Chemical Biology Flashcards
Commonest cause of hypercalcemia
primary hyperparathyroidism parathyroid adenoma
High calcium, PTH supressed, increased ALP
malignancy
no longer sensitive to PTH so high PTH despite high calcium
Tertiary hyperparathyroidism
This condition expresses 1 alpha reductase and causes hypercalcemia
sarcoid
The three commonest causes of hypercalcemia
primary hyperthyroidism, cancer, sarcoid
Rememberpatient coming over with constipation, kidney stones and some psychiatry symptoms, bone pain
malignacy
What is the best treatment of hypercalcemia
fluids, fluids, fluids,
Baby with seizures - Low Ca, Low PTH:
DiGeorge
The calcium stones in hypercalcemia have Ca in them and they are
radiopaque
What is secondary treatment of hypercalcemia?
Then after 4l of fluid within 24h was given, give frusemide
give IV pamidoronate in the patient with known cancer
If the patient has known cancer then you give X for hypercalcemia
IV pamidronate
What would the X-ray show of person with hypercalcemia?
Radial aspect cystic changes
If you have a patient with sarcoid –
give them steroids
how does sarcoidosis cause hypercalcemia?
Macropages express 1 alpha hydroxylase
What would the glucose be in someone with Impaired Glucose Tolerance, 2hr after a OGTT
Impaired glucose tolerance (IGT) is defined as fasting plasma glucose less than - 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l
raised ALT and AST
Cirrhosis
Woman with colicky abdominal pain, raised ALP markedly, others might have been deranged, unsure
Complete biliary obstruction
can cause hepatic cirrhosis and portal hypertension in some and cardiomyopathy in others
Haemachromatosis
Markers of synthetic function
Clotting albumin and PT
HONK
↓K, high glucose, high serum osmolality >320, high bicarb bicarbonate >15mmolL
Low sodium, high serum osmolality, 50 year old woman
Diabetes mellitus - high lipids create a pseudohyponatraemia with normal osmolality
3 days post prostatectomy with low sodium and everything else normal - fluid overload (they give plain water in TURP)
Post prostatectomy
↓K, ↑Na (hypertension), inadequate aldosterone synthesis, hyperandrogenism
Congenital adrenal hyperplasia-11 beta hydroxylase deficency
Pt with HTN - high Na, Low K, high aldosterone:low renin
Conns
The commonest cause of congenital adrenal hyperplasia
21 hydrozylase deficiency
Wchich metabolite would be raised in 21 hydroxylase deficiency?
17 hydrocyprogesterone
Increased levels are seen in the urine of CAH patients?
preganetriol
What is used to diagnose SIDAH
serum osmolality
Pt becomes drowsy 24 hours after RTA - high Na
Diabetes insipidus
Dementia/dermatitis/diarrhoea -
niacin (=pellagra): B3
Diet poor in veggies, nuts yeas. In coeliac disease, also caused by drugs
Folate
Indian lady who is vegan with tiredness and Imacrocytic anaemia -
B12
Coeliac disease with swollen tongue and macrocytic anaemia -
B12
Someone ‘lacking intrinsic factor’.
