clinical conditions Flashcards
what drug is given to alcoholics and how does it work
disulfiram - inhibits aldehyde dehydrogenase
what are the results of prolonged alcohol consumption
- the increased acetyl CoA causes a fatty liver
- the decreased amount of NAD+ leads to lactic acidosis, gout and hypoglycaemia
what is marasmus
deficiency in all nutrients leading to inadequate energy intake
what is kwashiorkor
protein deficiency but adequate energy intake
what are the consequences of kwashiorkor
develop fatty liver as theres no proteins too mobilise the fats in the liver
also oedema as albumin cant be produced so this lowers the oncotic pressure in the blood
what is refeeding syndrome
when those suffering from marasmus and kwashiorkor are given too much foo too fast and so they don’t have the enzymes to break down the food leading to a build up of ammonia
name some inhibitors of the ETC
cyanide and carbon monoxide
how do ETC inhibitors work
they bind to the terminal translocating complex preventing oxygen from binding
name some ETC uncouplers
dinitophenol, thermogenin, fatty acids
how do uncouplers work
they increase the permeability of the inner mitochondrial membrane, dissipating the hydrogen ion gradient, reducing the proton motive force
what drug is given to patients with high cholesterol levels and how does it work
statins works by inhibiting the enzyme HMG CoA reductase
what do ROS cause
lipid peroxidation, disulphide bridge formation, DNA damage, protein damage
what are the cellular defences against ROS
- superoxide dismutase converts superoxide to hydrogen peroxide then catalase converts this to oxygen and water
- glutathione
- vitamins A,C and E
what is galactosemia
deficiency in either galactokinase, UDP-galactose epimerase or uridyl transferase (most common)
what are symptoms of galactosemia
cataracts, renal failure, vomiting, brain damage
why does galactosemia lead to oxidative stress
the build up of galactose is converted by aldose reductase into galacticol (causing cataracts) this uses NADPH needed for cellular defence
what type of drug depletes NADPH
anti-malarials
how does a G6PDH deficiency affect ROS
less NADPH is produced which is used to reform glutathione
what is seen in a G6PDH deficiency
Heinz bodies which are aggregates of cross linked haemoglobin in RBC due to protein damage from ROS
how is paracetamol normally metabolised
broken down in the hepatocyte and conjugated with sulphate
what happens in a paracetamol overdose
NAPQI is produced which Is conjugated with glutathione but this gives less cellular defences against ROS
what drug is given in a paracetamol overdose
acetylcysteine which replenishes glutathione
what is the heel prick test
blood screen test in newborns to test for various diseases such as sickle cell, PKU
what is phenylketonuria
deficiency in phenylalanine hydroxylase giving s build up of phenylalanine which is converted to phenylketonuria
what is the treatment for PKU
low phenylalanine diet, avoid food high in protein
what are the symptoms of PKU
intellectual disability, seizures, hypopigmentation
what cant be produced in PKU
tyrosine
what is homocystinuria
deficiency in cystathioine beta synthase so methionine cant be broken down into cysteine giving a build up of homocysteine
what co factor is required by cystathioine beta synthase
vitamin B6
what is Von Gierke’s disease
deficiency in glucose 6 phosphatase
what occurs in lactose intolerance
don’t have the enzyme lactase so cant break down lactose in glucose and galactose
what are the different types of lactose intolerance
primary - occurs in adults as their lactase allele doesn’t persist
secondary - seen in children due to injury of small intestine
congenital - defect in the lactase gene
what occurs in type 1 hyperlipoproteinaemia
where there is a defective lipoprotein lipase
what occurs in type IIa hyperlipoproteinaemia
defective LDL receptor
what occurs in type 3 hyperlipoproteinaemia
defective apoE
what are the treatments for hyperlipoproteineamia
statins, bile salt seqestrants, increasing exercise, increasing fibre, reduce smoking
how do bile salt seqestrants help in hyperlipoproteinaemia
they bind to bile acids so that more are secreted meaning more cholesterol has to be used to make more bile
what are the symptoms of hypercholesterolaemia
xanthelasma, tendon xanthoma and corneal arcus
how do LDLs lead to atherosclerotic plaques
