Clinical conditions Flashcards
How is collagen linked to scurvy disease?
Fibroblasts secrete procollagen that forms collagen
Vitamin c is require to produce pro collagen
Vitamin c deficiency leads to poor wound healing and impaired bone formation
what is klinefelter syndrome and how is it caused?
triosomies 47,xxy
caused by meiotic non-disjunction
what is mosacism and how is it caused?
presence of two or more cell lines/ chromosomal populations in cells of an individual
caused by mitotic non-disjunction in zygote
what is Turner syndrome and why is significant?
monosomy 45,x
exception to be viable for life
what is huntington disease?
CAG repeats in HTT gene leads to polyglutamine repeats in Huntington’s protein
how is albinism inherited?
polygenic inheritance in a recessive manner
more than one gene responsible for presence of phenotype
how does sickle cell anaemia form?
mutation in HBB gene coding for beta haemoglobin
Single base substitution from A to T
Mutation of glutamate to valine
changes negative charged residues to neutral and hydrophobic on surface
so aggregation of molecules, change in shape in RBC, more prone to lyse, more rigid and less flexible
what causes Kwashiorkor?
insufficient protein intake
deficit in essential amino acids
young children displaced of breast milk
what are the symptoms of kwashiorkor?
bilateral pitting oedema hair changes flacky appearance of skin large, protuberant abdomen anaemia- cant make haemoglobin enlarged and fatty liver
what causes marasmus?
insufficient energy intake resulting in negative energy balance
nutrient deficiencies
severe malnutrition in children
what are the symptoms of marasmus?
muscle wasting
protuding ribs
diarrhoea or dehydration
-ve energy balance so fat store metabolism
muscle protein break down to release aa for gluconeogenesis
what is lymphadenopathy?
swelling and enlarged lymph nodes
can cause pain
can occur in all the nodal regions or affect lymphatic organs
what causes lymphadenopathy?
fighting infection- germinal centres fill with alot more lymphocytes
cancer metaphisise to lymph nodes via afferent lymphatics
lymphoma- malignancy(growth) of lymphoid tissue eg. hodgkins
describe the role of sentinel lymph nodes in metastatic cancer?
first set of lymph nodes to recieve lymph from area of primary tumour and first to swell
help with detection
describe the difference between primary and secondary lymphoedema?
primary- due to genetic inheritance to disease,
can onset within 2 years after birth(congenital) with age 2-35(praecox) or after 35 years(tarda),
absent or malformed lymph nodes/channels
secondary- due to cancer treatment, surgery, radiation therapy, infection and neoplasia,
obstruction of vessles, parasitic worms, pelvic masses
what is the treatment for lymphoedema?
manual lymphatic drainage
what is hyperkeratosis and how is it formed?
thickening of the outer layer of skin- large increase of keratin deposits(usually on palms)
can be painless
occurs due to inflammation and irritation in skin defences
what is albinism and why does it increase risk of skin cancer?
inability to make normal amounts of melanin- lack melanin
decrease in protection against UV and sun
what is the difference between psoriasis and eczema?
psoriasis- autoimmune disease, keratinised skin cells produce and replicate much faster, found on extensor parts of body, pitting in nail bed, dandruff, flares up due to stress, hormones and infection
eczema- chronic condition, dry, itchy skin and rash, found on flexor part of body, inflammatory response due to allergies and irritation
what is vitiligo?
long term condition
pale white patches develop on skin caused by lack of melanin pigment in the skin
varies from person to person
what is the difference between non-segmental and segmental vitiligo?
non segmental- symmetrical white patches appear on both sides of body, most common, auto-immune condition, t cells attack healthy melanocytes and kill them
segmental- the white patches only affect one area of the body, less common, ,caused by neuro chemicals released from nerve endings, melanocytes autolyse
what causes or increases risk of vitiligo?
non- segmental - family members have it, autoimmune conditions family history, presence of another autoimmune disease, melanoma or cancer of the lymphatic system
segmental- stress triggers, skin damage or exposure to dermatologic toxins
what is melanoma?
a type of skin cancer that can metastasise to other organs in the body
characterised by a new mole or change in a existing mole
what causes malignant melanoma?
sudden intense sunlight when abroad especially in people with pale skin and freckles
skin cells develop abnormally due to UV exposure
what is the difference between nodular and lentigo maligna melanomas?
nodular- changing lump on skin, black to red in colour, bleeding or oozing, develop on previously normal skin(head, neck, chest or back), faster-developing, grow downwards, more common
lentigo maligna- flat, develop sideways, slight larger, darker than a freckle, affect older people more
what causes psoriosis?
autoimmune disease
flared up by hormones, stress or infection
problems with immune system- t cells start to attack dividing cells
what is psoriosis?
fast production and replacement of keratinised skin cells
cells at surface lost very quickly
red, flaky, crusty patches
what is alopecia areata?
spot baldness
hair lost from some(scalp) or all areas of body
symptoms of psychosocial stress
what causes alopecia areata?
systematic autoimmune disease
body attacks own anagen(actively growing hair) and stops hair growth
genetic association with family inheritance
genetic risk factors with other autoimmune diseases eg type 1 diabetes, and celiac disease
which vitamins can cause bone instability?
vitamin D3- produces calcitrol, important for calcium absorpotion
vitamin C- synthesis of collagen
vitamin K and B12- synthesis of bone proteins
describe the features of bone affected by rickets and osteomalacia?
vitamin D deficiency poor calcium mobilisation low/ineffective mineralisation weakened bone development soft bones
what is the difference between osteomalacia and rickets?
rickets- in children, impaired mineralisation of cartilage growth plates, bowled legs, bone deformities and impaired growth
osteomalacia- impaired mineralisation of osteoid, increased osteoid, bone pain and tenderness
causes of osteomalacia and rickets?
vitamin D deficiency
due to inadequate intake, malabsorption or lack of sunlight exposure
describe the genetic basis of osteogenesis imperfecta?
mutation in COL1A gene
incorrect production of collagen 1 fibres
decribe the phenotypic changes of osteogenesis imperfecta?
weak bones
increased fracture risk
shortened height and stature
mainly neonates and children
describe the radiological and structural changes in osteoporosis?
associated with aging
incomplete filling of osteoclast resorption bays
loss of bone tissue- higher risk of fracture
irregular pattern
trabecular and cortical bone very thin
gaps in bone
list the most common risk factors for osteoporosis?
secondary osteoporosis…
drug therapy
weightlessness(space travel), malnutrition and prolonged immobilisation- affect bone remodelling
metabolic bone diseases eg hyperparathyroidism
explain the importance of osteoporosis as a risk factor for fractures in elderly?
primary type 1- in postmenopausal women, increase in number of osteoclasts, loss of oestrogen
primary type 2- in older men and women, loss of osteoblast function, loss of oestrogen and androgen
outline the cause of achondroplasia?
inherited mutation in the FGF3 receptor gene
FGF promotes collagen formation from cartilage
endochondral ossification affected
outline the characteristics of achondroplasia?
short stature
but normal sized head and torso
long bones cannot lengthen properly
describe the pathophysiology of myasthenia gravis?
autoimmune disease- neuromuscular
antibodies directed against ACh receptor- block
little or no ACh receptors
reduced number of endplate invaginations
reduced synaptic transmission
skeletal muscle weakness
describe the clinical feature of myasthenia gravis?
ptosis- dropping of the eyelid
state how neuromuscular transmission is disrupted in botulism?
toxin produced by clostridium botulinum bacteria
blocks neurotransmitter release at motor end plate
state the consequences of botulism?
don’t get muscle tone
non-contractile state of skeletal muscle- flaccid paralysis
what are the uses of botulism?
clinically treats muscle spasm
cosmetically reduces appearance of wrinkles
state how neuromuscular transmission is disrupted in organophosphate poisoning?
organophosphates inhibits function of ACh esterase(which is to stop signalling process by breaking down ACh)
increased ACh activity at neuromuscular junction
what are the symptoms of cholinergic toxidrome /organophosphate poisoning?
muscarinic symptoms SLUDGE Salivation Lacrimation Urination Defecation Gi cramping Emesis(vommiting)
nicotinic symptoms weekdays MTWTF Muscle cramps Tachycardia Weakness Twitching Fasciculations
explain the process and consequences of malignant hyperthermia?
severe reaction to anaesthetics- succinylcholine
autosomal dominant inheritance- RyR1 gene
males> females
massive contraction fasciculation
muscle rigidity- increase Ca2+ release
excessive heat and metabolic acidosis
increase muscle breakdown and hyperkalaemia(high blood k+ conc)
describe the pathophysiology of Duchenne muscular dystrophy?
inherited by X linked recessive pattern- boys mainly
mutation of dystrophin gene, so no dystrophin…
excess Ca2+ enter muscle cell, taken up by mitochondria, water follows, mitochondria burst, muscle cell burst(rhabodomyolysis), creatine kinase and myoglobin in high conc in blood
skeletal muscle symptoms and signs
muscle cells replaced by adipose tissue
what is troponin assay used for?
myocardial cell damage detection- cardiac ischaemia
smallest change in troponin levels indicate cardiac muscle damage- not proportional to degree of damage
must measure within 20 hours for accuracy
how is collagen linked to scurvy disease?
fibroblasts secrete procollagen that forms collagen
vitamin C is required to produce procollagen
vitamin C deficiency so poor wound healing and impaired bone formation
how is collagen linked to osteogenesis imperfecta?
abnormal type 1 collagen
manifests as blue sclera and bone malformation
what is amyloidosis?
misfolding of proteins results in formation of amyloid fibres with infiltrate organs and can lead to disease eg alzheimers
whats the difference between alpha and beta thalassemias?
a- decrease/absence of a chains in Hb, excess of b chains, form stable tetramers, symptoms before birth
b- decrease/absence of b chains in Hb, excess a chains, unstable, symptoms after birth
what is the cause and effects of ectopic pregnancy?
implantation at site not in uterine body- normally fallopian tube
can be life threatening if not treating quickly- rupture fallopian tube or internal bleeding
what is the cause and effects of placenta previa?
implantation in lower segment of uterine body- blocking cervical opening with the placenta
c- section required
can cause haemorrhage
describe systemic sclerosis?
excessive accumulation of collagen in organs
leads to hardening and impaired function
list the symptoms and signs of scurvy disease?
gum disease bruising of skin bleeding poor wound healing jaundice- yellowing of skin and eyes
describe the cause Marfans syndrome?
autosomal dominant disorder
fibrillin 1 gene is affected
elastic tissue is abnormal
describe the consequences of Marfans syndrome?
abnormally tall
exhibit arachnodactyly- spider like and long fingers, long limbs
frequent joint dislocation
at risk of catastrophic aortic rupture- aortic eneurysm
describe and explain ethlers-danlos syndrome?
deficiency in reticulin(type 3 collagen)- due to procollagen peptidase deficiency that causes tissues with high reticulin to rupture
causes unstable joints, flat feet and stretchy skin
why is acne caused?
blockage of pilosebaceous duct by sebum
explain the cause and symptoms of acromegaly?
excess growth hormone in adults after puberty
periosteal growth leading to thickening of bones
what is Barretts oesophagus- metaplasia?
