2 Pathology Flashcards
Describe necrosis types: Coagulative Colliquitive Caseous Fat
Coagulative - firm, maintains structure
>Haemorrhagic - blocked venous drainage
>Gangrenous
Colliquitive - liquefies (e.g. infarct/ abscess)
Caseous - mixture of both, “cheese-like” appearance
(e.g. granulomatous disease aka TB)
Fat - action of lipases to break down fatty tissue
How would hemorrhagic coagulative necrosis look in an organ (straight after damage and after necrosis occurred)
Straight away: bright red and haemorrhagic
After necrosis: yellow/scarred
What is the main difference between necrosis and apoptosis?
Necrosis releases cell contents and has membrane (and nuclear) breakdown. Apoptosis does not.
What is characteristic to pancreatic necrosis?
Fat deposition in pancreas
Physiological apoptosis situations (5)
1- Embryogenesis - deletion of cell populations
2- Autoimmune T/B cells - in thymus/marrow self-ag
3- Hormone dept involution - uterus/ovaries/breast
4- After inflammatory response - delete inflam cells
5- Deletion of cells in constantly renewing tissues
Pathological apoptosis situations (3)
1- Virus (cytotoxic T cells)
2- DNA damage
3- ischemia/ hypoxia
Stages of apoptosis (4)
1) Cell shrinkage
2) Chromatin condenses
3) Membranes intact
4) Cytoplasmic blebs -> phagocytosis
Stages of necrosis (4)
1) Cell swelling - reversible
2) Cell swelling - irreversible
3) Nuclear chromatin dissolution, shrinkage and fragmentation
4) Rupture of membranes
Characteristic microscopic appearance and stain of amyloid
Congo red stain - pink
Under polarised light - apple green birefringence
Histological appearance of depositions and organs: Steatosis Carbon Iron Haemosiderin Lipofuscin
> Steatosis - fat lobules in liver
Carbon - black lines in lung (mucosa) , blobs in macrophages (lymphatics)
Iron - brown depositions in liver, stains blue
Haemosiderin - brown staining in macrophages
Lipofuscin - brown pigment in liver/ heart etc
Dystrophic and metastatic calcification definition
Dystrophic = deposition in ABNORMAL tissues with normal blood calcium level Metastatic = deposition in normal tissues with RAISED blood calcium level
Causes of raised serum calcium
1y parathyroidism - tumour
2y parathyroidism - kidney disease
systemic - cancer
3 main changes to cells/vasculature in acute inflammation
1) Vasodilation - by histamine, prostaglandins, nitric oxide
2) Neutrophil activation - by complement, leukotrienes, bacterial products
- Activation, chemotaxis and phagocytosis
3) Endothelial activation - by complement, 5HT, bradykinin, histamine, leukotrines
- Increase vascular permeability for fluid/ inflammatory markers -> swelling
5 cardinal signs of inflammation and causes
Red - hyperaemia Heat - hyperaemia Swelling - hyperaemia and fluid exudate Pain - bradykinin and prostaglandins Loss of function - due to pain and swelling
Definition of exudate
Fluid leaking out from blood vessels, through endothelium to extracellular space in tissues
How granulomatous chronic inflammation is defined (3)
1) Granulomas
2) Epithelioid macrophages
3) Multinucleate giant cells
What cells are present in chronic inflammation (4)
+ what other substance is present
Lymphocytes (T/B/NK cells)
Macrophages
Eosinophils
Plasma cells
Fibrin
3 wound types
Abrasion
Incision
Laceration
2 things required for wound healing/repair
Granulation tissue
Fibrous scar
Difference between 1y and 2y wound healing/repair
1y - little granulation tissue and small neat scar, edges of would neat
2y - lots of granulation tissue, scab and large scar, edges of wound jaggy
Outcomes of acute inflammation (3)
1- complete resolution
2- healing by fibrosis
3- progression to chronic
Stages of a post-mortem examination
(background info - history, cause of death, clinical care etc.)
1) external - general exam
2) internal
a) Excavation - incision sternal notch-> symphysis pubis & remove thoracic/abdo/pelvic organs, incision posterior skull & remove brain
b) Organ dissection - macroscopic and sometimes microscopic (lab)
3) After Close up/ restore body and replace organs Write MCCD if not done so Report to PF/ GP & clinician Release body to family
How is a death certificate laid out
1a - disease/ condition directly causing death
1b/c/d - as a result/ consequence of …
2 - other diseases/ conditions contributing to death but not directly related to COD
Types of embolism (4)
air
thrombus
fat
amniotic fluid
Method of haemorrhage occurring (4) and e.g.
