chempath Flashcards

Question

why is it impt to know Corrected Calcium and not just the free ionised Ca levels?

Answer 1

\*impt because e.g. one has low albumin, bound ca may be low, but free ca still normal. thus, corrected ca tells you that the problem is w albumin and that the ionised ca is still normal. tx in this case would be albumin rather than calcium.

Answer 2

Hypocalcaemia detected by parathyroid gland Parathyroid gland releases PTH activating osteoclasts in bones to release calcium PTH “obtains” Ca2+ from 3 sources o **Bone** o **Gut** (increased absorption VIA increased calcitriol produced) o **Kidney** (resorption and renal 1 alpha hydroxylase activation)

Answer 3

* Peptide hormone thus cannot be given orally * Secreted from parathyroids * Bone & renal Ca reabsorption * Stimulates vit D synthesis (through 1alpha-hydroxylation) * Also stimulates renal phosphate wasting

Answer 4

in the skin. UV light from sun converts 7-dehydrocholesterol to cholecalciferol.

Answer 5

calcidiol = 25-hydroxycholecalciferol calcitriol = 1,25-dihydroxycholecalciferol

Answer 6

found in the liver. 100% of D3 is converted to 25-OH D3 in the liver.

Answer 7

in the kidney. rate limiting step regulated by PTH! converts 25-OH D3 to 1,25-(OH)₂ D3

Answer 8

D2 - a plant pased product.

Answer 9

1 alpha hydroxylase, regulated by PTH

Answer 10

**Gut**: Intestinal Ca and P absorption which is critical for bone formation **Kidneys**: increases ca reabsorption

Answer 11

* Structural framework, strong, lightweight, mobile, protects organs, capable of orderly growth and remodelling * Metabolic role in calcium homeostasis * Main reservoir of Ca, P and Mg

Answer 12

osteoporosis, osteomalacia, Paget's disease, PTH bone disease, renal osteodystrophy.

Answer 13

lack of sunlight exposure dark skin dietary malabsorption Vit D deficiency in the UK (\>50% of adults, 16% severe deficiency during winter and spring)

Answer 14

defective bone mineralisation

Answer 15

**renal failure** - no 1a hydroxylase **anticonvulsants** which break down Vit D e.g Phenytoin

Answer 16

Osteomalacia - defective bone mineralisation - **Loosers zones** - raised ALP as bones trying to make new osteoids. Low Ca and PO4 due to Vit D/ calcitriol deficiency

Answer 17

Bowed legs costochondral swelling widened epiphyses at the wrists myopathy when Ca really low

Answer 18

Osteoporosis asymptomatic until first fracture

Answer 19

NOF, verterbral, wrist e.g. Colle's

Answer 20

Using DEXA scan. T-score – sd from mean of young healthy population (useful to determine # risk) **Osteoporosis – T-score \<-2.5** \* Osteopenia – T-score between -1 & -2.5

Answer 21

Z-score – SD from mean of aged-matched control (useful to identify accelerated bone loss in younger patients)

Answer 22

Deficient sex steroids (menopause) old age childhood illness (failure to achieve peak bone mass) Lifestyle: sedentary, EtOH, smoking, low BMI/nutritonal Endocrine: hyperprolactinaemia, thyrotoxicosis, Cushings Drugs: steroids Others eg genetic, prolonged intercurrent illness

Answer 23

Weight-bearing exercise, stop smoking, reduce EtOH

Answer 24

Vitamin D/Ca Bisphosphonates (eg **alendronate**) –↓ bone resorption. Given if T-score \<2.5 but vit D is normal. Used by osteoblast to make bone which cannot be biologically broken down. Teriparatide (PTH derivative) – anabolic Strontium – anabolic + anti-resorptive (major side effects) (Oestrogens – HRT) given if patient has early menopause but risk of breast cancer SERMs eg raloxifene, tamoxifen. Agonist in bone, antagonist in breast. But hot flushes/ increased risk endometrial Ca

Answer 25

hyperCa symptoms after Ca \>3.0 mmol/L same symptoms as HyperPTH generally.

Answer 26

PTH should be zero (completely suppressed)

Answer 27

is it a genuine result? - repeat YES - what is the PTH?

Answer 28

INAPPROPRIATE PTH response to hyperCa 1. Most common- primary hyperparathyroidism 2. rare- familial hypocalciuric hyperCa

Answer 29

primary hyperparathyroidism

Answer 30

Parathyroid adenoma (80%) / hyperplasia (assoc w MEN1)/ carcinoma (2%)

Answer 31

Primary HyperPTH PO4 LOW (phosphate trashing hormone) Ca in urine HIGH (due to hyperCa) -\> so high ca, low or normal PO4

Answer 32

**BONES** (PTH bone disease – become weak and fractures eventually) and **STONES** (renal calculi) Hypercalcaemia -\> abdominal **MOANS** (constipation, pancreatitis), psychiatric **GROANS** (confusion)

Answer 33

Parathyroids: regulates PTH release Renal: influences Ca2+ resorption (PTH independent) Familial hypocalciuric (/benign) hypercalcaemia (FHH / FBH): CaSR mutation -\> higher set point for PTH release -\> mild HyperCa and reduced urine Ca

Answer 34

In malignancy: * Humoral hypercalcaemia of malignancy (eg small cell lung Ca) – PTHrP (normal in pregnancy to increase Ca levels, as babies will steal Ca from mom) * Bone metastases (eg breast Ca) – Local bone osteolysis * Haematological malignancy (eg myeloma) – cytokines * Sarcoidosis (non-renal 1α hydroxylation) * Thyrotoxicosis (thyroxine -\> bone resorption) * Hypoadrenalism (renal Ca2+ transport) * Thiazide diuretics (renal Ca2+ transport) * Excess vitamin D (eg sunbeds…)

Answer 35

_Acute management_ Fluids+++ and Fluids+++! Bisphosphonates (if cause known to be cancer) otherwise avoid. Treat underlying cause!

Answer 36

Neuromuscular excitability – Trousseau’s sign, Chvostek’s sign, hyperreflexia, laryngeal spasm (stridor), prolonged QT interval, convulsions

Answer 37

Ca + Vit D (give rapidly to avoid convulsions)

Answer 38

Is it a genuine result? Repeat and adjust for albumin. Secondly, what is the PTH?

Answer 39

Vit D deficiency - dietary, malabsorption, lack of sunlight Chronic kidney disease (lack of 1a hydroxylation) PTH resistance (pseudohypoPTH)

Answer 40

tertiary HyperPTH chronic low Ca and high PTH -\> high Ca and high PTH

Answer 41

surgical - post thyroidectomy autoimmune hypoPTH congenital absence of the parathyroids e.g. DiGeorges Mg deficiency (PTH regulation) - Mg necessary to make PTH

Answer 42

Pagets Disease focal disorder of bone remodeling **Highly elevated Alk Phos** Nuclear med scan / XR

Answer 43

Bisphosphonates for pain (good to stop rapid bone turnover)

Answer 44

osteitis fibrosa cystica loss of cortical bone- \> fracture risk

Answer 45

osteoporosis

Answer 46

Osteomalacia/ Rickets

Answer 47

primary HyperPTH

Answer 48

Renal osteodystrophy Vit D normal, but 1a hydroxylation low -\> low calcitriol activity. PO4 retention in renal failuer

Answer 49

Brain enzymes cannot function at v acidic pH

Answer 50

2 (Na +K) + Urea + Glucose

Answer 51

Na + K - Cl - bicarb

Answer 52

8-16 mEq/L if high -\> suggests high anions causing acidosis

Answer 53

Brain is v dehydrated First line tx: gradual fluid replacement

Answer 54

Lactic Acidosis - typically occurs in patients w renal insufficiency metformin contraindicated in renal impairment! AKI/ CKD/ metformin overdose-\> metformin accumulation. Cori cycle: Lactate in the liver converted back to glucose to be used by muscle. Metformin inhibits this conversion -\> lactate accumulation

Answer 55

Fasting glucose \>**7.0 mM** OGTT 2h post 75g \> **11.1mM** Impaired fasting glucose= 6.1-7.0mM Impaired Glucose tolerance = 7.8-11.1 mM Diagnosis = 1 abnormal result + symptomatic. If asymptomatic, diagnosis should be from 2 samples done on different days.

