Path Flashcards
Lines of Zahn
Ridges present on surface of thrombi
Alternate layers of platelets and blood clots form a lamina arrangement
Causes a differential contraction of platelets and fibrin and gives a rippled appearance
Phlegmasia cerulea dolens
Severe form of deep vein thrombosis with venous engorgement such that venous gangrene may supervene
Sequence of infarction
Dead tissue undergoes progressive autolysis of parenchymal cells and haemolysis of red cells
Living tissue surrounding the infarct undergoes an acute inflammatory response
Demolition phase: when there is an increase in the polymorphs, and after a few days macrophage infiltration
Repair phase: gradual ingrowth of granulation tissue
and the infarct is eventually organized into a fibrous
scar
Red or white infarct
Infarcts may either be described as red or white
(pale)
White infarcts: arterial occlusion of ‘end’ arteries in solid tissues, e.g. heart, spleen, kidneys
Red infarcts: venous infarcts and occur in loose tissues, e.g. the lung, where the bronchial arteries continue to pump in blood
Low flow water-shed areas
Splenic flexure: SMA - IMA
Deep myocardium: perfused directly from ventricles
Portal vasculature
-anterior pituitary is perfused by blood that has passed through hypothalamus
Tissues distal to stenosis / narrowing e.g. atherosclerotic areas
Metabolically active areas: undergo ischaemia first
Coagulative necrosis
Typically ischaemic injury (with exception of brain)
Denaturation of intracytoplasmic proteins
Dead tissue initially swollen and firm
Later becomes soft: e.g. ventricular rupture post MI
Colliquative necrosis
Seen in brain tissue - lack of supporting stroma
Necrotic brain tissue liquefies
Glial reaction at periphery with eventual cyst formation
Caseous necrosis
Characteristic of TB
Macroscopically cheese-like (caseous)
Microscopically structureless
Gangrenous necrosis
Necrosis with putrefaction of tissues due to presence bacteria
=e.g. clostridia, streptococci
Tissuesblack = iron sulphide from degraded haemoglobin
Gas gangrene = clostridium perfringens
Fibrinoid necrosis
Malignant hypertension
Necrosis of arteriole smooth muscle wall
Seepage of plasma into tunica media and deposition of fibrin
=smudgy eosinophillic appearance on H&E
Fat necrosis
2 Types:
Direct trauma to adipose tissue
Extracellular release of lipids e.g. Fat necrosis in breast
Enzymatic lysis of fat by lipases, e.g. pancreatic
lipase in acute pancreatitis
Fats split into fatty acids, which combine with calcium to precipitate as soaps
Mediators of apoptosis
p53: tumour suppressor, switches cells with damaged DNA into apoptosis
bcl-2: inhibits apoptosis, over-expressed in malignancy
fas (CD 95): death receptor (NK cells trigger when cells dont express self) - Plasma membrane receptor coupled to the activation of intracellular proteases
Caspaces: Present in all cells and unless inhibited lead to morphological changes of apoptosis.
p53
Tumour suppressor
Switches cells with damaged DNA into apoptosis
bcl-2
Inhibits apoptosis
Over-expressed in malignancy
Pernament cells
Never divide
If lost, lost forever
e.g. nerve cells, striated muscle cells, myocardial cells.
Labile cells
Have capacity to regenerate
e.g. surface epithelial cells constantly being replaced from deeper layers, e.g. skin, oesophagus vagina
Skin graft take process
Adherence:
- fibrin bonds the graft to the recipient site
- occurs in < 12 h.
Plasmic imbibition:
- graft absorbs essential nutrients from recipient bed
- occurs at 24–48 h.
Inosculation:
- revascularization of the graft via growth of vascular buds
- occurs at 48–72 h.
Random pattern flaps
Relies on dermal/subdermal plexus of vessels
Has maximum length:width ratio of 2:1 for safety
Non-random axial flaps
Non-random axial pattern flap: based on specific artery
Non-random island flaps
Non-random island flap: isolated on a vascular pedicle and can be moved to another site
Anterolateral thigh flap
—branches of lateral femoral circumflex artery and skin paddle
Radial forearm flap
-branch of radial artery and skin pedicle
DIEP / TRAM flap
DIEP/TRAM flap— branches of the deep inferior epigastric artery and skin paddle
TRAM: take muscle
Hydrofluoric acid burn
Requires calcium gluconate
Causes hypocalcaemia
Jackson’s burn wound model
Zone of necrosis:
= area of maximum damage
-suffers rapid and irreversible cell death due to coagulation of cellular proteins
Zone of stasis:
=adjacent to the zone of necrosis
-compromised tissue perfusion due to damaged microcirculation
- can progress to necrotic tissue if left untreated or inadequately resuscitated
Zone of hyperaemia:
=outermost burn zone, adjacent to zone of stasis
-tissue perfusion is increased due to local inflammatory mediator release
-will usually completely recover
Treatment of CO poisoning
Hyperbaric oxygen
Treatment is by displacing COHb with oxygen – COHb
has a half-life of 250 minutes in room oxygen levels
and 40 minutes with 100% oxygen.