Metaplasia- change of one type of differentiated cell to another
acid reflux from stomach changes normal stratified squamous cells of oesophagus epithelium into simple columnar with a mucous secreting function
describe and explain muscle atrophy?
destruction of muscle>replacement of muscle
due to denervation, misuse and age
describe and explain muscle hypertrophy?
replacement of muscle>destruction of muscle
increased work performed by muscle
leads to more mitochondria, glycogen, blood supply and proteins in muscle
describe the cause and effect of multiple sclerosis?
myelin sheath is removed from CNS axons and replaced by scar tissue (oligodendrocytes)
Axonal destruction & overgrowth of glial tissue
due to autoimmune attack(by T cells)
conduction of nerve impulse slowed
Relapsing and remission disease
Pregnancy tends to reduce symptoms and relapse
describe and explain the cause and consequences of tarui disease?
genetic defect
phosphofructokinase-1 enzyme is deficient
can’s catalyse the reaction of fructose-6- phosphate to fructose-1,6-biphosphate
inefficient pyruvate production
lack of lactate formation
describe what is meant by hypothyroidism?
underactive thyroid gland
decrease in T3 and T4 levels
increase in TSH
what is Hashimotos?
hypothyroidism
autoimmune disease blocking TSH receptors
antibodies in blood; anti-TPO and anti-TG
describe what is meant by hyperthyroidism?
overactive thyroid gland
increase in T3 and T4
decrease in TSH
what is grave’s disease?
hyperthyroidism
autoimmune disease activation of TSH receptors
antibodies in blood; TSI and anti-TSH which increase t3 and t4
what are the autoimmune features of graves disease?
exophthalmus- eyes putrude out
antibodies deposit glucosaminoglycans
thickening and redness of skin esp dorsal of foot
due to antibodies
how does TSI antibody cause hyperthyroidism?
mimics shape of TSH
competes with TSH to bind to TSH receptor
mimics TSH action
causes excess T3 and T4
how is hypo and hyper thyroidism diagnosed?
checking T4 and TSH levels
describe the symptoms of hyperthyroidism?
goitre diarrhoea sweating weight loss heat intolerance
why does goitre occur and what is it?
swelling of neck
follicles enlarge
describe the symptoms of hypothyroidism?
goitre dry skin weight gain cold intolerance tiredness depression
describe how hypothyroidism is treated?
oral thyroxine- increases T3 and T4 levels
increased iodine if necessary
describe how hyperthyroidism is treated?
carbimazole- prevents iodine being incorporated with thyroglobulin and thyroidectomy
radioactive iodine
what factors increase the risk of malignant melanoma?
genetic mutation
heritable deposition
What type of disease is sickle cel anaemia?
Autosomal recessive
What’s the most suitable was to get a newborns HBB gene for a genetic test?
PCR(part of) newborns HBB gene
Define lactic acidosis?
Build up of lactate in blood
Due to anaerobic respiration in low oxygen levels so pyruvate is converted to lactate
pH decreases, too much lactic acid
Explain why lactic acidosis may occur?
In strenuous excercise
Hearty eating
Shock
Congestive heart disease
What is lactose intolerance?
Caused by lactase deficiency- not producing enough lactase
Can’t digest lactose so it’s fermented by gut bacteria
Produce acids that iritate GI causing cramps, bloating and diarrhoea
Lactose in lumen of colon increases osmotic pressure, draw water out, diarrhoea
Explain the biochemical basis of galactosaemia?
Deficiency in..
Kinase: rare, galactose build up
Transferase: more common and serious, galactose and galactose-1-p build up, causes liver, kidney, brain and GI damage
What are the symptoms of galactosaemia?
Conversions of galactose to galactitiol uses NADPH causes cataracts
Galactose osmotic effects cause glaucoma
Depleted NADPH
Inappropriate disulphides bridge formation in proteins, loss of structure and function, aggregation, Heinz bodies
Increase in intraoccular pressure
Describe the clinical condition of glucose 6-phosphate dehydrogenase?
Inability to produce NADPH from NADP+ due to point mutation in gene coding for enzyme
Low levels of NADPH
Needed for reduction of oxidised glutathione back to active form- low levels
Oxidative damage to cells
RBC affected as only source of NADPH
Haemoglobin form Heinz bodies
Haemolytic anaemia
How does a vitamin C deficiency lead to defected collagen tissue?
in post translational modification of collagen
hydroxylation of lysine and proline by prolyl hydroxylase
requires vitamin C as a cofactor
hydroxylation increases H bonding- stabalises triple helix
Describe the 4 blood groups?
AB- co dominant, universal reciever O- homozygous recessive, universal donor A- heterozygous dominant B- heterozygous dominant use I as genotype
Describe what causes Ehlers-Danlos syndrome?
insufficient production of collagen type 4
connective tissue has a higher ratio of elastin than collagen
Describe the symptoms of Ehlers-Danlos syndrome?
stretchy skin
joint hypermobility
fragile skin that breaks and bruises easily
what is compartment syndrome?
muscles of limbs are separated by fascia
a build up of pressure in one or more compartments can push on structures in other compartments and compromise them
describe rhabdomyolysis?
muscle breakdown due to insufficient blood supply
release myoglobin and creatine kinase into blood
excreted via kidneys and makes urine dark
what is the role of growth hormones(gh) on bone abnormalities?
in adults- no epiphyseal growth plates so high gh effects bone width not length, increasing periosteal growth
excess gh- increase length of long bones, gigantism
lack gh- decreased epiphyseal cartilage deposition, pituitary dwarfism
what is the diagnosis clues of situs inversus and how is it caused?
heart on the right hand side of the body
immotile cilia, as during embryogenesis left and right programming is modulated by motile cilia.
if dont have motile cilia internal organs are on opposite sides
why is mucus thick and sticky in cystic fibrosis patients?
CTFR protein dosent release chloride ions, osmotic ion so water doesnt get released from epithelial cells, decrease in water in mucus so more thick and less lubricating
Describe how mutation can lead to hereditary spherocytosis?
Mutation in abjuring, spectrum, band 3, and band 4.1
Loss of functional RBC cytoskeleton
Less efficient spherical shape
Decrease in SA:volume
More fragile, unable to buffer physical forces
Osmotically fragile, shorter life cycle
Increased rates of splenic destruction, causes haemolytic anaemia
What are the symptoms of a defective mitochondrial fatty acid transport system?
Poor excercise tolerance
Large amounts of triacylglycerides in muscle cells
When does conc of ketone bodies increase in circulation?
In starvation
Untreated type 1 diabetes
Can cause ketoacidosis, smell of acetone on breath by lungs excretion
What triggers relapse of multiple sclerosis?
Infection Stress Heat Insomnia Poor diet Pack of sun exposure
What are the main symptoms of muscular sclerosis?
Spastic paralysis of both legs Fatigue Vision problems Shakin or tingling of limbs Muscle spasms/stiffness/weakness Cognitive dysfunction Mental or sexual health issues Difficult eating or talking
How is multiple sclerosis diagnosed?
Identify lesions(white areas on a t2 mri scan of brain and spinal chord) Has no cure
What are the similarities between Gillian-barré syndrome and multiple sclerosis?
Similar initial symptoms like numbness, muscle weakness, pain and loss of balance and co-ordination
Both autoimmune T cells destroy myelin sheath
Delayed neurotransmission
What are the differences between Gillian-Barré syndrome and multiple sclerosis?
GB is curable wheras MS isn’t
GB symptoms are bilateral and effect both sides of body at same time
GB also causes inability and difficulty in breathing- life threatening
What’s a splenectomy and it’s effects?
Surgeons remove spleen
Bone marrow and liver take over function of destroying old RBCs
Increases risk of infection by encapsulated bacteria and malaria
What is a splenomegaly?
Enlarged spleen due to response to localised infection(eg lymph nodes) or systemic infection(eg glandular fever or malaria)
How do skeletal muscle respond to injury?
Connective tissue endomysium and perimysium divide and differentiate into myoblasts that fuse to form muscle fibres
Satellite cells produce muscle fibres
How does smooth muscle respond to injury?
Proliferation and differentiation of primitive smooth muscle into new muscle fibres
Hep does cardiac muscle respond to injury?
Regenerates after injury in children
Can’t regenerate in adults- replaced by scar tissue
What’s myopathy?
Disease of muscles that is not associated with the nervous system or emotional disorder
What are some used of botulinum toxin covered by the NHS?
Sever underarm sweating
Overactive bladder syndrome
Blepharospasm- uncontrollable blinking
What is muscle atrophy?
Wasting of muscle due to lack of use
Muscle shrinks as muscle fibres die
What is muscle hypertrophy?
Increase size of muscle fibres due to excercise
What is hyperplasia?
Increase in number of myofibrils in each muscle fibres due to exceed use
When does muscle hypertrophy and hyperplasia occur?
