Pathology 1 Flashcards
Define infective endocarditis
Inflammation of the endocardial surfaces of the heart including the heart valves
What is marantic endocarditis
Non bacterial thrombotic endocarditis
Tends to occurs in the setting of malignancy
Why are patients with rheumatic heart disease/ replaced heart valves more at risk of IE
More susceptible to IE as they are damaged or artificial which allows for increased chance of bacterial colonisation
What is the pathology of rheumatic heart disease
Host immune response to Group A streptococcal antigens
Antibodies/ CD4/ T cells directed against streptococcal M proteins can recognise cardiac self antigens which results in damage to the heart tissues leading to inflammation, progressive fibrosis and narrowing of the valve leaflets - causing them to fuse and to retract
What are the gross findings in acute IE
Valvular vegetations - found along lines of closure, with minimal effect on function
What are the gross findings in chronic IE
Commisural fibrosis
Valve thickening and calcification
Shortened and fused chordae tendinae
What are the microscopic findings of IE
Aschoff bodies
Plasma cells
Anitschkow cells (activated macrophages)
What are Aschoff bodies
granulomatous inflammation with central zone of degenerating ECM infiltrated with lymphocytes
What are the 5 types of necrosis
Coagulative
Liquefactive
Caseous
Fibrinoid
Fat
What would you assess for on ECHO in the context of IE
Valvular regurgitation
Leaflet change
Annular dilatation
chordal elongation/rupture
Increased echogenecity of subvalvular apparatus
pericardial effusion
Ventricular dilation and dysfunction
What organisms commonly cause IE
Staph aureus
Staph epidermis
Strep viridians
Coagulase negative staph
Enterococci
HACEK group
What organisms are part of the HACEK group
Haemophilus species
Aggregatibacter species
Cardiobacterium hominis
Eikenella
Kingella species
What organism causes IE in early valve replacement patients
Staph epidermis
What organism causes IE in IVDU patients
Staph aureus
What scoring on the Dukes criteria gives a diagnosis of IE
2 major + 0 minor criteria
1 major + 3 minor criteria
0 major + 5 minor criteria
What are the major criteria in the Dukes criteria
Typical IE organism in 2 cultures
1 culture for Cox Burnetti
Persistently positive cultures
Positive ECHO
Abnormal prosthetic valve activity on CT
What are the minor criteria in the Dukes criteria
Predisposing risk factors - known heart disease, IVDU
Fever > 38 degrees
Vascular sequelae
Immunological sequelae
Positive blood cultures
ECHO findings
What are the vascular sequelae in IE
Arterial emboli
Janeway lesions
Conjunctival haemorrhage
What are the immunological sequelae in IE
Glomerulonephritis
Roths spots
Osler nodes
Which patients develop right sided IE
IVDU patients
Which lesions are painful - janeaway lesions or Osler nodes
Osler nodes
Risk factors for IE
Structural heart disease
Prev IE
Valve replacement
Acquired heart disease w stenosis and regurgitation
HOCM
Cardiac device
IVDU
DM
Malignancy
What infectious organism is associated with colorectal cancer
Strep bovis
What are the cardiac complications of IE
Acute MI
Pericarditis
Arrythmia
Valvular insufficiency
Congestive cardiac failure
Anuerysm of aortic sinus
Intracardial abscess
Arterial emboli
What are the non cardiac complications of IE
Endocarditis associated glomerulonephritis
AKI
Stroke
Mesenteric/Splenic abscess/infarct
What are the clinical features of IE
Fever
Roths spots
Osler nodes
Murmur
Janeway lesions
Anaemia
Splinter haemorrhage
Emboli
What is the treatment of native valve IE
Amoxicillin
Flucloxacillin
Gentamicin
What is the treatment of prosthetic valve IE
Vancomycin
Gentamicin
What are the challenges with ABx therapy in IE
Valves do not have a specific blood supply
Bacteria hide within vegetations
Bacteria form a biofilm and can therefore be shielded from ABx
What is a biofilm
Glycocalyx covering
What it the management of IE refractory to treatment
Valve replacement
Heart transplant
What happens if HLA antigen matching is not done in valve replacement
Type I hypersensitivity and graft rejection
What causes aortic stenosis
Post inflammatory scarring eg. rheumatic heart disease
Senile calcific aortic stenosis
Calcification of congenitally deformed valve
What is the pathophysiology of stenosis
Lipid accumulation
Inflammation
Calcification - leads to valve thickening and stenosis
What is the sequelae of aortic stenosis
As aortic valve progresses from sclerosis to stenosis the left ventricle encounters chronic resistance to systolic ejection
Results in increased afterload
After time this results in left ventricular hypertrophy
What are the consequences of high left ventricular after load
Decreased left ventricle myocardial elasticity and coronary blood flow
Results in increased myocardial workload and oxygen consumption
What are the late manifestations of LVH
Small ventricular chamber
Insufficient stroke volume, cardiac output and ejective fraction
Increased pulmonary pressures
What is the concern with aortic stenosis in the perioperative period
Patient has a fixed cardiac output and a limited coronary blood supply
They cannot respond to decreased after load which can occur with both anaesthesia and blood loss