due to their long half lives they are susceptible to oxidative damage. they are then engulfed by macrophages becoming foam cells which accumulate in the blood vessel walls
what do vit B12 deficiencies result from
dietary deficiency, autoimmune disease causing reduced IF production e.g. crohns
what can cause reduced erythropoiesis
- chronic kidney disease
- chemotherapy giving empty bone marrow
- viruses
- bone marrow infiltration by cancer cells
what are myrloproliferative disorders
overproduction of bone marrow cells
in hereditary spherocytosis which membrane proteins are affected
ankyrin and protein 4.2
what is haemolytic anaemia
increased RBC destruction
name 2 bone marrow tests
- trephine biopsy (remove bone marrow from iliac crest)
- aspiration (remove bone marrow cells)
what is haemochromatosis
excess iron causing organ failure due to deposition
what gene is mutated in hereditary haemochromatosis
HFE - now the HFE cant bind to transferrin receptors meaning too much iron enters cells
what does hepcidin do
binds to ferroportin channels preventing iron absorption from erythrocytes
when and where is hepcidin secreted
from the kidneys in iron overload
what is tested to look for an iron deficiency
ferritin levels (but this is an acute phase protein) and reticulocyte count (low in thalasaemias)
what is histologically seen in hyposplenism
Howell jolly bodies - DNA remnants in RBCs as the spleen isn’t removing these RBCs
what infections are patients with hyposplenism particularly at risk from with hyposplenism
pneumococcus, haemophilius influenza, meningococcus (encapsulated bacteria)
when is eosinophilia seen
asthma, parasite infection, allergic reactions, drug hypersensitivity
what is the most common cause of a goitre world wide
iodine deficiency
what is the most common cause of a goitre in the uk
multinodular goitre
what causes hypothyroidism
autoimmune (Hashimotos disease), TSH/TRH deficiency, inadequate iodine, removal of glands failure of gland
what are the symptoms of hypothyroidism
obesity, intolerance to cold, hoarse voice, bradycardia, puffy face, hair loss, menorrhagia
what is hypothyroidism in infants called
cretinism - gives dwarfed statue, poor bone development, muscle weakness
what is hypothyroidism in adults called
myxoedema - thick puffy skin, muscle weakness, mental deterioration
what is the treatment for hypothyroidism
oral thyroid hormone
what happens to TSH/TRH levels in hypothyroidism
they increase
what is used to view the thyroid glands
technetium 99
what are the causes of hyperthyroidism
toxic adenoma, toxic multinodular goitre, graves disease
what are the symptoms of hyperthyroidism
weight loss, intolerance to heat, tachycardia, increased appetite, warm sweaty hands, lid lad and starring eyes
what symtoms are specific to graves disease
pre-tibial myxoedema and bulging eyes
what is used to treat hyperthyroidism and how does it work
carbimazole which is converted into methimazole which prevents thyroid peroxidase
what is lingual thyroid
when part of the thyroid gland stays on the tongue
what is thyroglossal duct cyst
not all of the thyroglossal duct degenerates - it moves up on tongue protrusion
which cancers have osteoclastic bone metastases
breast, lung, thyroid, renal
what cancer has osteoblastic bone metastases
prostrate
what cancer produced parathyroid hormone related peptide
squamous tumours
what is primary hyperparathyroidism
PTH secreting adenoma
what is secondary hyperparathyroidism
when the parathyroid glands become hyperplastic either due to osteomalacia or renal osteodystrophy
what is osteomalacia
lack of vitamin D
what is renal osteodystrophy
renal failure giving low serum calcium
what are the symptoms of hyperparathyroidism
MOANS - tired, depressed
BONES - bone and muscle aches
STONES - kidney stones
GROANS - abdominal pain, constipation, ulcers
what is the difference between osteomalacia and osteoporosis
osteomalacia is where there is also a loss of minerals as well as bone
what can ALP show about bone turnover
it has increased showing osteoblast activity
what symptoms are seen in hypocalaemia
tingling and tetany
pituitary tumours impinging on the optic chiasm result in what
bitemporal hemi-anopia vision and headache
what does a deficiency in growth hormone result in in children
dwarfism
what are non-functioning pituitary adenomas
