Clinical Conditions Flashcards
To cover most clinical conditions you are required to know for ESA 1 I take no responsibility for any of the flashcards featured here...mistakes/shit happens.
What are the three main causes of atrophy?
-Disuse -Age -Denervation
What occurs to muscle fibres if they aren’t exposed against resistance frequently?
They shrink and weaken (smaller diameter due to loss of protein)…they don’t die
How can disuse atrophy occur?
-Bed rest -Limb immobilisation -Sedentary behaviour
How does denervation atrophy occur?
The muscle no longer receives contractile signals that are required to maintain normal size and muscle fibres are replaced with fibrous and fatty tissue
What is the consequence of muscle fibre being replaced by fibrous tissue?
It can lead to contractures and as the muscle shortens it may lead to debilitating and disfiguring contractures
What metabolic changes often occur during hypertrophy?
-Increased glycolysis enzyme activity -Increased mitochondria -Increased muscle glycogen stores -Increased blood flow
What is Myasthenia gravis?
-An autoimmune destruction of the end plate Ach receptors -Widening of the synaptic cleft -Loss of junctional folds at the end plate
What are the main presenting symptoms of myasthenia gravis?
-Ptosis (drooping eyelid) -Fatigue and sudden falling -Double vision
What is the crisis point of Myasthenia Gravis?
When it affects respiratory muscles
What is the main drug treatment for Myasthenia Gravis?
Acetylcholinesterase inhibitors
How is neuromuscular transmission disrupted in Botulism?
Toxins block the release of acetylcholine
How is neuromuscular transmission disrupted in organophosphate poisoning? What is the main consequence?
Irreversibly inhibits the actions of acetylcholinesterase meaning the receptors are constantly activated - permanent muscle contraction
How does muscular dystrophy occur?
Genetic faults cause the absence or reduced synthesis of specific proteins which anchor actin filaments to the sarcolemma (cell wall) to such a degree that muscle fibres may tear themselves apart during contraction
What are the main symptoms of Duchenne’s Muscular Dystrophy (DMD)?
-Gower’s sign (use of hands/knees for strength) -Contractures (shortened muscles, don’t stretch) -Pseudohypertrophy (enlarged calf/deltoid muscles before fat/CT show up) -Difficulty standing/weakness
What are the two main treatments for Duchenne’s Muscular Dystrophy (DMD)?
-Ataluren - makes dystrophin -Steroids - prednisolone
What is the difference between Becker’s and Duchenne’s muscular dystrophy?
Duchenne’s is the complete inability to produce dystophin whereas Becker’s is just an insufficient dystrophin production
What is malignant hyperthermia?
Malignant hyperthermia is a rare, autosomal dominant disorder that causes a life threatening reaction to certain drugs used for general anaesthesia due to a faulty protein channel for calcium
What are the main symptoms of malignant hyperthermia?
- Uncontrolled increase in skeletal muscle oxidative metabolism -Sharp CO2 increase, O2 decrease -Circulatory collapse
How do the symptoms of malignant hyperthermia occur?
-Exposure to the volatile anesthetic agents and the neuromuscular blocking agent, succinylcholine -Excessive calcium release -High amounts of ATP needed to put calcium back
What is the main treatment for malignant hyperthermia?
-Treat hyperthermia + complications -Discontinuation of triggering agent -Dantrolene which works by preventing calcium release
How do you treat Kwashiorkor?
Make alterations to the diet to ensure correct amount of protein intake. However, be aware of refeeding syndrome!
How do you treat Marasmus?
Changes to the diet - avoid REFEEDING SYNDROME!
What are the symptoms of Galactosaemia?
-Cataracts -Glaucoma -Damage to the kidney, liver and brain possible by galactose-1-phosphate
What are the symptoms of hypercholesterolaemia (hyperlipoproteinaemias Type IIa)?
-Corneal Arcus -Tendonal Xanthoma (fatty deposits on tendons) -Xanthelasma - fatty deposits under skin (around eyes) -Absence or deficiency of LDL receptors
What are the symptoms of Kwashiorkor?