How is coronary perfusion pressure calculated
Systemic diastolic pressure - LVED pressure
If on microscopy you visualised branching hyphae what type of organism is responsible and give examples
Fungal infection
Examples - candida, aspergillum, microsporum, triophyton, epidermophyton
What is the definition of a thrombus
Solid material formed from the constituents of blood
What factors does warfarin inhibit
Factors 2, 7, 9, 10
What are the clinical symptoms of aortic stenosis
Syncope
Anginal pain
Dysponea
Paroxysmal nocturnal dyspnoea
Orthopnea
What are the clinical signs of aortic stenosis
Pulsus arterans
Narrow pulse pressure
Ejection systolic murmur
Paradoxical splitting of S2
What is pulsus arterans
Pulse with alternating strong and then weak pulses
What is paradoxical splitting of S2
Occurs due to the closure of the aortic valves and pulmonary valve not being synchronous
What is severe aortic stenosis in terms of valve surface area and transvalvular pressure gradient
<1.0cm3
Confers to a transvalvular gradient of >40mmHg
What is giant cell arteritis
Inflammation of the large and medium sized blood vessels, predominantly affecting the temporal arteries
What is the pathology of giant cell arteritis
Medial granulomatous inflammation
Centred on the internal elastic lamina - producing elastic lamina fragmentation
Infiltrates of T cells and macrophages
What is meant by focal lesions in GCA
There are focal points of disease distribution along vessel with long segments of relatively normal artery
What are the clinical features of GCA
New onset headache in the temporal region
Scalp tenderness
Intermittent jaw claudication
Weight loss
Fever
Temporal artery thickening and modulatory
Visual field changes
What is the gold standard investigation for GCA
Temporal artery biopsy
What would a positive temporal artery biopsy show
Mononuclear cell infiltrates
Granulomatous inflammation with multinucleate giant cells
What is the management of GCA
Steroids
If eye involvement - IV Methylpred
When considering patients with steroids what should you think about
Immunosuppression
Bone quality
How should an addisonian crisis be avoided perioperatively
Double dose the patient steroids before theatre
Convert PO to IV hydrocortisone
What is osteoporosis characterised by
Low bone mass
Microarchitectural deterioration of bone tissue
Increased bone fragility
Loss of bone matrix
What are the pathological changes in osteoporosis
Histologically normal bone is decreased in quantity
Trabecullar plates become perforated, thin, and loser their interconnection - this leads to progressive micro fractures and eventually bone collapse
What is the mechanism of post menopausal osteoporosis
Increased osteoclast activity
What are the 3 main mechanisms of osteoporosis
Inadequate peak bone mass
Excessive bone reabsorption
Inadequate formation of new bone during bone turnover
What are the primary causes of osteoporosis
Idiopathic
Post menopausal
What are the secondary causes of osteoporosis
Addisons disease
TIDM
Hyper/hypothyroidism
Multiple myeloma
Hepatic insufficiency
Vitamin D/C deficiency
Malabsorption
Anaemia
Osteogenesis imperfecta
What is the mechanism of steroids on bone
Direct inhibition of osteoblast function
Direct stimulation of bone resorption
Inhibition of GIT calcium reabsorption
Stimulation of real calcium losses
Inhibition of sex steroids
What can cause pathological fracture
Multiple myeloma
Skeletal metastases
Pagets disease
Osteogenesis imperfecta
Radiotherapy
Osteomalacia
Rickets
What is multiple myeloma
Plasma cell neoplasm
What is multiple myeloma commonly associated with
Lytic bone lesions
Hypercalcaemia
Renal failure
Acquired immune deficiencies
What immunoglobulin is most commonly produced in multiple myeloma
IgG - 55%
IgA - 25%
What are the clinical features of multiple myeloma
M spike on protein electrophoresis
Ig light chains in urine - Bence Jone Protein
Hypercalcaemia
Anaemia
Bone lesions - lytic lesions, osteoporosis w compression #
What are Bence Jones proteins
Monoclonal globulin proteins/immunoglobulin light chains found in the urine
Produced by neoplastic plasma cells
What are the causes of fat embolism
Closed long bone fractures
Decompression sickness
Cardiopulmonary bypass grafting
Orthopaedic surgery - IM nailing, joint arthroplasty
Acute pancreatitis
DM
Define gangrenous necrosis
Necrosis of tissue with superadded putefraction
Define necrosis
Accidental and unregulated form of cell death resulting from damage to cell membranes and loss of ion homeostasis
What are the types of cell deaths
Apoptosis
Necrosis
Describe the pathogenesis of necrosis
Severe/prolonged ischemia results in severe swelling of the mitochondria, calcium influx into the mitochondria and into the cell with rupture of lysosomes and plasma membrane
Cytochrome is released from the mitochondria
What is the physiology of apoptosis
Programmed cell death/ cell death following DNA damage
Cell shrinkage, and fragmentation into nucleosome sized fragments, with intact plasma membranes
Released as small apoptotic bodies
What type of gangrene follow arterial occlusion
Dry
Where does dry gangrene commonly occur
Limbs
In which type of gangrene is there a clear line of demarcation
Dry