Weakness by disease (atherosclerosis > AAA > rupture)
Congenital weakness (berry aneurysm > SAH)
High pressure (hypertension > cerebral haemorrhage)
Erosion (bleeding from perforated gastric ulcer)
Most common sites of:
1- thrombus development
2- thrombus travel
1) leg veins, heart, carotid arteries
2) lungs, brain, other
Function of Von Willebrand factor in coagulation
Coagulation factor which helps attach fibrin to vessel wall with collagen
Difference between arterial and venous thrombus
Arterial - lots of platelets, little fibrin, fast flowing blood
Venous - lots of fibrin trapping RBCs, static blood
Classes of risk factors for abnormal thrombus (3)
Circulatory stasis
Hypercoagulative state
Vascular wall injury
Hypercoagulative state risk factors for abnormal thrombus (8)
Oestrogen therapy Pregnancy/ post-partum Malignancy Thrombophilia Trauma/ surgery of lower body Nephrotic syndrom IBD Sepsis
Circulatory stasis risk factors for abnormal thrombus (5)
Immobility/ paralysis
AF
LV dysfunction
Venous occlusion - tumour, pregnancy, obesity
Venous insufficiency/ varicose/ faulty valve
Vascular wall injury risk factors for abnormal thrombus (6)
Heart valve disease/ replacement Surgery/ trauma IV access (venepuncture) Atheroscleorsis Chemical irritation Indwelling catheter
What are the main deep leg veins (which DVTs form in) (4)? –> other veins (3)?
Posterior tibial Anterior tibial Popliteal Superficial femoral (Common femoral > Internal iliac > common iliac)
Causes of a DVT/ how it forms (2)
Slow blood flow
Faulty valves
How to confirm diagnosis of DVT (3 steps)
Clinical history/ exam - Well’s Score
Biochemical: D-Dimer
Imaging - Compression ultrasound, venography
What is D-dimer
Breakdown product of fibrin, containing parts (D2xD, 1xE) of fibrinogen
Difference between thrombus and post-mortem clots
Thrombus - attached to vessel wall, granular, maintains vessel shape
PM - slippy, shiny “chicken fat”, easy to remove
Risks after VTE (4)
PE
Recurrent VTE
Post thrombotic syndrome
Venous insufficiency - varicose veins, residual thrombus
What is a:
1) saddle embolism
2) paradoxical embolism
1) at pulmonary junction
2) transfers to arterial circulation e.g. by patent foramen ovale (>stroke)
Treatment of VTE (4)
Anti-coagulation 3-6 moths - warfarin, LMWH, direct factor Xa/IIa inhibitor
Compression stockings
Pain relief
Remove risk factors
Action of: Warfarin Herparins Adoxaban/Rivaroxaban/ Enoxaban Dibagatran
Warfarin - inhibits factors 7, 9, 10 and 2 (thrombin)
Heparins - indirect inhibitor of factors 2 (thrombin) and 10
Adoxaban/Rivaroxaban/ Enoxaban - direct factor 10 inhibitors
Dibagatran - direct factor 2 (thrombin) inhibitor
Diagnosis of MI/ACS (3 steps)
Clinical history/ exam
Biochemical marker - troponin levels
ECG - ST elevation/depression, T wave inversion
Imaging - cardiac catheterisation
What is acute coronary syndrome (3)?
Unstable angina (ST dep)
NSTEMI (ST dep/ T wave inv/ troponin)
STEMI (ST elev/ T wave inv/ troponin)
Treatment of acute coronary syndrome (atherosclerosis) (4)
1) Prevention of clot getting bigger - anti platelets (clopidogrel/aspirin), anticoagulant (heparin)
2) Removal of clot - catheter angiography, thrombolysis (-teplases)
3) Widen stenosis - balloon, stent
4) Prevent further clots - anti-platelet (clopidogrel/aspirin), statin
How does normal vs post-MI myocardium appear on H&E stain?
Normal: long light pink cells with central nuclei
Post-MI: dark pink cells (hyper-eosinophilic) with lots of inflammatory infiltrate (+ haemorrhaged oedema)
How long until micro/ macroscopic changes can be seen following MI?
Micro - 12 hrs
Macros - at least 24hrs
Investigation of suspected stroke (1)
CT of brain
Treatment of stroke (4)
1) Removal of cause of thrombus - correct AF (cardioversion), replace valve
2) Anticoagulation
3) Removal of other CVD risk factors
4) (Rarely remove clot - cardiac end-arterectomy, thrombolysis)
What is troponin?
Protein released by damaged myocytes, indicating ischemia/ trauma
What are the 3 components of cellular pathology
Autopsy
Histology
Cytology
Difference types of biopsy (and subtypes)
Small biopsy - mucosal, needle core, incision
Excisions biopsy
Ressection
What can special stains be used for (4)?
Mucin
Deposition
Infection
Normal elastic tissue
Uses of immunohistochemistry (4)
Tumour staging/ classification
Cancer prognosis estimates
Cancer treatment estimates (receptors)
Identification/ diagnosis of infectious disease
What is immunohistochemistry?
Staining technique which strains certain proteins brown (cytoplasmic/membranous/nuclear)
How is FISH used to determine gene over expression in tumour?
1) DNA denatured by heating
2) DNA separates exposing nucleotides
3) Fluorescent tag to mark gene is added (e.g. HER2)
4) Fluorescent tag to mark chromosome is added (e.g. cr17)
5) Compare dots for number of genes vs number of chromosomes, if there are more genes than chromosomes (by a lot), there is over expression
Define congenital and developmental anomalies
Congenital = any abnormality present at or before birth, can be structural or functional/metabolic
Developmental = congenital structural
How to VSDs go from L>R shunts to R>L shunts?
Increased pressure in low-pressure system > pul. hypertention > stenosis > higher pressure
Pressure then equalises and blood goes both ways
What is spina bifida?
Failure of complete closure of neural tube so contents of spinal canal protrude from back
Symptoms of spina bifida (5 & 3)
Motor interruption - muscle weakness/ limb paralysis
Autonomic interruption - bowel/ bladder problems
Hydrocephalus
Seizures
Orthopaedic problems - lower body
Syndactyly
Polydactyly
Cleft palate
Define Hamartoma
Disordered growth of normal tissue within an organ, growing at the same rate as surrounding tissues
Define Chondroid hamartoma
In the lung, on imaging as a “coin lesion”
Composition = epithelium, cartilage, fat, smooth muscle
Need to investigate as malignancy, can cause obstruction, and can mimic malignancy if endobronchial
Define ectopia cordis
Growth of heart outside the body
Define a diverticulum and state the 2 main types
Diverticulum = out pouching caused by herniation of mucosa through muscle wall
Diverticular Disease
Meckel’s Diverticulum
Describe diverticular disease/ diverticulitis and complications
Out pouching of intestine, usually in sigmoid colon
Can become inflamed (feral material) = diverticulitis
This can perforate/bleed/ fistulate
Or can heal by fibrosis > muscle hypertrophy > stenosis
Similar signs to malignancy - PR bleeding and altered bowel habit
Describe Meckel’s diverticulum and complications
Congenital - failure of complete obliteration of vitelline duct
2 inches, in terminal ileum
Difference between neoplastic and non-neoplastic growth
Neoplastic - uncontrolled and irreversible
Non-neoplastic - controlled and reversible
What are the grade and staging of a tumour based on?
Grade = level of differentiation of cells
Stage = how advanced aka size/invasion, involved nodes, mets
What cell/nuclear changes are present in dysplasia (3)?
Hyperchromatic nuclei (dark)
Increased nuclear:cytoplasmic ratio (bigger nuclei)
Irregular nuclear membranes
Define carcinoma in situ
> Full thickness epithelial dysplasia what has not yet invaded past the basement membrane (non-invasive)
Risk of mets is zero just now as there is no blood or lymphatics in epithelium above BM
Can progress to malignant
3 methods of metastatic spread and examples
Lymphatic - carcinoma
Haematogenous - sarcoma
Transcoelemic
Local effects of malignant tumours (6)
SOL Pressure effects - compression Nerve innervation - pain Ulceration/ bleeding (> anaemia) Local destruction Stromal reaction/ fibrosis - stenosis/obstruction
Raised tumour markers may suggest: CEA (carcinoembryonic antigen) AFP (a-feto protein) hCG (human chorionic gonadotropin PSA (prostate specific antigen) Ca125 Ca19.9 Ca15.3
> CEA (carcinoembryonic antigen) = various/ generic
AFP (a-feto protein) = liver, (& germ cells, testicular)
hCG (human chorionic gonadotropin) = germ cell tumours
PSA (prostate specific antigen) = prostate
Ca125 = ovarian (& uterine)
Ca19.9 = pancreatic
Ca15.3 = breast