-Abdominal distension due to enlarged liver (hepatomegaly) and odema (ascites) -Anaemia (low serum albumin) -Lethargy/apathy
What are the symptoms of Marasmus?
-Muscle wasting -Loss of body mass -Thin and dry hair -No oedema -Diarrhoea
What causes Galactosaemia?
The lack of the galactose kinase or galactose 1-phosphate uridyl transferase enzyme causes build up of galactose or galactose 1-phosphate and galactose respectively.
What causes Kwashiorkor?
A complete deficiency of protein, however, a small amount of carbohydrate remains in the diet
What causes Marasmus?
Marasmus is caused by a diet lacking in all types of food, it is not only a protein deficiency
What treatments are available for treating hyperlipoproteinaemias?
-Lifestyle -Diet -Statins (block the HMG CoA reductase enzyme) -Bile sequestrants (prevent reabsorption of bile into gut)
Which skin condition results in patchy hair loss? How is it caused?
Alopecia areata caused by the autoimmune destruction of hair follicles
Which skin condition results in patches of depigmentation? How is it caused?
Vitiligo - autoimmune destruction of melanocytes
What is the cause of multiple sclerosis?
An autoimmune condition where the myelin sheath around axons is destructively removed, in a patchy fashion, then replaced with scar tissue. The conduction velocity slows down, as salutatory propagation is impaired.
What is placenta praevia?
Implantation in the lower uterine segment which leads to the placenta growing and blocking the cervix.
What is an ectopic pregnancy?
Where there is implantation anywhere other than the uterus (possibly in the fallopian tube)
What intervention is usually given for placenta praevia?
Caesarian section
What intervention is usually given in ectopic pregnancy?
-Methotrexate - termination of pregnancy -Surgical removal
Why is it that ectopic pregnancy can quickly become a life-threatening emergency?
It can cause damage to the site it is growing in.
In cystic fibrosis which protein channel is affected? What does it transport?
Cystic fibrosis transmembrane conductance regulator (CFTR) channel transports chloride ions across epithelial membranes
If there is a defective CFTR protein what happens to the secretions of epithelial cells?
Becomes more viscous
What is the main problem cystic fibrosis causes for the lungs?
Thick and viscous mucous leads to recurrent infection
What is the main problem cystic fibrosis causes for the pancreas?
The mucous blocks the pancreatic ducts reducing the production of insulin and preventing digestive enzymes from reaching the intestines to aid digestion
What possible treatments and management steps are available for cystic fibrosis?
-Physiotherapy -Antibiotics -Infection management -Gene replacement
What are the signs and symptoms of glucose 6-phoshate dehydrogenase deficiency? How are they caused?
-Fatigue (heinz body formation) -Dark urine/Jaundice (bilirubin formation from haemolysis)
What is a glycogen storage disease?
An abnormality in one or many of the enzymes of glycogen metabolism.
What is phenylketonuria?
Inherited disorder in which the urine contains large amounts of phenylketones produced from phenylalanine (can’t break down phenylalanine)
Which enzyme is normally defective in phenylketonuria?
Phenylalanine hydroxylase
What builds up when phenylalanine hydroxylase isn’t functioning correctly?
Phenylalanine accumulates in tissues and blood and is metabolised by other pathways to produce various products (phenylpyruvate) that are excreted in the urine.
How is phenylketonuria treated?
Diet low in phenylalanine.
What is homocystinuria?
A rare inherited autosomal recessive defect in methionine metabolism, caused by a deficiency in the cystathionine β-synthase (CBS) enzyme
What does the CBS normally convert homocysteine to? What is this further converted to?
Cystathionine further converted to cysteine
What does elevated plasma levels of homocysteine cause?
Causes disorders of connective tissue, muscle, CNS and the cardiovascular system
What is homocystine?
The oxidised form of homocysteine
In children what other condition is homocystinuria often misdiagnosed as?
Marfan’s syndrome
What are the main symptoms of hyperammonaemia?
-Blurred vision -Tremors -Slurred speech -Coma
What is the main reason high levels of ammonia can be so damaging to the body?