B12
Crohn’s and macrocytic megaloblastic anaemia
could be methotrexate causing folate deficiency
Crohn’s – [as terminal ileum required to absorb and this is commonly affected in Crohn’s]
B12 deficiency
Woman with hypothyroidism, T1DM, adrenal failure (polyendocrinopathies – autoimmune and is hinting towards pernicious anaemia): autoimmune anthropic gastritis
B12, Shmidt Disease
High LH, FSH, everything else normal
Premature Ovarian Failure
Very high prolactin and everything else suppressed
prolactinoma/Macroadenoma
High GH, high prolactin? everything else suppressed
acromegaly
All values were within normal range
non-‐functioning adenoma
Everything normal but low TSH
subclinical hypothyroidism
Everything normal but high TSH and high prolactin (but less than 1000):
primary hypothyroidism
high TSH, low T3, T4, everything else normal
Myxoedema
(any tumor that secrets IGF-2) hypoglycaemia – incomplete low glucose, insulin, C peptide, FFA and ketones
non-islet cell tumor
○ Neonates: ■ Ketones present:
IUGR
Neonantes, ketones absent
inherited metabolic disorder
high prolactin as it presses on the stalk causing pituitary failure -> low dopamine and high prolactin
Non-functioning pituitary adenoma
Patient can’t fit in her shoes or put on her wedding ring and has prognathism,
Acromegalic symptoms – OGTT – (GH elevated), IGF (high through the day). Glucose normally suppresses the GH
Thin skin, proximal myopathy, impaired fasting glucose -> what test do you need to do to confirm
dexamethasone suppression test
Pt with ↓Na, ↑K + postural hypotension what test do you need to do to confirm
short synACTHen test. This is addisions, one causes of hyperkalemia (renal failure, drugs. adrenals)
Addison’s disease: investigations
In a patient with suspected Addison’s disease the definite investigation is a ACTH stimulation test (short Synacthen test). Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM. Adrenal autoantibodies such as anti-21-hydroxylase may also be demonstrated.
If a ACTH stimulation test is not readily available (e.g. in primary care) then sending a 9 am serum cortisol can be useful:
> 500 nmol/l makes Addison’s very unlikely
< 100 nmol/l is definitely abnormal
100-500 nmol/l should prompt a ACTH stimulation test to be performed
Associated electrolyte abnormalities are seen in around one-third of undiagnosed patients:
- hyperkalaemia
- hyponatraemia
- hypoglycaemia
- metabolic acidosis
Patient with low sodium, potassium: normal, low plasma osmolality and urine osmolality was 70
water deprivation test
To distinguish if it is cranial or nephrogenic diabetes insipidus you do
Vasopressin test
Polyuria, polydipsia, hyponatraemia and high ish serum osmolality -> blood glucose, as high lipids can cause pseudohyponatraemia.
OGGT
Impaired fasting glucose -
6.1-6.9
Impaired glucose tolerance -
2 hours post glucose ≥7.8 and <11.1
Diabetes - fasting glucose
fasting glucose ≥7.0, or 2 hour glucose ≥11.1. you do OGGT if fasting is less <7 mMN ○ Need symptoms + one of these tests OR ○ Both of these tests ○ WHO also recommends HbA1c ≥48
Rate limiting enzmye in Haem synthesis
ALA synthase
Deficiency resulting in urate overproduction
-linked HGPRT = Leach Nyhan (self mutilating, choreiform movements, mentally retarded, gout)
Seen in the kidney of someone with T1DM - renal sclerosis
AA
Emphysema in someone who hasn’t smoked
A1AT deficiency
Raised in someone with mumps
amylase
Boys with the salt-losing form typically present at 7-14 days of life with vomiting, weight loss, lethargy, dehydration, hyponatraemia and hyperkalaemia and can present in shock.
CAH – salt losing crisis (21 hydroxylase deficiency – presents at birth)
ALP + pain defecating
metastases
Fatty acid oxidation defects testing
blood spot for acylcarnitine profile
You take a urine sample from a hypoglycaemic neonate.Lab tells you amount of urine is not enough to do all tests. Which test/substance would you want to rule out ASAP?
Galactosaemia - commonest is Gal-1-PUT and is also the most severe
Vomiting since 5 years of age, followed by the failure to thrive.
Tyrosinaemia
Diarrhoea and bloody stools, vomiting, poor weight gain, extreme sleepiness, irritability, ‘cabbage like odour’ to skin or urine
Tyrosinaemia
Succinylacteonate is pathognomic
of tyrosinaemia
Muscular hypotonia, seizures, hepatic dysfunction, dysmorphia
Perioxisomal - disorders in metabolism of very long chain fatty acids
Perioxisomal disorders have LD and more eye signs
Zellweger
inverted nipples and subcutaneous fat pads-lipodystrophy
Glycosylation
cherry spot’ on the retina
Tay-Sachs
fat accumulation in the liver
Gaucherie Disease
Encephalopathy, respiratory alkalosis and irreversible neurological damage
Urea cycle
Encephalopathy, respiratory alkalosis and irreversible neurological damage: ○ High ammonia
the first test you would order
sweet smelling urine, also smell of ear wax, seem healthy at birth but quickly deteriorate with severe brain damage during times of metabolic crisis & can die of cerebral oedema. Also build-up of leucine, isoleucine and valine.