In what type of gangrene is the prognosis worse and why
Wet gangrene
Due to the profound toxaemia which accompanies it
What is the macroscopy in dry gangrene compared to wet gangrene
Dry - organ is dry, shrunken and black
Wet - parts moist, soft, swollen, rotten and dark
Describe coagulative necrosis
Loss of the nucleus with the cellular outline being preserved
commonly associated with ischaemia
What is the most common type of necrosis
Coagulative necrosis
Describe liquefactive necrosis
Enzymatic destruction of cells, with abscess formation following
Seen in the pancreas and the brain
Describe caseous necrosis
A combination of coagulative and liquefactive necrosis
Cheese like appearance of the necrotic material
What is caseous necrosis characteristic of
TB
Other than TB in what infections is caseous necrosis seen
Syphilis
Histoplasmosis
Coccidodomyosis
Describe fat necrosis
Results from the action of lipase on fatty tissue
Seen in breast, omentum and pancreatitis
Describe fibrinoid necrosis
Complexes of antigens and antibodies are deposited in the vessel walls with leakage of fibrinogen out of the vessels
Summarise atherosclerosis
Pathological process of the vasculature in which an artery wall thickens as a result of an accumulation of fatty materials, such as cholesterol
What are the risk factors for atherosclerosis
DM
FH
HTN
Smoking
Increased LDL
What is a pleural plaque a common manifestation of and how would you describe their appearance
Most common manifestation of asbestos exposure
Well circumscribed plaques of dense collegen, often calcified
What are the significance of pleural plaques
Increased risk of mesothelioma and lung adenocarcinoma
What are the two broad classifications of lung cancer
Small cell lung cancer
Non small call lung cancer
What are the different types of non small cell lung cancer
Adenocarcinoma
Squamous cell lung cancer
Large cell carcinoma
What is the most common lung cancer in non smokers
Adenocarcinoma
Which type of lung cancer is associated with paraneoplastic syndromes and why
Small cell lung cancers
They are cells of neuroendocrine differentiation so are able to release hormones
Where in the lung do squamous cell lung cancers arise
Centrally
How do you distinguish the epithelial origin of tumours
Immunihistochemistry
What can be used to treat epidermal growth factor positive tumours
Tyrosine kinase inhibitors - Imatinib
Imatinib is what kind of drug
Tyrosine kinase inhibitor
What are the systemic features of TB
Weight loss
Night sweats
Cervical lymphadenopathy
In younger patients with Hodgkin’s lymphoma where do they often experience lymphadenopathy
Anterior triangle
What are the investigations for TB
Culture
Ziehl neelson stain
Mantoux test
PCR
Quantiferon (interferon gamma assays)
If sending sputum cultures to the lab how should they be labelled and in what bag should they be sent
Labelled - Category B UN3373
Sent in a biohazard bag
What is BATEC/MIGT
Liquid media in which to culture TB
Mycobacterium growth indicator tube
What solid media is used to culture TB
Lowenstein Jensen media
Middlebrook media
What would FNAC in TB show
Necrotic tissues
Histocytes
Giant cells
Langherhan’s giant cells and Reed Sternberg cells are examples of what
Giant cells - multinucleate cells comprised of macrophages
What are some common causes of granulomas
TB
Sarcoidosis
Leprosy
Schistosomiasis
Crohn’s
RA
What needs to be done from a public health perspective in TB
Notify communicable disease control
Avoid working in food factory
Contact tracing
Direct observation of anti TB therapy
What ABx are commonly used in the treatment of TB
Isoniazid
Rifampicin
Pyrazanmide
Ethambutol
What are the different types of breast cancer
Ductal carcinoma
Lobular carcinoma
Medullary carcinoma
What is the most common type of breast cancer
Ductal carcinoma
What are the risk factors for breast cancer
Unopposed oestrogen (early menarche, OCP, HRT, nulliparous/ pregnancy >30, late menopause)
Obesity
Increasing age
FH - BRCA 1/2
What lead to unopposed oestrogen
Early menarche
OCP use
HRT use
Nulliparous
Pregnancy > 30
What are the clinical features of Paget’s disease
Itchy, red, flaking of the skin around the nipple
What imaging is used in suspected breast cancer and why does it differ
Differs depending on age
US < 35
Mammorgam >35
What findings on mammogram would make you suspicious of breast cancer
Speculated mass
Calcifications
What do pathology reports following WLE in breast cancer contain
Type of breast cancer
Number of positive LN
Margin status
HER2 receptor status
ER/PR receptor status
Ki67 proliferation status
What should be checked prior to any elective surgery
MRSA status
What is HER2 and where is it found
Human epidermal growth factor receptor 2
Found embedded in the cell membrane, it communicates molecular signals from outside the cell to inside the cell
In what percentage of breast cancer cases is HER2 over expressed
15%
What does immunohistochemsistry measure
The amount of a certain protein in cells (eg. the amount of HER2 protein in cells)
What does fluorescent in situ hybridisation measure
The number of copies of a gene in a cell (eg. HER2 in breast cancer cells)
What is Herceptin and what is it used for