tumours which block the movement of hormones from the hypothalamus to the anterior pituitary gland therefore the pituitary gland is not stimulated
what is prolactinoma
prolactin secreting tumour
what are the effects of prolactinoma
menstrual disturbances, fertility problems, galactorrhoea,
what do you treat a prolactinoma with
dopamine as this is a prolactin inhibitor
if the prolactin level is above 5000 what is the likely cause
prolactin secreting tumour
if the prolactin level is increased but is still below 5000 what is the likely cause
non-functioning pituitary adenoma
how do you treat a non-functioning pituitary adenoma
surgery
what pituitary hormones require a dynamic blood test
GH and ATCH
what do dynamic blood tests involve
stimulation and suppression tests
what condition results from an excess of GH
acromegaly
what results from an ADH deficiency `
diabetes insipidus - causes more aqua porins to be placed in the kidneys so you lose more water giving large volumes of pale urine
what is ADH also known as
vasopressin
what is pheachromocytoma
a chromaffin cell tumour which secretes catecholamines
what Is primary hyperaldosterone
where there is a defect in the adrenal cortex this could be hyperplasia of the cortex or an aldosterone secreting tumour (Conn’s syndrome)
what is Conn’s syndrome
hyperaldosterone caused by an aldosterone secreting tumour
what is secondary hyperaldosterone
high aldosterone due to problems with RAAS
would renal artery stenosis cause primary or secondary hyperaldosterone
secondary
what are the symptoms of hyperaldosterone
high bp, LV hypertrophy, hypernatraemia, hypokalaemia, stroke
what is given to treat hyperaldosterone
spironolactone which is a mineralcorticoid antagonist
what enzyme is missing in congenital adrenal hyperplasia
2,1-hydroxylase
what happens in congenital adrenal hyperplasia
an enzyme defect meaning that glucocorticoids and mineralcorticoids cant be produced so there are more androgens produced
give an example of a synthetic cortisol
prednisolone
what is cushings syndrome
excess cortisol
what are the causes of cushings syndrome
- cushing disease = ATCH secreting pituitary adenoma
- cortisol secreting adrenal tumour
- non-pituitary adrenal tumour (squamous tumour)
what are the symptoms of cushings syndrome
fat redistribution to the abdomen, back (buffalo hump), face
thin arms and legs and purple stretch marks due to protein breakdown
what is addisons disease
cortisol deficiency
what are the signs of addisons disease
hypotension, weight loss, increased skin pigmentation, hypoglycaemia
why do you get increased skin pigmentation in addisons disease
ATCH is increasing which comes from the POMC gene which also codes for MSH causing the activation of melanocytes
how do you treat addisons disease
lifelong treatment of synthetic cortisols
what are synthetic cortisols also used to treat
inflammatory diseases such as asthma, rheumatoid arthritis
what is an addisonian crisis
when there is very low cortisol levels causing nausea, vomiting, pyrexia, hypotension
what do you give to someone in an addisonian crisis
IV fluids and synthetic cortisol
what happens in type 1 diabetes
autoimmune disease destroying beta cells through auto antibodies
what happens in type 2 diabetes
there is a reduced sensitivity of the insulin receptors
what are the symptoms of type 1 diabetes
polyuria, polydipsia, weight loss and tiredness
if left untreated what can type one diabetes lead to
hyperglycaemia, ketoacidosis, dehydration
why does type 1 diabetes lead to ketoacidosis
there is a decrease in insulin so less cholesterol is produced and so the acetyl CoA is used to produce ketone bodies instead
why does ketoacidosis lead to hyperventilation
to try and expel the acidic CO2 to reduce acidity
what are the microvascular complications of type 1 diabetes
diabetic eye disease, retinopathy, nephropathy, neuropathy, diabetic foot
what are the macrovascular complication of type 1 diabetes
stroke, MI, poor circulation to peripheries
what tests would you use to look for diabetes
urine dipstick
HbA1c
smell of acetone
finger prick
what is a HbA1c test
looks for bound glucose to RBCs which shouldn’t be above 6.5
what are the normal glucose levels
3.6-6 mmol/L
what is the renal threshold for glucose
10 mmol/L
what is the management for type 1 diabetes
insulin, diet and exercise
what is the management for type 2 diabetes
metformin and sulphonylureas to increase insulin sensitivity
insulin
diet and exercise
