Pathology Book Flashcards
Types of necrosis
Coagulative - denaturing of intracytoplasmic proteins- occurs after ischaemia except brain- tissue becomes firm and swollen
Colliquative- seen in brain - hypoxia
Caseous - tuberculosis
Fat- trauma to apdipsoedue to lipase
Fibrinoid - arteriole smooth muscle wall due to malignant HTN
Cause of inflammation cellular wise
Contraction of endothelial cytoskeleton in venules
Due to release of chemical mediators
Main cell in acute inflammation
Neutrophil
Main cell in chronic inflammation
Macrophages
IL1,2 IF and TNF fucntion
IL1 neutrophil adhesion
IL2- differentiation of B and NK cells
IF- activation of macrophages and NK cells
TNF- fever, neutrophil adhesion
What is formed at inflammation sites that can limit spread of pathogen
Fibrin
What is a histological diagnostic feature of acute inflammation
Neutrophil polymorphs
Sequale of acute inflammation
Resolution - minimal injury, stimulus removed
Organisation - delayed removal of exudate
Suppuration - abscess, large quantity of dead neutrophils
Progression to chronic inflammation- usually when inadequately managed
Causes of chronic inflammation generally
Persisting infection
Prolonged exposure to non biodegradable substances
AI conditions
Vascular changes in chronic inflammation
Angiogenesis
Cells in chronic inflammation
Macrophages
Plasma
Lymphocytes
Resolution of chronic inflammation
Healing by fibrosis
What is a granuloma
Aggregation of macrophages
Large giant cells found at periphery
How TNFa induces apoptosis
TNF-alpha binds to both the p55 and p75 receptor
Reversible cell injury microscopically
Cellular swelling
Swelling of cell and organelles
Blebbing of plasma membrane
Detachment of ribosomes from ER
Clumping of chromatin
Fatty changes - hypoxic injury- in cells involved in and are unable to fat metabolism- hepatocytes and myocardial cells
Ulcer associated with burns
Curling
Microscopic changes in irreversible cell damage
Swelling and disruption of lysosomes
Presence of large amorphous densities in swollen mitochondria
Membrane disrupted
Which organelle is self replicating
Mitochondria
Which pigment is involved in ageing cells
Lipofuscin
Phases of bone healing
Reactive - haematoma forms
Fibroblasts, macrophages and new vessels invade area forming granulation tissue
Reperative- osteoblasts and chondroblasts in haematoma forming woven bone and fibrocartilage forming callus
Woven bone is replaced by lamellar bone
FInal- lamellar bone is replaced by compact bone
Hypertrophic vs keloid scars
Hypertrophic - within margins of wound - thick raised scar
Keloid- extend margins
Collagen in wound healing
Type 3 in early phase
1 in maturation phase, which is stronger
Rule of closing the abdomen
Suture 4x length of wound
1cm deep and apart
Primary vs secondary intuition of wound healing
Primary- margins closely brought together
Secondary- margins not apposed
Granulation tissue forms that contracts
Mylofibroblasts contract reducing scar size
Where keloid scars most commonly form
Sternum and deltoid area
Dorsal surfaces
4 stages of wound healing
Coagulative - vasoconstriction, platelet adhesion, fibrin clot
Inflammatory - vasodilation, exudation, phagocytosis
Fibroblastic/proliferative- granulation, contraction, epitheliasagtion
Remodelling - scar tissue and reorganising
Factors contributing to poor wound healing
Local- poor blood supply, infection, FB, haematoma, mechanical stress
Systemic- old age, anaemia, drugs, DM, malnutrition, obesity, infection, uraemia
Immediate complications of Central venous lines
Pneumothorax, tamponade, chlythorax, arryhtmia
RF of aortic dissection
Atheroscelrosis
HTN
Aortic valve defects
Turners
Marfans
Ehlers Danlos
Milroy disease
Congenital hereditary primary lymphedema- casted by aplasia of lymph trunks
Diabetic ulcer features
Pressure areas
Painless
Protein C and S function
Inhibit factor V and VIII
Therefore deficiency increases clot risk
What ascites type does a psuedomyoxoma cause
Exudative
Tumour of appendix
Types of acquired aneursym
Atherosclerotic
Mycotic
Dissecting
AV
Areas with stratified squamous cells
Keratonised - skin , tongue, outer lips
Non keratinised- cornea, oesophagus, rectum, vagina
Areas with pseudo stratified columnar
Epipidymis and trachea
Prostate
Areas with simple columnar
Colon and uterus
