Chem Path Flashcards
Difference between osmolality and osmolarity
Osmolality –> more accurate and based on mass of solvent
osmolarity –> more practical and based on volume of solvent
Calculated osmolality equation, what is normaly/abnorml?
2(Na+K) + glucose + urea
NOTE: Normal osmolality is between 275-295. If measured osmolality – calculated osmolality >10, it means there is other substances in the blood that aren’t part of the equation.
- HHS (Hyperosmolar Non-ketotic Coma – HONC) (highest glucose osmolality) - glucose in T2DM, Dx criteria = osmolality >320 ++profound dehydration
- DKA - glucose in T1DM + dehydration
- DI - either no ADH production (cranial) or collecting duct cells insensitive to ADH (nephrogenic), so less H2O reabsorption
- Pneumonia - can result in SIADH, but not all cases
- SIADH - ADH causes excess H2O reabsorption, so would expect serum osmolality <270, hyponatraemia
If both blood volume and osmolality low, which needs to be fixed first? When might this situation arise?
Fix blood volume first, may occur if patient has hypovolaemia due to haemorrhage
NOTE: Low volume –> increased ADH release, but low volume typically suppresses ADH release
Pseudohyponatraemia
Low sodium with normal/high plasma osmolality
Caused by myeloma/lab machine errorr and glucose respectively
MOST IMPORTANT THING TO ASSESS IF BOTH SODIUM AND OSMOLALITY ARE LOW
FLUID STATUS
Hypovolaemic hyponatraemia, how to differentiate between causes, how to manage?
How does urinary sodium differentiate between causes of hyponatraemia?
<20 - extra renal loss
>20 renal loss
Why not to correct hyponatraemia quickly?
central pontine myelinolysis (CPM) is a neurological disorder that most frequently occurs after too rapid medical correction of sodium deficiency (hyponatremia)
Hypervolaemic hyponatraemia, how to differentiate between causes, how to manage?
What medication can be used in hypervolaemic hyponatraemia if fluid restriction doesn’t work?
- DEMOCLOCYCLINE –> REDUCES RESPONSIVENESS OF COLLECTING DUCT TO ADH
- TOLVAPTAN –> V2 ANTAGONIST
Euvolaemic hyponatraemia, how to differentiate between causes, how to manage?
Management of SIADH if resistant
Demeclocycline: REDUCES RESPONSIVENESS OF COLLECTING DUCT TO ADH
Vaptans: V2 ANTAGONIST
Causes of SIADH
BRAIN (CRANIOPHARYNGOMA)
LUNG (PNEUMONIA, SMALL CELL LUNG CANCER - PARANEOPLASTIC)
DRUGS (SSRI, TCA, CARBAMEZAPINE, OPIODS, DOPAMINE ANTAGONISTS)
Osmolality levels in hypernatraemia
High
Investigations that need to be sent for euvolaemic hyponatraemia and respective results
Plasma sodium - low
Plasma Osmolality - low
Urinary sodium - high
Urinary osmolality - high
NOTE: Diagnosis of exclusion - need to check TFTs and cortisol first
Causes of hypernatraemia split by fluid status, and management
Causes of Arginine Vasopressin Insufficiency/resistance
CRANIAL DI –> ARGININE VASOPRESSIN INSUFFICIENNCY
NEPHROGENIC DI –> ARGININE VASOPRESSIN RESISTANCE
Diagnostic criteria for diabetes insipidus
NOTE: NEED TO EXCLUDE OTHER CONDITIONS, BEFORE REACHING THIS DIAGNOSIS. Serum glucose, potassium & calcium, plasma & urine osmolality BEFORE WATER DEPRIVATION TEST WHICH IS DIAGNOSTIC.
Blood and urine findings that suggest diabetes
- URINE OSMOLALITY: PLASMA OSMOLALITY RATIO <2
o DIABETES INSIPIDUS EXCLUDED IF URINE:PLASMA OSMOLALITY >2 - URINE VERY DILUTE DESPITE CONCENTRATED PLASMA
Management of diabetes insipidus
- CRANIAL –> DESMOPRESSION (selective agonist of V2 receptors – mimics action of endogenous ADH)
- NEPHROGENIC –> THIAZIDE DIURETICS
Give some causes of hypokalaemia due to renal loss
o XS CORTISOL AND ALDOSTERONE (COULD BE CONN’S OR CUSHING’S)
o LOOP DIURETICS AND THIAZIDES
o T1 AND T2 RENAL TUBULAR ACIDOSIS (ACID AND POTASSIUM LOW)
–> TYPE 1 ASSOCIATED WITH WILSONS
–> TYPE 4 CAUSES ACIDOSIS BUT POTASSIUM HIGH
o BARTER SYNDROME
o GIELTMAN SYNDROME
Difference between Barter and Gieltman syndrome and where they affect
- BOTH CAUSE HYPOKALAEMIA
- BARTER –> LOOP OF HENLE TRIPLE TRANSPORTER
- GIELTMAN –> DCT
NOTE: Both are autosomal recessive conditions with salt wasting, hypokalaemia, and metabolic alkalosis. Bartter has hypercalciuria and normal serum magnesium. Gitelman has low urinary calcium and low serum magnesium.
What does potassium do in comparison to Hydrogen?
Potassium goes hand in hand with Hydrogen, so if low potassium, low Hydrogen too so metabolic alkalosis –> low hydrogen concentration = high pH
What drugs can cause hypokalaemia?
Insulin + salbutamol
Management of hypokalaemia
- 3-3.5:
o ORAL POTASSIUM CHLORIDE TABLES (2 SANDOK TABLETS)
o RECHECK LEVELS - <3:
o IV KCL (MAX 10 MINS) IRRITANT TO VEINS
Drugs that can cause hyperkalaemia
o ACEi
o ARBs
o SPIRONOLACTONE (K+ sparing diuretics)
o NSAIDs
Causes of hyperkalaemia due to low aldosterone
o T4 RENAL TUBULAR ACIDOSIS (low pH but high K+)
o ADDISONS
Management of hyperkalaemia
NOTE: Treat if ECG changes or K+>6.5
- 10ML 10% CALCIUM GLUCONATE FOR 10 MINS
- 50ML 50% DEXTROSE WITH 10 UNITS OF INSULIN
- NEBULISED SALBUTAMOL
- TREAT CAUSE
Actions of PTH
- INCREASING CALCIUM REABSORPTION IN THE KIDNEY
- INCREASING TUBULAR HYDROXYLATION OF VIT D
- MOBILISING CALCIUM FROM BONE
NOTE: PTH affects phosphate by INCREASING EXCRETION OF PHOSPHATE IN THE KIDNEY
Signs + Sx of hypocalcaemia
(THINK CATs go NUMB)
- CHVOSTEK SIGN – tap cheek, twitching on ipsilateral side of the face
- TROUSSEEAU SIGN – carpopedal spasm induced by inflated BP cuff
- Convulsions
- Arrhythmia –> PROLONGED QT SEEN ON ECG
- Tetany
- Paraesthesia
What is Pseudohypoparathyroidism? What is it due to? How does it present? AKA? What is pseudopseudohypoparathyroidism?
Pseudohypoparathyroidism results from an inherited resistance to PTH. They have short 4th and 5th metacarpals, obesity and rounded facies. This syndrome is now known as Albright hereditary osteodystrophy. Pseudopseudohypoparathyroidism presents with the phenotypic appearances of Albright hereditary osteodystrophy but with normal biochemical findings and without resistance to parathyroid hormone (PTH).
Causes of secondary hyperparathyroidisim
CKD and VIt D Deficiency
Cause of tertiary hyperparathyroidism, blood findings?
PROLONGED SECONDARY HYPERPARATHYROIDISM (FROM DIALYSIS) AND RENAL TRANSPLANTS
Blood findings:
- HIGH CALCIUM
- HIGH PTH
- HIGH PHOSPHATE
Fatal complication of hypocalcaemia
Laryngospasm is a fatal complication of hypocalcaemia, hoarse voice & inability to swallow. Often occurs post-thyroidectomy as a complication.