Skeletal muscle- regular excercise they become stronger and larger
Smooth muscle- during pregnancy due to growing fetid
Cardiac muscle- to compensate for reduced blood flow
Why does rhabdomyolysis occur?
Inherited Eg lactose dehydrogenase deficiency or duchenne muscular dystrophy
Lipid lowering drugs eg statins
Why is urine brown in rhabdomyolysis
Myoglobin and creative kinase in urine
A sign of kidney damage
What is creatine kinase used for?
Blood assay to diagnose myocardial infarction, tissue damage, muscular dystrophy, rhabdomyolysis or kidney injury
What are the consequences of rhabdomyolysis?
Myoglobin release- kidney damage
Sodium release- tissue swelling and cell death as increases ca2+ conc outside sacroplasmic reticulum
ATP release- loss of energy, Ca2+ influx, disintegrated cells
Potassium release- electrolyte inbalance, prevents electrical conduction of cardiomyocyte, death
How is lactate blood conc controlled
Heart concert it back to pyruvate and CO2
Deliver and kidney convert it back to glucose in glucogenesis
What is the consequence of lactose dehydrogenase deficiency
Pyruvate can’t be converted into lactate to regenerate NAD+
Explain the key role of pyruvate dehydrogenase?
Converts pyruvate to acetyl coA
Irreversible- release co2
Sensitive to B1 vitamin
PDH Deficiency- pyruvate build up, lactic acidosis
What is the normal temperature range, hypothermia and hyperthermia?
40-42 hyperexia 42-38 hyperthermia 37.5- 36.5 normal 36.5-32 mild hypothermia 32-28 severe hypothermia <28 no vital signs
What is therapeutic hypothermia?
Comatose cardia arrest- neuroprotective
Neonatal encephalopathy
What is rigor?
Heat accompanied with shivering
What is a febrile seizure?
Seizure associated w high temperature without any serious health issues
Affects 6months- 5years
What is normal pH and how is it measured?
PH 7.35-7.45
pH= -log[H+]
Death <6.8 or >8
Acidosis if <7.35 causes headaches, confused, tremors, coma
Caused by metabolic acidosis- lactic acid build up or respiratory acidosis- hypo ventilation
What are the causes of oedema?
Increase in hydrostatic pressure
Decrease In oncotic pressure in capillaries
Increase in oncotic pressure in interstitium
Impaired lymphatic drainage
What are the symptoms of dehydration?
Adults: dry mouth, thirsty, fatigue, low urine output, concentrated urine
Elderly: confusion, low bp
Baby: sunken eye, cold skin
What’s water intoxication?
Too much water
Can cause reacted in [Na+] blood plasma
Muscle weakness, seizure, coma, unconscious
What is pheochromocytoma?
A tumour in chromaffin cells(adrenal medulla sympathetic post ganglionic neurones) resulting in increase adrenaline production
What is refeeding syndrome?
Feeding too much too quickly after starvation- someone with marasmus or kwashiorkor
Lack of nutrients and proteins for long time so live can’t synthesise albumina and lipoproteins, down regulating enzymes in urea cycle
Proteins can’t be digester completely
Toxic levels of ammonia build up in body
Why is someone with refeeding syndrome at risk of cardiac arrhythmias?
High glucose consumption Cause high insulin spike Moves potassium into cells Hypokalemia Leading to cardiac arrhythmia
Which step of collagen synthesis is affected in scurvy?
Hydroxyl action of proline and lysine groups
What is osteoarthritis and it’s effects?
Age related mechanical failure of articulate cartilage
Joint stiffness & pain
Cartilage degenerates, narrowing of joint space and bone rubbing against bone
Define and describe rheumatoid arthritis?
Autoimmune disease that attacks joints
Inflammation of synovial membrane and thickening of joint capsules
Damage to bone and cartilage
Joint pain and stiffness- takes longer to relieve stiffness than in osteoarthritis
Swelling and redness
Describe the normal process of fracture repair?
Haematoma formation- inflammation, phagocytes and osteoclasts remove damage
Fibrocartilogenous formation- soft callus, blood vessels infiltrate, granulation tissue develops, fibroblasts produce collagen, chondroblasts produce hyaline
Bony callus formation- endochondral ossification, replace hyaline cartilage with cancellous bone, trabeculae develop
Bone remodelling- cancellous bone to compact bone
Describe how long bones develop?
Endochondral ossification
Hyaline cartilage model
Collar of cortical bone around shaft formed
Nutrient artery penetrates cartilage and generates spiracles, supplying osteogenitor cells and generates primary ossification centres
Cartilage forms epiphyseal growth plates
Epiphysis develop secondary ossification centres and ossify
What is compartment syndrome?
Muscles segregated into compartments by fascia
Trauma to one compartment- internal bleeding- increased pressure- exerts pressure on other compartments
Results in: deep constant pain, paresthesia, compartment feeling firm and tight , swollen red shiny skin
A genetic defect in fibrilin1A causes what?
Abnormal elastic tissue
Elastin fibres made incorrectly
A genetic defect in collagen1A1 gene causes what?
Osteogenesis imperfecta
What does a genetic defect in FGFR3 cause?
Achondroplasia
What is an example of a disease cause by triosomy?
Down syndrome
Triosomy 21
What does a genetic defect in beta haemoglobin cause?
Sickle cell anaemia
What can cause rhabdomyolysis?
Infection, toxins, statins, crush or blast injury, long term immobilisation like stroke
Or inherited duchenne muscular dystrophy and lactate dehydrogenase deficiency
What type of inheritance does haemophilia a follow?
X linked recessive
What inheritance is sickle cel anaemia?
Autosomal recessive
Describe Cushing’s syndrome?
Excess cortisol
Excessive breakdown of proteins
Weakened skin structure
Striae formation
How is ALT and AST used clinically?
Blood tests
If high in blood suggests liver damage such as viral hepatitis, autoimmune liver diseases or toxic injury
what is hypoxia?
oxygen deprivation
what are the 4 causes of hypoxia?
1 hypoxaemic- arterial content of O2 is low
2 anaemic- decreased ability of haemoglobin to carry O2
3 ischaemic- inturruption to blood supply
4 histiotoxic- inability to utilise oxygen in cells due to disabled oxidative phosphorylation enzymes
what is phenylketonuria(PKU)?
phenylalanine metabolism defect autosomal recessive deficiency in phenylalanine hydroxylase accumulation of phenylalanine in blood accumulation of phenylketones
what are the symptoms of phenylketonuria?
severe intellectual disability development delay microcephaly(small head) seizures hypopigmentation mental retardation
what are the treatments for phenylketonuria?
strictly controlled low phenylalanine diet
avoid artificial sweeterners
avoid high protein food such as meat, milk and eggs
what are the clinical signs of hypercholesterolaemia?
1 xanthelasma- yellow patches on eyelids
2 tendon xanthoma- nodules on tendon
3 corneal arcus- obvious white circle around eye
what are hyperlipoproteinaemias?
raised plasma level of one or more lipoprotein classes
caused by- overproduction or over removal
6 types
what is the treatment for hyperlipoproteinaemias?
first; diet- reduced cholestrol and saturated lipid intake or increase fibre intake
excercise, stop smoking
drugs; satins- reduce cholestrol synthesis by inhibiting HMG-CoA reductase eg. atoravastatin
bile salt sequeastrants- forces liver to produce bile acids using more cholestrol
why does splenomegaly occur?
spleen growth…
1 back pressure- portal hypertension in liver disease
2 over work
3 extramedullary haemopoeisis
4 expanding as infiltrated by cells- cancel cells
5 expanding as infiltrated by other material- granulomas
how do you examine the spleen?
start to palpate right iliac fossa
feel for spleen edge to hit hand on inspiration(breath in)
feel for splenic notch
measure in cm from costal margin in mid clavicular line
what is the main consequence that occurs due to splenomegaly?
hyperslenism
low blood counts as pooling of blood occurs in the enlarged spleen
risk of rupture of spleen as no longer protected by rib cage- avoid contact sports and vigorous excercise
what causes hyposplenism?
lack of functioning spleen
- splenectomy
- sickle cell disease
- gastrointestinal diseases eg. crohns disease
- autoimmune disorders eg. rheumatoid arthiritis
what will be seen on a blood film from someone with hyposlenism?
howell jolly bodies- red blood cells that contain DNA remnants because spleen is not functioning as normal so hasnt removed them
what are patients with hyposplenism at risk of?
risk of sepsis from encapsulated bacteria
eg, streptococcis pneumonia, haemophilus influenza and meningocuccus
what would expect the packed cell volume of an anaemic patient be?
depressed hematocit %
less RBCs
what would expect the packed cell volume of an polycythemic patient be? how can u decide which type it is?
elevated hematocit %
more RBCs
true= RCC elevated pseudo= RCC normal
what is spondylolisthesis?
an anterior displacement of the vertebrae above on the vertebrae below
caused by a disconnection of the vertebral body from the vertebral arch
what symptoms can spondylolisthesis cause?
some people are assymptomatic
most complain of some dicomfort raging from occassional lower back pain to incapacitating mechanical pain, sciatica from nerve root compression and neurodenic claudation
what are5 red flag symptoms of cauda equina syndrome?
bilateral sciatica perianal numbness painless retention of urine faecal/urinary incontinence erectile dysfunction its a surgical emergency
how does neurogenic claudication present?
pain in legs whilst walking
what is neurological claudication?
compression of nerve roots, venous engorgement of nerve roots during excercise, reduced atrial flow, pain and paresthesia
is relieved by rest and by spine flexion
which vertebral level should a lumbar puncture needle be inserted? why?
L3/L4
causa equina- mobile spinal roots, less chance of neurological damage
what is sciatica?
pain caused by irritation or compression of one or more of the nerve roots that contribute to the sciatic nerve- L4-S3
describe the 4 staged of intervertebral disc herniation?