Ammonia may react with αlpha ketoglutarate to form glutamate in mitochondria via glutamate dehydrogenase removing α¬-ketoglutarate from the TCA cycle
What can reduced liver function can result in?
-Reduced uptake of conjugate bilirubin → Hyperbilirubinaemia → Jaundice - Decreased Urea production → Hyperammonaemia and increased Glutamine -Reduced Protein synthesis → reduced albumin, clotting factors and lipoproteins -Reduced Serum Albumin may produce oedema
What are the main treatments for defects in the urea cycle?
Low protein diet and replacing the essential amino acids with keto acids that use up NH4+ when converted to amino acids, therefore lowering NH4+ concentration.
What are the main symptoms of type 1 diabetes mellitus?
-Polyuria -Polydipsia -Weight loss
What are the main symptoms of type 2 diabetes mellitus?
-Triad of symptoms -Lack of energy -Persistent infection -Visual problems
What tests are used to diagnose diabetes mellitus?
-Random venous plasma glucose of or above 11.1mmol per litre -Fasting plasma glucose of or above 7mmol per litre -Oral glucose tolerance test of or above 11.1mmol per litre two hours after eating glucose
What are the 6 main features of diabetic ketoacidosis?
-Prostration -Nausea -Vomiting -Dehydration -Abdominal pain -Hyperventilation
What are the two main reasons for the creation of large amounts of ketone bodies in type 1 diabetes mellitus?
-High rate of Beta oxidation of fatty acids in liver -Low amount of insulin
What are the microvascular clinical complications of diabetes mellitus?
-Eye (glaucoma due to osmotic effects of glucose and blindness due to damaged blood vessels which is diabetic retinopathy) -Kidney (nephropathy poor blood supply and damaged glomeruli) -Neuropathy (damaged nerves leading to loss of sensation) -Feet (low peripheral blood vessels and nerves - might lose feet)
What are the macrovascular clinical complications of diabetes mellitus?
-Increased risk of MI -Increased risk of stroke -Poor peripheral circulation
What is used to manage type 1 diabetes mellitus?
Insulin injection
What is used to manage type 2 diabetes mellitus?
-Sulphonylureas (increase insulin release from beta cells) -Metformin (reduces gluconeogenesis) -Diet and exercise management -Insulin injection
List two problems, for molecules, of too much circulating glucose in persistent hyperglycaemia
-Aldose reductase converts glucose to sorbitol which depletes NADPH -Non-enzymatic glycosylation os plasma protein alters its structure and therefore function.
What occurs in systemic sclerosis (SSc)?
-Connective tissue disease where all organs have excessive accumulation of collagen (fibrosis) -Skin, digestive tract, muscles and kidneys hardening leads to functional impairment.
What occurs in kelloid?
Connective tissue disease where an abnormal amount of collagen forms scars of the skin
What is the cause of scurvy?
Vitamin C deficiency results in defective tropocollagen synthesis leading to degeneration of connective tissue as Vit C and Fe2+ needed for prolyl hydroxylase activity.
What are the main symptoms of scurvy?
-.Periodontal ligament (high collagen turnover) is affected -Loss of teeth and bleeding gums
What is the main cause of Marfan syndrome?
Genetic defect in chromosomes that code for fibrillin which is a component of elastic fibres - easier to rupture
What are the main symptoms of Marfan syndrome?
-Tall height + long arms and legs -Large elastic arteries (e.g. aorta) rupture high blood pressure due to size of wall -Streched lung tissue - pneumothorax
What is Osteogenesis Imperfecta?
Rare heritable (Autosomal dominant) disorder which results in the inability/decreased ability of osteoblasts and fibroblasts to produce correct fibres (normally type I collagen) and therefore connective tissue
What are the main symptoms of osteogenesis imperfecta?
-Blue sclera -Fragility of bones (leads to fractures) -Hypermobility of joints -Hearing loss
Why is the diagnosis of osteogenesis imperfecta of significant legal importance?
Symptoms and signs can often be confused with abuse
What is osteoporosis?
