Surgical Pathology Flashcards
Function of plasma proteins?
Albumin- binds and transports calcium, on oncotic pressure Immune system Completement cascade Clotting Enzymes
Causes of raised urate?
Idiopathic
Inborn errors of metabolism
Alcohol
Diuretics
Protein rich foods
Causes
Gout
Renal failure
Renal calculus
Role liver?
Bike production and conjugation Clotting factor production Drug metabolism Glycogen storage Plasma proteins Reticulendothelium system
Life cycle of bilirubin
RBCs broken down to haem and then biliverdin
Converted to bilirubin
Conjugated by binding to albumin by hepatocytes
Excreted in bile
Excreted in kidneys as urobilin- yellow
Farces- sterobiliogen- brown
Commonest renal stones?
Calcium oxalate- 77% Struivate- 15% Uris acid -5% (radiolucent) Cystine- 2% Xanthine- 1%
Gall stone commonest?
Mixed-85%- fat femal fair forty
Cholesterol-10%
Pigment-5% haemolysis
Bile volume per day and composition?
1500ml/day
Bike pigments Bike salts Cholesterol Electrolytes Water and bicarbonate
Amyloid definition?
A group of degradation resistant proteins with a beta pleated structure
How to diagnose amyloidosis?
Biopsy
Stain with Congo red
Apple green birefringence under polarised light
Isotope scan for hotspots
Types of amyloid?
AL- myeloma leading to global production of Ig amyloid
AA- chronic inflammation- macrophages releasing interleukins. Ra/ibd/tb
PrP- prion diseaze
Consequences of amyloid?
Organ failure
Localised deposits- larynx and thyroid
Medullary thyroid cancer
Organomegally
Cause of death in amykoidosis?
Myocardial amyloid
Leads to arrhythmia sand heart failure
Aetiology of microcytic anaemia?
Iron deficiency- bleeding, poor intake, low absorption, increase demand
Thalassaemia
Sideroblastic anaemia
Aetiology of macrocyclic anaemia?
B12/folate deficiency- megloblasts on blood film Alcohol Hypothyroidism Myelodysplasia All normoblasts on blood film
Normocytic anaemia aetiology
Chronic disease
Renal failure- epo
Sickle cell anaemia- hydrolysis
Spherocytosis
Microscopy of b12 anaemia?
Macrocytosis
Howell jolly bodies
Hypersegmented neuclei in neutrophils
Aetiology of b12
Poor intake
Pernicious anaemi
Ileal/ gastric resection
Crohns
Aetiology of folate deficiency
Decrease intake
High demand- pregnancy/cancer
Drugs- methotrexate
Malabsorption-coeliac
Sickle cell pathogenesis?
Autosomal recessive
10-20 day turnover of rbcs
Defective beta chains in HbA leads to less soluble hbS. Which leads to sickle cells
Veno-occlusive disease
Ischaemia
Pain crises
Blood film findings of sickle cell
Normochrmia Normocytic Reticulocytes Sickle cells Target cells Howell jolly bodies
Causes of sickle cell crises?
Infective
Low o2
Hypothermia
Dehydration
Thalassaemia features?
Autosomal recessive haemolytic disease 3 types Alpha Beta Delta
Beta thalassaemia blood film?
Hypochromic Microcytic Reticulocytes Target cells Howell jolly bodies
Process of haemostasis?
Vasoconstriction
Platelet aggregation and activation
Clotting cascade- secures platelet plug
Function of platelets?
Primary haemostasis
vWF and TXA2 for platelet activation
Phagocytosis
Cytokines signalling
Draw clotting cascade
https://www.osmosis.org/answers/coagulation-cascade
Which clotting factor is calcium?
Factor 4
What are the moa of heparin, clopidogrel and txa?
Heparin- inhibited factor 10a- potentiates antithrombin III
Clopidogrel- ADP receptor inhibitor- prevents platelet aggregation
TXA- inhibits plasmin, prevents clots from breaking down
How is blood processed to be ready for transfusion?