1 disc degeneration; disc dehydrate and buldge with age
2 prolapse; nucleus pulposus slightly impinges into spinal canal
3 extrusion; nucleus pulposus breakes through annulus fibrosus
4 sequestration; nucleus pulposus seperates from main body of disc, enters spinal canal
what is cauda equina syndrome?
usually secondary to prolapse disc
canal- filling disc compressing lumbar and sacral nerve roots
what is the benefit of the transverse pericardial sinus?
seperates aorta and pulmonary trunk from benous inflow
allow surgeons to get behind aorta and pulmonary trunk, enables you to clamp aorta
why does a sudden build up of fluid in pericardial sac prevent filling in diastole?
outer fibrous pericardium layer cant expand causing fluid to compress the heart
what can be heard and felt over a stenosed vessel?
turbulent flow= noisy, korotkoff sounds
thrill- felt, bruit- heard
what is the cardiac output of a 70kg man at rest?
5L/min
CO=SV X HR
what causes the first heart sound?
in isovolumetric contraction
atrialventricular mitral valve shuts
what causes the secound heart sound?
in isovolumetric relaxation
semilunar atrial valve shuts
where can QRS be seen in cardiac cycle?
isovolumetric contraction, ventricle depolarisation
where can p wave be seen in cardiac cycle?
atrial contraction, firing of SA node causes atrial depolarisation
where can t wave be seen in cardiac cycle?
reduced ejection, ventricles repolarise
what can cause pericardial collection or effusion?
viral and bacterial infection
stab wound
what is pericardiocentesis?
a procedure to remove blood or fluid from pericardial sac
what is a patient likely to have with a C4/5 prolapsed disk?
compression of c5 spinal nerve- emerge above
reduced sensation of later aspect of upper arm
what is the most common sites for a herniation of an intervertebral disc?
L4/5 L5/S1
what is a paracentral herniation?
slipped disc that compresses traversing nerve root- exits below
what are the 4 signs of osteoarthritis on x ray?
Reduced joint space
subchondral sclerosis
bone cysts
osteophytes
why is posterior dislocation of the hip most common?
weak ischiofemoral ligament posteriorly
what are the risk factors for primary osteoarthritis?
no known cause
age, female, ethnicity, genetics, nutrition
what are the risk factors for secondary osteoarthritis?
obesity, trauma, malalignment, infection, inflammatory
what are the symptoms of OA?
deep anchoring joint pain worsened with use, reduced ROM and crepitus(grinding), stiffness during rest, swelling and tenderness
what is the pathology of OA?
exce4ssive loading of joint and damage to articular cartilage
increased proteoglycan synthesis by chondrocytes
flaking and fibrilation of cartilage
erosion of cartilage- loss of joint space
what does altered joint biomechanics lead to?
Vascular invasion and increased cellularity of subbchondralar bone(sclerosis)
cystic degeneration of bone( cysts)
osseous metaplasia of connective tissue(osteophytes)
treatment of OA of hip?
weight loss
activity modification
stick/walker
physiotherapy
analgesia
anti-inflammatory (NSAIDS eg. ibuprofen and COX-2 inhibitors)
nutritional supplements
corticosteroids injections
viscosupplementation- hyaluronic injections
surgery- total hip replacement
why are intracapsular fractures of the neck of femur worse?
disrupt retinacular arteries(branches of circumflex femoral arteries) , artery of ligamentum terees cant supply demand
avascular necrosis of bone
increased risk w displaced fracture
what is the treatment for a displaced intracapsular NOF fracture?
hemiarthoplasty- replace femoral head
total hip replacement
what is an extracapsular NOF fracture?
interochanteric or subtrochanteric
intact retinacular artery supply
Symptoms of hip/NOF fractures?
reduced mobility- inability to bear weight on limb
pain felt on hip, groin or knee
what does a NOF fracture look like on examination?
hip shortened, aBducted and externally rotated
whats the most common cause of hip dislocation?
can be congenital or due to trauma
knee hitting dashboard in road traffic collision
what does a posterior hip dislocation look like on examination?
shortened,
aDducted
medial rotation(gluteus medius and minimus)
sciatic nerve palsy maybe present
what does a anterior hip dislocation look like on examination?
externally rotated
abducted
slightly flexed
what does a central hip dislocation look like on examination?
fracture dislocation always
femoral head palpable
intrapelvic haemorrhage
what are the complications of hip dislocation?
foot drop sciatic nerve injury post traumatic OA avascular necrosis infection
how do you locate the correct site for gluteal intramuscular injection?
palm of hand on greater trochanter of femur
thumb toward inguuinal region, index finger towards anterior superior iliac crest
fingers make a V
inject into gluteus medius
what is a febrile seizure?
a convulsion in a young child caused by a spike in body temp often from an infection not in CNS
when is the major peroid of congenital malformation in embryonic development?
embryonic peroid
3-8 weeks
what is situs inversus?
complete mirror image viscera
due to immotile cilia
explain how acute inflammation can cause appendicitis?
accumulation of bacteria and exudate inflammed appendix blocked lumen faecolith- solid lumps of faeces increased pressure causes perforation(bursting) presents w abdominal pain
explain how acute inflammation is linked to bacterial meningitis?
inflammation of meninges
compresses brain against skull
describe what an abscess is?
accumulation of dead and dying neutrophils
with associated liquefactive necrosis
describe the effects of an abscess?
compression of surronding structures
pain and blockage of ducts
name 3 disorders of acute inflammation?
1 Hereditary angio-oedema
2 Alpha-1 antitrypsin deficiency
3 Chronic granulomatous disease
what are the clinical signs of acute inflammation?
Rubor- redness Calor- heat Dalor- pain tumor- swelling loss of function
what are the 3 nuclear changes seen under a light microscope during cell injury?
pyknosis- shrinkage of nucleus and chromatin
karyorrhexis- fragmentation
karyolysis- dillusion of nucleus
what are the causes of infarction?
infarction= reduced arterial blood suplly, causes necrosis
athlerosclerosis
twisting
compression
occlusion by thrombosis or thromboembolism
what is ischaemic- reperfusion injury?
blood flow returned to damage tissue that isnt necrotic yet, worsens damage
what are the 4 types of hypoxia?
hypoxaemic- too low oxygen conc in arterials
anaemic- haemoglobin cant carry oxygen
ischaemic- interruption to blood supply
histiotoxic- cant use oxygen, non functioning oxidative phosphorylation enzymes
what type of hypoxia does carbon monoxide poisoning cause?
histiotoxic
name the causes of cell injury?
hypoxia trauma radiation poisons alcohol drugs microorganisms hypersensitive or autoimmune reactions genetic abnormalities
what is shock?
clinical syndrome caused by circulatory failure
what process cuases swelling in acute inflammation?
net flow of fluid our of bloodvessels forming exudate in tissues
explain how alcohol oxidation can cause liver damage?
build up of NADH- lactic acidosis, gout, hypoglyceamia
build up acetly CoA- fatty liver
explain the mechanism of hangover?
limiting factor is aldehyde dehydrogenase
excess alcohol consumption- build up of acetaldehyde
acetaldehyde is toxic and longterm exposure causes hepatitis and cirrhosis
describe and explain how alcohol dependence is treated?
disulfiram
inhibits aldehyde dehydrogenase
acetaldehyde not converted to acetate- accumulates
gives hangover symptoms- discouraging alcohol consumption by classical conditioning
which diseases can oxidative stress form?
cardiovascular rheumatoid arrthiritis alzheimers crohns COPD cancer parkinsons
what are the 3 enzymes that could be deficient in galactosaemia?
galactokinase
UDP- galactose epimerase
uridyl transferase
describe the pathophysiology of galactosaemia?
deficiency in enzymes
increase aldose reductase activity
build up of galacititol
consume excess NADPH
what are the symptoms of galactosaemia?
cataracts hepatomegaly and cirrhosis seizure, brain damage renal failure hypoglycaemia
describe the pathophysiology of G6PDH deficiency?
decrease Glucose 6 phosphate dehydrogenase activity
less NADPH
need NADPH for GSSG(oxidised glutathione) to GSH(reduced glutathione)
less GSH- cant protect against oxidative stress
describe the symptoms of G6DPH deficiency?
oxidative stress
lipid peroxidation- cell membrane damage, mechanical stress
protein damage- aggregates of cross linked hb- heinz bodies
haemolysis
explain the clinical relevance of using creatinine as a marker?
creatine and creatine phosphate breakdown to release creatinine in muscle
amount of creatinine in urine suggests an estimate for muscle mass
can also indicate kidney function- urine
describe the cause urea cycle defects?
autosomal recessive generic disorders
deficiences in one of the enzymes- partial loss of function
leads to… hyperammonaemia and accumulation of urea cycle intermediates
how is urea cycle defects managed?
low protein diet
replace aa in diet w ketoacids
what are the symptoms of a defective urea cycle?
ammonia toxicity
children can die
vomitting, lethargy, mental retardation, seizures, comma
describe the heel prick test?
screening for every new born in the uk
looks for genetic defects in amino acid metabolism
like sickle cell disease, cystic fibrosis, congenital hypothyroidism, phenylketonuria, homocystinuria
describe the pathophysiology of phenylketonuria(PKU)?
autosomal recessive- chromosome 12
deficiency in phenylalanine hydroxylase- cant convert phenylalanine to tyrosine
accumulation of phenylalanine- transamination to phenylketones
phenylketones accumulate in urine-musty smell
describe the symptoms of PKU?
lack of tyrosine production- cant synthesise catecholamines hormones, melanin and proteins severe intellectual disability development delay microcephaly(small head) seizures hypopigmentation
what is the treatment for PKU?
low phenylalanine diet
high tyrosine diet
avoid artificial sweetners
avoid high protein food eg. eggs, meat and milk
describe what homocystinurias is?
cant breakdown methionine
excess homocysterine and methionine
autosomal recessive- defect in crystathionine b synthase
treat with low methionine diet, avoid milk, meat, cheese, eggs, nuts
explain the process of paracetamol overdose?
produce NAPQI
causes oxidative damage to hepatocytes- lipid peroxidation, damage to proteins and DNA
treatment= acetylcysteine, replenishes GSH levels
why during a myocardial infarction can a person feel pain from both sides sometimes?
cardiogenic fields from embryonic development are bilaterally symmetrical and are on both sides
what feature of the left atrium can causes stasis of blood?
during atrial fibrillation blood collects in left auricle(small pouch formed from primitive atrium) whcih causes clotts
describe the first and second heart sounds?
first sound- lup, louder and longer
second sound- dub, shorter and quite
what causes the 3 shunts of the heart to shut at birth?
foramen ovale- as left atrial pressure exceed right atrial pressure
ductus venosus- umbilical cord cut, no umbilical vein
ductus arteriosus- first breath, increase oxygen pressure
how do you classify congenital heart disease?
acyanotic…
left to right shunts, obstuctive lesions
blood in pulmonary circulation is full saturated so p02 is maintained
eg. aortic stenosis, ASD, VSD
cyanotic…
complete right to left shunts
systemic oxygen low
eg. tetralogy of fallot, transposition of great arteries
describe the haemodynamic effects of atrial septal defects?
