MoD week 4-7 Flashcards
what is fibrous repair?
inflammatory, endothelial & fibroblasts cells infiltrate
blood clot forms (cytokines)
acute inflammation becomes chronic
clot is digested and replaced by granulation tissue
local hypoxia initiates angiogenesis (VEGF)
fibro/myofibroblasts produce ECM causing a scar
maturation is long lasting, cell population falls, collagen increases
myfibroblasts contract to reduce size
blood vessel differentiate and reduce
what are the 3 types of regeneration?
labile e.g. epithelial, in active cell division ATT
stable e.g. hepatocytes, enter cell cycle when required
permanent e.g. nerves, no stem cells to mitose
what is regeneration controlled by?
GF, hormones, proteins, contact between BM (e-cadherin) and between cells (integrin) - contact inhibition (cells stop growing when they meet)
what is healing by primary intention?
clean incised wound, apposed edges, minimal granulation & bleeding, loss of contact inhibition, epidermis regenerated, dermis undergoes fibrous repair
the wound closes first (epidermis) before dermis so can trap bacterial / infection
what is healing by secondary intent?
large skin defect, infarct or ulcer unopposed edges granulation tissue from wound edges loss of contact inhibition epidermis repairs from base up more myofibroblasts large scar takes longer
what are local factors which affect healing?
type, size, location apposition blood supply infection foreign material radiation surgery mechanical stress necrosis protection
what are general factors which affect healing?
age, drugs, diet, anaemia, obesity, general health, malignancy, genes, CVS status
how does the cardiac system heal?
limited, forms scar
how does the liver heal?
regeneration
enlargement of loves to compensate growth + replication of cells
How does a peripheral nerve heal?
schwann cells 1-3mm/day
regenerates proximal axon (elongate)
distal axon degenerates (wallerian degeneration)
use vacated schwann cells to guide axon growth
how does CNS heal?
gliosis
no healing as it is permanent
when damaged, support cells proliferate (glial cells)
how does muscle regenerate?
satellite cells (support)
what are some of the complications of healing?
- insufficient fibrosis
- excessive fibrosis (keloids)
- excessive contraction - contracture (pull on muscle) / stricture (narrowing of opening)
what is haemostasis?
body’s response to blood loss
cessation of bleeding, halting of blood loss
what are the stages of haemostasis?
- severed artery contracts to decrease pressure downstream
- platelet plug forms
- platelet plug stabilised by fibrin
- organisation and replaced by granulation tissue
how is haemostasis regulated? (think about thrombin, what stimulates and what inhibits)
positive feedback from thrombin (prothrombin –> thrombin –> fibrinogen –> fibrin)
thrombin inhibited by: antithrombin III & a-1 antitrypsin & protein C
what is haemostasis regulated by? (breakdown of fibrin)
plasmin breaks downs fibrin clots
plasminogen –(t-PA),(streptokinase)–> plasmin –> fibrin –> fibrin fragment
heparin enhances antithrombin III
warfarin –> antagonises vit K (needed for clotting)
what is thrombosis
formation of a solid mass in the blood stream during life
what is thrombosis caused by?
virchow’s triad, abnormalities in:
blood flow
blood component
endothelium wall (vessels)
what do arterial thrombosis look like?
pale, granular, lines of zhan, low cell content
what do venous thrombosis look like?
deep red, soft, gelatinous, high cell content
what are the fates of thrombus?
PORER
Propagation: thrombus spread and travel in direction of blood flow
Organisation: ingrowth of fibroblasts
Resolution: break down
Embolism: break off to lodge at different location
Recanalisation: blood vessels go through thrombus - supply
what is DIC?
clots everywhere - widespread around the body
what is embolism?
blockage of a blood vessel by a solid, liquid or gas at a site distant from its origin
what are the types of embolism?
