Cell And Tissue Pathology Flashcards
Which types of cells are present in granulomatus inflammation?
Macrophages, T cells, epitheloid cells (large macrophages) and giant cells (fused macrophages)
What are the two types of granulomas?
Foreign body granules and immune granules
What is an epitheloid cell?
A macrophage with an abundant cytoplasm
What is a giant cell?
A multinucleated cell formed by fusion of active macrophages
What are the inciting agents of immune granulomas?
Persistent microbe or self antigen
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
What causes crohns disease?
Intestinal bacteria and possibly self antigens
What is the tissue reaction in crohns disease?
Occasional noncaseating granulomas form in the intestine wall
What are the 4 characteristics of inflammation?
Calor
Rubour
Dolor
Tumour
What are the 4 stages of inflammation?
Vascular response
Inflammation
Cell proliferation
Remodelling
What are 3 types of inflammatory muscle disease?
Temporal arteritis
Dermatomyositis
Polymyositis
Which arteries are affected by giant cell arteritis?
Temporal arteries
Opthalmic arteries
Vertebral arteries
Aorta
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?
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
What are the symptoms of temporal arteritis?
Headache, fever, fatigue, weight loss, ocular symptoms
What is the pathogenesis of dermatomyositis?
Components of the MAC are found in the capillary beds in muscle and skin
What are the symptoms of dermatomyositis?
Rash Proximal muscle weakness Myalgia Dysphagia Elevated serum creatine kinase levels Interstitial lung disease
What is the pathogenesis of polymyositis?
CD8+ cytotoxic T cells infiltrate muscle cells
Vascular injury has no major role
What are the symptoms of polymyositis?
Proximal muscle weakness
No cutaneous features
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
Which diseases are associated with inflammatory bowl disease?
Ankylosing spondylitis and uveitis
Ulcerative colitis increases the risk of which two diseases?
Anaemia and bowel carcinoma
What causes gastric ulceration?
Excess stomach acid
Which bacteria is associated with gastric ulceration?
H. Pylori
How is gastric ulceration treated?
Proton pump inhibitors and antibiotics if have H. Pylori infection
Which tracts are affected by cystic fibrosis?
Respiratory tract
GI tract
Reproductive tract
What are the symptoms of CF?
Finger clubbing
Cough
Recurrent lung infections
Reduced FEV1
Where is the CFTR gene found?
7q31.2
What is the most common CFTR mutation?
DeltaF508 (60 %)
What inheritance is associated with Cystic fibrosis?
Autosomal recessive
How common is cystic fibrosis?
1 in 2000 have CF
1 in 20 are carriers
(In caucasian population)
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)
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
What are ENaC channels responsible for?
Na uptake into cells
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
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
What is a class 1 CFTR mutation?
No CFTR is trafficked to cell surface
What is a class 2 CFTR mutation?
DeltaF508 mutation
Some CFTR is trafficked to the cell membrane but none is functional
What is a class 3 CFTR mutation?
Normal amount of CFTR at cell surface
None is functional
What is a class 4 CFTR mutation?
Normal no of CFTR at cell surface
Some is functional
What is a class 5 CFTR mutation?
Some CFTR is trafficked to cell surface
All is functional
What is the chaperone protein that tried to fold CFTR?
HSP40
What are the treatments for CF symptoms?
Antibiotics Bronchodilators Physiotherapy DNAse High calorie diet Insulin Lung transplant
What is VX-809
A corrector. It increases the no of CFTR molecules which get to the cell surface
What is ivacaftor?
Potentiator. Increases CFTR channel opening
What is ataluren?
Ribosomal skipping agent. Allows stop codons to be skipped
What treatments are available to address Cl transport?
VX-809
Ivacaftor
Ataluren
What is a sarcoma?
Tumour of connective tissue or its mesenchymal precursor
What is atrophy?
Degeneration
What is dysplasia?
Cells that look abnormal but are not cancerous
What is metaplasia?
Reversible change where one cell type is replaced by another
What is pleomorphism?
Unusual nuclei
What is an adenoma?
Benign tumour in the glandular epithelia
What 2 component tissues are all tumours made up of?
Parenchyma and stroma
What is a papilloma?
Benign epithelial tumour which forms a finger-like or warty projection
What is a cystadenoma?
Benign epithelial tumour which forms hollow masses
What is a papillary cystadenoma?
Papillary pattern protrudes into a cyst-like space
What is the difference between a fibroma and a fibrosarcoma?
A fibroma is a benign fibroblast tumour. A fibrosarcoma is a malignant fibroblast tumour.
What is neoplasia?
Uncontrolled cell growth
What is anaplasia?
Lack of differentiation
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
What is karyolysis?
Loss of dna
What is pyknosis?
Nuclear shrinkage
What is karyohexis?
Nuclear fragmentation and disappearance
What are common causes of panceatitis?
Alcohol
Gallstones
Infection
Genetic
What are rare causes of pancreatitis?
Trauma
Corticosteroids
Hyperlipidaemia
How does alcohol causes pancreatitis?
It destroys acinar cells
How do gallstones causes pancreatitis?
If they move into the pancreas
What is a symptom of gallstones?
Elevated AST levels
How are gallstones treated?
By removal of the gallbladder
What are complications associated with pancreatitis?
Infection
Pancreatic necrosis
Pancreatic cysts
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
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
Why does the PRSS1 mutation cause pancreatitis?