Management of hypocalcaemia
Mild - >1.9mmol/L w/no Sx - oral Calcium, vit D supplement
Severe - <1.9mmol/L w/Sx present - IV calcium gluconate
What should PTH level be in hypercalcaemia?
0
Questions to ask if hypercalcaemia?
- Is it an anomaly? Repeat Test
- CHECK PTH:
o IF SUPPRESSED –> MOST LIKELY CANCER, THEN SARCOID ETC
o IF HIGH –> HYPERPARATHYROIDISM
Causes of hypercalcaemia, most common cause?
- HYPERPARATHYROIDISM –> MOST COMMON IN YOUNG, HEALTHY AND COMMUNITY
- CANCER –> MOST COMMON IN OLD AND ILL, IN SECONDARY CARE
MOST COMMON CAUSE OF HYPERCALCAEMIA IS PRIMARY HYPERPARATHYROIDISM
Causes of primary hyperparathyroidism in order of likelihood
- SINGLE ADENOMA
- HYPERPLASIA
- MULTIPLE ADENOMAS ASSOCIATED WITH MEN1
What fracture can primary hyperparathyroidism lead to? How does this occur?
NB: PRIMARY HYPERPARATHYROIDISM MOST COMMONLY AFFFECTS THE WRIST –> GET COLLES FRACTURE
NBB: COLLES FRACTURE –> FALL WITH HANDS OUT ON EXTENSORS, SMITHS –> FALL ON FLEXORS OF HANDS
Sign of hypercalcaemia on examination
SEE BAND KERATOPATHY (CORNEAL DEGENERATION) ON EXAMINATION
What to suspect if raised PTH with hypercalcaemia?
Suspect Men1 and 2a if primary, differentiate from tertiary by end stage CKD
Types of malignant hypercalcaemia
- PTHrP FROM SMALL CELL LUNG CANCER
- BONE METASTASES
- HAEMATOLOGICAL MALIGNANCY (E.G. MYELOMA)
Management of hypercalcaemia
What is Browns Tumour? What do you get? On histology?
Browns Tumour - Aggregations of osteoclasts caused by hyperparathyroidism. Causes hypercalcaemia. ON HISTOLOGY MULTINUCLEATE GIANT CELLS
What is familial hypocalcuric/benign hypercalcaemia? What’s the mutation?
Mutation in calcium sensing receptor –> don’t excrete PTH as early as should –> mild hypercalcaemia
Vit D synthesis process
- In the skin 7 dehydrocholesterol is converted to cholecalciferol (Vitamin D3)
- Liver converts to 25 hydroxycholecalciferol
- Kidney converts to 1,25-dihydroxycalciferol (calcitriol
Corrected calcium equation
CORRECTED CALCIUM = SERUM CALCIUM+0.02*(40-SERUM ALBUMIN)
What else can cause hypercalcaemia beside cancer?
- Sarcoidosis (non-renal 1α hydroxylation)
- Thyrotoxicosis (thyroxine -> bone resorption)
- Hypoadrenalism (renal Ca2+ transport)
- Thiazide diuretics (renal Ca2+ transport)
- Excess vitamin D (eg sunbeds…)
Blood findings of vit D deficiency
- LOW CALCIUM AND PHOSPHATE
- LOW VIT D
- RAISED PTH AND ALP
o GET HIGH ALP BECAUSE PTH GETS RAISED WHICH CAUSES IN EXCESS BONE RESORPTION
What deformity can be seen in colles fracture?
Dinner fork deformity
Classic fractures seen in osteoporosis
Colles fracture
Neck of femur
Vertebra
Osteoporosis diagnosis
- DEXA SCAN OF WRIST, LUMBAR SPINE AND NOF
- T SCORE LESS THAN -2.5
o Osteopenia between -1 and -2.5
Difference between T score and Z score
T score - healthy person comparison
Z score - age matched control
Medications that can be used for osteoporosis
o VIT D
o ALENDRONIC ACID (BISPHOSPHONATE) –> SE: GASTRIC IRRITATION –> LOW COMPLIANCE
o PTH ANALOGOUE (E.G. TERIPARATIDE)
o OESTROGEN
o SELECTIVE OESTROGEN RECEPTOR MODULATOR (SERM) E.G. RALOXIFENE
MUST LEARN TABLE FOR CALCIUM
- Osteomalacia – Vitamin D very low need for calcium absorption, calcium will fall the most
- 2° PTH – raised PTH 2° to low Ca (short term) (usually in chronic kidney disease, unable to retain Ca)
- Osteoporosis – calcium normal
- 1° PTH - mainly due to parathyroid adenoma/hyperplasia, PTH secretion less than carcinoma
- Parathyroid carcinoma – highest PTH - autonomous release of Ca2+ (lack of -ve feedback)
Commonest cancers that can metastasise to the bone
PB KTL (PROSTATE, BREAST, KIDNEY, THYROID, LUNG) are most common cancer to metastasise to bone
How is H+ buffered in ECF/ICF/RBCs?
Extracellular fluid (e.g. kidney) –> H+ buffered by Bicarb
Intracellular fluid –> H+ buffered by phosphate
In RBCs –> H+ buffered by Hb
Difference between types of RTA (just read)
NOTE: T1/2 are hypokalaemia, T4 is HYPERkalaemia
What is fanconi syndrome? How does it present? Management?
Fanconi syndrome is when there is complete failure of proximal convoluted tubule in kidney to reabsorb molevules –> can be inherited or acquired.
Will present with polyuria, polydipsia and dehydration, failure to thrive, hypokalaemia, T2 RTA, protein and glycosuria, hypokalaemia
supportive treatment.
Causes of metabolic acidosis
- INCREASED H+ PRODUCTION –> DKA, LACTATE, ASPIRIN OD, METFORMIN, UREA
- DECREASED H+ EXCRETION –> RENAL TUBULAR ACIDOSIS (RENAL FAILURE), ADDISON’S (RETENTION OF K+ AND H+)
- LOSS OF BICARB –> INTESTINAL FISTULA (E.G. PANCREATIC), HIGH OUTPUT STOMA, DIARRHOEA
Approach to diagnosis a metabolic acidosis (LEARN)
NOTE: IN METABOLIC ACIDOSIS LUNGS HYPERVENTILE TO SHIFT EQUATION
SEE A DROP IN CO2 WITH A COMPENSATED H+ IN COMPENSATED METABOLIC ACIDOSIS
Equation for anion gap
(Na + K) - (Cl + HCO3) –> normal is 14-18
Table showing metabolic acidosis
Causes of metabolic alkalosis
- INCREASED H+ EXCRETION (E.G. VOMITING – pyloric stenosis)
- POTAASSIUM EXCRETION (HYPOKALAEMIA, LOOP DIURETICS, CONN’S)
o Causes alkalosis as to retain potassium the kidney retains more soidum at expense of H+ - BICARB INGESTION
NOTE: Compensation for by hypoventilation
Table showing metabolic alkalosis
Difference between type 1 and type 2 respiratory failure
T1RF = low O2, normal CO2
T2RF = low O2, high CO2
Cause of respiratory alkalosis
- HYPERVENTILATION –> PANIC ATTACK, SALICYCYLATE OD –> STIMULATE BRAINSTEM EARLY
What blood gas results does aspirin OD present with?
GET MIXED RESPIRATORY ALKALOSIS AND METABOLIC ACIDOSIS –> RESP ALKALOSIS AS STIMULATES RESP CENTRE –> BUT THEN GET INCREASED EXCRETION OF BICARB –> METABOLIC ACID
Best marker of liver function
Prothrombin time
Liver enzyme abbreviations and what they stand for
AST/ALT: HEPATITIS
GGT: ALCOHOLIC HEPATITIS
ALP: OBSTRUCTIVE CAUSE
AST –> ASPARTATE TRANSAMINASE
ALT –> ALANINE AMINOTRANSFERASE
ALP –> ALKALINE PHOSPHATASE
GGT –> GAMMA GUTAMYL TRANSFERASE
Where is ALP found?