Answer 56

Under Section 3 of the Coroner’s Act 1887, The following deaths are reported to the coroner: 1. Violent 2. Unnatural or sudden 3. Cause of death is unknown A number of these require analysis for drugs and alcohol to establish the cause of death

Answer 57

Ante-mortem serum / blood (if hospitalised) \* Post-mortem blood - Heart blood, cavity blood (screening), femoral vein blood (screening & quantitation). Heart blood cannot be used for quantitation. \* Urine (shows what was taken yesterday), stomach contents, vitreous humor (if blood not available as in RTC, measure glucose in diabetic deaths as blood can’t be used) \* Hair, liver (for people who have decomposed) \* Others – bile, muscle, powders, syringes (can be misleading as does not prove use)

Answer 58

Never fatal alone, find in RTAs \* Driving after alcohol + cannabis, lethal combi

Answer 59

OD, accidents including RTAs o Additive effects other resp depressant drugs

Answer 60

measured as morphine iv injection, mix with tobacco, volatilised o Fatal OD with all routes of ingestion o Additive effects other resp depressant drugs o Few rapid deaths, most people die from respiratory depression or aspiration pnuemonitis o Tolerance

Answer 61

Methadone - drug to tx heroin addicts as a substitute. Tolerance, slow absorbed, taken once every 24h \* After ingestion, fatal amount takes 4-6hours to die \* Additive effects w other resp depressant drugs \* 5 mL can kill a child, 60 mL healthy adult male \* Maintenance dose can vary from 5 to 200 mL, usually 20-40m

Answer 62

Addicts usually take these after comedones and heroins for better effect Additive effects other resp depressant drugs \* Extremely rare to cause death alone

Answer 63

Widely used, injected with heroin, “speedball” Tolerance which encourages binging Acute dangers: **cardiac dysrhythmias** - acute heart failure, myocardial infarction Slowly developing damage to the myocardium (deaths due to long term use), ventricular arrythmias, sudden death Lethal syndrome of excited delirium - occurs in regular users within 24 hrs of last dose Body packers Effects prolonged if used with ethanol, get cocaethylene formed

Answer 64

e.g. methamphetamines, MDMA (ecstacy), mephedrone. Increasing number of deaths Large OD causes direct toxic effect on heart Cause hyperthermia, leads to rhabdomyolysis, leads to muscle necrosis and renal failure

Answer 65

PM blood conc cannot be used to calculate the dose, eg in antidepressants which have high distribution in blood, will have higher [] in PM blood e.g. 76yrs, male, had been on amitriptyline for 7 years Told psychiatrist had suicidal thoughts Daughter could not contact father Police called, broke it to flat Stab wounds to chest & stomach (total 7) Found pair blood stained trouser over a chair Steak knife had been washed up in kitchen Specimens: femoral vein blood, urine **Amitriptyline blood : 1.27 ug/ml** **Nortriptyline blood : 2.33 ug/ml** **Combined blood : 3.60 ug/ml** Combined therapeutic plasma conc: 0.12 to 0.25 Combined potentially fatal conc: \>2.0 No ethanol or other drugs detected in general screen blood Case 1 Interpretation: despite having higher []s of antidepressants, it is not an amitriptyline OD, as amitriptyline has high volumes of distribution. The results show chronic use of antidepressants.

Answer 66

Interpretation: amitriptyline OD as this patient does not have a drug history of antidepressants as the previous case.

Answer 67

extremely high desmethylclomipramine -\> OD of clomipramine

Answer 68

Degrades in pm blood (fluoride oxalate only slows the process) o pseudocholinesterases -\> EME o Chemical hydrolysis -\> BE \* PM blood [] and blood [] at time of death not same \* To interpret cocaine - witness behaviour, cardiovascular pathology, drug use history \* Addict can tolerate high levels \* Causes heart problems, death with low levels

Answer 69

Case 4 Interpretation: absent due to lack of info Drugs hx extremely impt!

Answer 70

Case 5 interpretation: with drug history, coroners were able to use tests to find specific drugs in the am blood to determine CoD. This can’t be done if no drug history is available.

Answer 71

Hair. Blood/serum: drugs typically can be detected for no more than 12 hours Urine, drugs typically detected for 2-3 days Drugs are incorporated into hair from the blood stream during the growth phase. Hair growth approx 1cm/month – “tape-recording of drug use” Can provide valuable evidence which cannot be provided by any other means. Segmental analysis provides pattern of past use (if present in blood but not in hair, means drug eg. morphine was taken in one dose) Established technique Increasingly used in crime investigation

Answer 72

* Demonstrate a history of drug use or lack of it e. g. cocaine can be detected in hair but not in other fluids \* avoid the need for a police investigation \* saving valuable resources \* help the family come to terms with the death. * Demonstrating tolerance or lack of it \* aid interpretation of drug conc found in post-mortem blood to help establish CoD. * Compliance with medication \* question frequently asked by the pathologist \* antidepressants, antipsychotics, anticonvulsants.

Answer 73

* Depression/suicide \* long term cocaine use → depression → suicidal intention. * \* Sudden unexplained death \* reliable drug history to distinguish heart disease caused by chronic cocaine use/ naturally occurring heart disease, which saves unnecessary investigations for hyperlipidaemia etc. * \* Excited delirium \* can be caused by long term use of cocaine \* evidence important if death occurs while being restrained

Answer 74

Environmental Contamination Absorbed from sweat or sebum coating hair Passive inhalation Cosmetic treatment - Shampoo washing, perming, dyeing, bleaching Hair colour – darker hair absorbs more drugs

Answer 75

\<135 mmol/L commonest electrolyte abnormality in hospitalized patients.

Answer 76

increased extracellular water

Answer 77

stimulated by **high serum osmolality** (mediated by hypothalamic osmoreceptors) and **low blood volume / BP** (baroreceptors in the carotids, atria and aorta) - \> ADH released from posterior pituitary - \> acts on **V2 receptors** in the **collecting duct** insertion of aquaporin 2 in distal collecting ducts to increase water reabsorption

Answer 78

V2 receptors in the collecting duct - insertion of aquaporin 2 to increase water reabsorption V1 receptors: - on vascular SM-\> vasoconstriction

Answer 79

serum osmolality by hypothalamic osmoreceptors. low blood volume/ pressure mediated by baroreceptors in carotids, atria and aorta.

Answer 80

Inhibited by **cortisol**! thus, in Addisons, with low cortisol, less inhibition of ADH and more water reabsorbed leading to HypoNa

Answer 81

assess pt's volume status. Hypo/Eu/Hypervolaemic?

Answer 82

tachycardia, postural hypotension dry mucous membranes, reduced skin turgor confusion/ drowsiness reduced urine output, **low urine Na+ (\<20)** Decreased blood vol -\> renin angiotensin system -\> increased aldosterone -\> increased Na reabsorption to retain fluids (cant interpret urine Na if pt is on diuretic)

Answer 83

Diarrhoea Vomiting Diuretics Salt losing nephropathy

Answer 84

SIADH - so many causes! Hypothyroidism Adrenal Insufficiency

Answer 85

CNS, lung pathology e.g. stroke/ bleed, pneumonia Drugs e.g. SSRIs, TCA, opiates, PPIs, carbamazepine Tumours, surgery

Answer 86

TFTs for hypothyroidism Short SynACTHen test for Addisons Plasma and urine osmolality for SIADH

Answer 87

Reduce Plasma Osmolality and High Urine osmolality Inappropriate ADH -\> increased water reabsorption (but not solute) so excess water. this causes the hypoosmolality (dilution of blood) and in turn decreases [solutes] -\> HypoNa and also low

Answer 88

no hypovolaemia no hypothyroidism/ adrenal insufficiency Reduced plasma osmolality AND increased urine osmolality (\>100)

Answer 89

Hypovolaemia: Volume replacement w 0.9% saline Euvolaemia: Fluid restriction, treat the underlying cause Hypervolaemia: Fluid restriction, tx underlying cause

Answer 90

Seek expert help! Tx w hypertonic 3% saline (3%NaCl) (if reduced GCS/ seizures) \*Serum Na must not be corrected \>8-10mmol/L in the first 24 h

Answer 91

Dont correct it \>8-10mmol/L in the first 24 h Risk of osmotic demyelination (Central Pontine myelinolysis) - quadriplegia, dysarthria, dysphagia, seizures, coma and death

Answer 92

most commonly overly rapid correction of low blood sodium (also assoc w refeeding in anorexia/ burns victims/ dialysis pt) w correction of HypoNa w IV fluids, if serum Na rises too rapidly, water will be driven out of the brain's cells. -\> cellular dysfunction and CPM characterized by acute paralysis, dysarthria, dysphagia etc.

Answer 93

Tx underlying cause Water resriction (750ml - 1L/day) Drugs: - **demeclocycline** (reduces responsiveness of collecting tubule to ADH- monitor U+Es due to risk of nephrotoxicity) - **tolvaptan** (V₂R antagonist)

Answer 94

Reduces responsiveness of collecting tubule cells to ADH used in SIADH when fluid restriction is insufficient.

Answer 95

V2R antagonist. used in SIADH to reduce ADH binding to V2R and triggering insertion of aquaporin-2

Answer 96

Serum [Na+] \>145 mmol/L

Answer 97

unreplaced water loss - GI loss, sweat loss, - renal loss: osmotic diuresis, reduced ADH release/ action (DI) Pt cannot control water intake - children/ elderly

Answer 98

Correct water deficit - 5% dextrose Correct ECF volume depletion - 0.9% saline Serial Na+ measurements every 4-6 h

Answer 99

hyperglycaemia draws water out of cells leading to hypoNa Osmotic diuresis in uncontrolled diabetes leads to loss of water and hyperNa

Answer 100

Serum Glucose (to exclude DM) Serum K (exclude hypoK) Serum Ca (exclude HyperCa) Plasma and urine osmolality Water deprivation test (dilute urine)

Answer 101

3.5 -5.0 mmol/L

Answer 102

Renin-Angiotensin system (AgII) and Aldosterone (High K+ stimulates release of aldosterone to increase Na reabsorption and K+ excretion)

Answer 103

Aldosterone stimulates Na reabsorption and K excretion in the urine, through the principal cells in the cortical collecting tubule. Even though Na is reabsorbed, serum [Na] does not change as water is reabsorbed as well. **Aldosterone thus, only affects [K+]** Aldosterone increases no of open Na channels in the luminal membrane, increasing Na reabsorption. This makes the lumen electronegative and creates an electrical gradient. Thus, K+ is secreted into the lumen.

