CSB520

(Y1 S2) disease processes

hypoxia

lack of oxygen

hypoxemia

lack of oxygen in blood supply

ischaemia

lack of blood supply

reperfusion

restoration of blood following ischaemic period

acute

sudden onset/ sudden severe

chronic

long duration

labile cells + eg.

continuously dividing.

epithelial eg. skin, GIT, reproductive, urinary tracts.

eg. haemopoietic stem cells.

stable cells + eg.

quiescent, divide when stimulated.

epithelial eg. liver, kidney, lung, pancreas.

eg. smooth muscle cells, fibroblasts, endothelial cells.

permanent cells + eg.

non-dividing.

eg. cardiac + skeletal myocytes, CNS neurons.

connective tissue cell types

myocytes, endothelial cells, chrondocytes, osteocytes + osteoblasts + osteoclasts, fibroblasts/ myofibroblasts, adipocytes.

‘other’ tissue types

melanocytes, mesothelial cells, germ cells, lymphoid tissue, ependymal cells, haemopoietic cells, erythrocytes, lymphocytes, neutrophils, macrophages.

apoptosis key points

programmed cell death/ cell suicide.

pathological + physiological, active process, kills single cell only, no inflammation.

necrosis key points

pathological only, passive process, kills neighbouring cells, stimulates inflammation. loss/ decreased tissue function via scarring, calcification, death.

infarct definition + process

area of necrotic tissue.

occurs dt. sudden, severe stress. cells lack energy, lyse, kill neighbouring cells.

autophagy

type of cell adaptation. decreases size + metabolic needs + rate of cell. active process.

does not kill cell, only removes contents/ organelles

tissue atrophy

cell adaptation: decreases size of tissue/ organ dt cell loss.

combination of autophagy + apoptosis/ only apoptosis in older cells.

irreversible in permanent tissues eg. heart.

hypertrophy

cell adaptation: cells increase size.

physiological (muscle growth) + pathological (diseased arteries -> heart). active, reversible process.

hyperplasia

cell adaptation: increased cells dividing.

physiological + pathological (hormonal imbalance). active, generally reversible process. cannot occur in permanent cells.

metaplasia

cell adaptation: change from normal/ well-differentiated cell type to another via sustained stress.

physiological (cervix) + pathological (airways, smoking). active, reversible process (w environmental reversal).

neoplasia

process of new abnormal growth (tumour), does not inform benign/ malignant

dysplasia

mutated, abnormal cells (genotype + phenotype)

tumour

new, abnormal tissue growth on/ in the body. can be benign/ malignant

angiogenesis

formation of new blood vessels.

in tumours: provide nutrients + blood flow = growth.

benign tumours key points

harmless, never metastasize, encapsulated, homogenous (uniform cells), well differentiated.

malignant tumours key points

potentially fatal, can potentially metastasize, infiltrative growth pattern, heterogenous (pleomorphic), well differentiated/ poorly/ undifferentiated (anaplastic)

anaplastic

cancer cells that divide rapidly + have little/ no resemblance to normal cells (poorly differentiated)

pleomorphic

having variation in size + shape of cells/ nuclei

encapsulated tumours

benign. proteinaceous wall surrounds = remove easily from tissue (not metastasized).

infiltrative/ invasive tumours

malignant. attached to other tissues (metastasis) = cut normal tissue out when removing cancer.

carcinoma-in-situ

abnormal epithelial cells that have not yet metastasized through the basement membrane.

metastasis

spread of malignant cancer cells from where they first formed (primary site) to another part of the body (secondary site).

benign tumours nomenclature

“-oma”

connective malignant tumours nomenclature

“-sarcoma” eg. osteosarcoma (bone)

epithelial benign tumours types

papilloma (finger like projections), adenoma (glandular), cystadenoma (glandular cyst)

connective benign tumours types

fibroma (connective tissue), leiomyoma (smooth muscle), chrondroma (cartilage), osteoma (bone), lipoma (fat), haemangioma (blood vessel).

epithelial malignant tumour nomenclature

-”carcinoma” eg. papillocarcinoma

why are carcinomas the most common diagnosed cancer in adults

epithelial cells are highly proliferative, and undergo more stress = higher chance of mutation + dysplasia resulting in malignancy.