Reduced bone density due to a high rate of bone turnover (osteoclasts more than osteoblasts)
What are the 5 main risk factors for osteoporosis?
-Age -Post-menopausal women (reduced oestrogen) -Smoking -Poor diet (not enough ions) -Exercise
What is the cause of rickets and osteomalacia?
Calcium deficiency where bone matrix (osteoid) does not calcify normally and the epiphyseal plate becomes distorted by strains of body weight and muscle activity. (bends)
What is the difference between rickets and osteomalacia?
-Rickets occurs in children -Growing bones in rickets (opposed to remodelling in osteomalacia)
What is a common cause of osteomalacia/rickets? Why?
Vitamin D defiency as involved in the absorption of calcium and phosphate by the small intestine
What is achondroplasia?
Congenital and often hereditary skeletal disorder, caused by failure of proliferation and column formation of epiphyseal cartilage cells. Results in defect in endochondral bone formation which impairs the longitudinal growth of the tubular bones
What are amyloidoses?
Incorrect folding of proteins which results in production of amyloid fibres infiltrating organs
How is sickle cell disease caused?
Autosomal recessive condition resulting in a mutation of A which turns to T resulting in a an amino acid change from glutamate to valine. This forms a sticky hydrophobic pocket, classic sickle shape and aggregation of these cells.
What problems are caused in sickle cell disease?
-Blockage of blood vessels due to aggregations - starvation of oxygen -Taken to spleen early producing excess bilirubin - Jaundice -Sickle cell shape - tears capillaries -Sickle cell anaemia - destroyed red blood cells results in not enough haem
What are the management steps for sickle cell disease?
-Manage underlying symptoms -Prevent sickle cell crisis
What type of thalassaemias result in not enough alpha chains in the protein?
Alpha thalassaemias
How is I-cell disease caused?
Deficiency of the N-acetylglucosamine phosphotranferase enzyme which results in mannose-6-phosphate not being added to proteins so they can’t be targeted to lysosomes and end up in the blood/urine
What triosomy is Downs Syndrome?
21
What triosomy is Edwards Syndrome?
18
What triosomy is Patau Syndrome?
13
What is the karyotype for Turners syndrome? What symptoms usually present?
45, X symptoms include short stature, low set ears and webbed neck
What is the karyotype for Klinefelters syndrome? What symptoms usually present?
47, XXY symptoms include infertility, male and tits
What is Ethlers-Danlos disease caused by?
A deficiency in reticular fibres (type III collagen fibres) causing ruptures in tissues with high amounts of these fibres - high elasticity
What are the symptoms of Ethlers-Danlos disease?
-Unstable joints -Bruise easily -Flat feet
Why is vitiligo considered psychologically less serious in caucasians?
Less noticeable in white people
What is the main symptom of Psoriasis?
Scaling of the skin
What is the main cause of Psoriasis?
Extreme proliferation of the epidermal basal layer - gross thickening of prickle cell layer + excessive stratum corneum production
What is malignant melanoma?
Malignant growth of melanocytes
When is malignant melanoma considered to have a poor prognosis?
Penetration through epidermal basement membrane
What are the two main types of osteoporosis and how are they caused?
Type 1 - Menopause Type 2 - Age
What can cause the hypocalcaemia in Osteomalacia?
Lack of Vitamin D as it helps the absorption of calcium in the small intestine
What is Achondroplasia?
Autosomal dominant condition resulting in decreased endochondral ossification and decreased cartilage matrix formation - common cause of dwarfism
What are the main symptoms of achondroplasia?
-Short limbs -Increased spinal curvature
What is acromegaly?
Excessive growth hormone release leads to an increase in bone width by periosteal growth - no lengthening occurs
What is cretinism?
A deficiency of thyroid hormones leading to mental and physical retardation
What problems can the accumulation of phenylpyruvate cause?
Competitive inhibition of pyruvate uptake by the brain: -Brain development inhibition -Seizures -Albinisim
What is lactose intolerance caused by?
Low activity of lactase enzyme results in lactose build up - has to be broken down by bacteria in the gut
What are the main symptoms of lactose intolerance?