Answer 104

Renal impairment: reduced renal excretion Drugs: ACEi, ARB, spironolactone Low Aldosterone: Addison's disease, Type 4 renal tubular acidosis (low renin, low aldosterone) Release from cells: rhabdomyolysis, acidosis (H+ taken up into cells, K+ out)

Answer 105

tall tented T waves loss of p wave broad QRS complex will lead to arrhythmia (VF/ asystole) and needs urgent tx

Answer 106

**10ml 10% calcium gluconate** - if K+\> 6.5 (to reduce the risk of cardiac arrhythmias) **50ml 50% dextrose** + **10 units insulin** (insulin will drive K+ into cells, but will also drive in glucose -\> making pt hypoglycaemic so give dextrose) **Nebulised salbutamol** Tx the underlying cause

Answer 107

**GI loss** - D+V, fistula **Renal loss** - Hyperaldosteronism (Conns), increased sodium delivery to distal nephron due to diuretics/ thiazides/ Bartter or Gitelman syndrome, osmotic diuresis in diabetics **redistribution into cells** - insulin, b agonists e.g. salbutamol, alkalosis Rare causes- renal tubular acidosis types 1 &2, hypoMg

Answer 108

Loss of K+ outside, causes K+ from the intracellular stores to move out. -\> H+ moves into cells to maintain charge. (-\> extracellular alkalosis) Low K+ also leads to increased H+ secretion in the kidneys. Increased excretion of H+ in exchange for Na+ leading to production of acidic urine and bicarbonates. Low H+ outside due to alkalosis causes H+ to move out of cells and thus K+ to move into cells. -\> HypoK Alkalosis also causes increased K+ secretion in the kidneys

Answer 109

muscle weakness -\> cramping, paralysis, parasthesiae cardiac arrhythmia polyuria and polydipsia (nephrogenic DI) ECG changes - flattened T waves, U wave elevation, ST segment sagging

Answer 110

Aldosterone:renin ratio conns

Answer 111

Oral KCl (two SandoK tablets tds for 48h) Recheck serum K

Answer 112

IV KCl, max rate 10mmol/hr Rates \> 20mmol/hr are highly irritating to peripheral veins, and need to be given via central line Tx underlying cause e.g. spironolactone

Answer 113

oral carbohydrates rapid acting e.g. juice/ sweets longer acting e.g. sandwich

Answer 114

Buccal glucose e.g. hypostop/ glucogel Start thinking about IV access

Answer 115

IV access 50ml 50% glucose OR 100ml 20% glucose Deteriorating/ refractory/ insulin induced/ difficult IV access: consider IM/SC 1mg Glucagon

Answer 116

Beware extravasation of IV glucose: irritant-\> phlebitis Glucagon mobilises glycogen stores so takes 15-20 mins to work - are there glycogen stores to mobilize? e.g. anorexia - danger of rebound hypoglycaemia as it will also cause insulin release

Answer 117

Whipple’s triad: low blood glucose, symptoms and relief of symptoms with glucose adrenergic symptoms: tremors, palpitations, sweating, hunger Neuroglycopaenic symptoms: somnolence, confusion, incoordination, seizures, coma Relief of symptoms w glucose administration Careful of patients with autonomic instability-\> hypo without the adrenergic symtoms

Answer 118

decreased insulin and increased glucagon -\> increased glycogenolysis, gluconeogenesis, lipolysis and reduced peripheral uptake of glucose. - \> increase glucose in serum and also increased FFAs - beta oxidation of FFAs and increased ketone body production also low neuronal glucose sensed in the hypothalamus - \> sympathetic activation - release of catecholamines - \> ACTH, cortisol and GH production

Answer 119

suppression of insulin! to allow production of ketones as secondary supply of energy. \*Insulin is a potent inhibitor of ketone production hence, T1DM with no insulin have DKA. whereas T2DM with high peripheral insulin (resistance) usually have Hyperosmolar Hyperglycaemic Nonketotic syndrome

Answer 120

Low neuronal glucose sensed by the hypothalamus 1. sympathetic activation - release of catecholamines 2. ACTH, cortisol and GH production these are late responses, occuring hours later

Answer 121

release of glucagon

Answer 122

confirm with blood glucose test (\*gold standard) (grey top- fluoride oxalate - inhibit glycolysis) -capillary blood glucose less sensitive at low levels.

Answer 123

commonest in diabetes - impaired awareness regarding medications - inadequate CHO intake/ missed meal - excessive alcohol, strenuous exercise - coexisting autoimmune conditions in non diabetics: - critically unwell, organ failure, hyperinsulinism - extreme weight loss, post gastric bypass, drugs - factitious

Answer 124

**_Sulphonylureas_** e. g. tolbutamide, glibenclamide, gliclazide, gli\_\_\_, - increase insulin release from Beta cells in the pancreas SE: weight gain, hypos **_meglitinides_** (same MOA as sulphonylureas, but much shorter-acting) e.g. repaglinide, nateglinide **_GLP-1 agents (glucagon like peptide 1 receptor agonists)_** e.g. exenatide, liraglutide, \_\_\_\_-glutide, lixisenatide aka incretin mimetics decreases blood sugar levels in a glucose-dependent manner by enhancing secretion of insulin SEs: weight LOSS, lower risk of hypos **_DPP4- inhibitors_** e.g. \_\_\_\_gliptins increase incretin levels eventually increases insulin secretion and decreases blood glucose levels.

Answer 125

GLP-1 agonist (glucagon like peptide-1 receptor agonist) aka incretin mimetics decreases blood sugar levels in a glucose-dependent manner by enhancing secretion of insulin SEs: weight LOSS, lower risk of hypos But is still w sulphonylureas and meglitinides in the group of oral hypoglycaemics

Answer 126

Sulphonylureas e. g. tolbutamide, glibenclamide, gliclazide, gli\_\_\_, - increase insulin release from Beta cells in the pancreas SE: weight gain, hypos

Answer 127

meglitinides (same MOA as sulphonylureas, but much shorter-acting) e.g. repaglinide, nateglinide stimulates insulin release from beta cells

Answer 128

Rapid acting with meals - hypos if they occur, most likely due to a missed meal e.g. Humalog (insulin lispro), Novorapid (insulin aspart) Long acting - hypos often occur at night e.g. Lantus (insuline glargine), Levemir (insulin detemir)

Answer 129

co existing renal/ liver failure alters drug clearance, and reduced doses of insulin/ oral hypoglcaemics are needed. autonomic neuropathy - impairs awareness hypo may occur when pt is asleep at night and unaware \*be aware a very good HbA1c in a diabetic could be due to recurrent hypos.

Answer 130

C peptide is a good marker of endogenous insulin production. Proinsulin breaks down into insulin and c-peptide. \*good to differentiate between exogenous / endogenous insulin production also good to help differentiate the cause of hypoglycaemia

Answer 131

low insulin and low c-peptide Hypoinsulinaemic hypoglycaemia

Answer 132

appropriate response to hypolgycaemia - fasting/ starvation - strenous exercise (catabolic activities) - critical illness, liver failure, anorexia nervosa - endocrine deficiencies - hypopituitarism, adrenal failure

Answer 133

e.g. of ketone bodies: beta hydroxybutyrate, acetoacetate, acetone absence of ketones suggests a FFA oxidation defect.

Answer 134

explainable - premature, comorbidities - inadequate glycogen and fat stores, IUGR, SGA should improve w feeding pathological: inborn metabolic disorders

Answer 135

islet cell tumours e.g. insulinoma drugs: insulin, sulphonylurea abuse islet cell hyperplasia e.g. infant of diabetic mother, Beckwith wiedemann syndrome, Nesidioblastosis

Answer 136

insulinoma or sulphonylurea abuse sulphonylurea drug screen (urine or serum) needed before diagnosing insulinoma.

Answer 137

usually small solitary adenoma, 10% malignant 8% assoc w MEN1 dx based on biochemistry and localisation tx: resection

Answer 138

factitious insulin - especially in patients with access to insulin/ drugs

Answer 139

Non islet cell tumour hypoglycaemia everything is low! secretion of 'big IGF-2' which binds to IGF-1 receptor and insulin receptor. This suppresses insulin production from islet cells. High IGF-2 mimics insulin action thus FFA and ketones low.

Answer 140

antibodies binding to insulin may precipitate hypoglycaemia

Answer 141

hypoglycaemia following food intake can occur post gastric bypass hereditary fructose intolerance early diabetes in insulin sensitive individuals - after exercise or large meal

Answer 142

review insulin dosing and injection technique, consider pump therapy and perform a short synacthen test.

Answer 143

GH, stimulated by GHRH Prolactin, inhibited by dopamine, stimulated by TRH TSH, stimulated by TRH LH, FSH stimulated by LHRH ACTH, stimulated by CRH

Answer 144

no, as hypotension is regulated by aldosterone which is released by adrenal glands.