Characteristics of dysplasia
Pre cancerous
Increased cell growth and decreased cell differential
Increased mitotic activity
Hyperchromatic nuclei with high nuclear to cytoplasm ratio
Define metaplasia
Reversible cell change due to environmental stress
Types of gangrene and pathology
Wet- arterial and venous obstruction causing stagnation and rapid infection and sepsis
Dry- arterial obstruction - lack of blood- reduced infection
Gas- clostridium perfrigens
Haemochromatosis, Wilson and a1at disease inheritance
HC- AD- 6
Wilson- AR- 13
A1AT- AR
Haemachromatosis vs Wilsons symptoms
HC- increased iron absorption in cells - myocytes, pancreas and liver- cardiac, liver failure, DM, pancreatitis
Wilsons- accumulation of copper in brain, liver and cornea
Familial cancer syndrome and their affected genes
Li-Fraumeni- p53
Retinoblastoma- Rb1
FAP- APC
vHL- VHL
MEN- RET
Familail breast cancer- BRCA1,2
Types of gene mutation for Down syndrome
Non disjunction- most common
Translocation- rare
Mosaicism- very rare- non disjunction in blastocysts formation- some normal some trisomy 21
What is a giant cell
Physiological examples and pathological
Union of small cells to formate a multinuclear cell
Physio- osteoclast, skeletal muscle, synctiotrophoblasts, oocytes
Pathological- reed steenberg, langerhans (sarcoid, TB, Crohns), CMV
Time for irreversible damage to neutrons vs myocytes
Neurons- 3-5 mins
Myocyes- 1-2 hrs
Which necrosis preserves tissue architecture
Coagulative necrosis
Types of cell degradation due to enzymes
Heterolysis - outside
Autolysis- inside cell
Compostiosn of amyloid and arrangement
Minor constant- amyloid p protein
Major
Chronic inflammation- Amyloid A protein
Monoclonal cell proliferation- myeloma- Amyloid light chain
Arranged in B pleats
Staining of amyloid
Congo red
“apple-green birefringence” when viewed under polarized microscopic light.
What happens in apoptosis
Energy dependent process
Cells- shrink and undergo fragmentation to form apoptotic bodies
Apoptotic bodies
Nuclear shrinking
Membrane integrity is preserved
No inflammatory response
Morphogenic apoptosis
During embryological development
Involved in alteration of tissue form
Hyperplasia vs hypertrophy and reversibility
Hyperplasia- increase number of cells
Hypertrophy- increase size of cells
Both reversible when stimulus removed
Change in bone marrow cells at altitude
Hyperplasia
Stages of cell cycle
G0- resting phase
G1- 1st gap- increase in size
S- DNA synthesis
G2- second gap - further increase in size
M- mitosis (pro, meta, ana, telophase)
Viruses that cause cancer
HPV 16,18- cervical
EBV- Burkitt lymphoma, hodgkin, nasopharyngeal
Herpes- lymphoma
Human T lymph virus- T cell lymphoma
Hep B- HCC
HIV- karposi
Rhabdomyosarcoma vs leimyosarcoma
Rhabdo- skeletal
Leio- smooth
Marker in seminoma
bhCG
Marker in teratoma
aFP
What is an adenoma
Tumour of glandular tissue
Most common area for prostate cancer to develop
Posterior side
Most common type of male breast cancer
Invasive ductal carcinoma
Types of paraneoplastic syndrome
Humoral
Cushing
SIADH
PTrP- high calcium
Carcinoid
Immuno- AI
Dermatomyositis
Membranous glomerulnepritis
Bacertial and fungal infections associated with cancer
H pylori- gastric lymphoma
Aspergillus- HCC
Schisto- bladder cancer
Clonorchis- cholangiocarcinoma
Transcolaemic transmission of cancer and examples
Across a body cavity
Lung- to pleura- pleural effusion
Stomach - to ovaries- Krunkenberg tumour
Ovarian - to omentum and peritoneum- ascites
Colon
Krunkenburg tumour arises and spread to were
From stomach to ovaries
Transcolemic spread
Adenocarcinoma
Most common bone cancer
Osteoscarcoma
Plummer Vinson sx and risks
Webbed oesophagus
IDA
Splenomegaly
Rf for SCC of oesophagus
Dukes staging
A- limited to mucosa
B1- MP, 2- through
C1- LN, C2- >4
D- distant mets
FNA results breast
C1- insufficient
2- benign
3- uncertain
4- suspected cancer
5- cancer
TNM for breast cancer
T1- <2cm
2- 2-5cm
3- >5cm
4- spread to chest wall or skin
N0- no LN
1- ipsilateral axillary mobile
2- ipsilateral fixed, or internal mammary
3- LN supra or infraclavicular
M1- distant mets
Types of hypersensitivites
Type 1- immediate allergic reaction- IgE
2- AB on cell surface
3- deposition of AB- antigen complex in tissues
4- delayed- T lymph