1 increased pulmonary blood flow
2 RV volume overload
3 pulmonary hypertension- rare, pulmonary oedema
4 eventual right sided HF
describe the haemodynamic effects of ventral septal defects?
1 left to right shunt
2 LV volume overload
3 pulmonary venous congestion
4 eventual pulmonary hypertension
membranous portion of septum fails to develop properly so primary interventricular foramen still open
Describe the pathophysiology and consequences of patent ductus arteriosus?
ductus arteriosus dosen’t shut with first breath
blood from aorta can enter pulmonary artery at high pressure
high volume of blood at pulmonary artery, increases preload
right sided heart failure- acyanotic blood fully saturated w oxygen
describe atrial ventricular septal defects?
caused by inproper development of endocardial cushions
hole in heart, with one common atriaventricular valve
common in downs syndrome
describe aortic/ pulmonary stenosis?
acyanotic
semi lunar valves dont develop properly eg aortic valve is bicuspid
hypertrophy and so heart failure
describe coarctation of the aorta?
narrowing of the aorta
radio femoral delay, strong radial pulse, weak femoral pulse
high bp
describe the pathophysiology of tricuspid atresia?
tricuspid valve fails to form
blood cant flow from right atrium to ventricle
r to l atrial shunt of entire venous return
blood flow to lungs VSD
oxygenated and deoxygenated blood mix in left side of heart so blood being pumped to rest of the body has low p02- cyanotic(r to l)
describe the pathophysiology of transposition of the great arteries?
septum dosent spiral
no oxygen- cyanotic
aorta on right side(rv) and pulmonary trunk on left(lv)
two circulations completely seperate, ASD and PDA shunts needed
bidirectional shunting
medical emergency, require prostagladins to maintai PDA to allow some oxygen in
describe the group of cardiac defects present in tetralogy of fallot?
1 over riding aorta- very large, most blood passes through aorta
2 pulmonary stenosis- pulmonary valve and artery narrowed, less blood
3 ventricular septal defect- right must pass from right to left ventrical
4 right ventricle hypertrophy- generate more force to pump blood through stenosed pulmonary artery
describe the pathophysiology of hypoplastic left ventricle?
mitral or artrial valves stenosed- less blood to LV underdeveloped Left Ventricle ascending aorta very small RV supports cirulation right to left shunt
explain how alcohol metabolism can damage the liver?
acetaldehyde produced from alcohol by alcohol dehydrogenase is toxic
increases acetyl coA, increase fatty acid synthesis and so TAG
oxidation to acetaldehyde and then acetate produces NADH
descreased NAD+/NADH ratio, favours formation of TAGs, reduced capactiy of liver to transport
TAGs accumulate- fatty liver
describe how disulfiram causes hangover symptoms?
inhitbits aldehyde dehydrogenase
acetaldehyde accumulation when drink alcohol
what are the 2 features that make LDL associated with atherosclerosis?
long lived- not efficiently cleared by liver
more susceptible to oxidative damage
Describe how raised serum LDL causes atherosclerosis?
oxidised LDL is recognised and engulfed by macrophages
foam cells(macrophages containing lipids) accumulate in intima of blood vessels to form fatty streaks
evolve into atherosclerotic plaques
if plaques grow blocking lumen- angina
if plaques rupture- thrombosis- stoke or MI
describe what is familial hypercholestrolaemia?
absence or deficiency of functional LDL receptors
elevated LDL and cholestrol in plasma
signs…
tendon xanthoma
xanthelasma
corneal arcus
describe what is dyslipoproteinaemias?
defect in plasma lipoprotein metabolism
primary- family inborn
secondary- diet, drugs
describe the classifications of hyperlipoproteinaemias?
raised level of one or more plasma lipoproteins
type1- defective lipoprotein lipase, chylomicrons present
type 11a- coronary artery disease association, defective LDL recpetor
type 11b- coronay artery disease association
type 111-raised IDL and chylomicrons, defective apoprotein, conory artey disease association
type 1v- associated w coronary artery disease
typev- raised chylomicrons and VLDL, associated w coronary artery disease
describe the treatment of hyperlipoproteinaemia?
diet and life style modification
reduce cholestrol and TAG intake
statins- inhibit HMG coA reductase, reduce cholesterol synthesis, increase lipoprotein lipase expression
what does deficiency in each of the lipid soluble vitamins cause?
A- dry eyballs, no tears
D- rickets, weak/soft bones
E- nerve and muscle damage, no protection against oxidative stress
K- defected blood clotting
why cant acetyl coA be converted to glucose in humans?
pyruvate dehydrogenase enxyme is irreversible so cannot form pyruvate and therefore cant be converted to glucose
explain why defective lecithin-cholestrol acytltransferase enzyme is a problem?
LCAT usually maintains lipoprotein structure
deficiency causes unstable and abnormal structure lipoproteins due to destruption in ratio of surface to core lipoproteins
general failure in lipid transport, lipid deposits and athlerosclerosis
why is the knee in flexion less stable?
curved surface of femoral chondyles and tibial plateau, small area of articulation
can only get rotation when flexed- more movement
what characteristic is seen with a superior gluteal nerve injury?
weakness is adductors of hip- gluteus medius and minimus
Trendelenburg Sign
what is the clinical significance of the blood supply to the menisci?
from periphery
blood supply decreases with age, centralminisci is avascular by aduthood
impaired healing after trauma
describe the mechanism of locking the knee?
internal(medial) rotation of femur 5 degrees on tibial plateau, cruciate ligaments tighten
describe the mechanism of unlocking the knee?
popliteus contracts, rotates femur laterally
what is the ‘unhappy triad’ of injuries?
ACL- anterior cruciate ligament
MCL- medial collateral ligament
medial miniscus
describe a ‘housemaids knee’?
pre-patellar bursitis, inflammation on front of knee, kneeling
describe a ‘clergymans knee’?
infra-patella bursitis, around tibical tibia, kneeling in a more erect position
why is it more common for the patella to displace laterally?
q angle- direction of pull of quadracepts is lateral on patella
how do you find the femoral pulse?
mid inguinal point- halfway between ASIS and pubic synthesis
which 3 x rays do we use to view the knee?
anterior posterior
lateral
patella axial- skyline
what are the common causes of femoral shaft fractures?
in young adults and children- high velocity trauma
site- proximal, mid shaft or suprachondylar
what are common complications of femoral shaft fractures?
tense swollen thigh
blood loss- hypovaleamic shock
traction splint
treeat with - surgical fixation
what is the usual mechanism of injury for tibial plateau fractures?
high energy injury
axial loading with varus or valgus angulation
describe the features of tibial plateau fractures?
articular cartilage of tibia damaged unichondylar(affect one condyle)- lateral tibial condyl more common or bicondylar(effect both condyles) post traumatic OA joint surface reduction instability
what is the usual cause for patella fractures?
direct or indirect injury
patients aged 20-50 years
on examination what is commonly seen for patella fractures?
palpable defect in patella
if extensor mechanism is disrupted the fracture completely splits patella- unable to do straight leg raise
how are patella fractures treated?
if displaced- reduce and surgical fix
if undisplaced- splint and protect
what is the difference between subluxation and dislocation?
subluxation is partial displacement
dislocation is complete displacement
what is the most common cause of patella dislocatiojn?
usually lateral dislocation
due to trauma- twistin action in slight flexion
athletic teenagers
describe the predisposing factors of patella dislocations?
weakness of quadriceps- VMO(vastus medicalis obliquus) ligamentous laxity(loose) shallow trochlear groove long patellar ligament previous dislocations
what is the treatment of a patella dislocation?
reduce and immobolise
physiotherapy to strengthen VMO
wwhat is the mechanism of injury in meniscal tearss?
most common knee injury
sudden twisting motion of wight bearing knee in high flexion
how does a patient present with meniscal injuries?
intermittent, localised pain
restricted motion
swelling
mechanical symptoms- locking, jamming, catching
how do you treat a meniscal injury?