Viral screening
Centrifugation
Leucofiltration- decreases cmv reaction
Irradiation- optional- prevent gvhd
What is FFP and cryoprecipitate
FFP- top layer of centrifuged blood- plasma, contains clotting factors, compliment, fibrinogen, vWF and albumin
Cryo- precipitate of ffp, factors 8, 13 and vWF.
Definition of oedema?
Generalised or localised collection extracellular fluid
Aetiology of lymphoedema?
Surgical treatment?
1- milroys
2- iatrogenic, malignancy, infection
Treatment surgical- homans/Charles/lympho anastomoses
What is starlings law of the capillaries?
Governs the net filtration across capillaries
= capillary pressure- interstitial hydrostatic pressure
- capillary pressure - oncotic pressure
Taking into account lymphatic drainage
Hydrostatic pressure- pressure blood exerts on the wall
Oedema aetiology?
Increase hydrostatic pressure- heart failure, fluid overload
Decrease oncotic pressure- liver/kidney failure
Capillary leakage- inflamm/anaphylaxis
Lymphatic failure
Drugs- nifedipine
Gravitational
Types of hypersensitivity reactions?
Acids
Type 1- allergic Type 2- cytotoxic- good pastures Type 3- immune complexes- sle Type 4- delayed- transplant related Type 5- stimulatory- graves
Name some cell mediators of the immune response?
Bradykinin- vasodilation and permeability
Histamine- same as above + puritus + gastric acid secretion
Leukotrines c4- bronchoconstriction + vascular permeability
Prostaglandins d2- neutrophil recruitment, vasodilation, bronchoconstriction
TXA2- vasoconstriction, bronchoconstriction, platelet aggregation
Name some cytokines?
Il4- cd4 t helper cell proliferator
B cell ige synthesis
Il5 histamine and leukotrine release
B cell proliferation, eosinophil recruitment
Il13 cd4 t helper cell proliferation
Tnfalpha neutrophil activation
What is the complement cascade?
Part of the innate immune system
Involved in the clearance of pathogens via production of MAC
4 pathways
Classic
Lectin- independent of ab-ag complexes
Alternative- same as above
Final common- leads to MAC production, opsonisation, chemotaxsis
What is the composition of Ig?
Fab region- heavy and light chains- fragment bindings region- variable region
Fc region- interacts with cell surface fc receptors- contstant
Types of immune response?
Cell mediated- T cell mediated- production of cd4 T cells, macrophages and NKCs
Humoral- B cell mediated- ab release, complement, opsonisation, phagocytosis
Roles of the Ig?
IgM- first released IgG- majority of humoral response Crosses placenta IgD on b lymphocytes and bind to Ag IgA primary Ab in bodily secretions IgE binds to basophils and mast cells to promote degranulations of cytokines and mediators
What is leukocyte margination and emigration?
Normally flow in centre of blood stream
Margination- move to plasmatic peripheral zone
Emigration- pavementing then active migration across endothelium
What is a granuloma?
Collection of modified macrophages +- time of surrounding lymphocytes
Seen in TB/sarcoid
What is the cellular process during chronic inflamm?
Lymphokine production- IFN gamma Activate macrophages release growth factors Fibroblast proliferation Neovascularisation Tissue destruction
What is a cyst and pseudo cyst?
Cyst abnormal membrane lined sac containing fluid- epithelial cells
Abnormal collection of fluid surrounded by granuloma/fibrous tissu
What is an abscess?
Why?
Localised collection of pus surrounded by granulation tissue
Neutrophils/macrophages release enzymes that split large molecules to small ones increasing the oncotic pressure
What is a fistula / sinus
Fistula is an abnormal communication between two epithelial surfaces
Sinus- blinding ending tract in communication with an epithelial surfsce
What is pus?
Pus is made out of fluid and solid components
Fluid- exudate of plasma proteins, water
Solid- live and dead- macrophages/neutrophils/bacteria
Dead human cellS
Fibrin
Describe the process of wound healing?
Cutting is pleasing repetitive
Coagulation- seconds
Inflammatory days
Proliferation weeks- granulation and epithelisation
Remodelling- years- reorganisation, regression, scar tissue
Epidemiology of SSIs?
5% of cases
Superficial skin
Muscle/fascia
Organ/cavity
What are endotoxins?