DVT pulmonary embolism thromboembolism paradoxical atheroma emboli causing TIA (stroke) fat and bone marrow post fracture gas: air, amniotic fluid, nitrogen
what is paradoxical embolism?
in arteries through arteriovenous anastomoses (AVA) or PDF (patent foramen ovale)
what is an atheroma?
accumulation of intra and extra cellular lipid in intima & media of large and medium sized arteries
what is an atherosclerosis?
thickening and hardening of arterial walls from formation of atheroma
what is arteriosclerosis
thickening of arterial & arterioles walls from hypertension and DM
what are macroscopic changes of atherosclerosis? (simple & complicated plaque)
fatty streak, simple plaque (irregular outline, raised yellow / white enlarge & coalesce) complicated plaque (calcification, thrombosis, haemorrhage, aneurysm formation)
what are microscopic changes of atherosclerosis
early changes: accumulation of foam cells from SMC
intermediate: fibrosis, necrosis, cholesterol clefts
later: disruption extends to internal elastic lamina, media, ingrowth of blood vessels & plaque fissuring)
what happens during endothelial damage?
platelets (plug) releases PDGF which stimulates smooth muscle cells to proliferate and migrate, taking up LDL causing them to become foam cells
macrophages also come and take up oxidised LDL to become foam cells
what are the risks of atheroma?
age, gender, genes, hyperlipidaemia, smoking, diabetes, alcohol, infection, obesity, homocysteinuria
which markers are shown in atheroma?
ApoE: changes in LDL
ACE increases chances of atheroma
what are the complications of atheroma?
coronary artery (MI), cerebral ischaemia (stroke), mesenteric ischaemia (gut), PVD, ulceration, calcification, aneurysm, haemorrhage, stenosis
what is aneurysm?
local dilations of an artery due to weak wall
saccular
dissecting
AAA
What are the markers of MI?
CK-MB
cTnT / cTnI
cardiogenic shock
caused by MI death to part of LV decreasing heart
PAD
intermittent claudication
changes on affected limb
impotence and thigh pain mean occlusion higher e.g. le riche syndrome
what regulates the cell cycle?
G1, S, G2 - all growth phases regulated by cyclin & CDK
cyclin-CDK complex phosphorylates protein RB
allowing progress onto next stage of cell cycle
p53 triggered by damaged DNA
GF stimulates cyclins and inhibits cdki
what is regeneration?
multiply to replace loss
what is reconstitution?
replacement of a lost part
what is hyperplasia?
increase in cell number
physiological: endometrium
pathological: goitre
what is hypertrophy?
increase in cell size
physio: muscle uterus
patho: ventricular cardiac cells, prostate
cardiac hypertrophic
increase in capillaries but not enough so relative ischaemia
compensatory hypertrophy
kidney
atrophy
decreased in cell size or number
physiological: thymus gland / ovaries
pathological: denervation, disuse, ischaemic
what is metaplasia?
REversible change from 1 cell type to another replacement of phenotype
adaptive: splenic issuing bone marrow tissue due to disease
detrimental: barrett’s oesophagus
what is aplasia?
failure of a tissue or organ to develop
aplastic anaemia of BM
what is hypoplasia?
abnormal maturation of cells within a tissue often precancerous
disordered organisation
reversible
what is involution?
normal programme shrinkage, thymus in early life
what is atresia?
no orofice (opening)
what is neoplasm?
abnormal growth of cells that persist after removal of initial stimulus
what is benign neoplasia?
rounded mass due to pushing growth at site of origin
cells are well differentiated
minimal pleiomorphism (viariation in size & shape)
low mitotic count with normal form
what is malignant neoplasia?
invades and spreads to distant sites irregular mass infiltration growth edges range of cells with varying differentiation nuclear pleiomorphism abnormal mitotic figures
tumour
any clinically detectable lump
cancer
any malignant neoplasm
insitu
all the features of malignant neoplasm but no invasion of BM
what is dysplasia?
pre-cancerous, reversible changes
the enlargement of an organ or tissue by the proliferation of cells of an abnormal type, as a developmental disorder or an early stage in the development of cancer
e.g. cellular change of cells lining the uterus