-Flatulence -Diarrhoea -Nausea
Why is paracetamol overdose an issue?
Saturation of the normal Phase II pathway and movement to Phase I pathway which produces toxic product NAPQI
What are the main symptoms of paracetamol overdose?
-Hepatic damage then necrosis -Liver damage -Kidney failure
What is the autoimmune cause of Grave disease and therefore main cause of hyperthyroidism?
Formation of an antibody that stimulates TSH receptors on the thyroid producing excess T3/T4
Name other things that can be causes of hyperthyroidism?
-Ectopic thyroid -Over secretion of TSH and T3/T4 by adenomas -Excessive therapy of hypothyroidism -Excessive treatment of other conditions with drugs - amiodarone
What are the main symptoms of hyperthyroidism disease?
-Exopthalmos -Osteoporosis (due to excessive bone turnover) -Weight Loss -Heat intolerance -Intestinal hypermotility
What is the main treatment for Grave’s disease and how does it work?
-Carbimazole which works by preventing the iodination of thyroglobulin. -Thyroid removal
What are the two main autoimmune causes of Hashimoto’s disease (primary hypothyroidism)?
-Antibody blocks a TSH receptor -Destruction of follicles
What can be other causes of hypothyroidism?
-Adenoma preventing secretion of TSH -Iodine deficiency
What are the main symptoms of hypothyroidism?
-Weight gain -Tiredness -Cold intolerance -Alopecia -Decreased BMR
What is the main treatment for hypothyroidism?
Oral thyroxine
What are the symptoms of hypocalcaemia? How are they caused?
-Convulsions -Arrythmia -Tetany (involuntary muscle contraction) -Paraesthesia (tingling) Due to low calcium at neuromuscular junctions which leads to easier depolarisation
What are the symptoms of hypercalcaemia?
Stoans, moans and groans: -Kidney stones (renal calculi) -Depression and tiredness -Constipation and dehydration
What does an increase in cortisol production result in?
-Increase in gluconeogenesis and glycogenolysis -Muscle proteolysis increases -Lipolysis increases (lipogenesis increases at very high levels) -Decreased immune system
What does a derease in cortisol production result in?
-Muscle weakness -Hypotension -Hypoglycaemia
What is the difference between Cushings syndrome and disease?
Cushings syndrome relates to an elevated level of cortisol detected whereas Cushings disease relates to a tumour in the pituitary resulting in the elevated cortisol
What are the main management steps for multiple sclerosis?
-Steroids (treatment for relapses of MS symptoms) -Beta interferons to modify the disease course
What are the main symptoms of multiple sclerosis?
-Numbness and tingling -Blurring of vision -Problems with mobility and balance -Muscle weakness and tightness
What is the karyotype for Triple X syndrome? What symptoms usually present?
47, XXX which results in a small head and tall stature
What are type I hyperlipoproteinaemias?
A defective lipoprotein lipase enzyme which means core TAGs cannot be removed from the chylomicrons - can’t break down fatty acids
What are the symptoms of type I hyperlipoproteinaemias?
-Eruptive xanthomata -Abdominal colic
What effect does excessive alcohol consumption have on the body?
-Low NAD+ -High Acetyl CoA -Decrease in liver function (due to cell damage from toxic acetaldehyde) -Effect on GI tract (impaired absorption of vitamins and minerals)
What problems does a low NAD+ in excessive alcohol consumption cause?
-Build up of lactate as NAD+ used for conversion from pyruvate -Reduces kidneys ability to get rid of uric acid - you get urate crystal and gout -Gluconeogenesis can’t be activated
Which clinical condition can be identified by a increased level of cortisol and ACTH caused by pituitary adenoma?
Cushings disease
Which clinical condition can be identified by a decreased level of cortisol due to adrenal adenoma?
Addisons disease
What is the treatment for alcoholism and how does it work?
Disulfiram blocks the 2nd enzyme of alcohol metabolism (acetaldehyde dehydrogenase) which causes a build up of acetaldehyde which causes serious “hangover” systems