Trypsin is overactive and causes autodigestion
What is trypsin?
A protease
How do SPINK1 and CTRC mutations causes pancreatitis?
Disrupt trypsin inhibition leading to autodigestion
What does cathepsin B do in the pancreas?
Turns trypsinogen into trypsin
What is CASR?
An extracellular calcium sensing receptor
What role does calcium play in the pancreas?
It prevents premature zymogen activation
How do CFTR mutations cause pancreatitis?
Distuption in bicarbonate transport (not chloride)
What are symptoms of pancreatitis?
Elevated amylase levels Abdominal pain Fever Nausea Diarrhoea
What causes gallstones?
An imbalance of bile salts and cholesterol
What do acinar cells do?
Store, synthesise, secrete digestive enzymes (exocrine pancreas)
What cells make up the islets of langerhans?
Alpha, beta, delta and pp cells
What do alpha cells secrete?
Glucagon
What does glucagon do?
Converts glycogen to glucose
What do beta cells do?
Secrete insulin and amylin
What does insulin do?
Promotes uptake of glucose by liver, fat and muscle cells and converts glucose to glycogen
What does amylin do?
Promotes satiety
What do delta cells secrete?
Somatostatin
What does somatostatin do?
Inhibits release of growth hormone
What do pp cells secrete?
Pancreatic polypeptide
What does pancreatic polypeptide do?
Regulates pancreas secretions
What is type 1 diabetes?
Where T cells attack beta cells in the pancreas
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
How is insulin synthesised?
As pre pro insulin
How many amino acids make up insulin?
51
What chains make up insulin?
A B C
What happens to the C chain on insulin?
Removed in the golgi
Name two types of type 1 diabetes
Familial hyper pro insulinaemia
Permanent neonatal diabetes mellitus
Why do diabetics get foot ulcers?
Neuropathy
Impairment of wound healing - blood vessels narrow due to high blood glucose levels
Infection (compromised immune system)
What gene is linked to ankylosing spondylitis?
HLA-B27*05
Is ankylosing spondylitis more common in men or women?
Men
Are autoimmune diseases more common in men or women?
Women
What is the median age of onset for ankylosing spondylitis?
23
What causes the bamboo spine seen in akylosing spondylitis?
Damage to the sacro-ileal joint
Which type of MHC is HLA-B27 a variant of?
MHC 1
What is the function of MHC 1?
To present cytosolic peptides to CD8+ T cells
What is the median age of onset for ankylosing spondylitis?
23
What causes the bamboo spine seen in akylosing spondylitis?
Damage to the sacro-ileal joint
Which type of MHC is HLA-B27 a variant of?
MHC 1
What is the function of MHC 1?
To present cytosolic peptides to CD8+ T cells
What complications are associated with ankylosing spodylitis?
Uveitis
Enthesitis
IBD
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
What suggests HLA-B27 may not be the sole factor in AS?
5% of AS patients do not have the HLA-B27 gene
HLA-B2705 is associated with AS but HLA-B2709 is not
HLA-B27 is expressed on all nucleated cells but AS has specific tissue involvement
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
Which gene is associated with rheumatoid arthritis?
HLA-DR4
On which chromosome are MHC genes found?
Chromosome 6
What job do MHC class 2 molecules have?
The present exogenous peptides to CD4+ helper T cells
What are the tests for rheumatoid arthritis?
X ray
Blood tests
What are the blood tests for rheumatoid arthritis?
Anaemia Elevated ESR Elevated gamma globulin Elevated C reactive protein High titre rheumatoid factor
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)
Which molecules help WBC leave blood vessels?
Selectins
What are the 4 stages of a WBC leaving a blood vessel?
Tethering and rolling
Activation
Firm adhesion
Transmigration
What is aneuploidy?
Unusual chromosome number
What does euploid mean?
Has normal numbers of chromosomes
What are the stages of the cell cycle?
G1, S, G2, M
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)
What controls the cell cycle?
Cyclins
When in the cell cycle do cyclin A levels rise?
During the s phase
When in the cell cycle do cyclin b levels rise?
During the m phase
When in the cell cycle do cyclin E levels rise?
After the r point and collapse during the s phase
When do cyclin D levels rise?
During the G1 phase
What is anoikis?
Apoptosis due to incorrect cell/ECM attachment
Why is epithelial to mesenchymal transition required for metastasis?
Epithelial cells cannot migrate
Mesenchymal cells can migrate
What are the local affects of interleukin 1B?
Endothelium activation (expresses e-selectin and ICAM1)
Leukocyte activation
Destroys local tissue
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
What are the local affects of interleukin 6?
Activates lymphocytes
Increases antibody production
What is the role of CXCL8?
Chemotactic. Recruits neutrophils, basophils and T cells
What is the role of IL-12?
Activates NK cells
Induces differentiation of CD4 T cells to TH1 cells
What is expressed on activated endothelium?
E-selectin
ICAM-1
How do leukocytes bind to e-selectin?
S-LEX
How do leukocytes bind to ICAM-1?
LFA-1
What is the function of histamine?
Dilates blood vessels
How is histamine synthesised?
From histidine via histidine decarboxylase
Where is histamine found?
In secretory vesicles bound to proteoglycan
How is CFTR activated?
Adrenergic receptor activity
How is CFTR inhibited?
LPA receptor activity
Cystic fibrosis and diabetes
Mucus causes scarring of pancreas = less insulin produced
Insulin resistance
