MSK, Genetics, Heam Flashcards
What causes klinefelters syndrome
When a male has an additional X chromosome
-so they are XXY
Give 6 Features of klinefelters syndrome (9)
- taller height
- wider hips
- gynocomastia
- small testicles
- weaker muscles
- reduced libido
- infertility
- shyness
-subtle learning difficulties
Mx of klinefelters
No treatment
- testosterone injections
- advanced IVF techniques
-breast reduction surgery
MDT input
-speech and language therapy
-occupational therapy
-physiotherapy for muscles
-educational support for learning difficulties
What is there an increased risk of in klinefelters (4)
-breast cancer in males
-osteoporosis
-diabetes
-anxiety and depression
How is Down’s syndrome caused
Three copies (trisomy) of chromosome 21
What features are common for people with Down’s syndrome
-hypotonia
-brachycephaly - small head and flat back
-short neck
-short
-flattened face
-prominent epicanthic folds
-single palmar crease
-upward sloping palpebral fissures
Complications associated with Down’s syndrome
- learning disabilities
- recurrent otitis media
- deafness
- visual problems
- hypothyroidism
- cardiac defects - PDA, ASD, VSD
- leukemia
- dementia
What are the antenatal tests offered to women for Down’s syndrome in the foetus
ALL women are offered screening
Combined test - 1st line As most accurate 11-14 weeks gestation
Triple test - performed between 14-20 weeks gestation
Quadruple test - performed between 14-20 weeks gestation
What does the combined test consist of?
-ultrasound - measuring nuchal translucency (thickness of back of foetus neck should be less than 6mm)
-maternal blood tests
Beta HCG - higher result mean higher risk
Pregnancy associated plasma protein A - lower result indicated a greater risk
What is the triple test for Down’s syndrome
During 14-20 weeks gestation involves:
-BETA HCG - higher means greater risk
-Alpha feta protein - lower means greater risk
-serum oestriol - lower result indicates greater risk
What does the quadruple test for Down’s syndrome measure
Same as triple test
Beta HCG
Alpha feta protein
Serum oestriol
+
Inhibin A - higher means greater risk
How can you test for Down’s syndrome antenatally (in the womb)
Chronic villus sampling - can only be done before 15 weeks
Amniocentesis
Mx of Down’s syndrome
management would involve members of the multidisciplinary team
E.g
-GP
-paediatrician
-SALT
-physiotherapy
-optician
-ENT specialist and audiologist
-social services
-cardiologist
What regular follow up investigations are important for children with Down’s syndrome
-regular thyroid checks
-ECG
-Audiometry for hearing impairment
-eye checks
What is turners syndrome
When a female has a single X chromosome sp they are 45 X0 (0 is the empty space)
Features of turners syndrome
-short **
-webbed neck**
-cubitus valgus
-high arching palate
-downward sloping eyes with Ptosis
-broad chest and wide spaced nipples
-underdeveloped ovaries
-late puberty
-infertility
What is cubitus valgus
Abnormal feature of elbow. Forearm angled away from body when elbow extended out
Mx of turners
No cure
-growth hormone therapy for shortness
-oestrogen and progesterone to help female sex characteristics
-fertility treatment
Give 6 Associated condition with turners syndrome
-recurrent otitis media
-recurrent UTI
-coarctation of aorta
-HTN
-Hypothyroidism
-obesity
-diabetes
-osteoporosis
-learning disabilities
What is Prader willi syndrome
Genetic condition caused by the loss of functional genes on the proximal arm of chromosome 45 inherited from the father
What are 6 features of prader willi syndrome
-constant insatiable hunger
-poor muscle tone as an infant (hypotonia)
-learning disability
-hypogonadism
-softer and fairer skin
-almond eyes
-strabismus
-narrow forehead
-downturned mouth
-thin upper lip
Management of prader willi syndrome
-growth hormone to improve muscle development
Supportive
-dietician - normal calorie intake
-education support
-physio
-psychologists
What is noonan syndrome
Genetic condition usually autosomal dominant associated with multiple genes
Features of noonan syndrome
Short stature
Broad forehead
Downward sloping eyes with ptosis
hypertelorism (wide space between the eyes)
Prominent nasolabial folds
Low set ears
Webbed neck
Widely spaced nipples
What are the associated conditons with noonan syndrome
-CHD particularly Pulmonary valve stenosis, ASD
-cryptorchidism
-learning disability
-lymphoedema
-increased risk of leukaemia & neroblastoma
What is angelman syndrome
Genetic condition caused by the loss of function of the UBE3A gene on chromosome 15 inherited from the mother
What are the three characteristic features of angelmans syndrome
-fascination with water
-Happy demeanour
-widely spaced teeth
What gene and chromosome is affected in angelmans syndrome
UBE3A gene on chromosome 1
Give 7 features of angelmans syndrome
-delayed development
-severe delayed speech abscence
-inappropriate laughter
-microcephaly- small head
-epilepsy
-abnormal sleep patterns
-ADHD
-Ataxia
-wide mouth And spaced teeth
-water fascination
-happy demenour
Mx of angelmans syndrome
NO CURE needs MDT approach
-parental education
-social support
-educational support
-physio - for ataxia
-occupational therapy
-Psychology
-anti epileptic mediation
What is Williams syndrome
A genetic condition caused by random deletion affecting the genetic material on one copy of chromosome 7.