Maple syrup urine disease
presents in early childhood, some remain completely asymptomatic; presents with metabolism is stressed
Acylcarnitines are elevated
excessive glycogen storage and prevents glucose export from gluocneogenetic organs. Present with hepatomegaly and splenomegaly, and ‘doll like faces’’
Von Gierke’s;
○ Classically chronic muscle weakness with hyperlactataemia ○ Elevated lactate after periods of fasting (overnight), elevated CK, CSF protein is raised in
Kearns-Sayre
How do we define osteporosis?
T score <-2.5
How do we define osteopenia?
T-score -1.0-2.5
What is T-score?
T-score is being used from a healthy population of patients
What are the symptoms of high calcium?
Constipations, Poluria, Polydypsia, Neuro, Seizures, Comas
- Low Na, high K, high urea, increased plasma osmolality and increased urine osmality indicated for
the renal cause of hyponatremia, CKD
Q) What are the criteria for SIDAH?
- Hyponatremia
- Plasma Osmolality <270 mMol/L
- Urine Osmolality>100 mMol
-high Urine Na > 20 mMol
- Euvolemia
- No renal adrenal, thyroid dysfunction
baby, hypotensive, hypotension, alkalosis
BAtter syndrome, defect in TAL loop of Henle
What factors lead to hyperkalemia ?
Addison
ACE inhibitors
Renal faulre
Potassium sparring diuretics
What causes hyperkalemia in the presence of low aldosterone?
ACE inhibtors
low pH with hypokalemia
renal tubular acidos
is
ALT, AST (in thousands) high both the same increaseed GGT AST:ALT<1
NAFLD
very high ALP (hundreds), AST and ALT elevated, GGT elevated, high bilirubin
Gallstones
total bilirubin elavted
Raised unconjugated bilirubin - all else normal
Gilbert
AST, ALT super high, ALP also high
Paracetamol overdose
high GGT (hundred) and ALP
Alcohol abuse
bilirubin <100, raised ALT, AST and GGT, bile salts >10
Intrahepatic cholestasis (pregnancy):
raised ALT and AST
Cirrhosis
very high ALT and AST, ALT>AST
Viral hepatitis
AST: ALT >2.5
Alcoholic hepatitis:
20 year old student with two weeks anorexia, fever and malaise - raised ALT, normal ALP and GGT.
Infectious mononucleosis
Isolatted GGT
enzyme inducing drugs
raised conjugated bilirubin
Dubin Johnson
very high constant unnjocugated hyperbilibuinamiea
Criglet-Najar
increased alpha-fetoprotein
hepatocellular carcinoma
Familial hypercalcaemia
abnormal secretion of thePTH despite high Calcium, results in the mutation of the recptor located on the kidneys and parathyroid glands (mutated receptor on both).
THIS WILL BE HYPOCALCURIS STATE LEADING TO REDUCE CALCIUM
The most common cause of secondary hyperparathyroidism
chronic renal failure
Autonomus productio of PTH causes hypercalcemia
tertiary hyperparathyroidism
resistance to PTH, high PTH, high Phospate, hypocalcemia
pseudohypoparathyroidism
ataxia and areflexia in cystic fibsosis patient is caused by which vitamin deficency ?
vitamin K
what sort of anemia is causing B6 deficency?
sideroblastic anemia
brittle hair and seizures
homocytinuria
developmental delay and musty smell also eczema
1) when was this child born?