other cells benign tumours types

meningioma (meninges, spine + brain), mature ovarian teratoma (“dermoid cyst”).

other cell malignant tumour types

mesothelioma, melanoma (skin, eyes, mucous membranes), testicular teratoma, leukaemia, glioma, lymphoma.

what are the 2 most common primary lung cancers

squamous cell carcinoma, adenocarcinoma (secretory epithelium = goblet cell mutation).

most common primary lung cancer pathogenesis

normal cell -> sustained stress -> metaplasia -> multiple mutations -> dysplasia -> further mutations -> malignant tumour (cancer).

metastatic routes

blood (haematogenous), lymphatics, direct seeding (through/ wi body cavities).

“blastoma”

abnormal, poorly/ undifferentiated cell

hyperaemia

active increase in blood flow to area

congestion

passive build up of blood in circulatory system. = increased hydrostatic pressure -> transudate oedema formation.

does not occur in high pressure circuits = pulmonary, systemic venous circuits.

oedema/ effusion

increased fluid in interstital fluid/ body cavities

transudate oedema

extravascular fluid w low protein conc

exudate oedema

inflammatory extravascular fluid w high protein conc. can contain WBC, RBC

pus def

purolent inflammatory exudate, high in neutrophils, cell debis, sometimes pyogenic organisms (produce pus)

ulcer

lesion/ ‘sore’ on body surface eg. skin, mucous membranes

abscess

swollen area w/i body tissue, containing accumulation of pus

sterile body site meaning

no microbes present (normally). eg. blood, bone + marrow, brain + CSF, lower respiratory, upper urogenital

non-sterile body site meaning

micro-organisms present for innate defence mechanisms. eg. skin, GIT, upper respiratory, lower urogenital

what form of cell death causes an inflammatory response?

necrosis

3 features of acute inflammation

early onset (secs-mins),

short duration (mins-days),

involves fluid exudation (oedema) + neutrophil emigration

outcomes of acute inflammation

resolution, organisation, chronic inflammation

resolution

healing w/o scarring, restoration of structure + function.

depends on: tissue type, injury extent, presence of factors impairing repair (eg. infection).

organisation def

healing by scarring/ fibrosis.

immature scar tissue = granulation tissue.

mature scar tissue = collagen protein.

main components of granulation tissue + role in repair

macrophages - remove debris.

myofibroblasts/ fibroblasts - secrete collagen.

angiogenesis - new blood vessels provide oxygen + nutrients.

once complete, macrophages + fibroblasts leave, new vessels die by apoptosis = acellular collagen scar.

adhesions

granulation tissue that is continuously forming. eg. endometriosis

consequences of healing through organisation

decreased functional tissue, distortion of surrounding tissue, scarring.

3 main causes of chronic inflammation

unresolved acute inflammation eg. appendicitis,

repeated acute inflammation eg. gall stones,

special cases eg. hypersensitivity, autoimmune diseases.

general features of chronic inflammation

later onset (days), longer duration (weeks-years), involves lymphocytes + macrophages, always results in organisation.

consequences of chronic inflammation

involves lymphocytes, ongoing injury, repeated repair attempts.

epithelial cells (if present) undergo hyperplasia = increased risk dysplasia + carcinoma.

healing by organisation = decreased functional tissue, distortion of surrounding tissue.

innate immune system

fast response, not specific, germline encoded.

cellular: neutrophils, macrophages, NK cells.

humoral: complement components.

adaptive immune system

slow response, differentiates btw targets, learns + remembers (‘memory’ cells).

cellular: T cells, B cells.

humoral: antibodies.

hypersensitivity

excessive reaction of immune system to stimulus.

are hypersensitive/ autoimmune patients immuno compromised?

no, they have very strong immune systems, which are causing disease.

autoimmune = targets normal, self cells.

in order to treat these conditions, patient immune systems often have to be dampened, which causes immuno-compromise.

indicators of acute inflammation

heat, redness, swelling, pain, loss of function.

haematoma

accumulation of blood (bruise)

thrombus

blood clot attached to wall (vessel/ heart chamber)

embolus

undissolved mass travelling in the blood

aneurysm

abnormal, localised dilation of artery/ ventricle

atherosclerosis def

process of chronic inflammation building up in artery wall. involves hardening of artery + build up of plaque + cholesterol.