Features of Williams syndrome, including the main three
-broad forehead
-starburst eyes
-flattened nasal bridge
-long philtrum
-small chin
-sociable and trusting personality
-wide mouth and widely spaced teeth
Associated conditions with Williams syndrome (4)
-hypertension
-hypercalceamia
-supraclavicular aortic stenosis
-ADHD
Mx of Williams syndrome
MDT approach
-SALT
-ECGs and BP monitoring to monitor for aortic stenosis
-low calcium diet to control hypercalceamia
How do you diagnose Williams syndrome
FISH study for micro deletion on chromosome 7
- test that looks for gene changes in cells
What is fragile X syndrome
A syndrome caused by a mutation in the FMR1 (fragile X mental retardation 1protein) on the X chromosome that plays a role in brain development
Which gender is affected more by fragile X syndrome and why?
Males are always affected due to XY
Females it can have varying affects because they have a spare normal copy of FMR1 gene on other X chromosome (XX)
Features of fragile X syndrome
-delay in speech And language development
-intellectual disability
-long, narrow face
-large testicles
-hyper mobile joints
-ADHD
-autism
-seizures
Mx of fragile X syndrome
-NO cure - management is supportive
-MDT approach to support:
-learning disability
-manage autism and ADHD
-treat seizures
What is patau syndrome also known as
Trisomy 13
Clinical features of patau syndrome
-small eyes
-cleft lip and palate
-polydactyly
-cardiac and renal malformation
-hypotonia
-low forming ears
Diagnosis of pataus syndrome
-genetic testing - amniocentesis
-prenatal ultrasounds
Management of Pataus syndrome
Educational support
SALT
Surgery to repair physical abnormalities (rare within first months)
What is muscular dystrophy
A name for a group of conditions that cause gradual weakening and wasting of muscles
Give 4 of the muscular dystrophies
-duchennes muscular dystrophy
-beckers muscular dystrophy
-myotonic dystrophy
-emery dreifuss muscular dystrophy
-Oculopharyngeal muscular dystrophy
-Limb-girdle muscular dystrophy
-facioscapulohumeral muscular dystrophy
What is Gowers sign
- a clinical finding in children with proximal muscle weakness
-where they they get onto their hands and knees and push their hips up and backwards and walk their hands up in order to stand
-most probably due to duchennes muscular dystrophy
What is the cause of duchennes muscular dystrophy
Defective gene for Dystrophin on the X chromosome
Dystrophin usually hold muscles together at a cellular level
What inheritance pattern is duchennes
X linked recessive
Management of Duchennes
Oral steroids - aloe down progression of muscle weakness
Creatine - shown to improvise muscle strength
General muscular dystrophy Mx
-occupational therapy
-physiotherapy
-wheelchair use
-surgical treatment of associated heart failure/ scoliosis
What is the beckers muscular dystrophy
-dystrophin gene is less severely affected than duchennes
-clinical course less predictable
Myotonic dystrophy typical features (4)
Progressive muscle weakness
Prolonged muscle contractions e.g not able to let go of someone’s hand after shaking it
Cataracts
Cardiac arrhythmias
What is oculopharyngeal muscular dystrophy
-muscular dystrophy in the ocular muscles and pharynx
How does Oculopharyngeal Muscular Dystrophy present
Bilateral ptosis
Restricted eye movement
Swallowing problems
Some degree of limb degree
Facioscapulohumeral Muscular Dystrophy presentation
-Weakness around face then progressing to the shoulders and arms
-sleeping with eyes slightly open
-weakness in pursing their lips
-unable to blow out their cheeks without air leaking out
How does emery dreifuss dystrophy usually present
Presents in childhood with contractures in elbows and ankles
Progressive weakness and wasting of muscles starting with upper arms and lower legs
What are contractures
Shortening of muscles and tendons that restrict range of movement of limbs
What is perthes disease
A disease causing disrupted blood supply to the head of the thigh bone causing avascular necrosis of the femoral epiphysis
Risk factors for perthes disease
-male gender
-Caucasian
-passive smoking
-deprivation
-obesity
-low birth weight
Clinal features of perthes disease
-atraumatic hip pain and limp (antalgic gait)
-activity worsens it
-tendellenburg gait - due to weak hip flexor