Liver
Bone
Placenta
Where else is AST present?
Heart
Specific blood test result for alcoholic liver disease
AST:ALT >2
ALT in the 1000s
viral hepatitis
Difference between prehepatic/hepatic/post hepatic jaundice and how they present
Prehepatic: No urine bilirubin because unconjugated BR (from haem break down by MØ in spleen) is tightly bound to albumin, unable to pass through glomerulus
Post-hepatic: Dark urine seen due to increase urobilinogen/conjugated BR (lots of them absorbed by blood), pale stool = low levels of stercobilinogen + dark urine
What does the type of bilirubin tell you about where the liver issue is?
NB: CONJUGATION OF BILIRUBIN OCCURS IN THE LIVER. SO UNCONJUGATED BILIRUBIN IS A PRE-HEPATIC ISSUE, CONJUGATED IS POST-HEPATIC. A MIXTURE IS INTRA-HEPATIC.
How to differentiate between Rotor syndrome and dubin-johnson? (Both causes of conjugated bilirubinaemia)
Rotor syndrome can be differentiated from other similar disorders, such as Dubin–Johnson syndrome. For instance, the liver has black pigmentation in Dubin–Johnson syndrome, while in Rotor syndrome liver has normal histology and appearance.
How to differentiate between gilbert and crigler-Najjar syndrome? (Both causes of unconjugated bilirubinaemia)
Gilbert’s - deficiency of UDP glucuronyl transferase
Crigler-Najjar syndrome - absolute syndrome
Table showing deranged LFTs and how to interpret
What to check if a patient has raised ALP?
Check GGT to ensure it is a biliary bilirubin
Which cell in thyroid gland prouces calcitonin?
Parafollicular cells
What does thyroperoxidase enzyme do?
responsible for oxygenation and iodination
How do T4/T3 work?
T4 is the primary hormone secreted from the thyroid however T3 is the primary ACTIVE hormone, and end organ tissues convert T4 to T3.
These feedback onto the pituitary and hypothalamus to inhibit further TSH release.
Causes of hypothyroidism
- IODINE DEFICIENCY (MOST COMMON WORLDWIDE)
- HASHIMITOS (ANTI-THYROIDPEROXIDASE ANTIBODIES – TPO)
o MOST COMMON IN UK - DRUGS:
o LITHIUM
o AMIODORANE
How does myxoedema coma present?
Altered consciousness, hypoglycaemia, low GCS, hypothermia
Biochemical pictures to be aware of in thyroid gland
NB: Sick euthyroid mimics subclinical hypothyroidism, body tries to shut down the thyroid gland directly to reduce energy expenditure. Subclinical hypothyroidism detects a failing thyroid gland (due to age, wasting etc), but pituitary is active enough to secrete TSH (high) and this normalises the T3/4 levels. Doesn’t always need treatment (can use levothyroxine), but can develop hyperlipidaemia. Medication non-adherence usually occurs when a patient has not been taking medication properly, and they try and take levothyroxine just before the appointment –> normalises T3/4 but TSH remains high as still acute.
Causes of hyperthyroidism in order of prevalence
- PRIMARY (IN ORDER OF PREVALENCE)
o GRAVES (ANTI-TSH RECEPTOR ANTIBODIES) –> Type 2 hypersensitivity reactions where anti-thyroid stimulating hormone antibodies attack the TSH receptor
o TOXIC MULTINODULAR GOTIRE
o ADENOMA –> Generally not functional, can sometimes cause hyperthyroidism
Why can molar pregnancies cause hyperthyroidism?
HCG has the same subunits as TSH
What is dequervains thyroiditis?
o Acute inflammatory thyroiditis in response to a viral infection –> causes hypersecretion of thyroid hormones initially, then a hypothyroid period, then euthyroid
WHat is post partum thyroiditis?
o Secondary to gland hypertrophy during pregnancy
Image showing iodine uptake in primary hyperthyroidism
NOTE: Focal lesions are consistent with adenomas, multiple patchy lesions are consistent with toxic goitre, and a graves’ would be assoicated with a generalised increased uptake, de Quervain’s generally shows a ‘cold’ thyroid.
How does thyroid storm present? How to treat?
acute shock secondary to very high levels of thyroxine - circulatory collapse, hyper-pyrexia, reduced GCS
Treatment often involves steroids, cooling, organ support in ITU and fast administration of antithyroid medications.
Difference in blood test results between primary and secondary hyperthyroidism
Specific signs and symptoms in graves disease
Pretibial myxoedema (soft tissue growth at the shins and skin changes)
Graves’ orbitopathy is also another specific sign (caused by retrobulbar soft tissue growth)
Lid lag
Exopthalmos
Opthalmoplegia
Management of graves disease
NOTE: carbimazole and propylthiouracil work by inhibiting the action of thyroid peroxidase and also have mechanisms to prevent antibody generation in graves’. Carbimazole is teratogenic. There is a risk of agranulocytosis with both.
Beta blockers are used to treat AF or palpitations
Risks of radioiodine
risk of permanent hypothyroidism.
Causes of thyroid cancer in order of prevalence
- PAPILLARY –> PSAMMOMA BODIES AND ORPHAN EYES ON HISTOLOGY, BEST PROGNOSIS
- FOLLICULAR
- MEDULLARY –> PRODUCES CALCITONIN
- ANAPLASTIC –> WORST PROGNOSIS
- LYMPHOMA –> risk in Hashimoto’s, DLBCL (monitored using CD20)
NOTE: Thyroglobulin levels are monitored for all cancers, apart from medullary –> calcitonin
Table showing MEN syndromes
Hormones produced in anterior pituitary, how are they split?
- ACTH-> affected by CRH
- TSH-> affected by TRH
- LH > affected by LHRH
- FSH-> affected by LHRH
- GH -> affected by GHRH
- Prolactin- affected by TRH and negatively from dopamine
Trophic cells are split into two categories:
- Acidotrophs – Lacto/cortico
- Basilotrophs – thyro/gonado/somato
Types of visual defects caused by pituitary tumorus
Bitemporal hemianopia caused by compression of the optic nerve fibres at optic chiasm
Superior quadrantanopia caused by damage to the inferior optic radiation (temporal meyer loop)
Inferior quadrantanopia caused by craniopharyngioma
Types of pituitary tumours differentiated by size
Macroadenoma – non-functional adenoma >1cm –> not hormone-secreting
Sx of non-functional – bitemporal hemianopia + Headache
Microadenoma – Sx related to hormone secretion <1cm
Summary slide for prolactinoma
1st line investigation for acromegaly, gold standard diagnosis
- PLASMA IGF-1 (1ST LINE)
- DO OGTT IF RAISED, TO CONFIRM DIAGNOSIS OF ACROMEGALY (GOLD STANDARD)
Blood findings of acromegaly
- HYPERGLYCAEMIA
- PROLACTIN
Management of acromegaly
- Transsphenoidal surgery
- OCTREOTIDE –> SOMATOSTATIN ANALOGUE WHICH REDUCES GHRH RELEASED
- CABERGOLINE –> DOPAMINE AGONIST, tumour expresses a lot of D2 receptors
Causes of Cushing’s in order of prevalence
- PITUITARY TUMOURS (CUSHINGS DISEASE) –> 85%
- ADRENAL ADENOMA/HYPERPLASIA 10%
What medication causes Cushing’s?
Iatrogenic steroids
What surveillance should be done in acromegaly?
Colonoscopy surveillance done as there is an increased risk of colonic polyps (colorectal cancer)
Causes of Cushing’s in regards to ACTH
- ACTH DEPDENDENT
o PITUITARY TUMOUR
o ECTOPIC ACTH PRODUCTION
–> SMALL CELL LUNG CACNER
–> CARCINOID TUMOUR - ACTH INDEPDENDENT
o ADRENAL ADENOMA (TUMOUR OF ZONA FASCIUCULATA)
o ADRENAL NODULAR HYPERPLASIA
o IATROGENIC STEROIDS –> MOST COMMON CAUSE OF CUSHING’S SYNDROME
What can non-functioning pituitary adenomas cause?
