clinical sciences 3 Flashcards
What is Cornea Verticullata?
Cornea verticillata is a condition that causes a whorl-like pattern of opacities in the cornea
What causes Corenal Verticillata?
Fabry disease: An inherited metabolic disorder that prevents the body from breaking down lipids
Medications: Amiodarone, chloroquine, hydroxychloroquine, indomethacin, and phenothiazenes can cause cornea verticillata
Disease byproducts: Metabolic substrates or disease byproducts can build up in the cornea
What is an angiokeratoma?
Angiokeratomas are noncancerous skin bumps that are caused by dilated blood vessels
Hard, red, blue, purple, or black bumps
Wart-like
Papules or plaques
Can have a rough or smooth surface
What is Fabry’s disease?
Fabry’s disease is an X-linked recessive disorder characterised by abnormal deposits of a particular fatty substance called globotriaosylceramide in blood vessel walls throughout the body. The primary defect which allows this to occur is the inherited deficiency of the enzyme, alpha-galactosidase A, which is normally responsible for the breakdown of globotriaosylceramide.
Clinial features of Fabry disease?
Limb pain
Sensory neuropathy
Raynaud’s disease
Cardiac arrhythmias, cardiomyopathy
Nephrotic syndrome
Dermatological manifestation; angiokeratomas, anhidrosis, cornea verticillata
WHat is released by the Adrenal cortex?
Adrenal cortex (mnemonic GFR - ACD)
* zona glomerulosa (on outside): mineralocorticoids, mainly aldosterone
* zona fasciculata (middle): glucocorticoids, mainly cortisol
* zona reticularis (on inside): androgens, mainly dehydroepiandrosterone (DHEA)
Where is Renin released from?
released by the renal juxtaglomerular cells
what is renin released in response to?
released in response to reduced renal perfusion
other factors that stimulate renin secretion include hyponatraemia, sympathetic nerve stimulation
hydrolyses angiotensinogen to form angiotensin I
What are the actions of Angiotensin II?
angiotensin II has a wide variety of actions:
causes vasoconstriction of vascular smooth muscle leading to raised blood pressure and vasoconstriction of efferent arteriole of the glomerulus → increased filtration fraction (FF) to preserve GFR. Remember that FF = GFR / renal plasma flow
stimulates thirst (via the hypothalamus)
stimulates aldosterone and ADH release
increases proximal tubule Na+/H+ activity
RAAS
When blood pressure drops, the kidneys release renin into the bloodstream.
Renin splits angiotensinogen into angiotensin I.
Angiotensin-converting enzyme (ACE) splits angiotensin I into angiotensin II.
Angiotensin II causes blood vessels to constrict, which increases blood pressure.
Angiotensin II also triggers the release of aldosterone and vasopressin.
Aldosterone and vasopressin cause the kidneys to retain sodium and water, which increases blood pressure.
where is aldosterone released from and what is it released in response to?
released by the zona glomerulosa in response to raised angiotensin II, potassium, and ACTH levels
What does aldosterone lead to?
causes retention of Na+ in exchange for K+/H+ in distal tubule
What statistical tests can be used for parametric data?
Student’s t-test - paired or unpaired*
Pearson’s product-moment coefficient - correlation
Non parametric tests?
Mann-Whitney U test
compares ordinal, interval, or ratio scales of unpaired data
Wilcoxon signed-rank test
compares two sets of observations on a single sample, e.g. a ‘before’ and ‘after’ test on the same population following an intervention
chi-squared test
used to compare proportions or percentages e.g. compares the percentage of patients who improved following two different interventions
Spearman, Kendall rank - correlation
Examples of autosomal recessive conditions?
Albinism
Ataxic telangiectasia
Congenital adrenal hyperplasia
Cystic fibrosis
Cystinuria
Familial Mediterranean Fever
Fanconi anaemia
Friedreich’s ataxia
Gilbert’s syndrome*
Glycogen storage disease
Haemochromatosis
Homocystinuria
Lipid storage disease: Tay-Sach’s, Gaucher, Niemann-Pick
Mucopolysaccharidoses: Hurler’s
PKU
Sickle cell anaemia
Thalassaemias
Wilson’s disease
AD vs AR?
Autosomal recessive conditions are often thought to be ‘metabolic’ as opposed to autosomal dominant conditions being ‘structural’, notable exceptions:
some ‘metabolic’ conditions such as Hunter’s and G6PD are X-linked recessive whilst others such as hyperlipidemia type II and hypokalemic periodic paralysis are autosomal dominant
some ‘structural’ conditions such as ataxia telangiectasia and Friedreich’s ataxia are autosomal recessive
which type of cell mediates organ rejection?