Proteins released by gram - bacteria. Lead to pyrexia/shock/dic
Activate clotting/complement
Cause fibrin degradation
Lead to cytokines formation
What are exotoxins?
Formed by gram + can lead to tetanus and gangrene
What are nosocomial infections?
Hospital acquired infections
Phases of the cell cycle
G0 resting phase
G1 regulation of the duration of cell cycle
R restriction point in G1. Rb tumour suppression gene
S synthesis phases
G2 rapid growth and 2nd check point p53
M mitosis
What stimulates and inhibits the cell cycle?
Stimulation
Cyclins d&e
Cyclin dependent kinase
Inhibition
P53
Rb gene
Difference between dysplasia, metaplasia and neoplasia?
Dysplasia is abnormal cell development. Premalignant
Metaplasia is replacement of one fully differentiated cell type with another
Neoplasia is an abnormal mass of tissue due to uncontrolled and progressive cell division
Tumour markers for testicular teratoma? And breast/pancreas/ovary?
Testicle- bhcg, afp
Breast ca153
Pancreas ca199
Ovary ca125
Carcinogens? Bladder Burkitts Cervix Cholangiocarcinoma HCC Kaposi Leukaemia Lymphoma Lung Nose Skin
Dyes and nitrosamines Ebv Hpv Liver flukes Afalatoxin, HBV HCV HHV8 HTLV Cyclophosphamide Asbestos and tobacco Sawdust UV light
Cellular features of malignancy
Macroscopic Growth Necrosis Infiltration Metastasis Haemorrhage
Microscopic High mitotic rate Pleomorphism Hyperchromatism High nucleus to cytoplasmic ratio
Commonest cancers and highest mortality?
Skin, lung, prostate, breast colorectal
Lung, colorectal, breast, prostate, oesophageal
Endocrine paraneoplastic syndromes?
Cushings- small cells lung and pancreas
SIADH- small cell lung cancer
Hypercalcaemia- squamous lung cancer, breast, ovarian, rcc
Carcinoid- lymphoma, gastric, pancreatic
Haematological paraneoplastic syndromes
Aplastic anaemia (pan cytopeni) - thymus Polycythaemia- RCC/HCC
MSK paraneoplastic syndromes
Acanthodians nigracans- gastric/lung cancer- EGF
Dermatomyositis (skin rash, muscle weakness) -breast/ lung
Neurological paraneoplastic syndromes?
Cerebellum degeneration- lung overian breast
Lamber Eaton syndrome- lung prostate cervix
Definition of of clot thrombus and embolus
A clot describes a collection of solid material (made of the constituents of blood) found in stagnant blood
Thrombosis is the progression of a clot with Virchow triad in the same place as it formed in flowing blood
Embolus is a clot distant to where it was formed
What is Virchow triad?
Endothelial damage
Hypercoagulable stage
Stasis or turbulent blood flow
Leads to thrombosis
Trauma triad?
Hypothermia
Acidosis
Coagulopathy
(Hypocalcaemia?- citrate theory)
Definition and RFs of an atheroma
Lipid collection within the tunica intima of arteries. May have foam cells
Congenital- fhx, make, familial hyperlipidaemia
Acquired- diabetes, smoking, hypertension, hyperlipidaemia
Theories of the formation of an atheroma?
Imbition- circulating lipoproteins
Proliferation- smooth muscle hyperplasia
Encrustations- lipid portion of atheroma derived from pre existing thrombus
Definitions of infarction and ischaemia?
Ischaemia- abnormal reduction in blood supply/drainage
Infarction- tissue/organ necrosis due to poor blood supply
Definition of an aneurysm?
Abnormal vessel dilation by more than 50%
Classification of aneurysms?
Aetiology- congenital/acquired- infection/trauma/hypertension
Morphology- saccular vs fusiform
Pathology- true/false/dissecting
Aetiology of aneurysms?
Congenital Atherosclerosis Htn Infective Ischaemia Traumatic Iatrogenic
Difference between true, dissecting and false aneurysms?
True involve all three layers of arterial wall
False does not
Dissecting- blood running through media/adventitia. Can lead to vessel occlusion
Composition of bones?