HYPERPROLACTIN BY PRESSING ON STALK WHICH PREVENTS DOPAMINE TRAVELLING TO APH
What is the only cause of CUshing’s disease?
Pituitary tumour
Investigations of cushing’s in order
- 24 HOUR URINARY CORTISOL
- OVERNIGHT DEXAMETHASONE SUPPRESSION TEST –> LOW DOSE
o IF NOT SUPPRESSED –> CONFIRMS DIAGNOSIS OF CUSHINGS SYNDROME - INFERIOR PETROSAL SINUS SAMPLING
Management of Cushing’s
NOTE: Management of primary cushing’s is through adrenalectomy and then steroid replacement afterwards [if bilateral]. Nelson’s syndrome is a rare complication resulting from adrenalectomy, if the primary pathology is a pituitary tumour or there is a co-existant pituitary tumour, this grows uncontrollably after the removal of the adrenal glands as there is unregulated ACTH secretion. Certain medications - ketoconazole/metyrapone are CYP450 inhibitors and can slow the generation of the steroid hormones but have many side effects
What visual defect does craniopharyngioma cause?
Inferior quadrantanopia
Causes of Hypopituitarism
Sheehan syndrome occurs when the anterior pituitary gland is damaged due to significant blood loss. Classically, this happens after delivery, in which the mother loses a significant amount of blood. This blood loss results in the pituitary gland not being able to produce hormones.
Apoplexy means bleeding into an organ or loss of blood flow to an organ. Pituitary apoplexy is commonly caused by bleeding inside a noncancerous (benign) tumor of the pituitary.
The underlying cause of Kallmann syndrome or other forms of hypogonadotropic hypogonadism is a failure in the correct action of the hypothalamic hormone GnRH – less FSH/LH.
Order of loss of pituitary hormones in hypopituirarism
GH first lost, then sex hormones, then ACTh, then TSH, then prolactin because when TSH is lost, TRH increases which stimulates prolactin, before stores are depleted and then it drops
How to perform a combined pituitary function test
Management of hypopituitarism
NOTE: MOST URGENT HORMONE REPLACEMENT IS HYDROCORTISONE. Then treat underlying cause
Regions of adrenal gland and what they produce
Glomerulosa - Mineralocorticoids (aldosterone)
Fasciculata - Glucocorticoids (Cortisol)
Reticularis - Sex hormones
Medulla - Catecholamines
Steroid synthesis pathway
NOTE: 21 hydroxylase – hypoaldosteronism picture. 11B hydroxylase – hyperaldosteronism picture, as no cortisol formed. 17a hydroxylase – congenital adrenal hyperplasia, disrupted sexual development and maturation.
Causes of addison’s disease (adrenal insufficiency)
- TB (MOST COMMON WORLDWIDE)
- AI (MOST COMMON IN UK)
- ADRENAL HAEMORRHAGE CAUSED BY MENINGOCOCCAL INFECTIONS WATERHOUSE FRIEDRICHSON SYNDROME
What is waterhouse friedrichson syndrome?
Adrenal haemorrhage caused by meningococcal infections that leads to addison’s disease
Blood findings on addison’s
LOW GLUCOSE, LOW SODIUM, HIGH POTASSIUM
Signs on examination of addison’s
SKIN DEPIGMENTATION, POSTURAL DROP IN BP
NOTE: skin depigmentation is due to gamma-melanocyte stimulating hormone (broken down product of POMC – where ACTH comes from)
Schmidt syndrome
HYPOADRENALISM AND HYPOTHYROIDISM OCCURING SIMULTANEOUSLY
Investigations and management of Addison’s
NOTE: double if intercurrent illness, if vomiting, have to admit to hospital
What is often seen alongside addison’s disease?
OFTEN SEE PRIMARY HYPOTHYROIDISM ALONGSIDE DUE TO CONCURRENT AI CONDITIONS (T1DM, HASHIMOTO’s)
Most common cause of primary hyperaldosteronism
MOST COMMON CAUSE IS BILATERAL ADRENAL HYPERPLASIA
How to differentiate between bilateral adrenal hyperplasia and conn’s syndrome?
Most common cause for a primary hyperaldosteronism is actually bilateral adrenal hyperplasia and not Conn’s Syndrome. Adrenal vein sampling (AVS) is used to differentiate between bilateral and unilateral disease.
Presentation of Conn’s syndrome, how to investigate?
- UNCONTROLLABLE HTN
- HIGH NA
- LOW K
PLASMA ALDOSTERONE:RENIN RATIO WILL BE HIGHER
What is phaechromocytoma? What is it associated with?
Tumour of the adrenal medulla
ASx with:
- MEN 2A/B
- NEUROFIBROMATOSIS-1
- VON-HIPPEL LINDAU SYNDROME
Investigation and management of phaeochromocytoma
Investigation:
- PLASMA AND URINARY 24 HOUR:
o METANEPHRINES –> BREAKDOWN PRODUCT
o CATECHOLAMINES
o VANILLYMANDELIC ACID (VMA) FINAL SYNTHESIS STEP
TREATED BY ALPHA BLOCKADE (PHENOXYBENZAMINE) –> BETA BLOCKADE –> SURGERY WHEN BP CONTROLLED
Signs of hypertensive retinopathy
Flame haemorrhages, AV nipping, silver wiring, papilloedema
How to treat hypoglycaemia acutely?
Order of body’s response to hypoglycaemia
- Suppress insulin
- Increased glucagon
- Sympathetic activation
- Cortisol, ACTH and GH all released
What is best measurement for hypoglycaemia?
VENOUS IS GOLD STANDARD, but cbg often done
How can hypoglycaemia be classified?
- HYPOINSULINAEMIC
- HYPERINSULINAEMIC
o CAN EITHER HAVE LOW OR HIGH C-PEPTIDE
Differential for hypoglycaemia, with high insulin and low C peptide
Factitious insulin
NB: This is often seen in someone with T1DM who injects themselves with too much exogenous insulin high insulin levels seen, but low C peptide as not endogenous insulin levels
Differentials for hyperinsulinemic hypoglycaemia with high C peptide
- ISLET CELL TUMOUR INSULINOMA
- SULPHONYLUREA TOXICITY (LEAD TO C PEPTIDE, AND ENDOGENOUS INSULIN RELEASE)
o DIFFERENTIATE BY DOING URINARY/SERUM DRUG SCREEN
If present with hypoglycaemia, low insulin and low c peptide, low FFA and ketones, likely diagnosis is
- PARANEOPLASTIC SYNDROME WHICH PRODUCE BIG IGF2 WHICH BINDS TO IGF-1 AND INSULIN RECEPTOR
- Can also be caused by quinine (anti-malarial) –> PPQ
Key concept of hypoglycaemia
endogenous insulin production will produce equal amounts of C-peptide
Summary slide showing causes of hypoglycaemia
How is diabetes defined?
- Fasting glucose over 7mm
- Glucose tolerance test over 11
- HbA1c over 48mmoL
Impaired glucose tolerance
OGTT BETWEEN 7.8-11.0
Imparied fasting glucose
FASTING GLUCOSE 6.1-6.9
Summary slide showing difference between T1DM and T2DM
Common skin condition seen in Diabetes
Acanthosis nigricans
NOTE: Acanthosis nigricans is a velvety, darkening of the skin that usually occurs in intertriginous areas. This hyperpigmentation has poorly defined borders, usually occurs in skin fold areas, such as the back of the neck, axilla, and groin, and may include thickening of the skin.
MOA of metformin
INCREASES SENSITIVITY TO INSULIN PERIPHERALLY, REDUCES HEPATIC GLUCOGENESSIS
MOA of acarbose
INHIBITS ALPHA GLUCOSIDASE ON BRUSH BORDER OF SMALL BOWEL
MOA of gliptins
INHIBITS DIPEPTIDYL DIPEPTIDASE IV (DPP-IV) WHICH INCREASES INCRETIN (e.g. sitagliptin)
MOA of sulphonylureas
INCREASE INSULIN PRODUCTION FROM BETA CELLS (e.g. gliclazide)
MOA of SGLT-2 inhibitors
SGLT-2 INHBITOR WHICH INCREASES EXCFRETION OF GLUCOSE (e.g. empagliflozin)
Management of Diabetes
NB: SPK –> replace kidney due to end-stage renal disease. SGLT-2 inhibitors –> v useful in heart disease, or renal disease.