Answer 145

- hypothyroidism High TSH and high TRH-\> prolactinaemia - non functioning pituitary tumour -\> dopamine cannot inhibit - prolactinoma - drugs etc

Answer 146

Prolactin suppresses LHRH -\> low LH and FSH

Answer 147

presentation: galactorrhoea, amenorrhoea commonly causesd by macroadenoma (\>1cm) complications: look for bitemporal hemianopia as pituitary adenoma is pressing on optic chiasm

Answer 148

Prolactinoma always a prolactinoma if prolactin \> 6000 tx: watch and wait, scan yearly to monitor size. prolactinoma rarely grows. if visual defect loss, then consider surgery

Answer 149

to ensure that the pituitary gland responds adequately to a metabolic stress (ACTH and GH) to ensure the gonadotrophs and thyrotophs are functional. Try to increase the levels of anterior pituitary hormones by administering LHRH + TRH + stress (hypoglycaemia)

Answer 150

1. testing the lvls of ant pituitary hormones in response to **LHRH + TRH + stress (hypoglycaemia)** - metabolic stress increases CRF -\> ACTH and increases GHRH -\> GH LHRH -\> increases LH and FSH TRH -\> increases TSH _Method_ fast patient overnight, ensure good IV access weight patient and calculate dose of insulin required. Give IV insulin, TRH and LHRH. Then take blood for glucose, cortisol, GH, LH, FSH, TSH and prolactin every 30 min up to 60 min. (0,30,60) Check glucose, cortisol and GH up to 120 min

Answer 151

Ensure no cardiac risk factors, angina and that ECG is normal + no history of epilepsy before introducing hypoglycaemia. Ensure good IV access before inducing hypoglycaemia as it is harder to put in line during hypoglycaemia. Give insulin to patient. When glucose is low, first sympathetic activation occurs -\> signs that patient is hypo.

Answer 152

Check blood glucose regularly, patient needs to have adequate hypo (\<2.2mmol/L.) When \<1.5mM, neuroglycopenia may occur and pt would be aggressive. - if \>2.2 -\> results cannot be interpreted as hypoglycaemia is not sufficient. if \<1.5 (severe hypoglycaemia) or unconsciousness, rescue pt with 50ml of 20% dextrose.

Answer 153

Normal response: cortisol reaches 550 nM and GH reaches 10 IU/l If tumour pressing pituitary \* GH, cortisol, LH, FSH, TSH are low \* Prolactin is high

Answer 154

replacement therapy w hormones needed. most urgent: hydrocortisone (maintains cell integrity when one is in shock) + thyroxine, oestrogen and GH replacement + dopamine agonist (bromocriptine / cabergoline) for prolactinoma.

Answer 155

hydrocortisone, thyroxine, oestrogen, GH replacement surgery usually done. dexamethasone given for large brain tumours before surgery is done.

Answer 156

Glucose tolerance test - failure of GH suppression suggests acromegaly Pituitary function test usually shows raised GH

Answer 157

1st line: pituitary surgery to remove tumour Octreotide - Somatostatin analogue Cabergoline - adjunctive D2R agonist

Answer 158

Schmidt's syndrome addisons and hypothyroidism occur together more commonly than by chance alone. Now it is galled Polyglandular autoimmune syndrome type II (PGA type II)

Answer 159

Short SynACTHen test Administer 250micrograms of synthetic ACTH by IM injection. Check cortisol at 30 and 60 mins. It will still be low in Addisons.

Answer 160

hyperpigmentation, hypotension addisons causes deficiency of mineralcorticoid and glucocorticoid due to failure of adrenal gland. Mx: fluids - normal saline. Hydrocortisone replacement.

Answer 161

Give hydrocortisone replacement first! thyroxine replacement after. as thyroxine will increase BMR and worsen lack of cortisol -\> addisonian crisis worsened.

Answer 162

Phaeochromocytoma Conn's - adrenal tumour secreting aldosterone Adrenal medullary secreting adrenaline Cushings- secreting cortisol

Answer 163

Urine catecholamines (Urine VMA Vanillylmandelic acid) it will be high in tumours secreting catecholamines.

Answer 164

Can cause severe HTN, arrhythmias and death. **Medical emergency** 1. alpha blockade e.g. phenoxybenzamine 2. beta blockade 3. arrange surgery

Answer 165

phenoxybenzamine

Answer 166

Conn's syndrome

Answer 167

1. Spironolactone- aldosterone antagonist 2. If unilateral disease- surgery to remove tumour. unilateral adrenelectomy

Answer 168

Dexamethasone suppression test - normally suppresses cortisol levels to undetectable lvls. Low dose - any cause of Cushing's syndrome High dose- if it suppresses \>50% (will not be completely suppressed), then pituitary dependent Cushings ***_disease_***

Answer 169

Iatrogenic- steroids pituitary dependent Cushings disease (85%) ectopic ACTH Adrenal adenoma

Answer 170

Pituitary MRI indicated as pituitaru dependent Cushings disease is the most common cause. High dose dexamethasone suppression is not specific enough.

Answer 171

Phototherapy converts bilirubin into lumirubin and photobilirubin which are isomers that do not need conjugation for excretion.

Answer 172

Autosomal recessive. 5-6% of the population have this. Worsened by fasting. Effects of phenobarbital: reduces jaundice **UDP glucuronosyltransferase 1** activity reduced to 30% unconjugated Br remains tightly albumin bound and does not enter urine -\> high Br, jaundice, normal liver enzymes

Answer 173

PT time. PT time is the most representative of liver disease. If PT in seconds is longer than overdose in hours (eg PT is 24 seconds for a patient who’s been in overdose for the past 24 hours, this patient has to go to liver unit – it is a serious problem) best marker in terms of survival outcome. This is because clotting factors are not being synthesised by the liver

Answer 174

suggests hepatocyte damage Alcoholic hepatitis (AST may be higher) Viral hepaitis (ALT may be higher) Autoimmune hepatitis Non-alcoholic steatohepatitis (NASH)

Answer 175

Same histoloigcal features e.g. fatty liver, mallory denk bodies and balloonying of hepatocytes To differentiate the two: clinical history

Answer 176

supportive, stop alcohol nutrition: vitamins (e.g. B1, thiamine) - B1 deficiency causes beri beri occasionally steroids

Answer 177

multiple spider naevi dupuytrens contracture palmar erythema gynaecomastia

Answer 178

ascites, splenomegaly, varices (oesophageal/ caput medusae)

Answer 179

oesophageal rectal umbilical vein recanalising spleno renal shunt

Answer 180

Bile duct obstruction - alk phos super high - scratch marks due to bile salts in the blood pale stools: lack of stercobilin dark urine: lack of urobilin but then high amounts of conj br excreted via kidneys

Answer 181

pancreatic cancer Courvoisiers law if gall bladder is palpable in jaundiced pt, the cause is pancreatic ca

Answer 182

275-295 mmol/Kg

Answer 183

nausea and vomiting, confusion (\<131 mmol/L) seizures, non-cardiogenic pulmonary oedema (\<125 mmol/L) coma (\<117 mmol/L) and eventual death. symptomatic hypoNa is a medical emergency

Answer 184

HypoNa + Low serum osmolality if serum osmolality is normal: consider spurious sample, drip arm sample -\> pseudo hypoNa as fluids being pumped in (diluted area) pseudohypoNa (**hyperlipidaemia, paraproteinaemia**) If serum osmolality is high: consider glucose/ mannitol/ ethanol infusion

Answer 185

raised JVP, pulmonary oedema, peripheral oedema.

Answer 186

1. Cardiac failure 2. Liver failure 3. Renal failure. tx. tx underlying cause and fluid restrict!

Answer 187

Non renal cause: Heart failure, Cirrhosis Inappropriate IV fluid (Cirrhosis causes hypoNa because in liver failure, poor breakdown of vasodilators like Nitric Oxide -\> cause Low BP -\> ADH release to increase water retention which dilutes the Na.) (HF-\> low cardiac output -\> ADH release) + BNP / ANP are natriuretic and thought to worsen HypoNa as well

Answer 188

Renal cause! e.g. AKI, CKD kidneys are not retaining sodium

Answer 189

Non renal cause: diarrhoea, vomiting excess sweating third space losses e.g. burns, ascites Kidney is doing its job and holding onto Na

Answer 190

renal cause (kidneys NOT holding on to Na) e.g. Diuretics Addisons Salt losing nephropathies

Answer 191

Oberhydration w hypotonic IV fluids (usually hypervolaemic) Transient increase in ADH due to stress of the surgery.

Answer 192

cerebral oedema!

Answer 193

8 h fluid deprivation test. clinical features: hyperNa, polyuria, polydipsia, clinically euvolaemic. plasma is extremely dilute despite concentrated plasma.

Answer 194

Cranial DI: lack of ADH causes: surgery, trauma, tumours. Nephrogenic DI: receptor defect, tx w thiazide diuretics, lithium, demeclocycline, hyperCa, hypoK! in Cranial DI and nephrogenic DI, urine will fail to concentrate after fluid deprivation. in cranial DI, after desmopressin is given, will concentrate.

Answer 195

Normal: urine conc above 600 mOsmol/kg Primary polydipsia: urine can concentrate \>400-600

Answer 196

consider a renal problem e.g. CKD, diuretics, SIADH (anything that acts on the kidney)

Answer 197

1.000 to 1.030 if urine specific gravity is high, then there are more solutes (high osmolality) and vice versa if it si low.

Answer 198

14-18 mmol/L

Answer 199

Ketoacidosis (DKA, starvation, alcoholic) Uraemia (renal failure) Lactic acidosis - metformin Toxins (e.g. salicylate, methanol, paraldehyde, ethylene glycol)

Answer 200

Osmolality - Osmolarity Normal osmolar gap \<10 elevated osmolar gap provides indirect evidence for presence of abnormal solute. e.g. ethylene glycol, methanol, mannitol. Helpful in differentiating the cause of elevated anion gap met acidosis

Answer 201

alpha fetoprotein

Answer 202

direct reaction measures conj Br indirect measures unconj Br

Answer 203

normal: 30-150 elevated in chronic alcohol use. also bile duct disease and metastases. useful to confirm hepatic source of increased ALP

Answer 204

\<40 raised when hepatocytes die \*\*AST also assoc w increase in heart/ kidney damage

Answer 205

HMB synthase (hydroxymethylbilane) aka PBG deaminase (porphobilinogen deaminase) -\> buildup of ALA and PBG in serum and urine.