Monoclonal antibody which interferes with HER2 and causes AB mediated destruction of cells overproducing HER2
What is Trastuzumab also known as
Herceptin
What is the normal mechanism of HER2
HER protein binds to EGF and stimulates cell proliferation, leading to the inhibition of MAPC + P13K AKt
When would a mastectomy be more appropriate that a wide local excision
In multifocal disease
When there is high tumour: breast tissue
If the patient would prefer this
What additional therapy is used in breast cancer if the tumour is found to be ER positive
Tamoxifen - If they are pre menopausal
Anastrazole - if they are post menopausal
What is the MOA of anastrozole
Aromatase inhibitor which prevents peripheral conversion to oestrogen
What is included in the Nottingham prognostic index
Maximum invasive carcinoma size
Lymph node stage
Histological grade
Which conditions characterise MEN 1
Pituitary adenoma
Parathyroid hyperplasia
Pancreatic tumours
Which conditions characterise MEN 2a
Parathyroid hyperplasia
Medullary thyroid cancer
Phaeochromocytoma
Which conditions characterise MEN 2b
Marfanoid body habitus
Mucosal neuromas
Medullary thyroid cancer
Phaeochromocytoma
The MENIN gene on chromosome 11 is associated with which condition
MEN 1
The RET oncogene on chromosome 10 is associated with which conditions
MEN 2a and MEN 2b
What is the common clinical presentation in a patient with MEN 1 syndrome
Hypercalcaemia
Define hyperplasia
Increase in the number of cells in a tissue or organ as a response to a stimulus
What is the microscopic appearance of parathyroid hyperplasia
Commonly chief cell hyperplasia
Can be in a diffuse or nodular pattern
Islands of oxyphil, poorly developed, delicate fibrous strands may envelope the nodules
What are the clinical features of an insulinoma
Stupor
Confusion
Hypoglycaemia
Symptoms often precipitated by fasting or exercise
What would be the biochemical findings in a patient with an insulinoma
High circulating levels of insulin
High insulin :glucose ratio
What are the causes of unresponsive hypoglycaemia
Abnormal insulin sensitivity
Diffuse liver disease
Inherited glycogenosis
Ectopic production of insulin
What is the 2 hit hypothesis in genetics
Gene mutations can occur through two routes - sporadic or familial
For more tumour suppressor genes the mutations are recessive in nature and therefore both genes would need to be mutated before this becomes apparent
Therefore for them to be deactivated they would need to be mutated twice (eg. one familial one sporadic)
What is a telomere and what is its function
A region of repetitive nucleotide sequence at the end of a chromosome
It protects the end of a chromosome from deterioration/from fusion with neighbouring chromosomes
What is the single best test for a diagnosis of a thyroid nodule
Fine needle aspiration and cytology
What is the microscopy findings from FNAC of a medullary thyroid cancer
Malignant cell features (lack of differentiation, BM invasion)
Amyloid deposits
Immunohistochemistry stains positive for calcitonin, negative for thyroxine
What is the cell source in medullary thyroid cancer
Parafollicular C cells
How does immunohistochemistry work
It is a method which localises specific antigen/cells based on AB recognition. Compliment fixation
Ab are linked to an enzyme/ fluorescent dye (antigen) which allows them to be visualised under microscopy
What is the management of medullary thyroid cancer
Total thyroidectomy with block neck dissection
At what T level is thyroid cancer extending beyond the capsule of the thyroid
T4
T1 < 1cm
T2 >1 cm <4cm
T3 >4cm
T4 - extending beyond the thyroid capsule
Below what age does staging of thyroid medullary cancer differ
< 45 y/o
What are the clinical features of a phaeochromocytoma
Headache
Tachycardia
Sweating
Intermittent nature of the symptoms
What investigations are needed for a diagnosis of phaeochromocytoma
Blood - plasma metanephrines, plasma catecholamines, catecholamine simulation test
Urine - fractionated metanephrines, total metanephrines, catecholamines, VMA
Imaging - US, CT, MRI, MIBG scintagraphy
What are the appearances of phaeochromocytoma on CT compared to MRI
CT scan - shows high enhancement
MRI scan - low fat content
Define pleomorphic
Remarkable histological diversity
What is the most common benign parotid swelling
Pleomorphic adenoma
What are the miscroscopic appearances of a pleomorphic adenoma
Consists of a mixture of ductal (epithelial) and myoepithelial cells
What clinical signs would make you suspicious of a parotid malignancy rather than a benign swelling
Facial nerve affected
Rapidly increasing in size
Fixity to the underlying structures
Invasion of the overlying skin
What are the benign parotid tumours
Pleomorphic adenoma
Warthin’s tumour
Oncocytoma
Other adenomas (basal cell)
Ductal papillomas
What are the malignant parotid tumours
Mucoepidermoid cyst
Adenocarcinoma
Acinic cell carcinoma
Adenoid cystic carcinoma
Malignant mixed cell tumour
Squamous cell carcinoma
Other carcinoma
What is the difference between cytology and histology
Cytology - study of cellular function and structure
Histology - study of tissue under a microscope
Describe the generic features of malignant cells
Invasive
Increased mitotic rate
Lack of differentiation - this can extend to complete anaplasia