Superifical partial thickness burn
Papillary demris only
Deep partial thickness burn
Papillary dermis
AND
Reticular dermis (adnexal structures involved)
Phases of the cell cycle
M phase:
- mitosis: nuclear division
- cytokinesis: cytoplasmic division
G1: gap varies between different cell types
S phase: DNA synthesis
G2: gap 2
G0 phase: cells can leave the cell cycle temporarily
and re-enter later; said to be in the G0 phase
G1 phase
Variation in replication frequency occurs due to duration in G1
Cells can leave the G1 phase permanently, lose the
ability to undergo mitosis, and become terminally
differentiated cells
Go
G0 phase: cells can leave the cell cycle temporarily
and re-enter later; said to be in the G0 phase
Growth factords act on cells in G0 –> G1 –> undergo protein synthesis and replication
Stimulated by growth factors: PDGF, EGF, IGF1 & 2
Renal agenesis
Unilateral or bilateral
Failure of mesonephric duct to give rise to ureteric
bud, with failure of induction of metanephric blastema
β-naphthylamine
–> bladder cancer
high exposure in dye and rubber industry
Cyclophosphamide increases risk of which cancer
Alkylating agents e.g. cyclophosphamide
Small risk of leukaemia
Cancer developing at the sites of previous radiotherapy treatment for breast cancer
Angiosarcoma
Clonorchis sinesis
Liver fluke
Sits in biliary system –> cholangiocarcinoma
Nickel exposure cancer
Nickel exposure is associated with nasal and
bronchial carcinoma
Betel nut
Chewing betel nut is associated with increased
risk of neoplasms of oral cavity
Li-Fraumeni
p53
Breast carcinoma
Ovarian carcinoma
Astrocytomas
Sarcomas
Retinoblastoma
Rb1
Genetically associated –> bilateral
Sporadic –> unilateral
Retinoblastoma
Osteosarcoma
Familial polyposis coli
APC gene
Chromosomal location 5q 21
Mainly colon cancer
Other GI tract malignancies
von Hippel-Lindau
VHL
Renal carcinoma
Phaochromocytoma
Haemangioblastoma
MEN syndromes
RET
Familial breast cancer
BRCA1
BRCA2
Breast caricnoma
Ovarian syndrome
Prostatic carcinoma
p53
Tumour supressor gene
Short arm of chromosome 17
Functions
- Arrest cycle in G phase to allow repair of damanaged DNA before S
- Apoptotic cell death if DNA damage is extensive
Inherited germ line mutations of p53 occur in the
rare Li–Fraumeni syndrome, giving an inherited
predisposition to a wide range of tumours.
Krukenberg tumours
Spread of stomach carcinoma –> ovaries
Signet ring cells - primary is gastric adenocarcinoma which are mucinous signet ring cell
Autoimmune disease trigerred by malignancy
Dermatomyositis
Membranous glomerulonephritis
Cervical screnning
Women aged 25–49 years old, screened every 3
years
Women aged 50–64 years old, screened every 5 years
Breast screening
Women aged 50–70 years old (currently being
extended to women aged 47–73 years old in some
areas of the UK as a trial extension of the
programme).
Repeated 3-yearly
C5a
Chemotactic for neutrophils
Increase vascular permeability
Release of histamine from mast cells
C4b, 2a, 3b
Opsonification bacteria
Kinin system
Activated by factor XII
Converts: prekallikrein –> kallikrein
Kallikrein cleaves kininogen –> bradykinin
Bradykinin controls vascular permeability and is a chemical mediator of pain
Serous inflammation
Abundant protein-rich fluid
-little cellular material
Inflammation of serous cavities
e. g. peritonitis
e. g. synovitis
e. g. conjunctivitis
Catarrhal inflammation
hyper-secretion of mucous in acute inflammation of mucous membrane
E.g. common cold
Fibrinous inflammation
Exudate contains much fibrinogen
Fibrin forms a thick coating, e.g. acute pericarditis,
fibrinous peritonitis.
Haemorrhagic inflammation
Accompanying vascular injury or coagulopathy
e. g. acute haemorrhagic pancreatitis due to proteolytic digestion of vessel walls
e. g. meningococcal septicaemia, resulting from associated disseminated intravascular coagulation (DIC).