Cellular- osteoprogenitor cells
Osteoclasts, osteoblasts
Matrix- inorganic- calcium hydroxapitate
Organic- type 1 collagen
Types of bone
Anatomically- Flat vs Long bone
Macroscopically- Cortical vs Cancellous
Microscopically- Lamellar vs woven
Flat bone- irregular structure- skull/scaphoid
Long- regular structure- diaphysos, metaphysis, epiphysis- femur/tibia
Woven- haphazardly organised collagen fibres, pathological/immature
Lamellar- regular parallel alignment of collagen fibres
Cortical- hard outer layer of bones. Composed of tightly tightly packed osteons with Haversian canals
Cancellous- porous central layer of bone, high turnover
What is the process of fracture healing?
Coagulation- haematoma formation
Inflammatory- granulation and fibroblasts proliferation
Proliferation- callous- woven bone- chondroblasts and osteoblasts. Lamellar bone formation.
Remodelling- cortical bone replaces woven bone
Principles of fixation principles
Reduce
Restrict
Rehab
Why does smoking lead to poor bone healing?
Decreased calcium absorption
Decreased vit d
Increased non union and malunion
Osteomyelitis aetiology
< 4 months
4months- teenager
Adults
DM
Immunocomprimised
HIV
Sickle cell
Vaginal flora- staph a/strep/ E. coli
Staph a/gas/hi
Staph a/enterococcus/gbs
Anaerobes
Aspergillosis/candida
TB
salmonella
Pathogenesis of osteomyelitis?
Acute inflam leads to compression of capillaries
Osteonecrosis
Dead bone fracture separate off necrosis
New bone formation around this
Aetiology of septic arthritis?
Direct trauma
Haematogenous spread
Dissemination- osteomyelitis/cellulitis
Iatrogenic
What is the reconstructive ladder?
Secondary intention
Primary closure
Skin graft
Flap (free vs pedicled)
Adjuncts- negative pressure dressings
What are the different types of graft?
Split skin graft- takes epidermis and portion of dermis- poor colour/contracts
Full skin graft- takes epidermis and Dermis- requires a well vascularised bed
Differences between keloid and hypertrophic scars?
Keloid- thick and raised. Extends beyond boarders. Appears over years. Afro Caribbean. Increased collagen synthesis
Hypertrophic- thick and raised. Within boarders, appears in weeks, regresses
Types of muscles
Skeletal- located at joints- striated and voluntary
Type 1- slow twitch, type 2 fast twitch
Cardiac- striated and voluntary
Smooth- vessels and viscera. Greater stretch ability and prolonged contraction. Calmodulling is binding agent
Draw a sarcomere and describe the sliding protein theory and muscle contraction
Types of cartilage
Fibrocartillage- type 1 collagen. Pubic symphysis. High tensile strength
Hyaline- type 2 collagen. Hard. Smooth articular surfaces
Elastic- lots of elastin. Pinna. Epiglottis.
Fibroelastic- meniscus
Physeal
Features of Men 1
Pancreatic tumour
Pituitary adenoma
Primary hyperparathyroidism
Features of men 2a/b
2a- phaeochrmocytoma, medullary thyroid ca, 1o hyperparathyroidism
2b- phaeochromyocytoma, medullary thyroid cancer, multiple neuromas, marfanoid habitus
Aetiology of gynaecomastia
Raised oestrogen to androgen ratio
Physiological- puberty/old age
Pathological- cirrhosis, hyperthyroidism, hypogonadism, kleitfelters, testicular tumours.
Pharmacological- steroids, spironolactone (anti androgen)
Draw out the pth and calcium homeostasis
https://www.researchgate.net/figure/Calcium-Homeostasis-and-Selected-Causes-of-Hypercalcemia-in-Pediatric-Patients-The-serum_fig1_49822084
Embryological Origins of superior and inferior parathyroid glands
Superior- 4th pharyngeal pouch
Inferior - 3rd pharyngeal pouch
Aetiology of hyperparathyroidism?
1o- single parathyroid adenoma (85%)
Parathyroid hyperplasia (10%)
Carcinoma (1%)
2o - physiological response to chronic hypocalcaemia secondary to renal failure
3o - hyperplasia of parathyroids from 2o leading to raised pth
Cushing’s syndrome clinical features?