Which cell kills viral infected cells and tumour cells
Nk cells
AB Production order and timescale
IgM
IgG- 3w
Change due to T cell switch
What happens if you’re IgA deficient
Mucosal infections
Since that is where IgA is secreted
Also need IgA deficient blood or else react against it
Types of transplant rejection
Hyperacute- preformed ABs to HLA or ABO
Acute T cell- type 4, epithelial damage
Antibody- anti HLA AB-endothelial damage
Chronic- may be antigen AB mismatches not suppressed by immunosuppressant
Complement activation pathway
Classical
Antigen AB complex binds to C1,4,2
C3- which activates C5
Alternative
Activated by cell wall
Mannose binding
Activated by c ell surface carbohydrates
Activates cascade via the classical pathway - via C2 and C4 (but NOT C1)
Final
C5- activates others for MAC
Features of leucocyte adhesion deficiency
Neuts unable to migrate
High neuts in blood
No pus
Features of chronic granulomatous disease
Failure of oxidative killing
Granuloma formation
Abnormal dihydrorhodamine test (-ve)
Di George syndrome characteristics
● Low T-cells, low IgA, low IgG
● Normal B-cell levels, normal IgM
Alter facial characteristics
Cardiac defects
Selective IgA def features
● - IgA provides mucosal immunity
● Associated with other AI diseases e.g. coeliac, SLE
● Risk of a naphylaxis after blood transfusion ( anti-IgA Abs
Endogenous pyrogens
TNFa
IL1
Chemoattractant for neutrophils
IL8
Cause of thrombocytopaenia
Aplastic
Viral infections
Myelodysplasia
Myeloma
ITP
Post transfusion
DIC
Hypersplenism
DIAPHM
Blood film of myelodysplasia
Pelger Huet abnormality
(hyposegmented neutrophils) - bilobed & dumbbell shaped nucleus
Function of apoptosis
Morphogenesis
Removal of cells with DNA damage
Removal of viral infected cells
Induction of tolerance in immunity
Medaitors of apoptosis
p53- tumour suppressor gene
bcl2- inhibits apoptosis
fas- receptor that leads
caspases
Mechanism of skin graft take
Adherence- fibrin bonds graft to recipient <12h
Plasmic imbibition- graft absorbs nutrients- 24-48
Insoculation- revascularisation- 28-72
Stages of formation of blood clot
Platelets sticking to endothelium- vWF
Fibrin and leucocytes adhere
Fibrin and red cells develop on this layer
Secondary layer of platelets
Adherence to wall- mural thrombus
Second stage- further platelets lay down on initial aggregate
Contraction of platelets and fibrin cause ridged- lines of Zahn
Fate of thrombi
Lysis- resolution
Recanalisation- new vessels
Propagation- causing further thrombi
Embolisation
Causes of non thromboembolic vascular insufficiency
Atherome
Torsion
Spasm
Steal- AV fistula- flow goes through cephalic instead of radial- poor perfusion distally
External pressure- tumour
Red vs white infarct
Red- venous - lung
White- arterial- e.g heart and spleen
Adenoma vs papilloma
Adenoma- glandular
Papiloma- non glandular
Blastoma meaning
Histological resemblance to embryonic form of origin
Harmatoma constituants
Usually 2 or more matures cells- but abnormally organised
Examples of premalignant conditions
Pagets- osteogenic sarcoma
Cirrhosis- HCC
Xeroderma pig- skin cancer
UC- colon adenoma, bile duct
Cervical dysplasia
Hyperplasia of breast
Colorectal polyp
Oncogenes examples
Genes that stimulate the development of cancer
May only need 1 to become abnormal
sis
ras
abl
myc
MARS
Tumour suppressor genes examples
Gatekeepers- inhibit proliferation or promote death with DNA damage
p53
Rb1
APC
Caretakers- maintain integrity of DNA by repairing damage
BRCA1,2
Steps of metastatic cascade
Detachment of tumour cells
Invasion of surrounding tissue
Intravasation into lumen of vessels
Evasion of defence
Adherence to endothelium at remote location
Extravascularisation
Survival
Establish blood supply
Which cancers spread often to bone
Breast
Bronchus
Kidney
Thyroid
Prostate
Spread via haematogenous
How do sarcomas spread
Haematogenous
How can cancers cause jaundice
Invasion of nodes in portal hepatis
Causing obstruction of hepatic bile duct
What is bad prognosis of malignant melanoma
> 4cm on breslow thickness
Composition of an antibody
Heavy- y, u, a, b, e
Light- k or l
Fab- contains binding site
Fc
N terminal region of the end of Fab fragment - variable region- specific to antigen
Which antibody crosses placenta
IgG
How many antigen binding sites are there in IgG, IgM, IgA
