What are the causes of abnormal systemic growth? (HINT: there’s 5)
- Hormones & growth factors
- Genetics
- Nutrition
- Environmental factors
- Diseases (can be a secondary consequence of disease e.g. CF, chronic kidney disease)
What terms are used to describe normal and abnormal cell growth? (HINT: there’s 3)
- Hyperplasia = increase in the number of cells but NOT an increase in the size of said cells
- Hypertrophy = increase in the size in cells but not an increase in number of cells
- Atrophy = can be a decrease in cell size, number, or both (and may require apoptosis)
List, and explain, the various examples of abnormalities in cell growth. (HINT: there’s 3)
- Pathological hypertrophy = R.ventricular hypertrophy. If there is a problem with the blood supply from the lungs to the heart, then the heart works harder to pump more blood => the wall thickens, putting the heart under more strain.
- Pathological hyperplasia = PSORIASIS; expansion fo keratinocytes in epidermis, and therefore expansion of s.corneum. Is an autoimmune disease
- Pathological atrophy
- muscles i.e. fractures
- nerves i.e. paraplegics
- blood supply i.e. circulatory problems (diabetics)
- pressure i.e. bedsores (combo of lack blood supply & pressure on tissues)
- diet i.e. anorexia
List, and explain, the various examples of abnormalities in cell differentiation. (HINT: there’s 5)
- Agenesis = failure to develop an organ/structure
e.g. renal agenesis - Atresia = failure to develop a lumen
e.g. oesophageal atresia, duodenal atresia, imperforate anus.
NOTE: it is not a failure to close lumen (spina bifida, cleft palate) - Hypoplasia = failure of an organ to develop to normal size (may only apply to a segment of an organ)
e.g. optic nerve hypoplasia - Ectopia/Heterotopia = small areas of mature tissue from one organ are present in another
e.g. endometriosis (lining of womb in cervix now appearing on outside) - Maldifferentiation = failure of normal differentiation due to persistence of primitive embryological features e.g. multicystic renal dysplasia
What terms are used to describe normal and abnormal cell differentiation? (HINT: there’s 3)
- Metaplasia = the change of an already differentiated cell type. It’s response is altered to the cellular environment and other epithelial/mesenchymal cells
e. g. epithelium of trachea and bronchi in smokers - Dysplasia = increased cell proliferation => decreased differentiation (often associated with pre malignant lesions)
- Neoplasia = abnormal uncoordinated (uncontrolled) excessive cell proliferation. It persists after the initiating stimulus is withdrawn (is growth factor independent growth)
What is the relation of hyperplasia to tissue repair? What problem can arise from this relationship?
Hyperplasia plays an important role in: - angiogenesis (new BV development) - wound healing - liver regeneration - heart If out of control, it can cause problems if the proliferation goes beyond what was need e.g. cirrhotic liver
What is SHOX? What syndrome is it the main cause of? Describe its relation to decreased cell growth.
SHOX = gene found on extreme tips of X and Y sex chromosomes. Expressed in the chondrocytes of the human growth plate and is a precursor for ossification. Therefore, if you don’t have the SHOX gene, cells won’t be as hypertrophic.
Main cause of Turner’s Syndrome, which only occurs in females and results in them being shorter than average, but still in proportion.
What is (i) Beckwith-Wiedemann Syndrome (ii) Pituitary Giantism ?
(i) when you inherit two copies of a chromosome from only ONE parent. Increased IGF-II, decreased H19.
(ii) Increased IGF-I and growth hormone. Often results from pituitary tumours
What is Achondroplasia?
It can be inherited from autosomal dominant.
FGFR-3 mutation (loss of FGFR-3 increases growth)
Short limbs but normal sized torso
What is a Wilms’ Tumour?
When cells lack the control to choose to either proliferate or differentiate
Tumour can weigh up to 2kg and contain bone, cartilage & smooth muscle
Describe the major causes of bone and joint inflammation and infection. (HINT: there’s 4)
- Haematogeneous Spread (via blood)
- asymptomatic as sepsis gone by time OM present
- usual source of it = skin sepsis
- organisms settle in growing metaphysis - Local Spread (from septic arthritis)
- Compound Fracture
- bone OUTside body - Foreign body
- prosthetics, bullets, shrapnel, trauma
What are the causes of osteomyelitis? (HINT: there’s 5)
Organism - Predisposition
- Salmonella - sickle cell disease
- Brucella - travel/foreign born
- S.epidermis - prosthesis
- H.influenzae - children
What are the organisms responsible for osteomyelitis?
s. aureus (>80%)
s. pyrogenes (about 5%)
m. tuberculosis (mainly in the spine)
What are the symptoms/signs of osteomyelitis?
- painful swollen site
- fever
- reduced movement (in v.young, this may be the only sign)
- paraplegia
What are the preliminary investigations of suspected osteomyelitis?
- Fever (can go from high to low in the space of a day)
- WBC (raised)
- ESR (not so much used these days)
- CRP (v.raised)
What investigations are done in someone being diagnosed with osteomyelitis?
- Blood culture
- 3 cultures taken as may be -ve early on in the infection - X-ray
- will see space where you shouldn’t see space (but this takes time) - MRI/CT/bone scan
- also has an initial -ve period, but is much shorter - Pus
- operative sample, this is got later on
What is the treatment for osteomyelitis?
- Standard empirical - flucloxacillin/fucidin
- Alternatives empirical
- fucidin/erythromycin OR rifampicin (for beta-lactam allergy)
- ciprofloxacin (for salmonella infection)
- isoniazid, rifampicin, pyrazinamide, ethambutol (tb) - Drainage/removal of involucrum (= layer of new bone growth OUTside existing bone
What are the predisposing conditions of septic arthritis?
rheumatoid arthritis
injection of joint
prosthetic joint
What are the causative organisms of septic arthritis?
s.aureus
s.pyrogenes
s.epidermis
m.tuberculosis
salmonella
brucella
What is the treatment for septic arthritis? (NOTE: v.similar to OM)
- Standard empirical - flucloxacillin/fucidin
- Alternatives empirical
- fucidin/erythromycin OR rifampicin (for beta-lactam allergy)
List the various post-infectious arthritides. (HINT: there’s 4)
- Rheumatic fever (70%)
- Rubella, meningococcus, Yersinia
- Salmonella, shigella, campylobacter, mumps
- Reiter’s syndrome
Describe the ABO blood group system.
- FUT1 and FUT2 genes (on chromosome 19) code for H substance
- A and B genes (chromosome 9) code for glucosyl transferases - which add further sugar groups
- there is naturally occuring anti A and/or B IgM antibodies in individuals that lack these antigens
Describe the Rhesus blood group system.
- Antigens = C c D e E
- coded for on chromosome 1, and from each parent a triplet is inherited e.g. cDe
- “rhesus -ve” = lack the D antigen
- there are no naturally occurring antibodies, however, they can develop in response to pregnancy/transfusion
Explain why HDFN occurs and how it can be prevented.
- Foetal red cells, carrying antigens from the father transferring to maternal circulation
- the mother then produces IgG antibodies to e.g. D, c, E, Kell etc
- Because they are IgG antibodies, they are small enough to cross the placenta, causing anaemia, jaundice, brain damage or foetal death