Diagnosis of hyperosmolar hyperglycaemic state
- PH >7.3 –> NO KETONES/ACIDOSIS
- GLUCOSE >30
- OSMLARITY >320
Summary slide of hyperglycaemic hyperosmolar state
Kussmaul breathing
deep sighing respiration in an attempt to blow off CO2 - respiratory compensation for a metaboloc acidosis
Diagnosis of DKA
The triad of things you need to have to diagnose DKA are in the title - diabetes (BM >15), a pH of <7.3 and ketones >3.
Most common cause of DKA
Sepsis
ALWAYS DO a septic screen
Summary slide for DKA
What are porphyrias? How do they differ from thalassaemias?
Porphyrias represent inherited disorders of haem synthesis (recall that thallasaemias are inherited disorders of globin synthesis)
Difference between acute and non-acute prophyrias
The main difference is that non-acute porphyrias ONLY give skin lesions.
Types of acute porphyrias
Acute (all autosomal dominant and have similar presentations)
* Acute Intermittent Porphyria (most common acute) -> Abdominal pain + psyhciatric disturbances + seizures. No skin lesions.
- Hereditary coproporphryia -> Similar to AIP, but also presents with skin lesions
- Variegate porphyria -> Similar to AIP but also has skin lesions with photosensitivity
Types of chronic porphyrias
- Congenital Erythopoietic porphyria (CEP) -> Presents in infancy, sun exposure causes severe blistering. Haemolytic anaemia may also be present.
- Erythropoietic protoporphyria (EPP) -> Sun exposure causes burning + itching sensation
- Porphyria Cutanea Tarda (PCT) (most common overall)-> Sun exposure causes crusting + scarring
Most common cause of acute prophyria in UK
ACUTE INTERMITTENT PORPHYRIA MOST USEFUL SAMPLE TO SEND IN ACUTE CASES IS URINE PORPHOBILINOGEN
Most common cause of porphyria in UK
PORPHYRIA CUTANEA TARDA
Only porphyria which presents in children
ERYTHROPOIETIC PROTOPORPHYRIA (Occurs immediately after sun exposure)
NOTE: Investigate with RBC PROTOPOPHYRIN LEVELS
Summary slide for porphyrias
What deficiency seen in acute intermittent porphyria
hydroxymethylbilane synthase (HMB)
Triggers for acute intermittent porphyria
premenstrual, stress or alcohol
Classical presentation of acute intermittent porphyria
young woman or teenager, who has recurrent seizures or abdominal pain around the times of exams. These patients are often mislabelled as having epilepsy plus mental health problems or IBS.
Diagnosis of acute intermittent porphyria
testing levels of aminolevulinic acid (ALA) and porphobilinogen (PBG) in urine during an acute flare.
Treatment of porphyria cutanea tarda
This can be treated with phlebotomy or chloroquine
Cause of porphyria cutanea tarda
- Uroporphyrinogen III decarboxylase deficiency (UROD)
How is CF screend for?
BY IMMUNE REACTIVE TRYPSIN MUST BE ABOVE 99.5TH CENTILE 3 TIMES IF +VE DO GENETICS
What defect in phenylketonuria? What triad? How to screen?
DEFECT IS PHENYLALANINE HYDROXYLASE DEFICIENCY –> CAN’T CONVERT PHENYLALANINE TO TYROSINE
- MENTAL RETARDATION
- BLONDE HAIR
- BLUE EYES
SCREENING IS FOR PHENYLALANINE IN THE BLOOD
How is Medium Chain AcylCoA Dehydrogenase Deficiency screened for? What is the blood finding?
SCREENED FOR BY ACYLCARNITINE BY TANDEM MASS SPECTROMETRY
BLOOD FINDING IS HYPOKETOTIC HYPOGLYCAEMIA AS CANT BREAK DOWN FATS
Triad of homocystinuria
- LENS DISLOCATION
- MENTAL RETARDATION
- THROMBOEMBOLISM
How do urea cycle disorders present? What are their blood findings?
- Resp Alkalosis
- Vomiting (Not Diarrhoea)
- Neuro encephalopathy
- Dietary avoidance of things
High ammonia and resp alkalosis on blood findings
Presentation of organic acidurias in neonates
o Unusual odour
o Limb hypertonia
o HYPERAMMONAEMIA WITH METABOLIC ACIDOSIS (HIGH ANION GAP) –> CALCULATE ANION GAP WITH (NA+K)-(CL+HCO3)
Sx of reye syndrome, triggers?
- VOMITING
- LETHARGY
- INCREASED CONFUSION
- RESP ARREST
REYE SYNDROME IS TRIGGERED BY SALICYCLATES, ANTI-EMETICS, VALPROATE
Mutation in galactossaemia? Main pathological finding?
Disorder of galactose metabolism where Gal-1-Put is mutated leading to elevated levels of Gal-1-phophatase causes kidney and liver disease
MAIN PATHOLOGICAL FINDING IS HIGH NEONATAL CONJUGATED BILIRUBIN
What infection do you get recurrent in galactossaemia?
- Recurrent E.Coli Infections
What is Von Gerkes disease? What blood findings?
Glycogen storage disease where can’t break down glycogen so liver accumulates glycogen
Blood findings:
- HYPOGLYCAEMIA
- LACTIC ACIDOSIS
- NEUTROPAENIA
3 main types of mitochondrial disorders and how they present, be aware - don’t need to learn
- Presents at birth:
o BARTH
CARDIOMYOPATHY
NEUTROPAENIA
MYOPATHY - Presents 5-15
o MELAS
MITOCHONDRIAL ENCEPHALOPATHY
LACTIC ACIDS
STROKE LIKE EPISODES - Presents 12-30
o KEARNS-SAYRE
CHRONIC PROGRESSIVE EXTERNAL OPTHALMOPLEGIA
RETINOPATHY
DEAFNESS
ATAXIA
Important facts to know about lipids
HDL TRANSPORTS CHOLESTEROL TO LIVER
PREDOMINANT TRANSPOROT OF CHOLESTEROL IN FASTED STATE LDL
CHOLESTEROL COMES FROM DIET & BILE IN GI TRACT
BILE ACIDS ARE ABSORBED IN TERMINAL ILEUM
CHOLESTEROL IS ABSORBED IN JEJUNUM
PREDOMINANT TRANSPOROT OF TRIGLYCERIDE IN FASTED STATE VLDL
Dominant genes involves in primary hypercholesterolaemia
o LDLR
o APOB
o PCSK9
Most potent LDL lowering drug in statin intolerant patients who have uncontrolled lipids
Evolocumab - PCSK9 inhibitor
Familial hypercholesterolaemia
gain of function in PCSK9 (LDL receptor mutation)
Function of PCSK9
BIND TO LDLR AND PROMOTE DEGRATION –> GAIN OF FUNCTION MUTATION CAUSES FH, LOSS OF FUNCTION PROTECTS AGAINST CVD
Example of lipid lowering medication used in treatment of familial hypercholesterolaemia
Lomitapide acts by inhibiting Microsomal triglyceride transfer protein (MTP), thereby blocking the release of VLDL from the liver. This in turn leads to reduced LDL levels
Best drug for reducing TG
FIBRATES
Cause of primary hypertriglyceridaemia
- FAMILIAL TYPE 1 LIPOPORETIN LIPASE OR APOC II DEFICIENCY
- FAMILIAL TYPE IV INCREASED SYNTHESIS OF TG
- FAMILIAL TYPE V APOA V DEFICIENCY
Causes of primary mixed hyperlipidaemia
- Familial combined hyperlipidaemia
- Familial dys-beta-lipidaemia type III CAUSED BY ABERRANT APO E/2
o APO E/4 ASSOCIATED WITH A RISK OF ALZHEIMERS DISEASE
o YELLOW PALMAR CREASE (PALMAR STRIAE) IS A PATHAGNOMIC SIGN - Familial hepatic lipase deficiency
NOTE: Human apolipoprotein E (ApoE) plays a crucial role in cholesterol and lipid metabolism. There are three major isoforms of ApoE: ApoE2, ApoE3, and ApoE4. ApoE3 is the most common isoform found in the majority of the population. ApoE4 is found with increased prevalence amongst those with Alzheimer’s disease and is thought to confer increased risk of the condition, whereas ApoE2 is thought to provide some protection against Alzheimer’s disease. ApoE2 is also the cause of Type 3 hyperlipoproteinemia (Familial dysbetalipoproteinaemia), a condition characterised by increased total cholesterol and triglycerides.
