pathophys of spinal stenosis
stenosis is the narrowing of space for spinal cord in central canal or intervertabral formaena
most commonly caused by degeneration- HNP, Facet OA (osteophyte formation), Lig flav thickening due to age and loss of elasticity, spondylothesis
can be caused by manual compression by muscles or odema
in the C spine it is UMN signs L spine LMN signs
symptoms relieved with flexion worsened with extension
pathophysiology of spondylothesis
Spondylothesis occurs due to instability either anteriorly or posteriorly that cause the vertebra to move and there are 5 types and causes
isthmic- Pars fracture by repetitive hyper ext leading to forwards translation
degenerative- facet athropathy and disc degen leads to instability morecommon in older adults
dysplastic- congenital facet malformation
traumatic- rare- acute fracture to areas other than pars
pathologic- caused by bone weakness caused by tumor, infection, metabolic disease
pathophys of spondylosis
spondylosis- age related degen of spine involving discs, vertbral bodies, facets
disc dehydration leads to loss of height which leads to more load through facet joints which can lead to OA
the OA can lead to osteophyte formation which can lead to neural compression
pathophys of HNP
degenerative- annulus becomes more brittle
The mechanical overload is usually flexion and rotation
can lead to neural compression either bi or unilaterally
leads to protective spasm and segmental instability
types of herniation
bulge
protrusion
extrusion
sequestration
Pathophys of OA
begins with mechanical stress which hinders the ability to repair
releases chondrocytes which release enzymes which break down type 2 collagen
cartilage becomes softer and more prone to sheer and bone becomes exposed leading to osteophytes, microfractures
the debris in joint leads to synovitis which causes pain aswell as bones
pathophys of RA
starts with genetics (HLA-DRB1) as well as smoking, and air pollution. Then there is a loss in immune tolerance
then the immune system starts attacking joints causing chronic synovitis and forms pannus which is an invassive tissue in joints
then cartalage desruction occurs due to loss of type 2 collagen
bone erosion occurs when synovium contcts bone
RA also argets lungs, heart, blood vessels
pathophys of PMR
inflamatiomn of synovial membrane, bursae bi laterally in hips and shoulders. the inflamation is non destructive
unknown trigger but causes release of macrophages possibly due to age related dysregulation
leads to morning stiffness over 45 mins difficulty moving from seated and pain that improves with movement
pathophys of AS
strongest risk is HLA-B27 gene
begins at enthesis due to mechancial stress leading to erosion at vertabral corners and osteoclast activation
then new bone forms at the entheses over time causing fusion of SIJ, Spine as well as loss of spinal mobility and hyper kyphosis
can be accompanied with IBD and psoraisis
pathophys of gout
starts with high levels of serum urate (hyperuricemia)
when uric acid is high it forms monosodium urate crystals with favoured factors being cold, dehydration and local trauma.
crystals deposit in, synovial fluid, cartalige
neutrophils ingest crystal leading to more inflamtion (redness, heat, swelling, pain)
flares resolve in 1-2 weeks
can form tophi which is large formatons of crystals
can form kidney stones
pathophys of septic arthritis
staph infection through blood, direct innoculation (surgery, injection) and contageous spread
neutrophils and macrophages release inflamatory markers leading to pain, heat swelling
cytokenes and enzymes damage articular cartalige and promote pus in joint and lead to irreversible cartilage destruction
pathophys of hyperparathyroidism
too much PTH which leads to bone fragility, nephrolithaisis
primary cause is from adenoma
secondary cause is chronic hypocalcemia leads to over compensation of PTH
tertiary cause is a longstanding secondary leads to it becoming autonomous
leads to fatigue, pancreatitis, pain, frqactures, mood changes
pathophys of hypoparathyroidism
defficeint PTH secretion- low calcium high phosphate
low calcium due to less release from the bone and low reabsorbtion in kidneys
5 causes
iatrogenic- post surgery like thyroidectomy
auto immune destruction
genetic- diGeorge syndrome
infilitrative- wilsons disease
hypomagnesaemia- impairs PTH secretion
can lead to tingling, cramps, seizues, soft tissue calcification
osteoporosis pathophysiology
Osteoporosis occurs when bone resorption exceeds bone formation
Oestrogen deficiency is a main cause because oestrogen inhibits resorption
oxidative stress- reactive oxygen impairs osteoblasts
epigenetics- DNA methylation alters osteoblasts and clasts
bone loss begins at around 35, so osteoperosis occurs
transient ischemia pathophysiology
starts with acute reduction in blood flow usually embolism, atheleroscelrsic plaque or systemic hypoperfusion