Suppurative inflammation
Production of pus
i.e. dying and degenerate neutrophils, organisms and liquefied tissues
May become walled-off by fibrin or fibrous tissue to produce an abscess, i.e. a localised collection of pus
May form an empyema (a collection of pus in a
hollow viscus, e.g. gall bladder)
Membranous inflammation
Epithelium coated with layer of fibrin, desquamated epithelial cells and inflammatory cells
e.g. grey membrane seen in pharyngitis due to diphtheria
Pseudomembranous inflammation
Superficial mucosa inflammation and ulceration with sloughing of mucosa, fibrin, mucus and inflammatory cells
e.g. pseudomembranous colitis in C.Difficile
Necrotising inflammation
Tense oedema may cause vascular occlusion and thrombosis
–>septic necrosis
e.g. gangrenous appendicits
Types of giant cell
Histocytic: ingestible material by macrophages
e. g. silica
e. g. tuberculosis
Langhans: horseshoe arrangement of peripheral nuclei at
one pole of cell
-characteristically seen in tuberculosis
Foreign body: large cells with nuclei scattered randomly
Touton: ring of central nuclei
-clear peripheral cytoplasm with accumulated lipid, seen at sites of adipose tissue breakdown and in xanthomas
Drugs causing hepatic granulomatous
Allopurinol
Phenylbutazone
Sulphonamides
Petechial haemorrhages in corpus callosum and cerebellar peduncles
= diffuse axonal injuries
Blood in CSF
= subarachnoid haemorrhage
Fibrous obliteration of subarachnoid space –> hydrocpehalus in those that survive
Most common cause of intracerebral haemorrhage
Hypertensive vascular disease
Diffuse petechial haemorrhage https://www.brainscape.com/decks/7516133/cards/quick#
Small pin-point haemorrhages scattered throughout
brain
Result from disruption of wall of small cerebral blood
vessels
Causes include:
- vasculitis
- acute hypertensive encephalopathy
- fat embolism
- head injury
Brain abscess sites
Temporal lobe or cerebellum - otitis media
Frontal love - paranasal sinus spread
Parietal lobe - haematogenou spread
Salmonella osteomyelitis
= sickle cell disease
Sickle cell osyteomyelitis
= Salmonella
Brucella abortis
Intervertebral discitis
Charcot joints
Degenerative joint disease which occurs due to loss of sensory nerve supply
Tabes dorsalis: knee or hip joints
Syringomyelia: shoulder or elbow joint
- -> recurrent swelling
- -> degenerative changes in ligaments and tendons, resulting in subluxation of the joint
HLA B27
Ankylosing spondylitis
HLA DR2
Goodpastures
HLA DR3
Addison’s
Hashimotos thyroidits
Myasthenia gravis
HLA D4
Insulin dependent diabetes
Classical complement
Antigen-antibody complex mediated
Alternative complement pathway
Bacteria cell surface mediated
C3b
Opsonification
+removal of immune complexes
C5a C4a C3a
Chemotactic
Inflammatory
Increase vascular permeability
Histamine release from mast cells
C5 - C9
MAC
Membrane attack complex
DiGeorge
T cell deficiency
Thymic aplasia
MHC complex
Chromosome 6
Cytokines important in graft rejection
IL-2
gamma interferon
Induction immunosuppression
IL-2R monoclonal antibodies
- basiliximab
- daclizumab
Acute rejection prophylaxis regimen
Calcineurin inhibitor: tacrolimus or ciclosporin
AND
Anti-metabolite: mycophenolate motefil or azathioprine
AND
Prednisolone
Maintenance therapy
Wean down doses of calcineurin inhibitor and anti-metabolite
Stop steroids, after weaning
If tacrolimus or ciclsporin not tolerated –> sirolimus used as a substitute e.g. if nephrotoxicity occurs
Anti-rejection therapy in suspected active rejection
Cell mediated:
=Three pulses IV methylprednisolone
ATG given if steroid resistant
Antibody-mediated
=plasmapheresis, IV IG
AND retuximab and anti CD-52 (alemtuzumab) –> B cells
Genetic mutation in HbS
Glutamic acid replaced by valine
Mx of hereditary spherocytosis
Delayed spelectomy until 10 years of age
–> reduced likelihood of post-splenectomy sepsis
After spelnectomy:
- Life-span of red cells increase
- Jaundice resolves
- Reduced pigment stones
- Hb increases
Extinsic pathway requires…
Tissue thromboplastin
-released by damaged endothelial cells
Intrinsic pathway requires…
Nothing additional
Formed by normal constituents of ciruclating bloods
Convergence of intrinsice and extrinsic pathway
Converge at Factor X –> Xa
Outline of intrinsic pathway
Vessel injury exposes collagen
-collagen initates first step
Circulating twelveE –> XII a
EleveN —> XIa
NinE –> IXa
Eight –> + IXa + platelet phospholipid = convergence on X
Outline of extrinsic pathway
Damaged endothelium released tissue thromboplastin
Thromboplastin + Factor VII
Converge on X
Factor V
Facilitates Xa acting on Porthrombin –> thrombin
-hence common pathway
Inatcivated by protein C + S
Production of clotting factors
All soluble clotting factors produced in liver
EXCEPT Factor VIII (8) - produced in endothelium
Plasmin
Breaks fibrin down into soluble fibrin breakdown products
Derived from plasminogen
Activated by tissue plasminogen activator released from endothelium
INHIBITION: Control of activation of plasminogen is provided by
plasminogen-activator inhibitor 1 (PAI-1)
-PAI-1 is released by endothelial cells and rapidly
inactivates tissue plasminogen activator.