Answer 206

autosomal dominant

Answer 207

5-ALA (5-aminolaevulinic acid) is neurotoxic

Answer 208

porphyrins. porphyrinogens become oxidised to porphyrins, which under light become activated porphyrins and oxygen. porphorinogens are colourless while porphyrins are highly coloured. also, porphyrinogens get oxidised in the circulation where there is high [O2] compared to in the cells where it is made.

Answer 209

At any one time C = (Ux V)/P U- urinary conc P- plasma conc V- vol of urine if marker is not bound to serum proteins, freely filtered at the glomerulus, and not secreted/reabsorbed by tubular cells, C = GFR Clearance = the volume of plasma that can be completely cleared of a marker substance/ time

Answer 210

inulin clearance

Answer 211

Derived from muscle cells (small amount from intestinal absorption). Freely filtered, actively secreted into urine by tubular cells Generation is not equivalent in different individuals. Depends on muscularity, age, sex and ethnicity (higher in black population).

Answer 212

Not plasma protein bound, freely filtered at glomerulus and not modified by tubules

Answer 213

**Cystatin C** (better than serum cr but not as widely used) but ultimately, the most robust value of serum cr measurement is the change within an indiv over time. The trend is more impt than the absolute value.

Answer 214

spot urine measurement can **quantify proteinuria** instead of a 24h urinary collection Measurement of creatinine corrects for urinary concentration

Answer 215

A negative result for leucocyte on dipstick is signficant.

Answer 216

Ethylene glycol poisoning antifreeze. classically calcium oxalate crystals. go for dialysis immediately.

Answer 217

KUB USS - if shrunken probably CKD. Renal biopsy still gold standard for making a diagnosis of CKD.

Answer 218

rapid reduction in kidney function, leading to inability to maintain electrolyte, acid base and fluid homeostasis. medical emergency necessitating referral to nephrologist for dx and tx. abrupt fall in GFR, potentially reversible and tx is targeted to precise diagnosis and reversal of disease

Answer 219

reduced renal perfusion w no structural abnormality of the kidney. - could be selective renal ischaemia or generalised reduction in tissue perfusion - pre renal AKI occurs when normal adaptive mechanisms fail to maintain renal perfusion.

Answer 220

True volume depletion (blood/fluid), hypotension, shock Oedematous states (fluid in wrong compartment, more in interstitium rather than vascular space eg. heart failure) Selective renal ischaemia – renal artery stenosis Drugs affecting glomerular blood flow e.g. NSAIDs, ACEi/ARBs, diuretics, calcineurin inhibitors

Answer 221

AKI: responds immediately to restoration of circulating volume Prolonged insult leads to ischaemic injury (acute tubular necrosis) - ATN does not respond to restoration of circulating volume

Answer 222

characterised by **obstruction to urinary flow** GFR is dependent on pressure gradient. obstruction results in increased tubular pressure and decline in pressure gradient. -\> immediate decline in gfr. e.g. ureteric obstruction, prostate (usually causes bilateral hydronephrosis), blocked urinary catheter

Answer 223

remove obstruction. immediate relief of obstruction fully restores GFR w no structural damage. But if prolonged obstruction -\> structural damage -\> glomerular ischaemia, tubular damage and long term interstitial scarring

Answer 224

Vascular - vasculitis glomerular disease - glomerulonephritis tubular disease - acute tubular necrosis interstitial disease - analgesic nephropathy

Answer 225

ischaemic. also endogenous toxins - myoglobin (crush injury, statin-induced myositis), immunoglobulins (myeloma, significant paraprotein levels) and exogenous toxins - contrast, drugs e.g. aminoglycosides, amphotericin, acyclovir

Answer 226

DPP-4 inhibitors dipeptidyl peptidase-4 inhibitor Class of oral hypoglycaemics used to treat T2DM Mechanism: to increase incretin levels (GLP-1 and GIP) which inhibits glucagon, increases insulin, decreases gastric emptying and decreases blood glucose levels. SEs: joint pain, heart failure, acute pancreatitis, IBD (specifically Ulcerative Colitis)

Answer 227

urine output and GFR

Answer 228

decreased renal perfusion e.g. important causes are predictable - contrast, drugs, postop, sepsis.

Answer 229

pulmonary oedema refractory hyperK metabolic acidosis uraemic encephalopathy drug toxicity e.g. lithium

Answer 230

Stage 1 \>90 GFR Stage 2 60-89 Stage 3 30 - 59 Stage 4 15-29 Stage 5 \<15

Answer 231

Diabetes, HTN atherosclerotic renal disease chronic glomerulonephritis PCKD infective or obstructive uropathy

Answer 232

Acid base homeostasis Endocrine function: EPO, Vit D, RAS Water, electrolye balance excretion of water soluble waste

Answer 233

1. Progressive failure of homeostatic function - Acidosis, hyperkalaemia 2. Progressive failure of hormonal function - Anaemia of chronic disease, renal bone disease 3. Cardiovascular disease - vascular calcification, uraemic cardiomyopathy (ie. LV hypertrophy, LV dilatation, LV dysfunction) 4. Uraemia and Death - need for dialysis/ transplant

Answer 234

Failure of renal excretion of protons results in muscle and protein degradation, osteopenia due to mobilization of bone Ca, cardiac dysfunction tx w Sodium bicarbonate PO when bicarb lvls \<20

Answer 235

Progressive decline in erythropoietin-producing cells with loss of renal parenchyma Usually noted when GFR\<30ml/min **Normochromic, normocytic anaemia** Give EPO/ESA (erythropoietin stimulating agents)

Answer 236

Complex entity resulting in reduced bone density, bone pain and fractures: osteitis fibrosa, osteomalacia, adynamic bone disease, mixed osteodystrophy. Low Ca, High PTH -\> secondary hyperparathyroidism and causes low bone density

Answer 237

Osteoclastic resorption of calcified bone and replacement by fibrous tissue assoc w hyperPTH

Answer 238

Excessive suppression of PTH results in low turnover and reduced osteoid **reduced osteoblasts and osteoclasts, no accumulation of osteoid and markedly low bone turnover** Increasing incidence due to excessive suppression of PTH in current CKD patients

Answer 239

**_Phosphate control_** - decreased dietary phosphate intake phosphate binders **_PTH suppression_** - cinacalcet (but if u overdo it can lead to adynamic bone disease) **_Vit D R activators_** - alfacalcidol, paricalcitol

Answer 240

Cardiovascular disease risk of cardiac event directly predicted by GFR Lots of people go straight from reduced GFR to death, due to x20 increased risk of CVD

Answer 241

in long term pts with uraemia LV hypertrophy -\> dilatation -\> dysfunction

Answer 242

renal vascular lesions usually heavily calcified plaques, rather than traditional lipid-rich atheroma

Answer 243

haemodialysis peritoneal dialysis

Answer 244

Should be Free of cancer for at least 2 years Active sepsis.

Answer 245

AST and ALT elevated but AST\>\>ALT

Answer 246

AST / ALT ratio increased both high

Answer 247

found in liver, kidney, pancreas, spleen, heart, brain, seminal vesicles in liver found in hepatocytes and epithelium of small bile ducts elevated in **chronic alcohol use**, also raised in bile duct disease and hepatic metastasis

Answer 248

liver isoenzyme located in sinusoidal and canalicular membranes thus markedly elevated if obstructive jaundice or bile duct damage other sources bone, small intestine, kidney, WBC’s, placenta etc other causes of a rise include bone disease (especially metastatic and pregnancy)

Answer 249

synthesized by liver half life 20 days contributes to oncotic pressure and binds steroids/ drugs/ br / calcium

Answer 250

PT time 1/2 life in hours. compared to Albumin (half life 20 days)

Answer 251

hepatocellular carcinoma also raised in hepatic damage/ regeneration raised in pregnancy and testicular cancer

Answer 252

haemolysis gilberts

Answer 253

gall bladder obstruction e.g. cancer/ gallbladders

Answer 254

drugs PBC PSC pregnancy

Answer 255

hepatic cause acute: toxins, acute hepatitis, paracetamol chronic

Answer 256

pale stools dark urine dark due to high amts of conjugated bilirubin can be detected on urine dip/ by naked eye if large amts urobilinogen is normally detected in urine but is absent in obstructive jaundice. br in urine increased in haemolysis, hepatitis, sepsis.

Answer 257

esp in cholestasis 10-100x in obstetric cholestasis 25 x in PBC/PSC

Answer 258

Diagnosis: drug induced cholestasis (intrahepatic / 2Y to Augmentin) from UTI

Answer 259

Diagnosis: pancreatic adenocarcinoma

Answer 260

Diagnosis: acute hepatitis A

Answer 261

Diagnosis: paracetamol overdose \* Treatment: N-acetyl cysteine

Answer 262

Liver biopsy confirmed cirrhosis Mx: antiviral therapy USS/AFP every 6 months for HCC

Answer 263

Present in high concentration in liver, bone, intestine and placenta Pathological increases most frequently due to liver or bone diseases Increased in bone diseases associated with increased osteoblastic activity Liver and bone ALP can be differentiated by: o GGT measurement o Electrophoretic separation o Bone specific ALP immunoassay

Answer 264

pregnancy from placenta childhood esp during growth spurt

Answer 265

NO unless complicated by fracture. then yes!