In regard to malignancy what does presence of anaplastic cells
Tends to indicate a very aggressive malignancy
List the features of anaplastic cells
Loss of normal tissue architecture
Pleomorphism - nuclei often very large and show prominent nucleoli
Hyperchromatic nuclei (stain darker)
High nuclear: cytoplasmic ratio
If you visualised epitheloid cells with brown cytoplasm under microscope following FNAC what would you be concerned about
Malignant melanoma
Lymphoid cells with pleomorphism is found in what conditon
Lymphoma
What is meant by a high sensitivity test
The ability to correctly identify a disease
True positive rate
What is meant by a high specificity test
The ability to correctly identify those without disease
True negative rate
What are the units of radiotherapy
Coulomb/kg
Gray (Gy)
Sievert
Becquerel
What is a Coulomb
The unit to express exposure in radiotherapy
What is a Gray
The unit to express dose in radiotherapy
The absorption of one joule of radiation energy per kg of matter
What is a sievert
The unit to express dose equivalent in radiotherapy
It takes into account the relative biological effectiveness of ionising radiation
What is a becquerel
The unit to express activity in radiotherapy
relates to the activity of a quantity of radioactive material in which one nucleus decays per second
What is one sievert equivalent to
The amount of radiation roughly equivalent in biological effectiveness to one gray
What are the risk factors for nasopharyngeal carcinoma
Male > Female
Ethnicity (China, Hong Kong, Singapore, Malaysia, Philippines)
Diet (consumption of salted fish containing carcinogenic volatile nitrosamines)
EBV/HPV infection
FH
Tobacco use
What are the main risk factors of oral candida
Immunosuppression - steroids, chemotherapy, biologics, ABx
Diabetes
What are the common clinical features of nasopharyngeal carcinoma
Headache
Sore throat
Neck swelling
Struggling with hearing/speaking
Airway obstruction
Recurrent ear infections
Why would first presentation of neck swelling in the context of nasopharyngeal carcinoma possibly indicate poor prognosis
Neck swelling often representative of metastatic spread to the lymph nodes
Why should recurrent ear infections in an adult be taken seriously
If adults are presenting with an ear infection out of the context of LRTI then it may represent nasopharyngeal carcinoma
What is Trotter’s syndrome
A cluster of symptoms associated with advanced nasopharyngeal carcinoma
What are the symptoms of Trotter’s syndrome
Unilateral conductive deafness due to middle ear effusion
Trigeminal neuralgia
Soft palate immobility
Difficulty opening mouth
What causes pain in Trotter’s syndrome
Neuralgic pain from the mandibular branch of the trigeminal nerve in foramen vale through which the tumour enters the calvarium
If nasopharyngeal carcinoma was to locally spread where could it spread to
Sphenoid and cavernous sinus
Nasal cavity
Orbital invasion
Oropharynx (Tonsillar pillars)
C1 vertebrae
Lateral parapharyngeal space
Middle ear cavity
Base of skull
Chivus
What are the common causes of LN tumours
Lymphoma (Hodgkins and Non-hodgkins)
Leukaemia
Metastatic
Define an abscess
A focal collection of pus that may be caused by a seeding of pyogenic organisms into tissues or be secondary infections of necrotic foci
Describe the structure of an abscess
Central, largely necrotic region
Rimmed by a layer of preserved neutrophils
Surrounding zone of dilated vessels and fibroblasts
Describe neutrophil activation and migration
Neutrophils activated by chemokine - resulting in margination and rolling along the vessel wall
Firm adhesion to the endothelium which is facilitated by increased activity of integrins
Stable adhesion
Migration between endothelial cells and into interstitial tissues towards a chemo attractant stimulus
What are carcinoid tumours
Slow growing neuroendocrine tumours
What cells do carcinoid tumours arise from
Enterochromaffin cells (Kulchistky cells) in the crypts of Lieberkilin
Where are carcinoid tumours most commonly found
Small intestine
Terminal 1/3 of the appendix
Rectum
Lung
Stomach
What hormones are released from carcinoid tumours
Serotonin
Bradykinins
Prostaglandins
Histamines
Substance P
Tachykinins
What are the common clinical features of a carcinoid tumour
Periodic abdominal pain
Periodic diarrhoea/constipation
Carcinoid syndrome
What are the features of carcinoid syndrome
Cutaneous flushing
Diarrhoea and malabsorption
Cardiac manifestations (Valvular heart lesions, fibrosis of the endocardium)
Wheeze/asthma like symptoms - due to bronchial constriction
Why do symptoms of carcinoid tumours only tend to present following metastasis to the liver
The hormones produced by primary carcinoid tumours cannot get into systemic circulation because of first pass metabolism
However following metastasis to the liver - the hormones produced bypass first metabolism and so are released into systemic circulation
What investigations are used in the diagnosis of carcinoid syndrome
Chromogranin A
Urinary 5 hydroxyindoleactic acid (5 HIAA)
Histolopathology - immunohistochemistry of samples positive for Chromogranin A
Define Type I DM
Absolute insulin deficiency of insulin secretion caused by pancreatic beta cell destruction