atherosclerosis risk factors

aging, male gender, genetics.

smoking, diabetes, systemic hypertension, dyslipidaemia, visceral adiposity.

atherosclerosis effects + vascular pathologies

decreased vascular elasticity, increased vascular resistance, swelling/ bleeding in plaque.

increased risk thrombus, embolus, aneurysm.

constituents of blood

55% plasma, 1% platelets + leukocytes, 44% eythrocytes.

pressure differences in systemic (arterial + venous) + pulmonary circuits

systemic arterial circuit = high pressure (supplies oxygenated blood to organs via arteries).

systemic venous circuit = low pressure (brings deoxygenated blood from organs via veins).

pulmonary circuit = low pressure (circulates blood between lungs + heart).

superficial venous thrombi

pain, ulcerated overlying skin, oedema distal to clot. rarely embolise.

deep venous thrombi

often silent/ asymptomatic, may cause limb swelling. often embolise.

arterial thrombi

initiated by endothelial injury + atherosclerosis.

venous thrombi

initiated by stasis + increased coagulation.

how do kidneys contribute to systemic hypertension

regulation of blood volume + pressure via RAAS.

haemorrhage

escape of blood from ruptured vessel.

can result in hypervolemic shock/ haemorrhagic stroke/ iron deficiency anaemia, depending on site, amt blood lost, speed of loss.

atherosclerosis consequences

atherosclerosis -> thrombus -> occlusion -> infarct/ ischaemic stroke.

atherosclerosis -> aneurysm -> thrombus -> embolus -> occlusion -> infarct/ ischaemic stroke.

atherosclerosis -> aneurysm -> rupture -> hypervolemic shock (body)/ haemorrhagic stroke (brain).

anaemia

decrease no/ quality of RBCs

renal function in blood synthesis/ maintenance

regulates plasma ions, pH, blood volume + pressure.

low blood o2 -> kidney -> EPO -> bone marrow increases RBC production. if EPO is inhibited, anaemia can occur.

liver function in blood synthesis/ maintenance

makes plasma proteins = colloid osmotic pressure (reabsorption of fluid to capillaries).

lymphoid organs, spleen function in blood synthesis/ maintenance.

filters circulating blood, immunological response against blood-borne antigens, removal of old/ damaged RBC

lymph nodes function in blood synthesis/ maintenance

filters interstitial fluid, which re-enters systemic circulation.

angina

transient ischaemic event. essentially “pre-MI”.

blood flow returns before necrosis occurs (when stressor removed).

insufficient oxgenated blood to cardiac muscle. lactic acid buildup causes pain.

healthy muscle can survive 20-40 mins before irreversible injury.

myocardial infarction

involves necrosis of cardiac muscle.

can be subendocardial = part of muscle/ transmural = full wall.

repair following myocardial infarction

necrosis = acute inflammation (hyperaemia, oedema, neutrophils).

healing by organisation = granulation tissue, fibroblasts, angiogenesis, macrophages -> collagen scar.

loss of cells + functional tissue = decreased contractility.

consequences of myocardial infarction

heart failure, aneurysm, arrhythmias.

left sided heart failure causes

ischaemic heart disease, systemic hypertension, aortic/ mitral valve disease.

left sided heart failure backward effects

pulmonary congestion (passive) -> increased hydrostatic pressure (dt increased fluid volume) -> pulmonary transudate oedema + pleural effusion.

left sided heart failure signs/ symptoms

dyspnoea (shortness of breath), cough w blood-tinged phlegm (may be exacerbated after lying flat).

heart failure (left or right) forward effects

renal response to decreased cardiac output = compensation via RAAS.

decreased renal perfusion = RAAS activation.

angiotensin 2 = increased vascular resistance + aldosterone release from adrenal glands.

aldosterone = kidneys retain salt + water = increased blood volume.

= maintains cardiac output.

right sided heart failure causes

usually dt left side failure.

pulmonary hypertension dt increased resistance w/i pulmonary circulation.

right sided heart failure backward effects

systemic venous congestion -> increased hydrostatic pressure -> peripheral transudate oedema.

liver/ spleen/ kidney disease dt pressure necrosis from congestion.