Answer 266

exocrine pancreas, salivary isoenzyme high serum amylase with acute pancreatitis and mumps (parotitis) small increases may be seen in other acute abdomen states

Answer 267

CK MM- skeletal muscle CK-MB (1 &2) - cardiac muscles CK-BB - brain CK-MM most widely used marker of muscle damage CK-BB activity minimal even in severe brain damage. CK-MB normally around 5% of CK.

Answer 268

myalgia -\> rhabdomyolysis Risk factors: polypharmacy high dose, genetic predispostion previous hx of statin related myopathy

Answer 269

muscle damage due to any cause myopathy e.g. Duchenne's (\>10 ULN) MI (\>10 ULN) Svere exercise (5x ULN) physiological - afro carribean (\<5 x ULN)

Answer 270

troponin (T/I) rises 4-6 hr post event and peaks 12-24h post MI remains elevated for 3-10 days \*measure 6 h and then at 12 h post onset of chest pain

Answer 271

typical rise and gradual fall of troponin or more rapid rise and fall of CK-MB + at least one: ischaemic symptoms pathologic Q waves on ECH ECG changes assoc w ischaemia coronary artery intervention pathologic findings of acute MI

Answer 272

ANP - secreted by atria BNP - secreted by ventricles BNP can be measured to assess ventricular function, can be used to exclude heart failure in the clinical setting

Answer 273

Azathioprine + 6-mercaptopurine and 6-thioguanine

Answer 274

U/L one international unit (U)

Answer 275

Vit A, D, E, K

Answer 276

colour blindness Night blindness dry skin/ hair + rash

Answer 277

exfoliation hepatitis

Answer 278

serum Vit A

Answer 279

osteomalacia rickets

Answer 280

hypercalcaemia

Answer 281

serum Vit D

Answer 282

low in cystic fibrosis, abetalipoproteinaemia anaemia neuropathy (ataxia/ areflexia) IHD ?malignancy

Answer 283

defective clotting Test: PT time

Answer 284

Vit B1, B2, B3 (niacin), B6, B12, C, Folate

Answer 285

Beri beri - wet: heart failure, SOB, oedema dry: ascending impairment of nervous function involving sensory and motor components Neuropathy Wernickes - triad of confusion, opthalmoplegia, ataxia can lead to Korsakoffs (amnesia and confabulation)

Answer 286

RBC transketolase

Answer 287

RBC glutathion reductase

Answer 288

glossitis, mucosal damage, corneal ulceration and anaemia

Answer 289

Dermatitis with cheilosis (scaling on the lips/ cracks at corners of mouth)/ microcytic anaemia glossitis Peripheral neuropathy sideroblastic anaemia

Answer 290

neuropathy

Answer 291

RBC AST starvation aspartate amino transferase

Answer 292

Pernicious anaemia (macrocytic megaloblastic) Subacute combined degeneration of cord Test: serum B12

Answer 293

Scurvy - bleeding of gums, skin, joint gum disease - bone weakness (brittle, micro#s)

Answer 294

renal stones

Answer 295

megaloblastic anaemic neural tube defect test: RBC folate

Answer 296

Pellagra - 3Ds Dementia, dermatitis, diarrhoea \*Casal's necklace

Answer 297

hypochromic anaemia haemochoromatosis - FBC, Fe, ferritin

Answer 298

hypothyroidism goitre Test: TFTs

Answer 299

dermatitis

Answer 300

anaemia in excess: wilsons Test: Serum Cu, Caeruloplasmin

Answer 301

dental caries in excess: fluorosis

Answer 302

Fasting glucose \> 6mmol/L HDL Men \<1.0 Women \<1.3 Waist circumference men \>102 women \>88 HTN BP \>135/80 Microalbumin insulin resistance

Answer 303

Exclude endocrine cause (Cushing’s, hypothyroidism, acromegaly) and obesity complications (resp, GI, PCOS, CVD) \* Educate, diet and exercise \* Medical (Orlistat, GLP-1 agonist) and surgical

Answer 304

Improvement in PCOS, GORD, osteoarthritis, CVD, liver function, pregnancy, psychological _Health benefits of bariatric surgery_ \* Resolution/improvement of T2DM, hypertension, sleep apnoea, PCOS and fertility \* Improved lipid profile with resulting in overall reduction in cardiac risk and mortality

Answer 305

shrivelled growth retarded severe muscle wasting no subcut fat

Answer 306

Oedematous, scaling/ulcerated, lethargic Large liver, s/c fat, protein deficient

Answer 307

HIGH cholesterol, triglycerides High LDL low HDL

Answer 308

corneal arcus artheroma in aortic root xanthelasma tendon xanthema e.g. back of achilles tendon

Answer 309

CETP deficiency increase in **HDL** benign presentations. often assoc w longevity

Answer 310

mutations of ABC G5 & G8 allows plant sterols to be absorbed. increasing risk of premature atherosclerosis as plant sterols more atherogenic than cholesterol

Answer 311

Familial hypercholesterolaemia Polygenic hypercholesterolaemia Familial hyper-alphalipoproteinaemia\* (not bad for u) Phytosterolaemia

Answer 312

Familial Type I: lipoprotein lipase/ apoC II deficiency (lack of degradation of TGs-\> diet can help) Familial Type V: sometimes due to ApoA V defic Familial Type IV: increased synthesis of TG Types IV and V: diet not as helpful as there is increased production of cholesterol.

Answer 313

PCSK9: binds LDL receptor and promotes its degradation Rarely FH caused by gain of function mutations -\> increased rate of degradation of LDLRs. -\> high LDLs loss of function mutations -\> Low LDL levels

Answer 314

eryptive xanthomas on skin

Answer 315

shiny palmar crease palmar striae diagnostic of type III eruptive xanthoma (type III) type III = familial dys(beta)lipoproteinaemia

Answer 316

Abeta-lipoproteinaemia: MTP deficiency Hypobeta-lipoproteinaemia: truncated apoB protein Tangier disease: HDL deficiency Hypoalpha-lipoproteinaemia - apo-I mutation (sometimes)

Answer 317

atorvastatin

Answer 318

nicotinic acid but alot of side effects

Answer 319

gemfibrozil

Answer 320

* Microsomal Triglyceride Transfer Protein (MTP) inhibitor (lomitapide) * \* Anti-PCSK9 monoclonal antibody (REGN727) * Anti-sense apoB oligonucleotide (mipomersen) * Lomitapide reduces LDL absorption however can cause fatty liver (as less is absorbed more is synthesised in the liver). Thus probably would only be used in FH homozygotes.

Answer 321

Apolipoprotein A-I or A-1 mimetic infusion therapy Cholesterol ester transfer protein (CETP) inhibitors (e.g. in familial hyperalpha-lipoproteinaemia)

Answer 322

if BMI \>40 Gastric banding (small meals feel full) Roux-en-Y gastric bypass (reduced absorption) Biliopancreatic diversion (only terminal ileum absorbs nutrients)

Answer 323

orlistat- malabsorption of TG side effects of steatorrhoea

Answer 324

intensive treatment of controlling BP in patients w previous MI can significantly reduce deaths - thiazide type diuretics first line e.g. chlorthialidone - loop diuretics (for those w advanced chronic kidney disease) - BB (for those w coronary artery disease) optimal medical therapy postMI - intensive lifestyle modification - aspirin - high dose statin - optimal BP control - thiazides

Answer 325

GLP-1 agonist - shown to reduce CV related mortality in diabetic patients

Answer 326

SGLT2 inhibitor pee more glucose to reduce blood glucose levels substantial reduction in CV mortality in diabetics

Answer 327

Phenylalanine hydroxylase deficiency Test- blood phenylalanine levels

Answer 328

restrictive diet to foods low in phenylanaline + special supplements to maintain Phe at non-toxic levels

Answer 329

sensitivity = true positive/ total disease (ie. True positives + false negatives) specificity = true negative / total negatives (true negative + false positive)

Answer 330

PPV = True positive / all those who tested positive ( TP + false positive) NPV = True negative / all those whoe tested negative (TN + FN)

Answer 331

Screens PKU, congenital hypothyroidism, SCD, CF, medium chain AcylCoA dehydrogenase done at days 5-8 of life

Answer 332

TSH under negative influence by perchlorate.

Answer 333

Iodide uptake into thyroid iodide-\> iodine with thyroid peroxidase iodine then taken up by thyroglobulin and bind to tyrosine iodotyrosines join to form thyroxine -\> secreted back into the lumen

Answer 334

Stimulates uptake of iodide from capillary lumen into cells, convert iodide into iodine Uptake of iodotyrosines back into the cell and secreted out into the lumen

Answer 335

MTC sporadic/ familial / part of MEN 2 C cells of thyroid that produces calcitonin Measure calcitonin / carcinoembryonic antigen (CEA) which are tumour markers

Answer 336

Autoimmune- Hashimotos Atrophic - congenital/ developed Post Graves- Radiotherapy, surgery post de quervains viral thyroiditis, drugs (amiodarone and lithium) iodide deficiency secondary hypothyroidism due to pituitary disease (low TSH) peripheral thyroid hormone resistance (receptor does not respond)

Answer 337

usually macrocytic anaemia can be normocytic

Answer 338

TSH high and low T4 antibody screen- anti thyroid peroxidase

Answer 339

T4 levothyroxine titrated to normal TSH - take note of any heart disease always start w small dose of thyroxine to prevent overworking of heart muscles and subsequently ischaemia

Answer 340

normal T4, T3, high TSH compensated hypothyroidism. unlikely to have symptoms. assoc w hypercholesterolaemia

Answer 341

HCG has same configuration as TSH Excess HCG-\> increased thyroxine released in first trimester, T4 will be higher than normal. Thyroid binding globulin also increases in pregnancy due to oestrogen. at the end of pregnancy, HCG level falls and T4 and TSH goes back to normal.