Platelet count needed for surgery
70
Spontaenous bleeding level for platelet count
20
Prolonged bleeding time
= platelet dysfunction
Normal bleeding time
- adequate platelet count
- adequate platelet function
- adeqaute vascular contraction
Whole-blood clotting time
Whole blood in glass tube
Measures:
- platelet ufnction
- intrinsic pathwya
- common pathway
Prothrombin time
Measure integrity of extrinsic pathway AND final common pathway
Factor VII
I, II, V and X
Activated partial thromboplastic time APTT
Tests intrinsic system AND final common pathway
All factors with exception of Factor VII
Bleeding + APTT and PT normal
= platelet dysfunction
Bleeding + APTT and PT abnormal
=defect in common pathway
Bleeding + APTT normal and PT abnormal
= defect in factor VII
factor VII deficiency
Bleeding + APTT abnormal and PT normal
= defect in intrinsic system
Thrombin time
Note difference to prothombin time
Increased if there is an inadequate concentration of fibrinogen.
Prolonged by heparin and presence of fibrin degradation
products.
von Willebrand’s disease
Due to deficiency of von Willebrand’s factor.
AD inheritance
Vascular endothelium releases decreased amounts of Factor VIII
Platelet count usually normal, but platelet interaction with endothelium is defective because of deficiency of von Willebrand’s factor
Haemophilia A
Inherited deficiency of Factor VIII
X-linked recessive disorder affecting males and carried by females
Severity of the disease depends upon the degree
of Factor VIII deficiency
Prothrombin time (PT) normal but activated partial thromboplastin time (APTT) prolonged
Antithrombin III deficiency
AD inheritance
Heterozygotes may suffer from recurrent deep vein
thrombosis (DVT), pulmonary embolism (PE) and
mesenteric thrombosis.
Homozygotes present in childhood with severe arterial and venous thrombosis
Protein C
Degrades Factors Va and VIIIa
Promotes fibrinolysis by inactivating plasminogen-activator inhibitor 1 (PAI-1)
Phenylbutazone
Inhibits warfarin-albumin binding
Cimetinide
Inhibits hepatic microsomial degredation of warfarin
MOA Clopidogrel
Inhibits activation and aggregation of platelets by
blocking the glycoprotein IIa/IIIb pathway
Stop 7 days pre-op
Cortex of lymph
Primary and secondary lymphoid follicles
Secondary = stimulated
Tightly packed
Paracortex of lymph
T-cell dependent area
Medulla of lymph gland
Contains the medullary cords and sinuses
Contains lymphocytes, which are much less densely packed than in the cortex together with macrophages, plasma cells and a small number of granulocytes
Haematological changes post splenectomy
Red cell count does not change but red cells with
cytoplasmic inclusion, e.g. Howell–Jolly bodies, may
appear.
Granulocytosis occurs immediately after splenectomy
but is replaced in a few weeks by lymphocytosis
and monocytosis.
he platelet count is usually increased and may
stay at levels of 400 000–500 000 × 109/L for over
a year
A thrombocytosis in excess of 1000 × 109/L may
occur –> anti-platelets
Most common cause of post-splectomy spesis
= pneumooccus
Splenectomy vaccines
Polyvalent pneumococcal PPV
Men ACWY
Hib
Influenza
Re-immunization every 5 years
+ 2 years penicillin
Infusion of platlets
Infuse rapidly via short-giving set with no filter
Usual adult dose is 6 units, which should raise the count by 40 000 × 109/L
Indications for cryoprecipitate
Haemophilia
Von Willebrand’s disease
Fibrinogen deficiency e.g. DIC
Rich in factor VIII, fibrinogen and vWF