Yellow palmar crease is a pathognomonic sign for what
- Familial dys-beta-lipidaemia type III CAUSED BY ABERRANT APO E/2
What is APO E/4 associated with?
Alzheimer’s disease
best drug for reducing high lipoprotein
NICOTINIC ACID
MOA of statin
HMG-CoA REDUCTASE INHIBITOR THAT REDUCES LIVER CHOLESTEROL SYNTHETIC FUNCTION
Causes of hypolipidaemia
- Alpha-beta-lipoproteinamia MTP DEFICIENCY
- Hypo-beta-lipoproteinaemia TRUNCATED APOB PROTEIN
- Tangier disease HDL DEFICIENCY
- Hypo-alpha-lipoproteinaemia APOA-I MUTATIONS
Management of obesity
- 1st line HYPOCALORIC CONSERVATIVE
- MEDICAL ORLISTAT
- SURGICAL BARIATRIC SURGERY IF BMI>35
Best way to determine obesity in a clinical setting
- WAIST HIP RATIO GOOD AT PREDICTING ADIPOSITY AND CHD RISK
- BMI affected by things such as race and muscle mass:
o CUT OFF FOR BMI IS 30
MINUS 2.5 FOR SOUTH ASIA
Fat soluble vitamins, stored where?
FAT SOLUBLE VITAMINS: A,D,E,K
STORED IN: ADIPOSE
WATER SOLUBLE VITAMINS ARE NOT STORED PASS THROUGH TO URINE FROM BLOOD
Features of Vit A
NAME: RETINOL
DEFICIENCY: COLOUR BLINDNESS
EXCESS: HEPATITIS AND EXFOLIATION
TEST: SERUM VIT A
Features of Vit B1
NAME: THIAMINE
DEFICIENCY:
- BERI-BERI
- WERNICKES
- NEUROPATHY
TEST: RBC TRANSKETOLASE
Features of Vit B2
NAME: RIBOFLAVIN
TEST: RBC GLUTATHIONE REDUCTASE
Features of vit B3
NAME: NIACIN
DEFICIENCY:
- PELLAGRA (THINK: 3 D’s)
o DIARRHOEA
o DEMENTIA
o DERMATITIS
Features of Vit B6
NAME: PYRIDOXINE
DEFICIENCY:
- SKIN CHANGES
- SIDEROBLASTIC ANAEMIA
EXCESS: NEUROPATHY
TEST: RBC AST ACTIVATION
Features of Vit B9
NAME: FOLATE
TEST: RBC FOLATE
Features of Vit B12
NAME: COBALAMINE
TEST: SERUM B12
Features of Vit C
NAME: ASCORBATE
DEFICIENCY:
- SCURVY
o BLEEDING GUMS
o TEETH CAN FALL OUT
o JOINT PAIN
o LOW MOOD
EXCESS; RENAL STONES
TEST: PLASMA VIT C
Features of Vit D
NAME: CHOLECALCIFEROL
DEFICIENCY: RICKETS OR OSTEOMALACIA
EXCESS: HYPERCALCAEMIA
TEST: SERUM VIT D
Features of Vit E
NAME: TOCOPHEROL
DEFICIENCY:
- ANAEMIA
- NEUROPATHY
- IHD IN LATER LIFE
TEST: SERUM VIT E
Features of Vit K
NAME: PHYTOMENADIONE
DEFICIENCY: DEFECTIVE CLOTTING
TEST: PTT
Features of Copper
DEFICIENCY:
- ANAEMIA BODY ABSORBS LESS IRON
- OSTEOPOROSIS
EXCESS: WILSONS
TEST: CU AND CAERULOPLASMIN
Features of Fluoride
DEFICIENCY: DENTAL CARIES
EXCESS: FLUROSIS WHITE AND BROWN SPECKLES ON YOUR TEETH
Features of Iron
TESTS:
- FBC
- SERUM FE
- FERRITIN
Features of Iodine
DEFICIENCY:
- GOITRE
- HYPOTHYROIDISM
Features of Zinc
DEFICIENCY: DERMATITIS
NB: MARASMUS IS DEFICIENCY IN ALL MACRONUTRIENTS LEADING TO:
- SHRIVELLING
- GROWTH RETARDATION
- MUSCLE WASTING
- NO SUBCUT FAT
NBB: KWASHIORKOR IS A LACK OF PROTEIN WHERE IT BECOMES OEDEMATOUS
Drugs that predispose to pre-renal AKI
- NSAIDS REDUCE AFFTERENT ARTERIOLE PRESSURE
- CALCINEURIN INHIBITORS REDUCE AFFTERENT ARTERIOLE PRESSURE
- DIURETICS
Most common cause of acute renal failure
ACUTE TUBULAR NECROSIS
Causes of hyperkalaemia in CKD
- SPIRONOLACTONE
- ACEi
- Eating foods like chocolate, dried fruits and tomatoes
Complications in CKD
- HYPERKALAEMIA
- ANAEMIA NORMOCHROMIC NORMOCYTIC ANAEMIA
o SEEN IN GFR <30
o TREATED WITH EPO STIMULATING AGENTS LIKE DARBAPOETIN - CARDIAC
o URAEMIC CARDIOMYOPATHY WITH 3 PHASES
LVH LV DILATION LV FAILURE - VASCULAR
o CALCIFIED VESSELS WHICH LEADS TO INCREASED CVD RISK
When does troponin rise post injury>
TROPONIN I BEGINS TO RISE 2 HOURS POST INJURY
POST MI, IT IS MEASURED INSTANTLY, AND THEN AN HOUR LATER LOOK FOR 50% RISE
Best marker for heart failure
IN HEART FAILURE, THE CARDIAC MARKER MEASURE IS NT PRO-BNP (NOT BNP AS SHORT LIFE TOO SHORT)
What is CK raised by? Who is it higher naturally in?
- MUSCLE:
o MYOSITIS
o STRENOUS EXERCISE
o MYOPATHY
o RHABDOMYOLYSIS - CARDIAC –> ANY INJURY
o HIGHER IN AFROCARRIBEANS NATURALLY
What is Lesch-Nyan deficiency? What is the deficiency?
The X-linked disorder results from an absolute deficiency of HGPRT (or HPRT), the key enzyme in the salvage pathway of purine metabolism. This results in hyperuricaemia causing juvenile gout.
Get a deficiency in the enzyme HPGRT which leads to primary hyperuricaemia
Presentation of Lesch-Nyan syndroem
- DEVELOPMENTAL DELAY AT 6 MONTHS
- CHOREIFORM MOVEMENTS AROUND 1 YEAR
- SELF MUTILATION (BITES LIPS AND FINGERS)
- SEVERE UMN DISEASE
- MENTAL RETARDATION
How does CAH present in neonates?
- ADDISONIAN CRISIS
- HYPOGLYCAEMIA
o 17-OH-PROGESTERONE IS THE METABOLITE RAISED IN CAH
What is Schmidt syndrome? What does it present with?
If you get hypothyroidism and addison’s at the same time –> SCHMIDT SYNDROME
Schmidt syndrome presents with:
- HIGH TSH
- LOW T4
- LOW GLUCOSE
- HYPONATRAEMIA
- HYPERKALAEMIA
patient presentats with tachycardia, hypotension, dilated pupils, ataxic gait, flushed extremities, dry mouth, and first degree heart block, what class of medication?
tricyclic antidepressant overdose
Tricyclic Antidepressants can cause anticholinergic effects, cardiovascular toxicity, and central nervous system depression, which align with the patient’s symptoms.