Define Type II DM
Combination of peripheral resistance to insulin action and an inadequate compensatory response of insulin secretion by the pancreatic beta cells (relative insulin deficiency)
What are the effects of insulin on adipose tissue
Increased glucose uptake
Increased lipogenesis
Decreased lipolysis
What are the effects of insulin on striated muscle
Increased glucose uptake
Increased glycogen synthesis
Increased protein synthesis
What are the effects of insulin on the liver
Decreased gluconeogenesis
Increased glycogen synthesis
Increased lipogenesis
Which hormones increased blood glucose levels
Glucagon
Catecholamines
Glucocorticoids
Somatrophin
When should a VRII be used in the pre operative period
When a patient is undergoing a major procedure or in patients with poor glycaemic control
Major procedure- surgery requiring fasting period >1 missed meal
When should a VRII be stopped
Should be stopped when the patient can be safely converted back to SC insulin, when E+D, once this has occurred should be stopped 30-60 minutes following the first meal
In the pre operative period what would be considered good glycemic control
HbA1C < 69mmol or 8.5%
What background fluids should be used alongside a VRII
KCl, Glucose, NaCl
Which anti diabetic drugs should be stopped if insulin is started
Acarbose
Meglitinides
Sulfonylureas
Pioglitazone
Gliptins
SGLT2 inhibitors
Can be restarted when the patient is E+D normally
Why should SGLT2 inhibitors be stopped in the perioperative period
When taken in periods of stress (dehydration, acute illness) they can be associated with DKA
Why should sulfonylureas be stopped in the preoperative period
They are associated with hypoglycaemia when taken in the fasted state
When should metformin be stopped
In the perioperative period if a patient is going to miss more than one meal, or if they are at risk of developing an AKI
What are the immediate and late complications in a surgical patient with DM
Early - Hypo/hyperglycaemia, dehydration +/- electrolyte imbalances, HHS, DKA
Later - infection, impaired wound healing
What is the presumed aetiology of ulcerative colitis
Genetic susceptibility with abnormal host response to colonic flora
Genetic polymorphism in TLR, loss of homeostasis between host mucosal immunity and microflora
Disrupted balance between regulatory and effector T cells
What does ulcerative colitis look like when visualised on colonoscopy
Hyperaemic/haemorrhagic colonic mucosa
Pseudopolyps
Inflammation confined to the mucosa - makes it friable and oedematous
What is the histology of of ulcerative colitis
Crypt abscesses
White cell infiltrate into the lamina propia
Mucin depletion
What is the difference between distal colitis and extensive colitis
Distal colitis - inflammation extends to the splenic flexure
Extensive colitis - extends to the hepatic flexure
What are the extra-intestinal manifestations of ulcerative colitis
Clubbing
Apthous ulcers
Erythema nodusum
Pyoderma gangrenosum
Iritis/uveitis/episcleritis
Primary sclerosis cholangitis
What are the intestinal symptoms of ulcerative colitis
Episodic/chronic diarrhoea +/- blood and mucus
Crampy abdominal pain
Tenesmus
Systemic - fever, malaise, anorexia, weight loss
What is the Timeline and Witts criteria used for
Severity scoring in ulcerative colitis
What are the potential complications of ulcerative colitis
Obstruction
Toxic megacolon
fistula formation
abscess
malabsorption
malignancy
gallstones
What medication can be used in ulcerative colitis but has no place in the management of Crohn’s
5 ASA - Mesalazine, sulfasalazine
What are the endoscopic findings in a patient with Crohn’s disease
Transmural granulomatous inflammation which is uncontinous
Skip lesions between areas of active disease
Bowel is thickened with a narrowed cobblestone appearance due to deep ulcers and fissures
What are the intestinal symptoms of Crohn’s disease
Bowel ulceration
Abdominal tenderness +/- RIF mass
Perianal fistula /abscess
Skin tags
Anal strictures
Dysphagia
Apthous ulcers
The terminal ileum is affected in 70% of patients with which disease
Crohn’s disease
What is the Montreal classification used for
Severity scoring in Crohn’s disease
A string sign on barium XR is seen in what disease
Crohn’s disease
Methotrexate is used in the management of which inflammatory bowel disease
Crohn’s disease
Why do patients with Crohn’s disease often develop vitamin A, D, E and K deficiency
Crohn’s disease most commonly affects the terminal ileum, which is where Vitamin A,D, E and K are absorbed.
Describe the adenocarcinoma sequence
It is the stepwise accumulation of mutations of oncogenes and tumour suppressor genes
1. Loss of APC gene leads to hyperplasia
2. KRAS mutation leads to dysplasia
3. Loss of p53 results in adenocarcinoma
APC and p53 are what type of genes
Tumour supressor genes
KRAS gene mutation is known as what type of gene
Oncogene
What are oncogenes
Mutated proto-oncogenes
They encode oncoprotein which have the ability to promote cell growth in the absence of normal growth promoting signals
Why can oncogenes result in excessive cell proliferation
Cells expressing oncogenes are freed from normal checkpoints and controls that limit growth.
What is the function of tumour suppressor genes
Genes which inhibit cell proliferation or promote death of cells that have damaged DNA
What is KRAS
GTPase - converts GTP to GDP
What may result in more p53 protein
DNA damage and stress signals
What does increased amount of p53 protein result in
Growth arrest - stops progression of cell cycle with damaged DNA
DNA repair - can be activated during growth arrest
Apoptosis - ‘last resort’ to avoid proliferation of cells containing abnormalities
What does the loss/mutation of p53 result in
DNA damage no longer induces cell cycle arrest/repair therefore genetically damaged cells proliferate giving rise to malignant neoplasms
What is the function of APC
It encodes a factor that negatively regulates the WNT pathway in colonic epithelium by promoting the formation of a complex that degrades beta-catenin
What happens with a mutated APC
The factor which binds to beta catenin is not formed. Therefore excess beta catenin accumulates which can translocate to the nucleus where it binds to a transcription factor and activate cell proliferation - it does this irrespective of the WNT pathway
What does TNF do in IBD
Causes epithelial tight junction permeability to increase causing a flux or luminal bacterial components which activate an innate and adaptive immune response
What does FAP stand for and what is it also known as
Familial Adenomatous Polyposis, also known as Gardeners syndrome
What is FAP
An autosomal dominant condition characterised by the lack of APC tumour suppressor gene on the long arm of chromosome 5
Leads to the development of hundreds of tubular adenomas, conferring a 100% risk of CRC by 40
What chromosome is APC found on
Chromosome 5
What is the findings of FAP on colonoscopy
Multipel polyps
Largest around 7mm
What are the non neoplastic types of polyps
Harmatomatous
Metaplastic
What are the neoplastic types of polyps
Villous
Tubulovillious
Tubular
What are the extracolonic manifestations of FAP
Mandibular osteomas
Desmoid tumours
Sebaceous cysts
What is the management of FAP
Prophylactic near total colectomy by the age 25
If a patient with FAP had a child what would you recommend
Endoscopic surveillance from 12 y/o
Define dysplasia
Disordered cellular development characterised by increased mitosis, pleomorphism without the ability to invade the basement membrane
Define ulcer
A lesion in the mucous membrane or the skin resulting from the gradual disintegration of surface epithelial cells
What are the risk factors for gallbladder cancer
Age >70 y/o
Female > male
FH
Gallstones
Chronic cholecystitis
Ethnicity - Mexican/ native american
Smoking
GB polyps >1cm
Obesity
Porcelain GB
Chronic typhoid infection
ABPJ
Choledochal cyst
Where does GB cancer directly invade
Segments 4 or 5 of the liver
Common sites of metastasis in GB cancer
Liver
Stomach
Duodenum
Porta hepatic LN
CBD
what is the histolopathology of GB cancer
Adenocarcinoma
What is the most common organism implicated in SSI
Staph aureus
Surgical site infection in a POD3 patient, with yellowish granules is likely to be caused by what organism
Actinobacillus
What causes yellow discharge in an actinobacillus infection
Sulphur granules
What organisms cause necrotising fascitis
Group A streptococcus
Staph aureus
Clostridium perfinges
Bacteroides fragilis
MSRA
What is the scoring system that can be used in necrotising fascitis patients
Laboratory risk indicator for necrotising fasciitis
Score >6 indicative
What is the pathophysiology of necrotising fasciitis
Rapidly progressing
Extensive acute inflammatory reaction involving the subcutaneous fat which can go deep into skeletal muscles and further
Extensive suppuration and bacterial colonisation with associated intravascular thrombosis
What ABx are used in the management of necrotising fasciitis
Clindamycin
Flucloxacillin
Gentamicin
Metronidazole
Penicillin
What would be the differential diagnosis for post operative bloody diarrhoea
Pesudomembranous colitis
Bowel ischaemia
Curling’s ulcer
Infective gastroenteritis
What is the pathophysiology of pseudomembranous colitis
Often triggered by ABx therapy which disrupts normal microbiota and allows C.Difficile to colonise and grow.