MRI- usually sagital
if traumatic- mecisectomy or meniscal repair
if degenerative/ chronic process- leave alone and rehabilitate
what is the mechanism of injury for collateral ligament injuries?
contact/ direct blow- sporting injury
medial collateral- valgus strain, more common
lateral collateral- varus strain
describe the presentation and treatment of collateral ligament injuries?
pain + instability
associated w unhappy triad injuries
brace and rehabilitate
what is the mechanism, presentation and treatment of anterior cruciate ligament injury?
mechanism- non contact injury
presentation- feel ‘popping’, swelling, recurrent instability(giving way), anterolateral rotatory instability, lachmans test
treatment- rehabilitation and/or surgical reconstruction
what is the mechanism, presentation and treatment of posterior cruciate ligament injury?
mechanism- ‘dashboard injury’, knne isflexed and experiences large force, fall onto knee, hyperextension
treatment-brace and rehabilitation
describe the mechanism of injury for knee dislocation?
uncommon
high energy trauma
must have 3 out of 4 ligaments ruptured
describe a complication of knee dislocation?
popliteal artery tethered in popliteal fossa, angiogram (mra)to check for vascular injury
what is an effusion?
accumulation of fluid
describe acute knee effusions?
haemarthrosis- blood in the joint, due to ACL rupture
lipo- haemarthrosis- blood and fat in joint, fracture
what is bursitis?
inflammation of bursae
describe what a suprapatellar bursitis is?
common w knee effusion…
OA, rheumatoid arrthiritis, infection, gout
describe what semimembranosus bursitis is?
popliteal(bakers) cyst
swelling in poploteal fossa
what is Osgood-schlatters diseas(OSD)?
inflammation of apophysis of patella ligsment into tibial tuersosity
pain and swelling- athletic teenagers
rest and ice
describe the typical symptoms of knee OA?
swelling
stiffness
knee pain
describe knee OA?
high prevelance
fluctuating symptoms– provoked by activity, relieved by rest
predispositions- age, sex(female), weight, post trauma
treatment- strengthening excercises, analgeasia, weight loss, surgery
describe the pathophysiology of septic arthritis?
invasion of joint space by micro-organism
recent surgery?
bacterial cause- most common= straphylcoccus aureus, articular cartilage damage
risk factors- extreme age, diabetes mellitus, RA, immunosuppression, intravenouse drug use
how does a patient present with septic arthritis?
pain swelling redness + warmth reduced ROM non wight bearing
describe the treetment of septic arthritis?
aspirate to confirm diagnosis and define organism
antibiotics and surgical washout
what is the tried of symptoms patients with septic arthritis present w?
fever
pain
reduced ROM
what are the complications of chronic inflammation?
tissue destruction
excessive fibrosis- deposits of collagen eg. gall bladder
impaired function- eg. inflammatory bowel disease
atrophy- eg. atrophis gastritis
what is cirrhosis?
end stage liver damage
fibrosis and attempted regeneration
whqt are the 4 causes of liver cirrhosis?
1 alcohol
2 hepatitis
3 drugs and toxins
4 fatty liver disease
compare and contrast the 2 types of inflammatory bowel disease?
crohns... affects all of GI skip lesions- discontinous transmural- affects full thickness less like to rectal bleed
ulcerative collitis... large bowel only continous mucosa and submucosa only more likely to have rectal bleeding
describe the symptoms of anaemia?
shortness of breath, palpitations, headaches, claudation, angina, weakness, confusion
describe the signs of anaemia?
pallor, tachycardia, systolic flow murmur, tachypnoa(high RR), hypotension
define anaemia?
a haemoglobin concentration lower than normal range
describe the causes of microcytic anaemia?
T halassamia A naemia of chronic disease I ron deficiency L ead poisoning S ideroblastic anaemia
small RBCs
descrie the causes of normocytic anaemia?
anaemia of chronic disease
blood loss
sickle cell disease
bone marrow failure
describe the causes of macrocytic anaemia?
vitamin B12 deficiency folate deficiency liver disease alcohol toxicitiy myelodyplasia
describe how b12 and folate deficiency causes megloblastic anaemia?
required for DNA synthesis
so cytoplasm matures faster than nucleus
cell division delays, cytoplasm just gets bigger, larger RBCs, large immature nucleus
what can b12 and folate deficiency macrocytic anaemia develop into?
sub acute degeneration of the spinal chord
pancytopenia
all low blood count- neutropenia and thromboytopenia
what does megaloblastic anaemia look like on a bloodfilm and investigations?
tear drops schistocytes macrocytic RBCs hypersegmented neutrophils low HB MCV raised low erythrocytes, reticulocytes, leukocytes and platelest raised serum ferritin, LDH and bilirubin
describe percinicous anaemia?
decrease or abscent intrinsic factor, insufficient absorption of B12 reserves, autoimmune
causes vitamin b12 deficiency
describe how you treat b12 deficiency?
if percincous anaemia- hydroxycobalamine intramuscular for life(van cause hypokalaemia)
other causes- oral cyanocobutamine
change diet- eat meat, fish, milk, cheese and eggs
describe how you would treat folate deficiency?
oral folic acid- in pregnancy too
change diet- eat more vegetables
describe the causes of iron deficiency?
1 insufficient iron from diet 2 malabsorption of iron 3 bleeding- heavy menstration 4 increased requirement- pregnancy 5 anaemia of chronic disease
what are the epithelial changes you can get with iron deficiency?
angular cheilitis
koilonychia(spoon nails)
glossitis- glossy tongue with atrophy of lingual papillae
describe the pathophysiology of anaemia of chronic disease?
inflammatory condition(eg. rheumatoid arthritis) causes immune cells to release cytokines(eg.IL6)
cytokines inhibit erythropoeitin production by kidneys
cytokines increase production of hepcidin by liver
inhibits ferroportin
decreases iron release from reticular endothelial system and decrease iron absorption in gut
plasma iron reduced
inhibition of erythropoeisis in bone marrow
describe how iron deficiency anaemia is diagnosed?
low MCV-microcytic anaemia low MCHC low serum ferritin microcytic and hypochromic RBCs anisopoikocytosis- change in size and shape pencil cells target cells
reduced plasma ferritin
describe how you treat iron deficiency?
diet alterations oral iron supplements intramuscular iron injedctions IV iron blood transfusion
describe why excess iron is dangerous?
exceed binding capacity of transferrin- haemosiderin deposits in organs and promotes free radical formation…
hydroxyl and hydroperoxyl radicals cause lipid peroxidation, damage to proteins and DNA
describe the pathophysiology of hereditary haemochromatosis?
autosomal recessibe mutation in HFE gene loss of negative influences onf iron uptake- no hepcidin and increase affinity of transferrin receptor excess iron damage to organs
describe the symptoms and tratment of heriditary haemochromatosis?
liver cirrhosis, diabetes mellitus,hypogonadism, cardiomyopathy, increased skin pigmentation
venesection
describer transfusion associated haemeosiderosis?
excess iron
repeated blood transfusions, treat with desferriociamine
slate grey colour of skin, same symptoms of HH
which 2 enzymes can cause defects in red cell metabolism and there3fore anemia?
G6PDH deficiency- limits NADPH cant reform GSH, less protection against oxidative stress, heinz bodies, haemolysis, spleen destroys RBCs
pyruvate kinase deficiency- final enzyme in glycolysis,, deficient in ATP cant do glycolysis, undergo haemolysis
why are reticulocytes useful for evaluating anaemia?
immature RBCs- slightly larger than erythocytes so increase MCV
shows if bone marrow is working- would ecpect an increase in number if bone marrow working to produce more RBCS
if suffering from haemolytic anaemia what cells would you expect to see on a blood film?
schistocytes
describe what causes sideroblastic anaemia?
iron is present but cant be incorporated into haemoglobin
see ringed sideroblasts on blood film
heriditary or accquired by myelodyplastic syndromes
describe the causes of splenomegaly?
enlarged spleen
1 back pressure- portal hypertension in liver disease
2 over work
3 extramedullary haemopoeisis
4 expanding as infiltrated by cells- cancer
5 expandind as infiltrated by other cells- granulomas
how would you exam splenomegaly?
palpate in right iliac fossa
measure and feel for splenic notch
describe the risks of splenomegaly?
hypersplenism, low blood counts due to pooling of blood
risk of rupture- no longer protected by rib cage, avoid contact sports
describe hyposplenism?
reduced spleen function
increased risk of sepsis by encapsulated bacteria
Holly jolly bodies(nuclear remenants in RBCs on blood film
describe the causes of hyposplenism?
sickle cell anaemia
GI disease
splenectomy
autoimmune disease
describe what effect b12/folate deficiency has on the nervous system?
folate deficiency- in pregnancy causes neural tube defects
vit b12 deficiency- associated w focal demyelination
serious condition- subacute combined degeneratrion of the cord
what is the normal range for blood pressure?
diastolic- 80-60 mmHg
systolic- 120-90 mmHg
list the organs or tissues that can be damaged by hypertension?
heart- LV hypertrophy arteries- aneurysms kidneys- damage due to neuphrosclerosis retina- arteries narrow, haemorrhage brain- stroke, atherosclerosis
list some modifiable risk factors for developing hypertension?
obesity high salt diet liw in fresh fruit and veg excess alcohol lack of excercise stress
describe the effects of pherapeutic dose if adrenalin on vasomoto tone?
circulating adrenaline preferentially binds to B2 reeptors on smooth muscle- vasodialation
noradrenalin from sympatheitc or higher dose of adrenaline(pherapeutic dose)- activates A1 receptors- vasoconstriction
describe the drugs you can use to treat hypertension?
ACE inhibitors, Renin inhibitors or Angiotensin receptor bocker….
block actions of angiotensin II- stop vasoconstriction, stops aldosterone release and the reabsorption of Na and water
angiotensinogin by renin to angiotensin 1
angiotensin I by ACE to angiotensin II
diuretics…
increase na and water excretion by inhibiting NA/CL cotransporter so reduce circulating volume
vasodialators…
L type calcium blockers- decrease Ca, relax
a1 receptor blocker- reduce sypathetic
describe the side effect of ACE inhibitors?
ACE also breakdown bradykinin(vasodialator) to peptide fragments causing vasoconstriciton
if inhibited build up of peptide fragments, cough in lungs
which electrode is the grounding electrode?
right leg electrode- black
how many electrodes are there and how many leads/views are there in an ECG?
10 electrodes- 6 chest, 4 limbs
12 views/leads- limb leads I, II, III, aVF, aVL, aVR, v1, v2, v3, v4, v5, v6
what is the positive electrode for each of the leads?