Ulcers Cataracts Diabetes Fluid retention Atrophy Pancreatitis
Aetiology of Cushing’s syndrome?
ACTH dependent- cushings disease- pituitary adenoma. Paraneoplastic cancer
Independent- steroids, adrenal cortex neoplasm
Carcinoid syndrome definition?
Neuroendocrine tumour arising from APUD cells
Intestinal- appendix/ small bowel
Extra intestinal- lung ovary testis
Classical carcinoid syndrome and diagnosis?
Abdo cramps Bronchoconstriction Cardiac failure Diarrhoea Flushing
24 hr urinary 5-HIAA
octreo scan- hot spots
Ct/mri
Laparotomy
Draw the thyroid hormone homeostasis
Aetiology of hyper and hypo thyroid
Hyper- iodine excess, graves (anti tsh receptor abs), toxic nodule, subacute thyroiditis
Hypo- iodine deficiency, hashimoto’s (anti tpo abs anti thyroglobulin abs)
Role of thyroid hormone
Cellular metabolism and glycogenolysis
Growth and development
Increased sensitivity to adrenaline
Increased gut motility
Types of amyloid disease?
AL amyloid- Clonal expansion of plasma cells producing amyloid Ig
AA amyloid- chronic inflam lead to macrophages stimulating hepatocytes to produce precursor to amyloid
Prions disease
Complications of EVAR?
Intraop- rupture, failure of op- endo leak
Post op- mesenteric/renal ischaemia, infection, MI
Causes of appendicitis?
Faecoliths
Tumours- carcinoid
Lymphoid tissue
Foreign object
Ascites aetiology? More detail
Exudate- increased vascular permeability
4Ps- peritonitis, post irradiation, peritoneal mets, pancreatitis
Transudate
Increased interstitial pressure- cirrhosis, budd chiari, RHF
Decreased oncotic pressure- liver/renal failure
Underlying process of atherosclerosis?
Endothelial damage leading to inflam response (caused by trauma/htn)
Foam cells and lipid core (aided by hypercholesterolaemia)
Stenosis/thrombosis
What is the carcinogenic version of fibroadenoma?
Phyllodes tumour
Worry if rapid growth and in >35yo
Management of breast abscesses?
Lactational vs non lactational (smoking association)
USS + Drain for MCS
IV Abx
Causes of gynaecomastia?
Physiological
Lower testosterone- testicular tumour/atrophy
Raised oestrogen- leydig cell tumour, liver disease, obesity, adrenal tumours
Medication- spironolactone, antipsychotics, chemo
Idiopathic
Causes of nipple discharge?
Physiological Prolactinoma Duct ectasia Intra-ductal papilloma Hyperplasia
Causes of a cholangiocarcinoma?
Developed world- PSC
Non developed- Liver flukes
HIV/Chronic liver disease
Difference between PSC and PBC?
PBC- interlobar ducts affected
Chronic granulomatous disease leading to cirrhosis/cholestasis
AMA +ve
PSC- intra and extrahepatic ducts
Fibrosis and stenosis
pANCA
Types of bone tumours?
Benign- osteochondroma (10-20yrs old), giant cell tumours
1o- multiple myeloma
Osteosarcoma
Ewings- onion skin, 5-20 yo
2o- mets Breast Lung Thyroid Kidney Prostate
BLT and a packet of KP crisps
Layers of the GI tract?
Mucosa (epithelium, lamina propria, musclaris mucosa)
Submucosa
Musclaris propria
Adventitia
What is the adnoma carcinoma sequence?
A series of mutations leading to hyperproliferation metaplasia and dyslplasia
APC, KRAS, p53
What is a neoplasm?
A tumour
Abnormal mass of tissue
Demonstrating uncoordinated growth
And continued growth despite removal of the stimulus
What is metaplasia and dysplasia?
Reversible change in cell type
Dysplasia- uncoordinated cellular development, no basement membrane invasion, mitosis and pleomorphism
What type of cells involve a carcinoma and a sarcoma?
Carcinoma- epithelial cells
Sarcoma- connective tissue
Causes of hypoparathyroidism and hypothyroidism?