IgG-2
IgA- 4
IgM- 10
Role of IgG
Crosses placenta
Opsination
Neutralise toxins
Role of IgM
Primary response
Great agglutination
Types of T cell
CD4- helper
CD8- cytotoxic
Classification of MHC
1- A, B, C (all nucleated cells)
2- DP, DR, DQ (B cells, activated T cells and APC)
How T cells recognise antigens
T cells have TCR
Will only recognise an antigen as part of a complex of the antigenic peptide and MHC
Endogenous antigens are presented by MHC class 1 to CD8 cells
Exogenous antigens are presented by MHC class 2 to CD4
Structure of lymph node and where cells are located
Cortex- primary follicles of B cells, dendritic cells- APC
Paracortex- T cells
Medulla- contained lymphocytes less packed, with macrophages, plasma cells
Sinuses lined with macrophages that phagocytose
Primary follicles turn into secondary on antigen stimulation which contain germinal centre of B cells (antigen activated) and a few CD4 cells
Activated B cell migrate from follicle to medulla- develop into plasma cells and release AB into efferent limb
Organisation of spleen
Lymphoid tissue is in white pulp arranged around arterioles
T cells surround central arteriole
B cells in white pulp- may form germinal centres when activated
Produce ABs
Red pulp- remove old RBC, abnormal WC, phagocytosis by macrophages
Types of T helper cell
Th1- secrete TNFa and IFNy and mediate cellular immunity
Th2- secrete IL4,5,10,13- stimulate B cell to produce AB
Types of immunosuppressive dugs
Corticosteroids- inhibit T cell activation, neutrophil pahgocytosing, anti inflammatory effects
Antiproliferative
Azathioprine - interferes with nucleic acid- purine- T cells prolif
Mycophenolate- prevents guanine synth- more effective for acute- prevents both T and , prevents smooth muscle prolif
Calcinerin- inhibit T cell activation- prevent IL2 release from helper cells
Ciclosporin
Tacrolismus
Clinical features of haemolytic anaemia
Palloe
Jaundice
Gallstones
Splenomegaly - more susceptible to infection due to reduced function
Frontal bone bossing
Bone marrow expansion- weaken
Sickle pathophysiology
HbS
glutamic replaced by valine
Causing them to polymerise on deoxygenation
Sickle in venous blood- due to lower O2 levels
Increased rigidity- plug small vessels- infarction and painful crisis
Anaesthetist needs to avoid hypoxia
Hereditary spheorcytosis features and tx
Defect on cell membrane
Raised bilirubin
Cholecystitis
Splenectomy- as prevents destruction of RBC- Hb rise, reduce bilirubin
Degradation of fibrin
Tissue plasminogen activator released by endothelial cells
This is inhibited by PAI1- plasminogen inhibitor 1
This is also released by endothelial cells
TPA activated it to plasmin which degrades fibrin into degradation products.
This process is inhibited by antiplasmin
Min level of plts for surgery
70
Days before surgery that each anticoagulant needs to be stopped
Warfarin- 5d, Vit K should be given day before if INR >1.5
LMWH- 24 hrs before, started 48hrs after if high risk for bleeding
DOAC- 24 hrs before low risk, 48 in high
Cause of massive splenomegaly
CML
Myelofibrosis
Lymphoma
Which vaccines are required for patients who are undergoing splenectomy
Pneumococcal
H influenza
Meningococcal
Needs to be at least 2w before surgery
Conditions causing abnormal growth in thymus
MG
SLE
Dermatomyositis
Aplastic anaemia
Indication of platelet transfusion
Haemorrhage with thrombocytopaenia
Thrombo prior to procedure
Consumption coagulopathy- DIC
Indication for FFP transfusion
Replace clotting factors in major haemorrhage
Liver disease, rapid reversal of warfarin
Prophylaxis with specific deficiency
Indication for cryoprecipitate transfusion
Rich in VIII, fibrinogen, vWF
Haemophillia
vWD
Fibrinogen disease
Staph aureus shape and staining
Gram + cocci arranged in clusters
Coagulase positive
Streptococci Shape and stain
Gram + cocci arranged in pairs or chains
Gram + cocci coagulase neg
S epididimis- prosthetics, HV
S Saprolyticus- UTI
Gram positive rods
Actino
Bacillis
Clostridium
Listeria
Gram negative cocci
Neisseria
Gram negative bacilli
Anaerobes
E coli
Klebsiella
Salmonella
Shigella
Aerobes
Psudomonas
Campylobacter- curved or spiral rods
H influenza
H pylori - spiral
Definition of when SIRS can be diagnosed
Temp >38 or <36
Tachycardic >90
Tachypnoeic >20 or CO2 <4.
WCC >12/ <4