I= leftarm II and III= left leg avL= left arm aVR= right arm aVF= left leg
describe when you would get an upward deflection on an ECG?
wave of depolarisation towards + electrode
wave of repolarisation away from + electrode
describe when you would get a downward deflectioon on an ECG?
wave of depolarisation away + elctrode
wave of repolarisation towards + electrode
what does the amplitude of deflection depend on?
size of muscle changing potential
how fast
how directly wave is traveling towards electrode
explain the shape of the ECG looking at the apex of the heart(lead II)?
p wave- atrial depolarisation
QRS- ventricle depolarisatio
q- left to right at right angle to left leg + electrode so small down wards
r- depolarisation towards left leg
s- depolarisation around apex
Twave- repolarisation of ventricles
wave of repolarisation away from + electrode so upward deflection
describe what is meant by sinus rythm on an ECG?
if every QRS complex has a p wave before
describe the abnormalities on a ventricular ectopic beats ecg?
wider QRS
describe the abnormalities on a atrial fibbrulation beats ecg?
no p waves
wavey baseline
irregular R-R intervals
describe the abnormalities on a ventricular fibrilation beats ecg?
no coordination
quiver wigley line
describe the abnormalities on a first degree heart block ecg?
PR interval longer than 0.2 seconds
what is a normal PR INTERVAL on an ECG?
0.12-0.2 secs
describe the abnormalities on a second degree heart block- mobitz type 1 ecg?
successively longer PR intervals until one QRS is dropped
describe the abnormalities on a second degree heart block- mobitz type 2 ecg?
PR intervals dont get longer, one QRS dropped
describe the abnormalities on a third degree heart block ecg?
wide QRS
bradychardia
describe the abnormalities on a bundle branch block ecg?
W or M shape
wide QRS with little notch
describe the changes with hypokalaemia on an ECG?
low conc K+ extracellular- hyperexcitabilty increase amplitude and width of p wave longer PRI flattened and inverted t wave ST depression prominant u waves
describe the changes with hyperkalaemia on an ECG?
high conc K+ extracellular- RMP less negative
loss of p wave
tall, tented t waves
fiden QRS- sin wave
where is the subtalar joint and whats its purpose?
between calcaneous and talus of foot
allow inversion and eversion
how are the phalanges orientated in the foot?
first big toe only has 2 phalanges
all the rest have 3 phalanges
what are the functions of the foot arches?
allow weight to be transferred around foot
gives stability
why is the ankle more stable in dorsiflexion than plantarflexion?
trochlea of talus is wider anteriorly than posterior
describe movement of the ankle joint?
only dorsiflexion and plantarflexion as ligaments limit movement medially and laterally and joint capsule weakest anterior and posterioir
weaker ligaments laterally than medially(deltoid ligaments), inversion has greater mobility than eversion
where does the sciatic nerve bifocate?
at apex of popliteal fossa into tibial nerve and common fibular nerve
what are the 4 pilses of the lower limb and how do you examine them?
femoral artery- mid inguinal point, halfway between ASIS and pubis symphysis
popliteal artery- bend knee, thumbs on tibial tuberosity, midline of popliteal fossa
posterior tibial-posterior to medial malleoulus, invert foot
dorsalis pedis- dorsum of the foot, lateral to tendon of extenser hallicus longus
describe what is comp0artment syndrome?
muscle compartment seperated by fascia, trauma to a fascia compartment may lead to haemorrhage or oedema, causing a rise in intra-compartmental pressure
describe the clinical signs of compartment syndrome?
severe pain in limb, excessive for degree of injury
not relieved by analgesia
pain worsened with passive stretch of muscles
perform surgical decompression
what are the short and long term consequences of compartment syndrom?
short term- decreased muscle perdusion, ischaemia, rhabdomyolysis, acute kidney injury
longterm- necrotic muscle, volkmanns ischaemic contracture
why is it important to consider combodities with a fracture patient?
can significantly impact healing time eg, someone with diabetes is double
what makes an ankle fracture unstable?
if has ruptured of broken 1 bone and 2 ligaments
descrie what a talus shift is?
disruption of any two medial or lateral ligaments
ankle mortise is unstable and widens so talus can move medially or laterally
unstable ankle fracture
how do you treat stable ansd unstable ankle fractures?
stable- aircast boot or fibreglass cast, low case of secomndary complications, can weight bare safely
unstable- surgical stabilisation
whats the mechanism of injury for ankle fractures?
inversion or eversion
describe what is a ankle sprain?
ligaments fail first
partial or complete tear of one or more ligament
usually anterior tibiotalar ligament
inversion injury effecting plantar flexion and wightbearing
in a severe ankle sprain why do you find sometimes an avulsion fracture of the fifth metatarsal tuberosity?
fibularis brevis tendon is attached to a tubercule on the base of the 5th metatarsal
inversion injury- 5th metatarsal under tension and pull off fragment of bone
describe an achilles tendon rupture?
middle aged
explosive excercise, kicked on back of heel
vascular watershed- thinner and less vascularity so more common site of injury
describe signs and symptoms of achilles tendon rupture?
- sudden, sever pain at back of ankle
- sound of loud pop
- palpable depression in tendon
- initial pain and swellin, bruising
- cant stand on tiptoe
thompson’s test(simmonds)
positive test for achilles tendon rupture- squeeze calf and foot dosent automatically plantarflex
MRI or ultrasound
how are achilles tendon ruptures treated?
conservatively
describe the 4 lesser toe(little toes 2-5) deformities?
claw toe- neurological abnormality, can be a secondary condition to eg. diabetes or rheumatoid arrthritis
hammer toe- idiopathic, zig zag bend, hallux valgus
mallet toe- idiopathic, walk on nail
curly toes- in children, normally go with age
describe hallux valgus?
type of bunion- big toe deviation away from midline
middle aged females, genetic factors, laxity and shoe wear(heels)
unattractive, and can be painful
treat- change shoes, surgery
describe hallux rigidus?
type of bunion- OA of 1st MTPJ
presents as pain and lump over joint
conservative management, painkillers, steroid injections, activity modifications
what are the 4 arthritis surgical treatments?
1 osteotomy- realignment
2 excisiion athroplasty- remove
3 arthrodesis- fusion
4 arthroplasty- replacement
describe OA of ankle?
usually secondary- post traumatic or inflammatory
treat with athrodesis(fusion), can use arthroplasty(replacement)
describe flat foot?
= pes planovalgus medial arch of foot collapsed foot ang;ed in valgus formation mainly assymptomatic children normal
describe achilles tendonopathy?
degenerative, overuse and strain, obesity and diabetes
pain and stiffness of achilles tendon- thickeni9ng and swelling
worsened w activity
what is the difference between fexible and rigid flat feet?
flexible- no medial arch, valgus formation when standing; on tip toes have medial arch and normal alignment
rigid- tarsal coalition and abnormal, when on tip toes no medial arch and valgus alignment
describe flat foot(planovalgus) adult onset?
change in foot shape, pain, middle aged females, tibialis posterior dyfunction
treat- insoles, physiotherapy
operation if dont get better- reconstruction
describe how diabetes can cause foot problems?
loss of sensation die to peripheral neuropathy- continue to weight bear worsening problem
ischaemia due to peripheral artery disease and microvascular disease
immunosupression due to poor glyceamic control can lead to foot ulcers and infections
describe charcot arthopathy?
associated with poorly controlled diabetes
destruction of bone joints ans soft tissue, usually ankle and foot
neuropathy- lack of pain so worsen injury
soft bone and loss of bone stock
rocker bottom could beseen
how to treat and prevent diabetic foot problem?
diabetic foot screening- check feet, sensation, callouses and perfusion
tight glyceamic control- prevent neuropathy and vascular disease, and maintain immune system
what are the 5 important attributes for a normal gait?
stability in stance foot clearance during swing phase pre-positioning for initial contact adequate step length energy conservation
how do we conserve energy with our gait?
minimise of excursion of centre of gravity
control momentum
transfer energy between body segments
phasic muscle atrophy
describe antalgic gait?
trys to reduce pain 'limp', uneven gait shorten stance phase on affected leg short swing phase on unaffected leg lack body weight shift to affected leg use walking stick on unaffected leg- to reduce weight on afffected leg
describe trendelenburg gait?
hip aBductor weakness(gluteus medius and minimus)
pain, neurological damge and trauma
pelvis drops on unaffected side in stance phase
can compensate- torso swings to affected side
‘wadling’
describe hemiplegic gait?
paralysis of one side of the body
eg. from stroke, cerebral palsy or trauma
spasticity(continous contraction) of affected side
flexed upper limb, extended lower limb
short step unaffected leg, circumduction affected leg
describe diplegic gait?
spasticity of both lower limbs in cerebral palsy scissoring tight muscle groups- psoas, aDductors, hamstrings and calf ankles plantar flexed forefoot initial contact
describe high steppage gait?
weakness of ankle dorsiflexion- ‘foot drop’
due to sciatica(L4 dorsiflex), common peroneal nerve palsy, neuromuscular disorders
toes hanging down
excessive hip flexion affected side
foot slap
describe parkinsonian gait?
neurological disorders- parkinsons reduction in dopamine short steps hard to initate movement- lean forward shuffling forward flexed no arm swing
describe ataxic gait?
three causes…
proprioceptive- loss of awareness of joints
cerebellar disease-inherited, sensory or intoxication
vestibular
broad base
‘reeling’
inco-ordination
arms balancing
describe the difference of healing with primary or secondary intention?
primary- incised wound, opposed edges, minimal clott and granulation tissue, fibrous repair, less scar
secondary- tissue loss, unapposed edges, alot of clott and granulation tissue, scar forms, takes longer
describe the complications of fibrous repair?
excessive wound contraction from myofibroblasts
loss of function
overproduction of scar tissue- keloid scars
fibrous adhesions form- block tubes
disruption of tissue relationship with organs
wound dehiscence- insufficient fibrosis
what are the 3 functions of granulation tissue?
fills the gaps
angiogenesis- cappilaries supply oxygen and nutrients
contracts and closes- prevent infection
describe alport syndrome?
inherited x linked disease type IV collagen abnormal chronic renal failure neural deafness eye disorders
describe the pathophysiology of sickle cewll anaemia?