Iatrogenic- surgery/ DTx
Autoimmune- Parathyroid- addison’s, thyroid- hashimotos
PTH- hypomagmanesia
Thyroid- iodine deficiency
What is the LN drainage of the tongue?
Tip- submental
Ant 2/3- submandibular
Post 1/3- deep cervical LNs
How does H pylori evade destruction?
Burrows into mucus lining
Produces urease which neutralises HCL
Forms Ammonia- which cause inflammation of gastric lining
How to Dx h pylori?
Urea breath test
Stool Ag
Biposy + CLO testing
Are chief cells and oxyphyill cells present in normal parathyroid tissue?
Yes
Components of the corpus callosum?
Rostrum
Genu
Body
Sternium
What are the stages of acute inflammation?
Rubor, Dolor, Calor, Tumour
Vascoconstriction then dilation Permeability Neutrophil migration Phagocytosis Resolution/chronicity/abscess/death
Which cells are present in chronic inflammation?
Macrophages
Lymphocytes
Plasma cells
What is a granuloma and giant cell?
Granuloma- collection of epitheloid macrophages (lots of giant cells)
Giant cell- fusion of epitheloid cells (derived from macrophages)
Difference between branchial cyst, dermoid cyst and cystic hygromas
Branchial cyst- anterior triangle, failure of obliteration of branchial arch
Dermoid cyst- teratomas, neck midline
Cystic hygroma- lymphatic system blockage, lymphangioma
Post triangle- kids
What is the procedure called to remove a thryoglossal cyst?
Sistrunk’s- removal of middle part of hyoid bone
Types of necrosis?
Coagulative- MI in heart Liquefactive- Stroke in brain Caseous- TB Fat- Breast trauma Fibrinoid- Type III hypersensitivity
Examples of hypertrophy and hyperplasia?
Hypertrophy- exercise and muscles, uterus in preg
HOCM
Hyperplasia- grave’s, bph
Breasts in puberty/thyroid in pregnancy
What does the glasgow score for pancreatitis tell you?
> /3 in 48 hours- ITU discussion- severe pancreatitis
Difference classically between a DU and GU?
DU- pain relieved by eating, returns after 3 hours
GU- pain related to meals
Dumping’s syndrome?
Rapid gastric emptying of undigested foods
Leading to fluid shifts (secondary to increased intestinal osmolality)
Hypotension, bloating, flushing, abdo pain
Types of intestinal polyps?
Benign- harmatomas, inflammatory
Neoplastic- commonest- tublar, villous, tublovillous
Malignant potential- tublovillous, villous, tubular
What is PSA?
Prostate specific antigen
Tumour marker for Prostate cancer
Enzyme that liquifies semen
Types of dialysis?
Haemodialysis- cheaper, simpler, diffusion across PPM
Haemofiltration- convection of fluid, iTU
Peritoneal dialysis
Complications of renal transplants?
Rejection- dx via biopsy Delayed function Thrombosis/stenosis of artery/vein Ureteric stricture Infection Lymphocele Failure of anastamosis
What tumour markers do testicular tumours produce?
Teratomas- bHCG and AFP
Seminomas- bHCG
What is the role of the white and red pulp of the spleen?
Red pulp- filtration of rbc/wbc/platelets
White pulp- Ab production
Causes of splenomegaly?
Infective- EBV, TB, malaria Portal HTN Lymphoma/leukaemia Sickle cell/thalassaemia Systemic- sacroid/amyloid/RA
Difference between staging and grading of cancers?
Staging- size and spread
Grading- differnetiation of a tumor from original cells
Causes of SqCC of the bladder?
Chronic inflam
Schisto
Catheter- long term
Bladder stones
How does hypercalcaemia lead to groans?
Leads to increased HCL release- ulcers
How to Dx TB?
Active disease- biopsy + PCR, CT/CXR
Latent- quanterferon gold/mantoux test
Causes of granulomas?
INfective- TB/schisto/fungal
Non infective- sarcoid/RA/Crohn’s
Types of bones?
Long vs flat
Macroscopically- cortical vs cancellous
Microscopically- lamellar (organised), woven (pathological/growing)
