPA receptor activity

149

Cystic fibrosis and diabetes

Mucus causes scarring of pancreas = less insulin produced

Insulin resistance