autosomal recessive, abnormal HbS
mutate b globin, glutamine to valine now uncharged hydrophobic outer RBC
low O2 state RBCs polymerise and form sickle shape, loose elasticity and deformable- vasoclusion
acute chest pain
describe the clinical manifestations of sickle cell anaemia?
vasooclusion causes
acute chest pain, joint damage- avascular necrosis, chronic kidney damage
anaemia- shorten RBC lidespan, haemolytic crisis 20-30 days
Jaundice and gallstones- increased billirubin, chronic haemolysis
splenic atrophy- infarction, infectrion by encapsulated bacteria
end organ damage - O2 deprivation
describe the difference between sickle cell disease and thalasseamia?
sickle cell- abnormal Hb due to mutation in b chain
thalassaemia- reduced Hb due to reduced epression in a or b chains
explain the haematological abnormalities that come with alpha and beta thalasseamia trait?
heterozygous
can be assymptomatic, or mild anaemia
explain the haematological abnormalities that come with alpha and beta thalasseamia major?
homozygous
severe anaemia
a- all genes in a deleted- tetramers of a globin, unable to deliver oxygen, excess y globin
b- transfusion debendent
describe the causes and consequences of heridetary spherocytosis?
autosomal dominant
mutation in spectrin, ankyrin band 3 or protein 4.2
less flexible, form spherocyte, reduced lifepan
consequences…
anaemia, jaundice, howell jolly bodies, spleenomegaly
what are the 4 main complications of heriditary spherocytosis?
megoblastic anaemia
aplastic crisis
haemolytic crisis
pigment gall stones
describe the causes and consewuences of pyruvate kinase deficiency?
inherited- autosomal recessive
deficient in pk
consequences…
can catalyse last step of gycolysis
no ATP, na/k/atpase pump stops and loose k+ watermoves out, cells shrink, cell death and haemolytic anaemia
describe the causes and consequences of G6PDH deficiency?
x linked recessive inherited
consequence…
cant produce NADPH, less production against oxidative stress, dont maintain reduced glutathione, damaged rbc digest y spleen, increase billirubinb
name the 4 types of myeloproliferative neoplasms?
1 polycytheamia vera- excess erythrocytes
2 essential thrombocytheamia- excess megakaryocytes and platelets
3 primary myelofibrosis- pancytopenia
4 chronic myeloid leukaemia- excess granulocytes
describe the different types of polycytheamia vera?
relative- decrease in plasma volume
absolute- increase in erythrocyte number
primary- abnormality in bone marrow, mutation in gene for Janus kinase 2
secondary- increased erythropoeitin, csan be due to tumour, hypoxia or renal disease
describe the clinical features of polycytheamia vera?
thrombosis haemorrhage headaches- dizziness plethora burning in hands and feet pruritus(itching) splenic discomfort gout arrthritis
manage by venesection and CVS RISKS
DESCRIBE THE CUASES of essentialb thrombocytopenia?
primary- originates in bone marrow, mutations in JAK2 and CALK
secondary- extrinsic stimulus
redistributional- platelets move from splenic pool to bloodstream
describe common symptoms of essential thrombocytopeni?
burning hands and feet thrombosis numbness of extremities headaches distribution in hearing and vision
describe the causes and symptoms of myelofibrosis?
mutation, reactive bone marrow fibrosis, scar tissue
mobolisation undergo extramedullary erythropoeisis
splenomegaly, hepatomegaly
tear drop rbcs
fever, weight loss, bruiing ad fatique
describe the causes and symptoms of chronic myeloif leukaemia?
unregulated growth og myeloid cells, accumulation of mature granulocytephilidelphia chromosome recipricol translocation
clinical features
high WBC count
hyperviscous blood
splenomegaly
describe the function of JAK2 ?
tyrosine kinase receptor
mutated in most myeloproliferative neoplasms
multipotent stem cells survive longer and proliferate more eg. polycythemaia vera
describe what is petechiae?
a symptom of severe thrombocytopenia(low platelets)
a small red or purple spot on the skin caused by a minor bleed from a broken capillary
describe the function of tumour necrosis growth factors?
promotw fibroblast migration and proliferation
describe the formation of scar?
bleeding and hoemeostasis
inflammation - phagocutpsos of necrotic tissue debris
proliferation- angiogensis, and granulation tissue
remodelling- muturation of fibrose scar
what 4 factors activate platelets?
collagen surfaces
ADP
thromboxane A2
thrombin
describe the action of platelets?
adhesion- von willebrand factor on subendothelial basement membrane
secrete factors from alpha and dense platelet granules that aid clotting
aggregate to form platelt plug
swell and change shape into sticky, spiny spheres
how does aspirin decrease platelet aggregation?
inactivated cycloxygenase that makes thromboxane A2
what triggers the intrinsic pathway?
exposed collagen surface with blood vessel daqage
contact activator
what triggers the extrinsic pathway?
damaged endothelial release thromboplastin
tissue factor
describe the different anti-coagulation tests?
APTT- intrinsic pathway,
PT- extrinsic pathway,
TCT- final step, fibrinogen to fibrin by thrombin
describe the results of anti-coagulation tests?
prolonged APTT- deficiency in factor VIII, IIX, IX, XI, intrinsic pathway
prolonged PT- deficiency in factor VII, extrinsic pathway
prolonged PT + APTT- factors X, V, thrombin and fibronogen
PT expressed as INR- INR above 1 slow clotting- warfarrin
prolonged bleeding time- deficient platelt aggregation
describe the pathophysiology of Von Willebrands disease?
inherited bleedind disorder, autosomal dominant VWF is deficient or abnormal can undergo normal functions.... - asist in platelet plug formation - stabalise factor VIII(8)
describe the clinical manife3stations of Von Willebrands disease?
bleeding time and APTT raised- defected inntrinsic pathway
spontaneous bleeding from muccous membrane
decrease platelt function and adhesion
excessive bleeding from wounds
menorrhagia(heavy menstaul bleeding)
normal no. of platelets but prolonged bleeding time
describe the different types of Von Willebrands disease?
type 1+3- reduced quantity of circulating VWF
type 2- qualitive defects, multiple subtypes of VWF(2a) vWF expressed in normal amounts but dosent function properly
describe the difference between haemophilia A + B?
haemophilia A…
factor VIII(8) deficient
intrinsic pathway
life threatening bleeding, spontaneous haemorrage, trauma haemorrhage, petechaie absent
both…
X linked recessive(effects men more)
prolonged PTT, normal PT
haemophilia B... factor IX(9) extrinsic pathway increased risk of bleeding treat with infusions of recombinant factor 9
describe thrombocytopenia?
deficiency in platelets in blood due to bleeding into tisues, bruising and slow clotting after injury
- low platelet count
- prolonged bleeding time
- normal PT and APTT
presents.. spontaneous mucosal bleeding, purpura, petechia
describe thrombophillia?
inherited or accquired defects in homoestasis
increased risk of thrombosis (DVT)
describe the pathophysiology of Disseminated Intravascular Coagulation (DIC)?
excess activation and consumptio of coagulation factors and platelets leading to multiple microthrombi forming in circulation
RBC sheared and damage passing through occlused vessels- anaemia
consumes platelts and fibrin
activates fibrinolysis
when actually need clott, haemorrhage- anaemia
triggered by infection, malignancy and massive trauma
describe the symptoms, signs & management of DIC?
symptoms and signs... haemorrhage, tissue hypoxia and infarction nucleated, immature RBCs schistocytes low platelets raised D dimers low fibrinogen at risk of gangrene and renal failure
treatment…
treat underlying cause
transfusion of platelts and clotting factors
anticoagulants
describe the causes of thrombocytopenia?
1 decreased production- marrow dysplasia/infiltration, infection, druga
2 increased consumption- immunological destruction, or non immune eg. DIC
3 sequestation- enlarged spleen
4 dillutional- massive blood transfusions
describe how aspirins works?
irreversibly inactivates cyclooxygenase-1, so thromboxane A2 not made, decreased platelet aggregation, no platelt plug formed
anti-coagulant used after MI or Stroke
describe how Heparin works?
anti-thrombogenic
forms irreversible complexes with antithrombin III, activating it, decrease thrombin formation
uses…
low MR, used against an to treat thrombosis
iV or subcataneously given
describe how Warfarin works?
interferes with vitamin K metabolism- factors II, VII, IX, X, protein C + S
oral medication
againnst and treat thrombosis
name the natural anti-coagulants?
antithrombin III, protein C + S
work by opposing formation of fibrin
describe how filters work to prevent thrombus formation?
pulmonary emboli specifically
put umbrella shape filter in inferior vena cava
which 3 factors will increase the risk of thrombus forming?
Virchows triad
1 change in Vascular wall(endothelial damage)
2 change in blood flow(stasis, turbulent, laminar)
3 change in blood components(hypercoagulability)
describe the stucture of a thrombi?
laminated structure
lines of Zahn- in arterial thrombi(blood flow)
why do you have increased risk of DVT in lower limbs during pregnancy?
stasis due to pressure on large veins of pelvis by gravid uterus
hypercoaguble blood
blood isn’t flowing so not laminated, no ligns of zahn
describe the steps of thrombi formation?
1 platelets catch in crevices
2 platelets agggregate and stick on vessel wall
3 haemostasis fibrinogen binds platelets together and traps RBCs
4 more blood flows, platelets join and aggregate- white layer of platelets
5 RBCs get caught and aggregate- red layer of fibrin and RBCs
6 process repeats to form laminar
describe the 5 outcomes of thrombosis?
1 lysis- breakdown of thrombus, most favourable- blood flow restablished
2 propagate- progressive spread of thrombus
- distal in arteries, proximal in veins
3 organise- fibroblasts act on thrombus and lay down scar tissue, lumen still obstructed due to fibrotic scar
4 recanalisation- one or more channels fromed through thrombus, blood flow incompletely re-established
5 embolism- part of thrombus break off and travel through blood stream, lodging at a distant site
describe what an embolism is?
sudden blocking of a vessel, at a distant site from origin
majority are thromboemboli