B cells mediate hyperacute organ rejection
What cells are involves in the adaptive immune response?
Helper T cells
Cytoxoc T cells
B cells
Plasma cells
Functions and properties of Helper T cells?
Involved in the cell-mediated immune response
Recognises antigens presented by MHC class II molecules
Expresses CD4
Also expresses CD3, TCR & CD28
Major source of IL-2
Mediates acute and chronic organ rejection
Functions and properties of cytotoxic t cells?
Involved in the cell-mediated immune response
Recognises antigens presented by MHC class I molecules
Induce apoptosis in virally infected and tumour cells
Expresses CD8
Also expresses CD3, TCR
Mediates acute and chronic organ rejection
Functions and properties of B cells?
Major cell of the humoral immune response
Acts as an antigen presenting cell
Mediates hyperacute organ rejection
Functions and properties of plasma cells?
Differentiated from B cells
Produces large amounts of antibody specific to a particular antigen
What does the adrenal medulla secrete?
The adrenal medulla secretes virtually all the adrenaline in the body as well as secreting small amounts of noradrenaline. It essentially represents an enlarged and specialised sympathetic ganglion
Examples of interlukins ?
The sources and functions?
what is macrophage activation syndrome?
Macrophage activation syndrome (MAS) is a rare, life-threatening condition that occurs when the body’s immune system overreacts. It’s a complication of infections, rheumatic diseases, and hematopoietic malignancies.
Symptoms of macrophage activation syndrome?
High fever without a clear cause
Bleeding and clotting problems, such as nose bleeds, easy bruising, and vomiting blood
Large lymph nodes (lymphadenopathy)
Large liver and spleen (hepatosplenomegaly)
Headaches
Mental status changes, such as confusion, lethargy, irritability, seizures, or coma
Causes of macrophage activation syndrome?
Infections, such as viruses, fungi, or bacteria
Rheumatic diseases, such as systemic juvenile idiopathic arthritis (SJIA) and systemic lupus erythematosus (SLE)
Hematopoietic malignancies
Treatment of macrophage activation syndrome?
MAS requires prompt recognition and aggressive treatment. Treatments include:
Tocilizumab, an IL-6-receptor inhibitor
Canakinumab, an IL-1β inhibitor
IFN-γ, a therapeutic target
What cytokine is most likley to be activated in macrophage activation syndrome?
Interferon-γ is responsible for activating macrophages and is heavily implicated in the pathogenesis of this condition.
What clasification is used for hypersensitvity reactions?
The Gell and Coombs classification divides hypersensitivity traditionally divides reactions into 4 types:
Type I - anaphylactic
Type II - cell bound
Type III - immune complex
Type IV delayed hypersenstivity
Mechanism of hypersentivity reactions and examples?
what is a Type V hypersensitivity reaction?
What type of hypersensitivty reaction is ITP?
Type II
What is Achondroplasia?
Achondroplasia is an autosomal dominant disorder associated with short stature.
What is the gene mutation seen in achondroplasia?
mutation in the fibroblast growth factor receptor 3 (FGFR-3) gene
Features of achondroplasia?
short limbs (rhizomelia) with shortened fingers (brachydactyly)
large head with frontal bossing and narrow foramen magnum
midface hypoplasia with a flattened nasal bridge
‘trident’ hands
lumbar lordosis
As an autosomal dominant condition, two affected parents can expect:
1 in 4 chance of an unaffected child
1 in 2 chance of an affected heterozygous child
1 in 4 chance of an affected homozygous child. With achondroplasia children unfortunately don’t live past the first few months of life
what is fanconi syndrome?
Fanconi syndrome describes a generalised reabsorptive disorder of renal tubular transport in the proximal convoluted tubule resulting in:
type 2 (proximal) renal tubular acidosis
polyuria
aminoaciduria
glycosuria
phosphaturia
osteomalacia
Causes of Fanconi syndrome?
cystinosis (most common cause in children)
Sjogren’s syndrome
multiple myeloma
nephrotic syndrome
Wilson’s disease
What does the presence of glucose in the urine (glycosuria) indicate despite normal blood glucose?
A defect in reabsorption within the proximal convoluted tubule
What are the consistent findings in type 2 RTA?
Hypokalaemia and reduced bicarbonate level
What leads to bicarbonate wastage and subsequent acidemia in type 2 RTA?