Answer 342

occurs with any severe illness. body tries to shut down metabolism and thyroid gland has reduced output low T3 and low T4 when severe. slightly high/ normal TSH then later low TSH. Normal physiological response. NO hypothyroid symptoms. \* always interpret TFT results in the clinical context of the patients

Answer 343

high uptake in technetium scan: graves toxic multinodular goitre single toxic adenoma Low uptake: subacute thyroiditis postpartum thyroiditis silent thyroiditis factitious thyroiditis (taking thyroxine) TSH induced, thyroid cancer induced trophoblastic tumour and Struma Ovarii-\> too much HCG

Answer 344

TFTs technetium scan thyroid autoantibodies (TSHR) tx dependent on aietiology

Answer 345

symptomatic BBs NSAIDs for dequervains

Answer 346

BB if pulse \>100 carbimazole/ propylthiouracil (rarely used now due to risks of aplastic anaemia) Radioiodine/ surgery

Answer 347

smooth diffuse goitre- smooth palpable thyroid gland graves opthalmopathy - exophthalmos pretibial myxoedema thyroid acropachy other AI disease or family hx

Answer 348

inhibits thyroid peroxidase Propylthiouracil- assoc w aplastic anaemia titration for 18 months

Answer 349

thyroiditis viral de quervains tx is actually thyroxine replacement after the thyroid gland stops working

Answer 350

papillary or follicular thyroid cancer surger +/- radioiodine thyroxine to lower TSH levels, as TSH can stimulate cancer cells to regrow and relapse.

Answer 351

Thyroglobulin - indicates functioning thyroid tissue - check for recurrence!

Answer 352

common before 34 wks lack surfactant that keeps small air sacs in the lung from collapsing. Treatment with surfactant helps affected babies breathe more easily. May need additional oxygen and mechanical breathing assistance to keep their lungs expanded. The sickest babies may temporarily need the help of mechanical ventilation to breathe for them while their lungs mature.

Answer 353

Bleeding in the brain occurs in some very LBW premature babies, usually in the 1st 3 days of life. Brain bleeds usually are diagnosed with an ultrasound Most brain bleeds are mild and resolve themselves with no lasting problems. Drugs can be used to reduce fluid buildup. More severe bleeds can cause pressure on the brain that can lead to brain damage. In such cases, tube may be inserted into the brain to drain the fluid and reduce risk of brain damage.

Answer 354

common in premature babies Before birth, the ductus arteriosus lets the blood bypass the baby’s nonfunctioning lungs. The ductus normally closes after birth so that blood can travel to the lungs and pick up oxygen. Otherwise, can lead to heart failure. Diagnosed with echocardiography or other imaging tests. Babies with PDA are treated with NSAIDs (ibuprofen/ indometacin) that helps close the ductus, although surgery may be necessary if the drug doesn’t work. if severe, complications present -\> surgery may be recomended. or catheter procedures in the full term baby

Answer 355

common in premies Inflammation of the bowel wall progressing to necrosis and perforation Bloody stools, abdominal distension Can lead to feeding difficulties, abdominal swelling and other complications. Treated with antibiotics and fed intravenously while the intestine heals. In some cases, surgery is done to remove damaged sections of intestine.

Answer 356

Osteopenia due to deficient activity of Vit D Presentation: frontal bossing, bowlegs/knock knees, muscular hypotonia Alternative presentation: tetany / hypocalcaemic seizure, hypocalcaemic cardiomyopathy - due to hypoCa

Answer 357

fraying, splaying and cupping of long bones Biochemistry of osteopenia – normal Ca, PO4 \<1mmol/L, ALP \>1200 U/l (10 x adult ULN) Treatment - PO4/Ca supplements, 1α-calcidol

Answer 358

Extremely common in first 10 days of life due to: o High level of synthesis (rbc breakdown) o Low rate of transport into liver o Enhanced enterohepatic circulation

Answer 359

Kernicterus as free bilirubin can cross the BBB

Answer 360

In full term babies, if bilirubin \>350μmol/L, use phototherapy; 450μmol/L, exchange transfusion In prem, the threshold are 120μmol/L and 230μmol/L, as they have less albumin.

Answer 361

- not fully mature - low gfr compared to their surface area - reduced concentrating ability w maximum urine osmolality of 700mmol/kg - increased loss of sodium and reduced K excretion - \> hence, babies need 6x more fluid, 30x more Na and 2x more K+ compared to adult (in terms of body weight ratio)

Answer 362

Hypernatraemia after 2 weeks is uncommon and is usually associated with dehydration. Salt poisoning and osmoregulatory dysfunction are rare but should be considered in cases of repeated hypernatraemia without obvious cause. Routine measurement of urea, creatinine and electrolytes on paired urine and plasma on admission may differentiate these rare causes.

Answer 363

Congenital adrenal hyperplasia (1in15000) – missing 21-hydroxylase -\> loss of aldosterone and cortisol -\> excess loss of salt Excess androgens due to excess precursors hypoNa and hyperK with marked volume depletion hypoglycaemia ambiguous genitalia in female neonates

Answer 364

High insensible water loss - high surface area, skin blood flow, metabolic/respiratory rate and transepidermal fluid loss (skin not keratinised yet) **Drugs** o Bicarbonate (for acidosis) causes high Na content as GFR function not fully developed to excrete the excess Na from Na2CO3 o Antibiotics – almost always Na salts o Caffeine/theophylline (for apnoea) – increases renal Na loss o Indomethacin (forPDA) – causes oliguria

Answer 365

Lysosomal storage disorders e.g. Tay Sachs, Fabry's disease causes intraorganelle substrate accumulation leading to organomegaly (connective tissue, solid organs, cartilage, bone and nervous tissue), w consequent dysmorphia and regression

Answer 366

Ix: Urine mucopolysaccharides and/or oligosaccharides, **leucocyte enzyme** activity Mx: BM transplant, exogenous enzyme

Answer 367

Peroxismal disorder - cannot catabolise very long fatty acids or make bile acids Test: very long chain fatty acid profile

Answer 368

glycosylation disorder defect of post translational protein glycosylation Lab: transferring glycoforms in the serum mortality: 20% in the first year

Answer 369

Glycogen storage disease failure to mobilize glucose from glucogen accumulation of glycogen-\> hepatomegaly high risk of hepatoblastoma Mx: regular CHO

Answer 370

affects any organ, age Birth: barth (cardiomyopathy, neutropenia, myopathy) 5-15: MELAS (mitochondrial encephalopathy, lactic acids and stroke like episodes) 12-30: Kearns-Sayre (Chronic progressive external ophthalmoplegia, retinopathy, deafness, ataxia) CSF protein raised in Kearns-Sayre High CK + high lactate -\> indiactes mitochondrial disorders Muscle biopsy mitochondrial DNA analysis

Answer 371

Galactossaemia most common: deficiency of Gal-1-PUT enzyme. Raised GAL-1-Phosphate Tx: galactose- free diet Galactitiol is formed by the action of aldolase on gal-1-phosphate leading to bilaterial cateracts

Answer 372

phenylketonuria

Answer 373

Fatty acid oxidation disoders -\> Hypoketotic hypoglycaemia test blood ketones, urine organic acids Tx w regular carbohydrates

Answer 374

Reye Syndrome low blood sugar, raised ammonia

Answer 375

isolvaleric acidaemia maple syrup urine disease

Answer 376

Isovaleric acidaemia disruption of normal metabolism of leucine -\> buildup of isovaleric acid hyperammonaemia + metabolic acidosis and high anion gap Tx: dietary protein restriction especially leucine. remove ammonia acutely by giving sodium benzoate/ dialysis

Answer 377

Maple syrup urine disease dx: by gas chromaography + mass spec high ammonia metabolic acidosis and high anion gap

Answer 378

homocystinuria fair skin, brittle hair lens dislocation downwards compared to marfans (upwards) due to cystathionine beta synthase deficiency -\> increased conc of homocysteine

Answer 379

HMB synthase deficiency - activity of enzyme usually 50% of normal * ALA synthase inducers (cytochrome P450 inducers which overwhelms activity of HMB synthase) - barbiturates, steroids, ethanol, anticonvulsants * COCP * Stress - Infection, surgery * Reduced caloric intake * Endocrine factors - more common in women and premenstrual

Answer 380

Urine sample! keep it shielded from light Increased **ALA and PBG in urine** 'port wine urine' as seen by person when PBG gets oxidised to porphobilin (deep yellow -\> purple)

Answer 381

Avoid precipitating factors - adequate nutritional intake, avoid precipitant drugs, prompt treatment of infection/ illness **IV Carbohydrate + IV Haem Arginate (key tx)** - inhibits ALA synthase, which turns off the pathway and reduces [ALA]

Answer 382

Auto dominant inheritance HMB synthase deficiency accumulation of PBG and ALA -\> neurovisceral attacks abdo pain, nausea and vomiting, tachycardia, HTN constipation and urinary incontinence hypoNa (SIADH) seizures, psych distrubances NO cutaneous manifestations

Answer 383

extremely Rare build up of ALA neurovisceral symptoms e.g. coma, bulbar palsy, motor neuropathy, 90% present w abdo pain can have psychiatric symptoms

Answer 384

Hereditary coproporphyria Variegate porphyria Both produce excess coproporphyrinogen III which can be detected in stool, VP also produces excess protoporphyrinogen IX. These 2 syndromes have acute neurovisceral attacks as PIX and CIII are both potent inhibitors of HMB synthase. Increased PIX and CIII thus reduces HMB synthase activity, accumulating ALA which causes neuro-visceral attacks.