phenylketonuria
baby with enlarged liver, kidneys and hypoglcemia
von Gieerke
baby with sweaty feet
maple syrup disorder
cheery spot on the trunk
Fabry
hypotension, ataxia, heart block are consequency of which drug toxicity
Phenytoin - antieplieptic
diarrohoea, vomitting, tremor and signs of which drug toxicity
Lithium
the tocxic effects of this drug are potentiated by cipro or erythromycin
theophylline
the potassium you would see in untreated DKA
high
calculate osmolarity
2(Na + K) + urea + glucose
calculate anion gap
(Na + K ) – (Cl+HCO3-)
- what would bicarbonate be in pyloric stenosis is hypochloremic hypokalemic metabolic alkalosis
(40)
- What would the glucose be in someone with Impaired Glucose Tolerance, 2hr after a OGTT
Impaired glucose tolerance (IGT) is defined as fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l
Low Na, high K, high urea, increased plasma osmolality and increased urine osmality
renal cause of hyponatremia
Markers of synthetic function:
Clotting albumin and PT
Impaired fasting glucose -
6.1-6.9
Impaired glucose tolerance
2 hours post glucose ≥7.8 and <11.1
diabetes definition
-
fasting glucose ≥7.0, or 2 hour glucose ≥11.1. you do OGGT if fasting is less <7 mMN
- Need symptoms + one of these tests OR
- Both of these tests
- WHO also recommends HbA1c ≥48
What is the normal range of anion gap?
The normal range = 10-18 mmol/L
- T1DM (DKA) (↑K, ↓Na, ) – (↓Cl, + bicarbonate: (BG)) > 12 mmol/L. (anion gap) normal
Respiratory alkalosis, hyperventilation caused by hypoglycaemia
metabolic acidosis, high anion gap -
DKA
- Hyperosmolar hyperglycaemic state (HHS) is confirmed by:
- Dehydration
- Osmolality >320mosmol/kg
- Hyperglycaemia >30 mmol/L with pH >7.3, bicarbonate >15mmolL and no significant ketonenaemia <3mmol/L
A low urine osmolality high serum osmolality (±↑Na, ↑±Ca, ↓±K)
Diabetes Insipidus
Q) What atre the causes of hyperkalemia?
Renal problem
Drugs: spironolactone ACE inhibitors Angitensin recptor blocage like Lozartan
Low aldersrone (Addison Disease)
type IV renal tubular acidosis (low renin, low aldosterone)
How would you manage a patient with hyperkalemia?
- 10 ml 10% Calcium glucoganate to stabilise the heart
- 50% 50 ml glucose plus 10 units of insulin
- nebulised salbutammol
How does loop diuretics and Batter syndrome lead to hypokalemia?
Increased Na delivery to the distal nephron
What are the causes of hypokalemia?
- GI loss
- Renal loss (hyperaldosteroidism, increased Na delivery to the distal nephron, osmotic diuresis)
- Redistribution of the insulin into the cells:
- insulin, beta aginist, alkalosis
Rare causes: renal tubular aicdosis, 1, 2 hypomagnesemia
-
How would you manage the patient with hypokalemia
K 3-3.5
two Sandok tablets
How would you manage the hypokalmeic patient with serum K < 3.0 mmol/L
IV K chlorride
10 mmol/hour
Hypokalemia is a side effect of which drug?
Frusemide
Hyperkalemia is side effect of which commonly presribed drugs?
Ramipril, Losartan, sprironolactone
Which drugs are causing SIDAH?
STOCK
SSRI
TCA
Opiates
Carbamazepine
What are the causes of hypernatremia (rare)?
GI loses
sweatings
Renal causes
- osmotic diuresis
- disbetes inispidius
What is the most reliable method to establish hyponatremia?
low urinary sodium
•How would you manage a hypovolaemic patient with hyponatraemia?
Volume replacement with 0.9% saline
•What is the most important point to remember while correcting hyponatraemia?
–Serum Na must NOT be corrected > 8-10 mmol/L in the first 24 hours
Why?
Due to risks of central pontine myelinosyits
Drugs used to treat SIADH if water resitriction is insufficent?
•Demeclocycline
–Reduces responsiveness of collecting tubule cells to ADH
–Monitor U&Es (risk of nephrotoxicity)
•Tolvaptan
–V2 receptor antagonist
•What is the first step in the clinical assessment of a patient with hyponatraemia?
B.1st Clinical assessment of volume status
A.2nd Measure plasma & urine sodium
What tests would you use for the diagnosis of agromelay?