Impaired bicarbonate reabsorption in the proximal tubule
What effect does Amphotericin B have on renal tubular cells?
Increased permeability leading to loss of potassium, bicarbonate, and other solutes
Why is it important to monitor renal function in patients on amphotericin B therapy?
Due to potential side effects of increased permeability and solute loss
What supplies each nephron with blood?
Each nephron is supplied with blood from an afferent arteriole.
What happens to blood after it flows through the glomerular capillary bed?
Blood flows to an efferent arteriole, supplying the peritubular capillaries and medullary vasa recta.
What percentage of resting cardiac output does the kidney receive?
The kidney receives up to 25% of resting cardiac output.
What is the range of systolic pressures that the kidney can autoregulate its blood flow?
The kidney can autoregulate its blood flow between systolic pressures of 80-180 mmHg.
What mechanisms are responsible for autoregulation of renal blood flow?
Myogenic control of arteriolar tone, sympathetic input, and hormonal signals (e.g. renin).
Which has a greater blood flow: renal cortical blood flow or medullary blood flow?
Renal cortical blood flow is greater than medullary blood flow.
i.e. tubular cells more prone to ischaemia)
What type of molecules are unable to cross the basement membrane of the glomerulus?
Larger negatively charged molecules such as albumin are unable to cross.
What is the formula for calculating the glomerular filtration rate (GFR)?
GFR = (urine concentration (mmol/l) x urine volume (ml/min)) / plasma concentration (mmol/l).
What substance is typically used in clinical practice to measure GFR?
Creatinine is used because it is subjected to very little proximal tubular secretion.
What is the typical GFR in clinical practice?
The typical GFR is 125 ml per minute.
Define renal clearance.
Renal clearance is the volume of plasma from which a substance is removed per minute by the kidneys.
List the features of substances used to measure GFR.
- Inert
- Free filtration from the plasma at the glomerulus (not protein bound)
- Not absorbed or secreted at the tubules
- Plasma concentration constant during urine collection
What happens to glucose during filtration and clearance?
Glucose is freely filtered across the basement membrane but is usually reabsorbed from tubules, giving a clearance of zero.
Where does reabsorption and secretion of substances occur in the nephron?
In the tubules.
What substrates are co-transported with sodium in the proximal tubule?
Glucose, amino acids, and phosphate.
How much filtered water is reabsorbed in the proximal tubules?
Up to two thirds of filtered water is reabsorbed.
What effect does reabsorption of water have on urea concentration?
It increases urea concentration in the distal tubule, allowing for its increased diffusion.
What is para-aminohippuric acid used to measure?
It is used to measure renal plasma flow.
How is tubular reabsorption of ions like calcium and phosphate influenced?
It is influenced by plasma PTH levels.
What happens to potassium in the nephron?
Potassium may be both secreted and reabsorbed and is co-exchanged with sodium.
How much water containing sodium enters the descending limb of the loop of Henle in 24 hours?
Approximately 60 litres of water containing 9000 mmol sodium.
What is the permeability of the thin ascending limb of the loop of Henle?
It is impermeable to water but highly permeable to sodium and chloride ions.
What occurs in the thick ascending limb of the loop of Henle?
Reabsorption of sodium and chloride ions occurs by both facilitated and passive diffusion pathways.
What helps maintain the osmotic gradient in the kidneys?
Energy-dependent reabsorption of sodium and chloride in the thick ascending limb.
What are the two main types of pneumocytes?
Club cells (previously termed Clara cells) are non-ciliated dome-shaped cells found in the bronchioles. They have a varied role including protecting against the deleterious effects of inhaled toxins and the secretion of glycosaminoglycans and lysozymes.
Alveolar macrophages?
Alveolar macrophages are found on the internal lumenal surfaces of the alveoli. They phagocytose foreign particles and are not known to produce surfactant.
What cells secrete mucus in the respiratory tract?
Goblet cells secrete mucus in the respiratory tract.
Dermatomes
C2
C3
C4
C5
C6
C7
C8
Dermatomes
T4
T5
T6
T10
L1
L4
L5
S1
S2
S3
How to calculate relative risk reduction?
Relative risk (RR) is the ratio of risk in the experimental group (experimental event rate, EER) to risk in the control group (control event rate, CER). The term relative risk ratio is sometimes used instead of relative risk.
EER = rate at which events occur in the experimental group
CER = rate at which events occur in the control group
Relative risk reduction (RRR) or relative risk increase (RRI) is calculated by dividing the absolute risk change by the control event rate
RRI = (EER - CER) / CER
How to calculate sensitivity, specificity, PPV, NPV, Likelihood ratio for a positive test result, Likelihood ratio for a negative test result
what is precision?
The precision quantifies a tests ability to produce the same measurements with repeated tests.
what is p53?
p53 is a tumour suppressor gene located on chromosome 17p. It is the most commonly mutated gene in breast, colon and lung cancer
p53 is thought to play a crucial role in the cell cycle, preventing entry into the S phase until DNA has been checked and repaired. It may also be a key regulator of apoptosis
what does mutation in p53 gene lead to?
Li-Fraumeni syndrome is a rare autosomal dominant disorder characterised by the early onset of a variety of cancers such as sarcoma, breast cancer and leukaemias. It is caused by mutation in the p53 gene.
What is Ubiquitination?
Ubiquitination is a post-translational modification process that tags proteins for degradation. The ubiquitin-proteasome system (UPS) is the main machinery for protein catabolism in the cytosol and nucleus. Proteins tagged with ubiquitin are recognised and degraded by the proteasome, an organelle that disassembles unneeded or damaged proteins into smaller peptides.
Ubiquitin tagging destines proteins to proteasome for degradation
Types of DNA mutation?
what is the complement system?
The complement system, an integral part of the innate immune system, consists of a series of plasma proteins that collaborate to eradicate pathogens, promote inflammation, and fine-tune the adaptive immune response. Complement proteins are involved in chemotaxis, cell lysis and opsonisation. Deficiencies in the complement system can increase susceptibility to infections, autoimmune disorders, or other conditions.
what does C1 inhibitor (C1-INH) protein deficiency lead to?
causes hereditary angioedema
C1-INH is a multifunctional serine protease inhibitor
probable mechanism is uncontrolled release of bradykinin resulting in oedema of tissues
What does C1q, C1rs, C2, C4 deficiency (classical pathway components) lead to?
predisposes to immune complex disease
e.g. SLE, Henoch-Schonlein Purpura
What does C3 deficicency lead to?
causes recurrent bacterial infections
What does C5 deficiency lead to?
predisposes to Leiner disease
recurrent diarrhoea, wasting and seborrhoeic dermatitis
What does C5-9 deficinecy lead to?
encodes the membrane attack complex (MAC)
particularly prone to Neisseria meningitidis infection
what cancers may EBV lead to?
Burkitt’s lymphoma
Hodgkin’s lymphoma
Post transplant lymphoma
Nasopharyngeal carcinoma
What cancrs may HPV 16/18 lead to?
Cervical cancer
Anal cancer
Penile cancer
Vulval cancer
Oropharyngeal cancer
what cancer may HPV8 lead to?
Kaposi’s sarcoma
What cancer may Hep B and C lead to?
Hepatocellular carcinoma
what type of cancer may Human T-lymphotropic virus 1 lead to?
Tropical spastic paraparesis
Adult T cell leukaemia
what is pulmonary surfactant and where is it realsed from?
Surfactant is a mixture of phospholipids, carbohydrates and proteins released by type 2 pneumocytes. The main functioning component is dipalmitoyl phosphatidylcholine (DPPC) which reduces alveolar surface tension.
Pulmonary surfactant
when is it first detectable
what is its role?
first detectable around 28 weeks
as alveoli decrease in size, surfactant concentration is increased, helping prevent the alveoli from collapsing
reduces the muscular force needed to expand the lungs (i.e. decreases the work of breathing)
lowers the elastic recoil at low lung volumes and thus helps to prevent the alveoli from collapsing at the end of each expiration
what is the role of Ghrelin?
Ghrelin stimulates hunger. It is produced mainly by the P/D1 cells lining the fundus of the stomach and epsilon cells of the pancreas. Ghrelin levels increase before meals and decrease after meals
What is Paroxysmal nocturnal haemoglobinuria (PNH)?
An acquired disorder leading to haemolysis of haematological cells
PNH is mainly characterized by intravascular haemolysis.
What causes the increased sensitivity of cell membranes to complement in PNH?
Lack of glycoprotein glycosyl-phosphatidylinositol (GPI)
GPI is essential for anchoring surface proteins to the cell membrane.
What condition are patients with PNH more prone to?
Venous thrombosis
This includes conditions like Budd-Chiari syndrome.
What role does GPI play in cell membranes?
It acts as an anchor for surface proteins to the cell membrane
This includes complement-regulating proteins.
Which complement-regulating surface proteins are affected in PNH?
- Decay-accelerating factor (DAF)
- CD59
Their lack leads to increased susceptibility to haemolysis.
What is a key feature of PNH related to blood cell counts?
Pancytopaenia may be present
Haemolytic anaemia
This can affect red blood cells, white blood cells, and platelets.
What is haemoglobinuria and how is it characterized in PNH?
Classically dark-coloured urine in the morning
However, it can occur throughout the day.
What are some potential complications of PNH?
- Thrombosis
- Aplastic anaemia may develop in some patients
These complications can arise due to the underlying mechanisms of PNH.
What is the gold standard investigation for diagnosing PNH?
Flow cytometry of blood to detect low levels of CD59 and CD55
This has replaced Ham’s test.
What does Ham’s test involve?
Acid-induced haemolysis
Normal red cells would not undergo haemolysis in this test.
What are the main management strategies for PNH?
- Blood product replacement
- Anticoagulation
- Eculizumab
- Stem cell transplantation
Eculizumab is a monoclonal antibody targeting terminal protein C5.
What is eculizumab and its role in PNH?
A monoclonal antibody directed against terminal protein C5
It is currently being trialled for reducing intravascular haemolysis.
what is the mechanism of action of eculizumab?
The patient was initiated on eculizumab, a monoclonal antibody that inhibits terminal complement activation (C5-C9) which prevents complement-mediated intravascular haemolysis.
what are the adverse effects of eculizumab?
he resulting deficiency of C5-C9 due to eculizumab predisposes to Neisseria meningitidis infections. It is therefore essential to vaccinate for this pathogen prior to initiation of treatment.
What conditions are inherited AR?
Albinism
Ataxic telangiectasia
Congenital adrenal hyperplasia
Cystic fibrosis
Cystinuria
Familial Mediterranean Fever
Fanconi anaemia
Friedreich’s ataxia
Gilbert’s syndrome*
Glycogen storage disease
Haemochromatosis
Homocystinuria
Lipid storage disease: Tay-Sach’s, Gaucher, Niemann-Pick
Mucopolysaccharidoses: Hurler’s
PKU
Sickle cell anaemia
Thalassaemias
Wilson’s disease
What is selection Bias?
Error in assigning individuals to groups leading to differences which may influence the outcome. Subtypes include sampling bias where the subjects are not representative of the population. This may be due to volunteer bias. An example of volunteer bias would be a study looking at the prevalence of Chlamydia in the student population. Students who are at risk of Chlamydia may be more, or less, likely to participate in the study. A similar concept is non-responder bias. If a survey on dietary habits was sent out in the post to random households it is likely that the people who didn’t respond would have poorer diets than those who did.
what is recall Bias?
Difference in the accuracy of the recollections retrieved by study participants, possibly due to whether they have disorder or not. E.g. a patient with lung cancer may search their memories more thoroughly for a history of asbestos exposure than someone in the control group. A particular problem in case-control studies.
what is publication Bias?
Failure to publish results from valid studies, often as they showed a negative or uninteresting result. Important in meta-analyses where studies showing negative results may be excluded.
what is work up bias?
In studies which compare new diagnostic tests with gold standard tests, work-up bias can be an issue. Sometimes clinicians may be reluctant to order the gold standard test unless the new test is positive, as the gold standard test may be invasive (e.g. tissue biopsy). This approach can seriously distort the results of a study, and alter values such as specificity and sensitivity. Sometimes work-up bias cannot be avoided, in these cases it must be adjusted for by the researchers.
What is Expectation Bias?
Only a problem in non-blinded trials. Observers may subconsciously measure or report data in a way that favours the expected study outcome.
What is the Hawthore effect?
Describes a group changing it’s behaviour due to the knowledge that it is being studied
what is procedure bias?
Occurs when subjects in different groups receive different treatment
What is lead-time bias?
Occurs when two tests for a disease are compared, the new test diagnoses the disease earlier, but there is no effect on the outcome of the disease
What is turners syndrome?
Turner’s syndrome is a chromosomal disorder affecting around 1 in 2,500 females. It is caused by either the presence of only one sex chromosome (X) or a deletion of the short arm of one of the X chromosomes. Turner’s syndrome is denoted as 45,XO or 45,X.
Features of turners syndrome?
Features
short stature
shield chest, widely spaced nipples
webbed neck
bicuspid aortic valve (15%), coarctation of the aorta (5-10%)
an increased risk of aortic dilatation and dissection are the most serious long-term health problems for women with Turner’s syndrome
regular monitoring in adult life for these complications is an important component of care
primary amenorrhoea
cystic hygroma (often diagnosed prenatally)
high-arched palate
short fourth metacarpal
multiple pigmented naevi
lymphoedema in neonates (especially feet)
gonadotrophin levels will be elevated
hypothyroidism is much more common in Turner’s
horseshoe kidney: the most common renal abnormality in Turner’s syndrome
Cardiac features in turners syndrome?
bicuspid aortic valve (15%), coarctation of the aorta (5-10%)
an increased risk of aortic dilatation and dissection are the most serious long-term health problems for women with Turner’s syndrome
regular monitoring in adult life for these complications is an important component of care
What autoimmune disease are patients with turners syndrome more at risk of?
There is also an increased incidence of autoimmune disease (especially autoimmune thyroiditis) and Crohn’s disease
risk of downs syndrome with maternal age?
Cytogenics in Down’s syndrome?
Nondisjunction is the commonest cause of Down’s syndrome
what is the wilson and junger criteria for screening?
- The condition should be an important public health problem
- There should be an acceptable treatment for patients with recognised disease
- Facilities for diagnosis and treatment should be available
- There should be a recognised latent or early symptomatic stage
- The natural history of the condition, including its development from latent to declared disease should be adequately understood
- There should be a suitable test or examination
- The test or examination should be acceptable to the population
- There should be agreed policy on whom to treat
- The cost of case-finding (including diagnosis and subsequent treatment of patients) should be economically balanced in relation to the possible expenditure as a whole
- Case-finding should be a continuous process and not a ‘once and for all’ project
Short stature and primary amenorrhoea?
turners syndrome
what investigation is used to detect underlying mutated oncogenes?
PCR
What is PCR?
Polymerase chain reaction (PCR) is a molecular genetic investigation technique. The main advantage of PCR is its sensitivity: only one strand of sample DNA is needed to detect a particular DNA sequence.
what is PCR used for?
It now has many uses including prenatal diagnosis, detection of mutated oncogenes and diagnosis of infections. PCR is also extensively used in forensics.
how is PCR carried out?
Initial prep
sample of DNA is added to the test tube along with two DNA primers
a thermostable DNA polymerase (Taq) is added
The following cycle then takes place
mixture is heated to almost boiling point causing denaturing (uncoiling) of DNA
mixture is then allowed to cool: complimentary strands of DNA pair up, as there is an excess of the primer sequences they pair with DNA preferentially
The above cycle is then repeated, with the amount of DNA doubling each time
Reverse transcriptase PCR
used to amplify RNA
RNA is converted to DNA by reverse transcriptase
gene expression in the form of mRNA (rather than the actually DNA sequence) can therefore be analyzed
what is kearns-Sayer syndrome?
Kearns-Sayre syndrome (KSS) is a rare, progressive disorder that affects the eyes, heart, and other parts of the body. It’s caused by a defect in the DNA of mitochondria, which produce energy for the body.
Symptoms of Kearns-sayer syndrome?
Investigations
Drooping eyelids (ptosis)
Pigmentary retinopathy, which causes a speckled appearance in the retina
Cardiac conduction defects
Ataxia, which causes unsteadiness while walking
High levels of protein in the cerebrospinal fluid
Diagnosis is confirmed by muscle biopsy which is characteristic with ‘ragged red fibres’ - this is often supplemented by polymerase chain reaction analysis of mitochondrial DNA for mutation detection.
examples of mitochondrial disease?
- Leber’s optic atrophy
symptoms typically develop at around the age of 30 years
central scotoma → loss of colour vision → rapid onset of significant visual impairment - MELAS syndrome: mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes
- MERRF syndrome: myoclonus epilepsy with ragged-red fibres
- Kearns-Sayre syndrome: onset in patients < 20 years old, external ophthalmoplegia, retinitis pigmentosa. Ptosis may be seen
- sensorineural hearing loss
Characteristics of mitochondrial inheritance?
inheritance is only via the maternal line as the sperm contributes no cytoplasm to the zygote
none of the children of an affected male will inherit the disease
all of the children of an affected female will inherit the disease
generally, encode rare neurological diseases
poor genotype:phenotype correlation - within a tissue or cell there can be different mitochondrial populations - this is known as heteroplasmy
Histology of mitochondrial disease?
muscle biopsy classically shows ‘red, ragged fibres’ due to increased number of mitochondria
what is roboflavin?
Vitamin B2
Riboflavin is a cofactor of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) and is important in energy metabolism.
Consequences of riboflavin deficiency?
angular chelitis