Profound metabolic acidosis and persistent hypokalaemia
T1RTA
drug used in the treatment of non-acute gout to reduce urate levels by increasing the fractional excretion of uric acid
Probenecid
MOA of colchicine
reducing inflammation and acts by inhibiting polymerisation of tubulin to reduce migration of neutrophils
MOA of allopurinol
inhibits the enzyme xanthine oxidase to reduce urate synthesis
pH imbalance is associated with hypokalaemia
alkalosis
The 24 year old patient has type 1 diabetes and appears very dehydrated. What is the anion responsible for the patient’s metabolic acidosis?
Ketones
Causes of rasied anion gap metabolic acidosis
G: Glycols (ethylene glycol and propylene glycol) [overdose]
O: Oxoproline [chronic paracetamol use, usually malnourished women]
L: L-lactate [sepsis]
D: D-lactate [short bowel syndrome]
M: Methanol [overdose]
A: Aspirin [overdose. Initially causes respiratory alkalosis but in moderate/severe overdose causes metabolic acidosis]
R: Renal failure
K: Ketoacidosis [DKA, alcoholic, starvation]
Causes of normal anion gap metabolic acidosis
Addison’s disease
Bicarbonate loss (diarrhoea, laxative abuse, Renal Tubular Acidosis)
Chloride gain (Sodium Chloride 0.9% infusion)
Drugs (acetazolamide)
What condition describes inadequate function of the proximal renal tubules of the kidney and is associated with glucosuria, hypophosphatemia and hyperuricosuria?
Fanconi syndrome
In bile acid synthesis Acyl-CoA cholesterol acyltransferase (ACAT) is the enzyme that converts cholesterol into what?
Cholesterol ester
What is the most potent pharmacological agent at reducing low density lipoprotein concentration in blood?
Evolocumab (PCSK9 inhibitor)
A 26 year old man presents to his GP with a yellow nodule on his achilles tendon.
You notice a bluey grey ring around his cornea and yellow irregularly shaped deposits around his eyelids.
Low density lipoprotein (LDL) is raised whereas high density lipoprotein (HDL) and triglycerides are normal.
Genetic studies reveal a LDL receptor mutation.
What is the diagnosis?
Familail hypercholesterolaemia
Lomitapide is a low density lipoprotein lowering drug.
What protein does Lomitapide inhibit?
Microsomal triglyceride transfer protein, therefore blocking release of VLDL from liver and reducing LDL levels
The van den Bergh reaction is used to measure serum bilirubin via fractionation. What kind of bilirubin is measured with the direct reaction?
conjugated
NOTE: The direct reaction measures conjugated bilirubin whereas a complete reaction measures total bilirubin. The indirect reaction refers to the difference between these two and measures unconjugated bilirubin.
A patient is hypocalcaemic, has an elevated serum phosphate and has an elevated parathyroid hormone (PTH).
Upon examination you notice they have short 4th and 5th metacarpals.
What is the most likely diagnosis?
Pseudohypoparathyroidism
An infant with dysmorphic facies and congenital heart disease and cleft palate is found to have hypocalcaemia.
What is the most likely diagnosis?
DiGeorge syndrome
A 29 year old man presents with eruptive xanthomas and a yellow discolouration to the palm.
Blood tests reveal high total cholesterol and triglyceride levels. Genetic studies reveal ApoE2 present.
What is the diagnosis?
Type 3 hyperlipoproteinemia
What is the name of the cholesterol transport channel targeted by the drug Ezetimibe?
NPC 1L1
What is the most common joint to be affected in acute gout?
1st metatarsophalangeal
How to differentiate gout and pseudogout?
Monosodium urate crystals of gout are negatively birefringent which means under polarised light they appear orange when parallel to a red light filter and blue when perpendicular. This allows them to be differentiated from calcium pyrophosphate crystals of pseudogout which show positive birefringence.
What is gout caused by?
deposition of monosodium urate crystals in the synovium of joints
What happens in acute gout?
Acute gout (podagra) presents as a rapid build-up of severe pain in a red and swollen joint. The most common joint to be affected is the 1st metatarsophalangeal joint and it is more common in men.
What happens in chronic gout?
In chronic gout (tophaceous) there may also be deposition of crystals (tophi) around joints and at other locations such as the ear lobes.
Which protein, found in blood plasma, exchanges triglycerides and cholesterol esters between lipoproteins?
Cholesteryl ester transfer protein (CETP)
A middle aged man presents to A&E with an exquisitely painful left knee.
He is carrying a half empty bottle and says it contains moonshine.
Blood tests show hyperuricaemia and a low Hb. He is under investigation for a sideroblastic anaemia.
Intoxication of what element is responsible for causing his condition?
Lead
NOTE: Saturnine gout presents similarly to primary gout but with acute attacks more common in the knee. It is caused by lead toxicity, often associated with drinking homemade alcohol. Lead toxicity reduces renal urate excretion leading to hyperuricaemia.
In a patient with pseudopseudohypoparathyroidism, what would you expect the serum calcium level to be?
normal
A 43 year old man presents to his GP complaining of very smelly stool that is difficult to flush.
He has been taking a new medication supposed to help him lose weight prior to his bariatric surgery in a few months’ time.
However, he continues to eat takeaways most days of the week.
What medication is this patient most likely taking to explain his symptoms?A 43 year old man presents to his GP complaining of very smelly stool that is difficult to flush.
A 43 year old man presents to his GP complaining of very smelly stool that is difficult to flush.
He has been taking a new medication supposed to help him lose weight prior to his bariatric surgery in a few months’ time.
However, he continues to eat takeaways most days of the week.
What medication is this patient most likely taking to explain his symptoms?
He has been taking a new medication supposed to help him lose weight prior to his bariatric surgery in a few months’ time.
However, he continues to eat takeaways most days of the week.
What medication is this patient most likely taking to explain his symptoms?
Orlistat
A 9 year old boy presents to the GP with enlarged orange coloured tonsils.
Examination elicits a peripheral neuropathy and blood tests show very low plasma HDL levels.
What is the most likely diagnosis?
Tangier disease
NOTE: Tangier disease is an inherited disorder caused by mutations in the ABCA1 gene. This prevents the release of cholesterol and lipids from cells which results in them accumulating in certain organs. This may present as hepatomegaly, splenomegaly, or classically as enlarged orange tonsils in children. The condition is characterised by low HDL levels in the blood conferring an increased risk of cardiovascular disease.
In the liver which cytochrome P450 enzyme catalyses the first step in the formation of bile acids via the classical pathway?
Cholesterol 7 alpha-hydroxylase
NOTE: The classical pathway begins with the conversion of cholesterol into 7-alpha-hydroxycholesterol. This is the first and rate limiting step in the classical pathway and is catalysed by the cytochrome P450 enzyme cholesterol 7 alpha-hydroxylase (CYP7A1).
Which term is used to describe increased bone density?
Osteosclerosis
What is the effect of taking prednisolone on the levels of circulating low density lipoprotein in the blood?
Increases
A 14 month old boy presents showing signs of delayed motor development and self-mutilation of the lips and fingers. He is found to have hyperuricaemia.
What enzyme is deficient in this condition?
HGPRT
NOTE: A young boy with developmental delay and self-mutilation of the lips and digits is characteristic of Lesch Nyhan syndrome. The X-linked disorder results from an absolute deficiency of HGPRT (or HPRT), the key enzyme in the salvage pathway of purine metabolism. This results in hyperuricaemia causing juvenile gout.
A 3 year old child is seen in the paediatric clinic after concerns about failure to thrive.
He has already been diagnosed with rickets and is on appropriate calcium and vitamin D replacement.
Blood tests show him to be hypokalaemic.
Urine dip shows the presence of protein and glucose. The pH of the urine is 8.6 (alkaline). There are no ketones in his blood.