Answer 385

coproporphyrinogen oxidase deficiency excess corprophoryinogen III

Answer 386

acute porphyrias w skin lesions acute neurovisceral attacks + skin lesions - classically sun exposed places like back of hand/ neck) - blistering , skin fragility. both are autosomal dominant

Answer 387

protoporphyrinogen oxidase deficiency accumulation of coprophorphyrinogen III and protoporphyrinogen IX CPIII and PPIX

Answer 388

urine samples, protected from light - **raised PBG** (but not ALA like in AIP) ## Footnote **raised porphyrins in faeces/ urine**

Answer 389

only present w skin lesions e.g. blisters, fragility, pigmentation, erosions no neuro visceral manifestations CEP- congenital erythorpoietic porphyria PCT - porphyria cutanea tarda EPP - erythropoietic protoporphyria

Answer 390

no blisters most common in children burning, itching, oedema following sun exposure (photosensitivity) assoc w MDS

Answer 391

Ferrochetolase deficiency Ix: RBC [protophorphyrin]

Answer 392

blistering inherited/ acquired e.g. liver disease/ drugs formation of vesicles on sun exposed areas of skin crusting, superficial scarring, pigmentation

Answer 393

uroporphyrinogen decarboxylase deficiency Ix: raised urinary uroporphyrins + coproporphyrins + increased ferritin mx: avoid precipitants (alcohol, hepatic compromise)

Answer 394

ADH and oxytocin

Answer 395

compression of optic chiasm -\> bitemporal hemianopia signs and symptoms of raised ICP obstructive hydrocephalus

Answer 396

produced in parafollicular cells (C cells) of th thyroid gland calcitonin involved in opposing the effects of PTH, reducing blood calcium and promoting absorption of calcium by the skeletal system

Answer 397

**Solitary** nodules more often neoplastic than multiple nodules (as in multinodular goitre) **Solid** nodules more likely to be neoplastic than cystic nodules Nodules in **younger patients/males** more likely to be neoplastic than in older patients/females Nodules that do not take up radioactive iodine (**cold nodules**) more commonly neoplastic than ‘hot’ nodules \*Ultimately it is the morphology that provides the answer - FNA cytology or core biopsy histology

Answer 398

Thyroid adenoma

Answer 399

Papillary (75-85%), follicular (10-20%) Medullary (5%), anaplastic (\<5%)

Answer 400

Papillary carcinoma 10yr survival up yo 90%

Answer 401

Medullary carcinoma

Answer 402

follicular carcinoma

Answer 403

Anaplastic carcinoma

Answer 404

80-90% - solitary adenoma 10-20% hyperplasia of all 4 glands - sporadic or component of MEN type 1 \<1% carcinoma of parathyroid

Answer 405

Neuromuscular irritability - tingling, muscle spasms, tetany Cardiac arrhythmias, fits, cataracts

Answer 406

Zona glomerulosa

Answer 407

zona fasciculata

Answer 408

zona reticularis

Answer 409

10% arise in association with a familial syndrome inc. MEN 2A and 2B, von Hippel-Lindau disease and Sturge-Weber syndrome 10% are bilateral, 10% are malignant 10% of catecholamine-secreting tumours arise outside the adrenal (paragangliomas)

Answer 410

porphyrins

Answer 411

heparan sulphate contributes to the negative charge on the filtration barrier

Answer 412

basal like carcinoma - often assoc w BRCA mutations and have a propensity to vascular invasion and distant metastatic spread

Answer 413

lobular carcinoma in situ -ALWAYS incidental finding on biopsy. cells lack adhesion protein E-cadherin. RF for subsequent invasive breast carcinoma

Answer 414

Phyllodes tumour. often arises from pre-existing fibroadenoma majority are benign. more stromal cellularity and the presence of atypical cells denote a more malignant process.

Answer 415

metronidazole to cover for anaerobes found in the GI tract.

Answer 416

food allergy these allergies resolve as children get older, which is why it is impt that children are retested w the gradual introduction of specific food products into their diet.

Answer 417

intranasal antihistamine (H1 receptor antagonist) where predominant symptom is nasal blockage -\> intranasal corticosteroid is recommended

Answer 418

Beta-myosin heavy chain

Answer 419

thickening of septum narrows the L ventricular outflow tract

Answer 420

squamous cell carcinoma

Answer 421

low arterial BP distended neck veins distant, muffled heart sounds

Answer 422

paradoxical rise in JVP on inspiration, or a failure in the appropriate fall of the JVP with inspiration

Answer 423

streptococcus pyogenes

Answer 424

hypoNa \<135 Plasma osmolality \<270 Urine osmolality \>100 High urine Na \>20 Euvolaemia no adrenal, renal or thyroid dysfunction

Answer 425

not a true hypoNa as serum osmolality is high. (\>295) just a relative hypoNa

Answer 426

bartter syndrome

Answer 427

hypoK + acidosis. defect in H ion secretion in renal tubules. K secretion therefore increases to balance sodium reabsorption. type 1 (distal tubule) type 2 (proximal tubule)] type 3 (both distal and proximal) type 4 (defect in adrenal glands)- metabolic acidosis + hyperK

Answer 428

methanol / metformin Uraemia DKA Paraldehyde Iron Lactate Ethanol Salicylates

Answer 429

autosomal recessive disorder results in raised **conjugated br** level due to reduced secretion of conjugated br into the bile. AST/ALT are normal.

Answer 430

hereditary disease either complete (type 1) or partial (type 2) reduction in the conjugating enzyme UDP glucuronosyl transferase -\> **unconjugated hyperbilirubinaemia**

Answer 431

distinguishes between primary (addisons) and secondary adrenal insufficiency. In secondary adrenal insufficiency- the defect is in the pituitary gland -\> low ACTH -\> low cortisol and aldosterone. Long synACTHen test reveals a high cortisol \>900, as there is a delayed rise in production in the adrenal glands. (would still be low in addisons)

Answer 432

Vitamin E tocopherol is an impt anti-oxidant which acts to scavenge free radicals in the blood stream. Deficiency leads to haemolytic anaemia as RBCs encounter oxidative damage and are consequently broken down in the spleen. Spino-cerebellar neuropathy is also a manifestation, characterized by ataxia and areflexia.

Answer 433

sideroblastic anaemia dermatologically - seborrhoeic dermatitis

Answer 434

Vit A impairs production of rods and hence causes night blindness. ocular epithelial changes causes conjunctival Bitot's spots.

Answer 435

Homocystinuria + skeletal abnormalities mx: supplement w vitamin B6 or maintaining child on low methionine diet.

Answer 436

lysosomal storage disorders fabrys tay sachs

Answer 437

maple syrup urine disease toxic compounds (leucine, isoleucine, valine) accumulate causing toxic encephalopathy -\> FTT, lethargy, hypotonia, seizures

Answer 438

phenylketonuria lack phenylalanine hydroxylase present w developmental delay, severe IQ impariment + seizures/ eczema

Answer 439

gylcogen storage disorder e.g Von Gierke's Pompe's Cori's McArdle's

Answer 440

SCAD deficiency Short chain acyl coenzyme A

Answer 441

stimulates production of vasopressin (ADH) so presents similarly to SIADH

Answer 442

2 low in the blood- hypoNa, hypoosmolality 2 high in the urine - high urinary sodium \>20, high urine osmolality three exclusions - no renal/ adrenal/ thyroid/ cardiac disease, no hypovolaemia and no contributing drugs e.g. carbamazepine

Answer 443

aka Albright's osteodystrophy PTHR insensitivity in the kidney -\> HIGH PTH, low Ca and High PO4 + physical signs e.g. short height, short 4th and 5th metacarpals, reduced intelligence, basal ganglia calcification and endocrinopathies e.g T2DM, obesity, hypothyroid, hypogonadism

Answer 444

similar physical features of pseudohypoPTH (albrights osteodystrophy) but no biochemical abnromalities - genetic imprinting e. g. prader willi and angelmans

Answer 445

carbohydrate deficient transferrin. Ppl with alcohol abuse have a reduction in bound carbohydrates and increase in their carbohydrate deficient transferrin. about 70% sensitive but 95% specific for alcohol abuse. other tests include presence of macrocytic anaemia, raised GGT

Answer 446

allowed to drink 1.5 x the total urine output of the first 8 h e.g. if 1L was the urine output, allowed to drink 1.5 L if pt drinks too much water, the test is nullified

Answer 447

difference between estimated **osmolarity** and lab **osmolality** usually \<10 mmol/L if higher, then consider presence of additional solutes e.g. ethanol, methanol, ethylene glycol and acetone

Answer 448

galactosaemia galactose-1-phosphate uridyltransferase genn