Release of C.Difficile toxin disrupts epithelial function
Subsequent inflammatory response
Neutrophil eruption form colonic crypts which spreads to form mucopurulent psuedomembranes
What infetion is pseudomembranous colitis associated with
C. difficile
What are the appearances of pseudomembranous colitis on colonoscopy
Yellowish plaques
Describe the pathophysiology of diverticulosis
Colonic diverticula result from the unique structure of the colonic muscularis propria and the elevated intraluminal pressure in the sigmoid colon
Where nerves, arterial vasa recta and their connective tissue sheaths penetrate the inner circular muscular coat focal discontinuities are created - so when there is increased pressure are such points outpouching can occur
Why does diverticulosis occur in the large bowel and not the small bowel
In the colon the wall is not reinforced by external longitudinal layer of muscular propria, as this is gathered as the Taenia coli
What is the cause of diverticulitis in diverticular disease
Obstruction of the diverticular leads to inflammatory changes producing diverticulitis and peridiverticulits. Because the wall of the diverticulum is only supported by the muscularis mucosa and a thin layer of subserosal adipose tissue, inflammation and increased pressure within an obstructed diverticulum can lead to perforation
What is the Hinchey Classification
The classification for perforated diverticulitis
Describe the different grades of the Hinchey Classification
I - Pericolic abscess
IIa - Distant abscess amenable to percutaneous drainage
IIb - Complex abscess with fistula that is not amenable to drainage
III - Generalised purulent peritonitis
IV - Faecal peritonitis
Define diverticulosis
Presence of diverticula but asymptomatic
Define diverticular disease
Diverticula and symptoms
Define diverticulitis
Evidence of diverticular inflammation +/- localised symptoms and signs
What is the link between endometriosis and ovarian cancer
Endometriosis increases the risk of ovarian cancer by 3.5x
What are the different theories of the pathogenesis of Endometriosis
Regurgitation theory - retrograde mensturation, explains endometriosis within the endometrial cavity
Benign metastasis theory - spreads via the blood and lymphatic system
Metaplastic theory - directly arises from coelomic epithelium
Extrauterine stem cell/progenitor cell theory - differentiation into endometrium
How would intrapertioneal endometriosis be described
Burn powder
Dark blue/black
Chocolate cysts
What is the epithelium of the uterus
Simple columnar epithelium supported by thick vascular stroma
Endometrium - inner layer, along with mucus membrane
What are the two layers of endometrium
Basal layer
Functional layer - thickens and then is sloughed during mensturation
What is the cause of pain in endometriosis
Cyclical pain as tissue under hormonal control
Intrapelvic bleeding
Periuterine adhesions form
What are the risk factors for peptic ulcer disease
H Pylori infection
NSAIDs
Smoking
What is the CLO test
Campylobacter like organism test
Dependent on the presence of H. Pylori and urease produced by the bacteria (converts urea to ammonia which increases the pH)
What enzymes does H Pylori produce
Ureases - catalyses the hydrolysis of urea to ammonia
Proteases
Phospolipases
What is the action of the enzymes produced by H Pylori
Infects the stomach
Produces ureases, (allows pH to increase to allow survival), proteases, phospholipases
The production of ammonia, and the damage to gastric mucosa from other enzymes produced causes inflammation
What is the pathophysiology of H Pylori colonisation
Flagella allows motility
Urease - generates ammonia from endogenous urea, thereby elevates local gastric pH around the organism and protecting the bacteria from the acidic pH of the stomach
Adhesins - enhance bacterial adherence to surface alveolar cells
Toxins - such as cytotoxin associated gene A (saga) may be involved
What types of gastric cancer are associated with H Pylori
Adenocarcinoma
Mucosal associated lymphoid tissue tumour (MALT)
Hashimotos thyroiditis is associated with what infection
H Pylori
What is the MOA of PPI
Binds irreversibly to the H+/K+ ATPase on gastric parietal cells - stops the secretion of H+ and therefore HCl does not form
What does H Pylori eradication therapy entail
7 days
Omeprazole 20mg BD
Clarithromycin 500mg BD
Amoxicillin 1g BD (Metro if pen allergic)
Confirmation of healing of gastric ulcers on endoscopy after 6-8 weeks
What is the action of HCl
Activates pepsinogen to pepsin which helps in proteolysis
Antimicrobial
Why can NSAID use precipitate PUD
Topical irritation of epithelium by NSAIDs - impairs the barrier properties of the mucosa
Suppression of gastric PG synthesis - due to inhibition of cycloxygenase
Reduction of gastric mucosal blood flow
Interference with superficial healing
How is hypercalcaemia linked to PUD
Hypercalcaemia leads to increased gastrin release, which leads to increased HCl production
What are the common causes of hypercalcaemia
Malignancy
Renal failure
Hyperparathyroidism
How are parathyroid glands localised intraoperatively
Pathological lab procedure to perform rapid microscopic analysis of a specimen
Specimen fixed onto a metallic disc and then rapidly frozen to -20/30 degrees
Embedded into gel like medium, cut and then stained
What is the normal epithelium of the gastric mucosa in the antrum of the stomach
Simple columnar with mucosal and goblet cells
What is the histology of a parathyroid adenoma
Uniform polygonal chief cells with small centrally placed nuceli
A few nests of oxyphil cells are present
A rim of compressed, non neoplastic parathyroid tissues generally separated by a fibrous capsule
If the parathyroid glands are not in their normal position where may they be found and why
Superior mediastinum
Thymus originates from the third branchial arch - so will occasionally drag the inferior parathyroid glands down into the mediastinum
What are the clinical features of hypercalcaemia
Nephroliathis with resultant polyuria and polydipsia
Bone pain/#
Tired and depressed
Pancreatitis
PUD
Constipation
N+V
What are the three types of hyperparathyroidism and the common causes of each
Primary - usually a solitary adenoma, parathyroid carcinoma
Secondary - Chronic renal failure
Tertiary - Autonomous ongoing parathyroid hyperplasia
In which kind of hyperparathyroidism is the calcium normal or low
Secondary
In which kind of hyperparathyroidism is phosphate increased
Secondary