What is the probable explanation for his failure to thrive, blood test result and urine dip findings?
Fanconi syndrome
NOTE: Fanconi syndrome (NB: Fanconi anaemia is something else) is an inherited or acquired condition where there is almost complete failure of the proximal convoluted tubule in the kidney to reabsorb molecules.
What is Fanconi syndrome?
Fanconi syndrome (NB: Fanconi anaemia is something else) is an inherited or acquired condition where there is almost complete failure of the proximal convoluted tubule in the kidney to reabsorb molecules.
A patient’s blood tests have returned and show they have a low serum sodium level. What investigation should be done to determine if this is a true hyponatraemia?
Serum osmolality
NOTE: A low serum osmolality tells you this is a true hyponatraemia. A normal or high serum osmolality tells you this is a pseudohyponatraemia.
A urine dipstick positive for blood but negative for erythrocytes on direct microscopy suggests the presence of what molecule?
Myoglobin
A 43 year old lady with Type II Diabetes and previous suicidal ideation presents to A&E confused and drowsy. She is fluctuating in and out of consciousness.
She appears sweaty and is shaking.
Her blood sugar is 1.3 mmol/L.
She has high levels of insulin and a high C-peptide level.
What investigation should be performed to exclude a factitious hypoglycaemia?
Blood sulfonylurea levels
ApoE4 classically gives an increased risk of developing which neurodegenerative condition?
Alzheimer’s
Where in the gut are bile acids reabsorbed?
Terminal ileum
What class of drug must not be co-administered with azathioprine in individuals with TPMT deficiency, else a potentially fatal buildup of toxic metabolites may occur?
Xanthine oxidase inhibitors e.g. allopurinol
Which enzyme forms the rate limiting step in de novo purine synthesis?
Phosphoribosyl pyrophosphate amidotransferase (PAT)
A 24 year old lady is referred to a cardiologist.
She has irregular yellow growths on her hands and one on her achilles tendon.
The cardiologist informs her she has premature atherosclerosis.
Blood tests show grossly raised levels of plant sterol in her blood.
Which autosomal recessive disorder does she most likely have?
Phytosterolemia
A 36 year old man with Wilson’s disease is noted to be hypokalaemic on routine bloods performed at his GP.
He denies any nausea, vomiting or diarrhoea. His oral intake is normal for him and he doesn’t feel he is losing weight. He does not drink any alcohol. He is on no regular medications.
A urine dip is normal.
What condition is associated with Wilson’s disease which may cause hypokalaemia?
Fanconi syndrome - T1RTA
A 14 year old type 1 diabetic has just got home after walking from school. He feels a little dizzy and a bit drowsy. He also notices he is shaking. He skipped lunch at school and is now feeling very hungry. What is the diagnosis?
Hypoglycaemia
A 16 year old presents to A&E following an overdose of medications from the family medicine cabinet 4 hours ago.
She says she feels very unwell, nauseous and has vomited 4 times in the last 3 hours. She says the room is spinning and that she can hear a high pitched ringing in her ears.
Observations show that she is tachypneic and is feverish at 38c.
What medication is she likely to have overdosed on?
Salicylates cause ringing in ear
In familial hypocalciuric hypercalcaemia (FHH), which receptor has suffered a mutation?
calcium sensing receptor
What vitamin converts cyanide to a renally cleared, less toxic, metabolite and is the first line medication for cyanide poisoning?
Hydroxocobalamin
A 23 year old woman is admitted to Intensive Care with a BMI of 13.7 for treatment of her Anorexia Nervosa. She is started on a strict diet by the ICU team and is only allowed occasional visitors. After a few days she becomes increasingly confused and reports severe palpitations. Blood tests show low levels of potassium, phosphate and magnesium. What is the most likely diagnosis?
Refeeding syndrome
A 24 year old gentleman is brought into hospital by ambulance. He was recovered by firefighters from a house fire. He has a reduced GCS (M6 V4 E4) and is confused. He has no visible burns and there is no obvious airway oedema. However, he has a cough productive of black sputum.
He is complaining about a severe headache and a bitter almond taste in his mouth.
Observations reveal he is tachycardic and hypertensive. An ECG shows first degree AV block.
What chemical compound is responsible for his symptoms?
Cyanide
NOTE: Cyanide is the best answer because the symptoms described (confusion, coughing up black sputum, bitter almond taste, tachycardia, hypertension, and first degree AV block) are consistent with cyanide poisoning, which can occur from inhalation of smoke from a house fire.
Purines can be made via a de novo synthesis pathway.
What is the name of the other pathway by which purines can be made?
Salvage
Cholestyramine is a cholesterol lowering drug.
What does Cholestyramine bind to in the gut in order to cause the liver to break down more cholesterol?
Bile acids
Looser’s zones are a pathognomonic X-ray finding of which condition?
Osteomalacia
What kind of inheritance is shown by the Multiple Endocrine Neoplasia syndromes?
AD
A 23 year old woman is reviewed in the outpatient neurology clinic. She has a past medical history of epilepsy for which she takes levetiracetam.
Due to ongoing seizures, her neurologist asked her to produce a seizure diary which suggested that her seizures are often triggered by alcohol consumption, although she states that her overall alcohol consumption is low at less than 10 units a week.
On further questioning, she has also been given a diagnosis of IBS by a specialist and that her symptoms seem to flare shortly before she develops seizures.
What first line test would be highly suggestive of the underlying condition for all of her symptoms?
Urine porphobilinogen
What enzyme is deficient or absent in acute intermittent porphyria?
Hydroxymethylbilane synthase
What drug can be offered as a treatment during a flare of acute porphyrias?
Haem arginate
A 6 month old infant is taken on holiday by its parents to the South of France in Summer.
Whilst there, the infant develops severe blisters over sun exposed sites. In hospital, there is evidence of a haemolytic anaemia.
A urine test is positive for haem precursor proteins.
What is the likely diagnosis?
Congenital Erythopoietic Porphyria
Which thyroid cancer most commonly metastasises to LNs?
Papillary
T1DM with hypoglycaemia, what is the management option if no IV access?
IM glucagon
Raised Na, low K, HTN but raised renin
RENAL ARTERY STENOSIS –> raised renin means this
Man who has been in a car accident, raised sodium and plasma osmolality, low urine osmolality
Cranial diabetes insipidus
Woman comes in with bitemporal hemianopia, 2cm mass, and a raised prolactin 1400
non functional macroadenomas can compress dopamine stalk and cause raised prolactin, they are most likely to cause visual defects
Woman comes in with no visual change, 4mm mass, and raised prolactin 1400
Prolactinoma
Raised prolactin, raised TSH, raised T4
TSHoma, TSH releases prolactin too
A 57 year old man presents following hematemesis and is found to have high ALT + GGT, slightly raised ALP, and low Albumin
Cirrhosis, albumin low indicates chronic liver disease
Deficiency of which enzyme leads to hyperuricemia?
HGPRT
Which enzyme regulates the rate limiting step in the haem biosynthesis pathway?
ALA synthase
enzyme that is raised in mumps
amylase-S
biomarker/enzyme raised in rhabdomyolysis
Creatine kinase
Cause of dark urine with no blood on microscopy
Myoglobin
Marker of HF
NT-pro BNP
Denosumab MOA, used in? SE?
targets RANKL on osteoclasts, used in osteoporosis, can cause avascular necrosis of jaw
Vitamin deficiency that causes megaloblastic anaemia and neural tube defect.
FOLATE - VITAMINE B9
PCSK9 inhibitor - evolucumab, what does it halve?
LDL levels
Which molecule takes cholesterol and moves it to liver and steroidogenesis organs?
HDL
Low plasma sodium (124) and urine specific gravity of 1.000 cause?
Psychogenic polydipsia
What would be high in the most common cause of CAH?
Sex steroid hormones and ACTH
Woman presents worried because she has low glucose when she tests using daughter’s meter (her daughter has T1DM) but denies taking any drugs. Low glucose, high insulin, low C peptide, she has a high BMI?
Factitious/surreptious insulin