Investigations for perthes disease
First line -pelvic X rays
-increasing reduction in size and lucency of the epiphysis
-joint effusion
-fragmentation of epiphysis at later stages
Second line - MRI
Management of perthes diseases
Often resolves without tx
Symptomatic and Pain relief
-restrict weight bearing activities
Regular x -rays
Physiotherapy
Surgery
-osteotomy - to improve alignment
What is osteogenesis imperfecta
A genetic condition affecting formation of collagen resulting in brittle bones that are prone to fracture
Presentation of osteogenesis imperfecta
- **recurrent and inappropriate fractures **
- **hyper mobility **
- blue/ grey sclera
- triangular face
- short stature
-deafness from childhood - joint and bone pain
-dental problems - malformation of teeth
How is osteogenesis imperfecta diagnosed
X -rays
Genetic testing
Mx of osteogenesis imperfecta
Medications
MDT
NO cure
Prevention of fracture
-bisphosphonates - increase bone density
-vitamin D supplements - prevent deficiency
MDT approach
-physio
-occupational therapy
-ortho surgeons to manage fractures
-specialist nurses
-social workers
What is transient Synovitis
Temporary irritation and inflammation in the synovial membrane of the joint
What is transient synovitis commonly associated with
Viral upper respiratory tract infection
Presentation of transient synovitis
Often occur few weeks after viral illness
Limp
Refusal to weight bear
Groin or hip pain
Mild or low grade temperature
Mx of transient synovitis
-Simple analgesia
-exclude septic arthritis
-if they develop a fever send to A and E
What is osgood schlatters disease
Inflammation at the tibial tuberosity where the patella ligament inserts.
Common in adolescents
Is osgood schlatters typically unilateral or bilateral
Unilateral
Pathophysiology of osgood schlatters
-patella tendon inserts at tibial tuberosity at epiphyseal plate
-Stress from running, jumping and other movements at the same time as growth in the epiphyseal plate result in inflammation on the tibial epiphyseal plate
- avulsion fractures can then lead to visible lump below the knee which can be tender
Presentation of osgood schlatters
Gradual onset of :
-Visible or palpable hard and tender lump at the tibial tuberosity
-Pain in the anterior aspect of the knee
-The pain is exacerbated by physical activity, kneeling and on extension of the knee
Mx of osgood schlatters
Initial Managment to reduce pain and inflammation:
-Reduction in physical activity
-Ice
-NSAIDS (ibuprofen) for symptomatic relief
Once settled Can do stretching and physio
What is rickets
A condition affecting children where there is defective bone mineralisation causing soft deformed bones
-in adults it is called osteomalacia
Causes of rickets
- Deficiency in vitamin D / calcium can be due to poor diet or genetics
What is the hereditary form of rickets called and how is it inherited
- Hypophosphataemic rickets
- X linked dominant
Bone deformities seen in rickets (5)
Bowing of legs - curve outwards
Knock knees - curve inwards
Rachitic rosary - ribs expands at costochondral junctions causing limos in the chest
Craniotabes - soft skull
Delayed teeth - under development of enamel
Presentation of rickets
May be ASX
-lethargy
-bone pain
-swollen wrists
-bone deformity
-poor growth
-muscle weakness
-abnormal fractures
-bone deformities
Risk factors for rickets (5)
Things that can cause vitamin D deficiency
-dark skin
-lives northern latitudes where there is less sun
-lots of time indoors
-premature birth
-medical condtions - IBD, CF, coeliac due to malabsorption of vitamin D
Ix for rickets (8)
Serum 25 hydroxyvitamin D - less than 25 nmol/L
X-ray - may show radiolucent bones (osteopenia)
Serum calcium - low
Serum phosphate - low
Serum ALP - high
PTH - high
Malabsorption screen - anti TTG (coeliac) , autoimmune tests- for IBD
Kidney function test
TFT
FBC
ferritin - aneamia
CRP and ESR
LFT
Management of rickets
Prevention
- breastfed babies - given formula feed with fortified vitamin D, mothers given b vitamin D supplements
Children with vitamin D deficiency
-ergocalciferol - 6000IU pd
Children with rickets
-refer to paediatrician
-calcium and vitamin D supplements
What is osteomyelitis
Osteomyelitis refers to inflammation in a bone and bone marrow, usually caused by bacterial infection.
What is haematogenous osteomyelitis
when a pathogen is carried through the blood and seeded in the bone. This is the most common mode of infection
What is direct contamination osteomyelitis example
at a fracture site where bacteria can enter through
Most common bacterial cause of osteomyelitis
Staphylococcus aureus
Risk factors for osteomyelitis (6)
Open fractures
Orthopaedic operations, particularly with prosthetic joints
Diabetes, particularly with diabetic foot ulcers
Peripheral arterial disease
IV drug use
Immunosuppression
Presentation of osteomyelitis
Fever
Pain and tenderness
Erythema
Swelling
Investigations of osteomyelitis
X rays
- periostea reaction - changes to bone surface
- localised osteopenia - thinning
- destruction
US guided aspiration - for MC+S
MRI - best imaging investigation
Blood tests - WBC, CRP and ESR raised
Blood cultures - causative organism
Bone cultures
Mx of osteomyelitis
-Antibiotic therapy
Acute cases:
- 6 weeks - flucloxacillin (+ Rifampicin/fusidic acid for first 2 weeks)
Clindamycin/ vancomycin if Penecillin allergy
Chronic cases - 3 months + of antibiotics
Surgical - debridement and drainage
What is developmental dysplasia of the hip
A conditon where there is structural abnormality in the hips caused by abnormal development of the fetal bones during pregnancy
What two things can occur due to DDH
Subluxation - partial dislocation
Dislocation
Risk factors for DDH (3)
-first degree FHx of DDH
-breech presentation (born feet first)
-multiple pregnancy (due to crowding in the foetus)
How is DDH picked up
During the newborn examination and 6-8 week
What are the two special tests used to identify DDH
Ortolani test
Barlow test
What is ortalani test
-baby on their back
-hips and knees flexed
-palms placed on baby’s knees and gently abduct the hips
-apply pressure behind the legs with fingers to see if hips dislocate anteriorly
What is barlows test
-baby on their back
-hips adducted and flexed
-knees flexed
-put downward pressure placed on knees through the femur
-see if femoral head will dislocate posteriorly
What are some findings upon examination that may indicate DDH (5)
-different leg lengths
-difference in knee level when hip flexed
-restricted hip abduction on one side
-bilateral restriction in abduction
-clunking of the hips on the special tests
How do you diagnose DDH
Ultrasound scan of hips
-in older infants can use x ray
Mx of DDH
Below 6 months - Pavlik harness
-keeps baby in hip flexion and abduction
-holds femoral head in the acetabulum allowing for correct growth and normal shape
After 6 months or harness failure - surgery to realign the hip
How long is pavlik harness used for
Permanently for 6-8 weeks
What is septic arthritis
Infection of joint that is a medical emergency and can leaf systemic illness
What are the main causative organisms of septic arthritis in children
S.aureus is the main pathogen
Others:
Nisseria gonorrhoea - think especially is sexually active teenagers
Group A strep
H.influenza
E.coli
Most common joint affected in septic arthritis
Knee most common Also:
Hip
Ankles
DDX of septic arthritis
Hip - transient synovitis, perthes, Psoas abscess, osteomyelitis
Knee - osteomyelitis
General - cellulitis, HSP, reactive arthritis
Signs and symptoms of septic arthritis
-decreased range of movements in that joint
-hot, warm, swollen joint
-inability to weight bear
-fever
-lethargy
Ix for septic arthritis
Bloods - FBC, ESR, CRP
X-ray of joint - widened joint space (effusion), erosive signs
Joint aspiration - send for MC+S
LP - if haemophilias influenza due to increase meningitis risk
Tx for septic arthritis
Urgent admission to hospital
-IV ABX - for 3 weeks - oral ABX for 4-6 weeks
-surgical - irrigation and debridement of joint
-splintage - to allow inflammation to settle
-physio to avoid stiffness
What antibiotics are used for septic arthritis for:
first line
If there is a penecillin allergy
If MRSA
Neisseria gonorrhoea
1st line - Flucloxacillin
Penicillin allergy - clindamycin
MRSA - vancomycin
Neisseria gonorrhoea - Ceftriaxone
Complications of septic arthritis
Chondrolysis
Bone destruction
Avascular necrosis - femoral head
What is scoliosis
LATERAL curvature in the frontal plane of the spine
Causes of scoliosis (3)
Idiopathic scoliosis - mainly females
Congenital scoliosis - from congenial structural defect e.g spina bifida
Secondary scoliosis - related to neuromuscular imbalance/ connective tissue disorder e.g cerebral palsy or JIA
Wha is the most common form of scoliosis
Idiopathic scoliosis
Pathology of congenial scoliosis
-embryological malformation of one or more vertebrae in the spine
- one area of the spinal column lengthens at a slower rate than the rest causing curvature
Examination of people with scoliosis
-examination of spine and its curvature
-examination of movements e.g flexion, extension in all segments of spine
-Adam forward bend
-cobb angle
-scoliometer - measures trunk asymmetry
-pulmonary function test - scoliosis can lead to poor ventilation
What is Adam forward bending test
Patient bends forward at the waist until the back is in horizontal plane
Look for:
-spinal asymmetry
-unlevel shoulders and hips
-scapula asymmetry
What is cobbs angle
measurement to quantify the magnitude of spinal deformities
Scoliosis = lateral curvature of greater than 10 degrees
10-20 - mild
20-40 - severe
Management of scoliosis
Surgical treatment - spinal fusion two vertebrae are fused
Conservative treatment -
Braces - if children bones still growing to prevent further curve
Physiotherapist
What is a discoid meniscus
Where the meniscus is shaped like a disk making it more prone to injury due being more likely to tear
What are the three types of discoid meniscus
Incomplete - lateral meniscus is thicker and wider than normal
Complete - tibia completely covered by the meniscus
Hyper mobile Wrisberg - meniscus has no posterior attachment to the tibia ( ligament of wrisberg)
Clinical presentation of discoid meniscus
-visible or audible snap on terminal extension
-pain and swelling
-locking
Diagnosis of discoid meniscus
MRI
-detect tears in meniscus
-show ratio of meniscal width vs maximal tibial width >75% means discoid meniscus
Examination
-lateral joint space is sensitive and swelling
-twisting flexion and extension - Popping and clunking
Management of discoid meniscus
Surgery - Arthroscopic partial meniscectomy
Control pain:
-NSAIDS
-analgesics
-cryotherapy
Physiotherapy
Strengthen leg muscles
What is anaemia
Low levels of haemoglobin in the blood
What are physiologic causes of anaemia in infants (4)
- prematurity
- blood loss
-haemolysis
-twin- twin transfusion - blood unequally distributed between twins in placenta
What are causes of haemolyisis aneamia (3)
-hereditary spherocytosis
-G6PD deficiency
-haemolytic disease of newborn - Blood incompatibility
Why is there a natural dip in haemoglobin in infants
-high oxygen delivery to tissues due to high haemoglobin levels at birth
-causes negative feedback
-suppression of EPO in kidneys therefore reduced haemoglobin by bone marrow
Why do premature infants become anaemic (4)
-less time receiving iron in utero from mother
-RBC creation cannot keep up with the necessary rapid growth in first weeks
-reduced EPO levels
-blood tests remove significant volume of the blood volume
Pathology of haemolytic disease of newborn
1.Mother is rhesus D antigen negative
Foetus is rhesus D antigen positive
2.blood from foetus can enter the mothers bloodstream - mother immune system will produce antibodies to foreign Rhesus D antigens from foetus - SENSITISED
- Doesn’t affect during first pregnancy unless exposure happen early
- During late pregnancies mothers anti D antibodies can cross the placenta to foetus, if baby is rhesus D positive they will attack
- Causing haemolysis of RBCs and excess bilirubin causing aneamia
How do you check for haemolytic anemia a of newborn
Direct Coombes test
Common causes of anaemia in older children
Iron deficiency anemia - most common
Blood loss - especially in menstruation
In developing countries - helminth infection
What worms are responsible for a helminth infection chronic anemia
Round worms
Hook worms
Whip worms
Treatment for helminth infection
Single dose albendazole/ mebendazole
Causes of microcytic anemia
T- thalassaemia
A- anaemia of chronic disease
I- iron deficiency
L- lead poisoning
S- sideroblastic anemia
Causes of normocytic anemia
A- acute blood loss
A- anaemia of chronic disease
A- aplastic anemia
H- haemolytic anemia
H- hypothyroidism
S - sickle cell
What is the megoblastic anemia
Megoblastic - result of DNA synthesis preventing the cells dividing normally and instead grows into large cells
Examples of megoblastic aneamia
B12 deficiency
Folate deficiency
Example of normoblastic macrocytic anaemia
Alcohol
Reticulocytosis - too many immature RBC
Hypothyroidism
Liver disease
Drugs such as azathioprine
Sx of anaemia
generic symptoms of anaemia:
Tiredness
Shortness of breath
Headaches
Dizziness
Palpitations
Worsening of other conditions
There are symptoms specific to iron deficiency anaemia:
Pica- dietary cravings for abnormal things such as dirt and can signify iron deficiency
Hair loss can indicate iron deficiency anaemia
Signs of iron deficiency anaemia
Koilonychia - spoon shaped nails
Angular stomatitis - inflammation around corners
Atrophic glossitis - smooth tongue due to papillae atrophy
Brittle nails and hair
General signs of anemia
Pale skin
Conjunctival pallor
Tachycardia
Raised respiratory rate
Numbness or tingling in hands and feet
What anaemia can cause jaundice
Haemolytic anaemia
Investigations for anaemia
FBC - haemoglobin and MCV
blood film
Reticulocyte count - high in haemolysis/ blood loss
Ferritin - low in iron deficiency
B12 and folate levels - macrocytic megoblastic
Bilrubin levels - raised in haemolysis
Direct Coombes test - autoimmune haemolytic anaemia
Haemoglobin electrophoresis - for spherocytosis/ G6PD deficiency
Mx of iron deficiency anemia
Increase iron in diet - meat, leafy greens
Iron supplementation
Severe cases - blood transfusion
What is a slipped upper femoral epiphysis
Hip condition where femoral head epiphysis is displaced posteroinferiorly due to weak growth plates
-imagine ice cream (femoral head epiphysis) coming off an ice cream cone (rest of the femur)
What group is slipped upper femoral epiphysis more present in (2)
Males between 8-15
Obese children
Clinical presentation of slipped upper femoral epiphysis
-pain in the hips/thigh/knee/groin
-loss of internal rotation of leg in flexion
-want to keep leg externally rotated
-painful lump
-history of minor leg trauma
Investigations for slipped upper femoral epiphysis
1st line - X-ray
Others:
Blood test - CRP, ESR exclude other causes
Technetium bone scan
CR/MRI
Mx of slipped upper femoral epiphysis
Surgery - internal fixation across the growth plate - screws to keep it stable
What is the definition of haemolytic anaemia
anaemia secondary to reduced survival of RBCs
What are the three types of INHERITED haemolytic anaemias and give examples
Metabolic abnormalities - G6PD deficiency
Haemoglobin abnormalities - sickle cell/ thalassaemia
Membrane abnormalities - Hereditary spherocytosis
What are the two types of acquired haemolytic anaemias and give examples
Immune mediated - antibodies target RBC membrane - e.g autoimmune haemolytic anaemia
Non immune mediated - mechanical distortion or infections e.g having a prosthetic heart valve, hypersplenism
What would characteristic RBC forms would you see on a blood film in:
Hereditary Spherocytosis
Microangiopathic haemolytic anaemia
Sickle cell disease
Spherocytes
Schistocytes
Sickle cells
Reasons for children being iron deficient (3)
-not enough in diet (most common)
-loss of iron - menstruation
-inadequate iron absorption e.g crohns
Where is iron most commonly absorbed
Duodenum
Jejunum
How do PPIs reduce iron absorption
-Acid in the stomach keeps iron as SOLUBLE Fe2+
-PPIs reduce acid production so it changes to insoluble Fe3+
What investigations can be done for iron deficiency anaemia? (4)
-Total iron binding capacity
-transferrin saturation
-serum ferritin
-serum iron
What is total iron binding capacity
Total space on the transferrin molecules for the iron to bind
What is thalassaemia
genetic defect in the protein chains that make up haemoglobin leading to anaemia
What are the 2 types of thalassaemia
Alpha - defect in the alpha globin chains
Beta - defect in the beta globin chains
What inheritance pattern is thalassaemia
Autosomal recessive
How does thalassaemia lead to splenomegaly
-In thalassaemia RBCs are more fragile and break down easier due to defects in structure
- this causes higher turnover rate of RBCs which are destroyed in the spleen
-leading to Splenomegaly
Signs and symptoms of thalassaemia
Fatigue
Pallor
Jaundice
Chipmunk facies - due to hameoatopoeisis in the bones of the face
Gallstones
Splenomegaly
Poor growth and development
How to diagnose thalassaemia (5)
Full blood count - microcytic anemia
Blood films - hypochromic RBCs
DIAGNOSTIC - Haemoglobin electrophoresis - show globin abnormalities
X-ray - hair on end sign due to increase BM activity
DNA testing - looks for genetic abnormality
(Screening pregnancy women in UK offered test)
How does thalassaemia cause iron overload
- regular blood transfusions leading to accumulation of iron
- ineffective eryhtropoiesis causing excessive iron absorption in the GI tract
What chromosome does ALPHA thalassaemia affect
Chromosome 16
What chromosome does BETA thalassaemia
Chromosome 11
Mx of alpha thalassaemia (5)
Monitoring FBC and complications
Iron chelation + serum ferritin - for iron overload
Blood transfusions
Splenectomy
Bone marrow transplant - curative
Mx of alpha thalassaemia (4)
Monitoring FBC and complications
Blood transfusions
Splenectomy
Bone marrow transplant - curative
What is HBH Bart’s syndrome
-A severe form of alpha thalssaemia
-due to inactivation of alpha globin alleles leading to alpha globin chains of Hb
-causes haemoglobin to have an extremely high affinity with oxygen so doesnt deliver oxygen to tissue
HBH Bart’s syndrome symptoms
Not normally compatible with life
Severe aneamia
Hepatosplenomegaly
Heart failure in utero
HBH Bart’s syndrome symptoms
Not normally compatible with life
Severe aneamia
Hepatosplenomegaly
Heart failure in utero
What is beta thalassaemia minor
A subtype of beta thalssaemia where they have one abnormal and one normal beta globin gene
Causes microcytic anaemia but usually no treatment needed
What Thalassaemia intermedia
Two abnormal copes of beta globin gene
-either 2 defective genes
-or one defective and one deletion gene
What is thalassaemia intermedia treatment
-occasional blood transfusion
-iron chelation to prevent iron overload
What is thalassaemia major
-most severe form
-both genes are deletion genes and no functioning beta globin genes
What complications does thalassaemia major cause
Severe microcytic anaemia
Splenomegaly
Bone deformities - bone marrow expands due to trying to produce more RBC
Mx of thalassaemia major
-regular blood transfusions
-iron chelation - for iron overload
-folate supplements
-splenectomy
-bone marrow transplant
Mx of thalassaemia major
-regular blood transfusions
-iron chelation - for iron overload
-folate supplements
-splenectomy
-bone marrow transplant
What is sickle cell anaemia
Genetic condition causing sickle (crescent) shaped red blood cells
Making them more fragile and easily destroyed and sticky
Protective conditions against malaria
Sickle cell anemia
Thalassaemia
Pathology of sickle cell anaemia
-autosomal recessive condition due to single nucleotide polymorphism affecting beta globin on chromosome 11
-abnormal variant of haemoglobin called HbS resulting in sickle cells
How is sickle cell anaemia diagnosed
New born blood spot
Pregnant women at high risk of being carriers of the sickle gene offered testing
Complications of sickle cell anaemia
Anaemia
Increased risk of infection
Chronic kidney disease
Sickle cell crises
Acute chest syndrome
Stroke - RBC clump together causing block
Avascular necrosis in large joints such as the hip
Pulmonary hypertension
Gallstones - excess bilirubin due to RBC breakdown
Priapism (painful and persistent penile erections)
Complications of sickle cell anaemia
Anaemia
Increased risk of infection
Chronic kidney disease
Sickle cell crises
Acute chest syndrome
Stroke - RBC clump together causing block
Avascular necrosis in large joints such as the hip
Pulmonary hypertension
Gallstones - excess bilirubin due to RBC breakdown
Priapism (painful and persistent penile erections)
What are vaso occlusive crisis caused by
Caused by sickle cells clogging capillaries causing distal ischemia
Can lead to :
Priapism - urological emergency
Fever
Swelling
Pain
How do you treat priapism
Aspirating blood form penis
What is splenic sequestration crisis
red blood cells blocking blood flow within the spleen causing enlarged and painful spleen
Leading to:
Hypovolaemia shock
Anaemia
Complications of sequestration crisis (3)
-Splenic infarction
-hyposplenism
-susceptible to infections (strep pneumoniae, H.influenzae
Mx of splenic sequestration crisis
Treating anaemia and shock
-blood transfusions
-fluid resuscitation
Treating crisis
Splenectomy
What’s aplastic crisis in sickle cell anemia
Triggered by parvovirus B19- temporary absence of the creation of new red blood cells
Tx of aplastic crisis
Blood transfusions
What is Acute chest syndrome in sickle cell anemia
Vessels supplying the lungs become clogged with red blood cells
In the case of sickle cell anaemia it is caused by vaso occlusive event
Acute chest syndrome symptoms
Fever
SOB
Chest pain
Cough
Tx of acute chest syndrome
Supportive Management
-analgesia
-hydration (IV may be required)
-ABX/antivirals for infection
-blood transfusions
-incentive spirometry - encourages deep breathing
- resp support
General management of sickle cell anaemia
-Avoid triggers for crisis
-up to date vaccines
-ABX prophylaxis - penicillin V - protect against infection
-hydroxycarbamide - stimulates HBF
- crizanlizumab
-blood transfusions
-bone marrow transplants - curative
How does hydroxycarbimide work for sickle cell aneamia
Fetal haemoglobin does not lead to the sickling of red blood cells
-It reduces the frequency of vaso-occlusive crises, improves anaemia and may extend lifespan
How does crizanlizumab work in sickle cell anaemia
-monoclonal antibody that targets P-selectin.
-P-selectin is an adhesion molecule found on endothelial cells on the inside walls of blood vessels and platelets.
-It prevents red blood cells from sticking to the blood vessel wall and reduces the frequency of vaso-occlusive crises.
What’s the main inheritance pattern of Von willbrands disease
Autosomal dominant
Presentation of VW disease
-Bleeding gums with brushing
-Nosebleeds (epistaxis)
-Easy bruising
-Heavy menstrual bleeding (menorrhagia)
-Heavy bleeding during and after surgical operations
Diagnosis of VW disease
-Hx of abnormal bleeding
-FHx
-VWF antigen test
MX of Von willebrands disease
To stop significant bleeding:
-Desmopressin (stimulates the release of vWF from endothelial cells)
-Tranexamic acid
-Von Willebrand factor infusion
-Factor VIII plus von Willebrand factor infusion
To stop Heavy menstrual periods:
-tranexamic acid
-mefenamic acid
-mirena coil - progesterone stops shedding
-COCP
-norethisterone -synthetic progesterone
-hysterectomy
What is fanconi anemia
An inherited form of aplastic anaemia resulting in decreased production of all types of blood cells
Symptoms of fanconi anaemia
-heart or kidney abnormalities
-low birth weight and height
-abnormal skin pigmentation
-skeletal abnormalities - no thumb or radius bone
-easy bruising
-tiredness
-scoliosis
How is fanconi anaemia diagnosed
Before birth - if someone has it in the family
-amniocentesis
-chorionic villus sampling
After birth
Bone marrow testing
Blood tests - check RBC, WBC, platelet levels
Genetic tests
Fanconi anaemia Tx
-IV transfusion of RBC and platelets
-androgens - increase number of RBC and platelets
-Abx for infections
-synthetic growth factors - increase WBC
Curative - bone marrow transplant
What inheritance pattern is haemophilia
X linked recessive
What respective factors are affected in haemophilia A and B
Haemophilia A - factor 8
Haemophilia B - factor 9
Presentation of haemophilia
In children
-Spontaneous bleeding
-haematomas
-cord bleeding
-Intracranial haemorrhage
-haemothrosis - blood in the joints can cause bone deformity
-compartment syndrome - bleeding into the muscle
Mx of haemophilia
-Given the appropriate clotting factor via IV infusion
What is a complciation of giving IV clotting factors
Formation of antibodies (inhibitors) against the treatment so it becomes ineffective
Dx of of haemophilia (3)
bleeding scores,
coagulation factor assays
genetic testing.
What is immune thrombocytopenic purpura
Condition where Antibodies created against platelets
Leading to destruction of platelets and low platelet count
Mx of ITP (5)
-prednisolone
-IV immunoglobulins
-thrombopoietin receptor agonists - avatrombopag
-Rituximab- Monoclonal antibody that targets B cells
-Spleen taken out