this leads the body to switch to anaerobic metabolism and drop in ATP production leading to angina, weakness, and transient focal deficits
blood flow is spontaneously improved leading to no cell death or permanent damage
but does signal underlying illness or disease
pathophys of parkinsons
starts with degen of dopaminergic neurones reducing dopamine use impairing initiation and control
next lewy body formation starts killing neurones
Microglia activation leads to chronic inflammation, worsening neuron loss
increase in vascular permiability allows harmful substances to enter the brain worening neuron loss further
The loss of dopamine leads to overactive indirect movements and underactive direct movements
pathophys of diabetes
Type 1 diabetes
autoimmune destruction of beta cells in the pancreas, leading to insulin deficiency, triggered by genetics
Without insulin, glucose can’t enter cells, leading to hyperglycemia. The body tries to get energy from lipolysis, which increases ketone production, leading to ketoacidosis
type 2-
Insulin resistance in muscles and the liver leads to overactive beta cells in the pancreas till exhaustion, causing hyperglycemia
lead to retinopathy, neuropathy, CHD, stroke, and peripheral vascular disease
begnin prostate hyperplasia
non-malignant enlargement of the prostate caused by hormonal changes and age related aleterations
Age-related hormonal shifts increase DHT and oestrogen
leads to growth factor dysregulation, leading to stromal hyperplasia
leads to chronic inflammation, fibrosis and remodelling
increased stromal size increases smooth muscle tonicity
leads to mechanical obstruction of bladder
tamulosin- relaxes smooth muscle
finasteride- DHT reduction
surgery
prostate cancer
starts in peripheral zpne luminal cells
driven by androgens, oestrogen imbalance chronic inflamation and gene mutations
progreses from PIN to adenocarcenoma then metastesise
eventually becomes castration resistance
Reading over 10 for psa is a cancer risk
treatment- hormone therapy, chemo, surgery
ALS
starts with TDP-43 agregation which impairs RNA process
leads to mitochondrial dysfunction which causes apoptosis pathways and precedes clinical weakness
excess glutamate leads to oxidative stress and neuronal death
MN rely on long distance transport protiens and ALS disrupts these leading to axonal degeneration
causes both UMN and LMN signs
endo
origins of ectopic tissue-
-menstural tissue refluxes through fallopian -tube to peritoneal cavity
- peritoneal cells transform to endometrial like cells under hormonal stress
-lymph and blood spread
immune dysfucntion allows for implanted cells to survive
excess oestrogen promotes proliferation and inflamation and progesterone reduction leads to persistent inflamation and reduced apoptosis
Neuroangiogenesis means new nerve and blood supply causes severe pain
asthma
chronic airway inflamation caused by infiltration of lymphocytes macrophages and neutrophiles
this causes bronchoconstriction where smooth muscle contracts due to irrtation by allergens, cold air and exercise leading to reduced airflow
mucus hypersecretion caused by goblet cell hyperplasia leading to increased mucus causes mucus plugging limintg airflow further
overtime the airway remodels due to smooth muscle hypertrophy and subepithelial fibrosis leading to less reversible obstruction
bone tumr types and causes and effects
osteosarcoma- comes from osteoblasts, produces immature osteoid which has high mitotic activity then osteoclasts are stimulated to destroy bone which can metastasise commonly in the lung
chondrosarcoma- comes from chondrocytes which produce cartalige matrix which is slow growing and destructive
ewing sarcoma- EWSR1-FLI1 fusion creating small round blue cell tumour which is highly agressive and causes bone destruction and creates huge inflamatory response
UC
abnormal inflammatory response of epithelial cells in rectum and colon only
begins with goblet cell depletion leading to thinner mucus layer and increasd epithelial apoptosis allowing bacteria to penetrate membrane triggering inflamation
neutrophils acumulate leading to cryptitis and cryptic abcesses
genetic risk only explains 8% of the disease, which is very environmentally based such as western diet, stress, quitting smoking
causes bloody diahorrea, urgency, abcesses,
chrons disease
chrons is a genetic and environmental disease which causes epithelial barrier damage affecting any part of gi tract
starts with NOD2 mutation leading to impaired bacteial sensing leading to immune system to not be able to handle normal immune function
reduced mucus production and latered bacterial adhesion allows bacteria to penertrate easier
macrophages respone abnormally and there is increased leukocyte adhesion causing inflamation which is patchy due to skip leisions, segmental and transmural leading to abcesses, and fibrosis of smooth muscle
triggered by smoking and ultraprocessed food