OGGT and IGF
Oral glucose tolerance test
in normal patients GH is suppressed to < 2 mu/L with hyperglycaemia
in acromegaly there is no suppression of GH
may also demonstrate impaired glucose tolerance which is associated with acromegaly
everything normal but decreased bone mineralisation; ALP can be raised if recent fracture
osteoporosis
low calcium and phosphate, high ALP and PTH
osteomalacia
High calcium, PTH supressed, increased ALP
malignancy
no longer sensitive to PTH so high PTH despite high calcium
Tertiary hyperparathyroidism -
low calcium and PTH was in the normal range [but you expect it to be low
hypoparathyroidism
10 year old with seizures- Low Ca, low PO4 , High PTH
rickets
Low Ca, Low PTH: Hypoparathyroidism
DiGeorge
Band kerpatpahy of the eye is complication of whaT?
hypercalcemia
Lists four complications of hypercalcemia?
- Pancreatitis
- Peptic Ulcers
- Skeletal changes
- Renal stones
What test would you do to diagnose SIDAH?
Hyponatremia
low plasma osmolalaity
high urine osmolality
high urine sodium
euvoleia
no urine, renal, thyroid dysfunction
low calcium, low phosphate, high PTH and high ALP
Vitamin D
- All values of pititary hormones were within normal range
(non-‐functioning adenoma)
Everything else supressed, high prolactin but less than <6000
non-functioning adenoma
C-peptide levels are high:
- C peptide levels are high in insulinoma, and elevated with oral sulfonylureas (stimulate insulin secretion), type 2 diabetes, indulin resitance
C-peptides levels are low:
type I diabetes, exogenous insulin, liver disease
- incomplete low glucose, insulin, C peptide, FFA and ketones
Non islet cell tumour (any tumor that secrets IGF-2)
The presence of ketones in neonates suggests:
that the baby is premture and this might be IUGR
The absence of ketones in neonate suggest that
this might inherited metabolic disorder
low dopamine and high prolactin
Non-functioning pituitary adenoma
Rate limiting enzmye in Haem synthesis
ALA synthethase
self mutilating, choreiform movements, mentally retarded, gout)
Deficiency resulting in urate overproduction –X-linked HGPRT
What happens to the kidney of someone with T1DM
renal scleriosis
- Boys with the salt-losing form typically present at 7-14 days of life with vomiting, weight loss, lethargy, dehydration, hyponatraemia and hyperkalaemia and can present in shock.
- crisis (21 hydroxylase deficiency – presents at birth)
Woman with problems in urinating (stones) and defecating (constipation)
- ALP + pain defecating =metastases
Tests for metabolic disorders. [urine reducing substances; urine amino acids; etc]
- You suspect Acute Intermittent Porphyria. What test? Urine sample protected from light
- What does the Guthrie test measure? Phenylalamine
- Urine reducing substances. Galactosemia
- Urine amino acids. Homocystinuria Organic acidurias LIV (leucine, isoleucine, valine)
- Fatty acid oxidation defects blood spot for acylcarnitine profile
Muscle biopsy: Glycogen storage disease
Diarrhoea and bloody stools, vomiting, poor weight gain, extreme sleepiness, irritability, ‘cabbage like odour’ to skin or urine, liver issues
Tyrosinaemia
- Succinylacteonate is pathognomic
tyrosinaemia
- : large fontanelle, osteopaenia of long bones, often with calcified stippling in the patellar region
- Very long chain fatty acid profile
paroximal disorders
inverted nipples and subcutaneous fat pads-lipodystrophy
Glycosylation defect
Tay (opthamologist who discovered the ‘cherry spot’
Tay Sachs
- Encephalopathy, respiratory alkalosis and irreversible neurological damage
- Urea cycle
Acylcarnitines are elevated
MCADD:
- excessive glycogen storage and prevents glucose export from gluocneogenetic organs. Present with hepatomegaly and splenomegaly, and ‘doll like faces’’
von gierke
- Classically chronic muscle weakness with hyperlactataemia
Elevated lactate after periods of fasting (overnight),
Kearns Sayre:
