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Chem path Flashcards

1
Q

Define hyponatraemia

A

Serum Na+ < 135mmol/L

most common electrolyte abnormality

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2
Q

Pathogenesis of hyponatraemia

A

Increased extracellular water due to excess ADH

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3
Q

How does ADH work?

A

Acts on V2 receptors on collecting duct cells in nephron

Leads to insertion of aquaporin-2 channels

Leads to water retention, increasing extracellular water

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4
Q

What stimulates ADH secretion?

A

Increased serum osmolality (detected by osmoreceptors, also leads to thirst)

Decreased blood volume/pressure (detected by baroreceptors)

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5
Q

First step in mx of pt with hyponatraemia

A

Volume status

  • hypovolaemic
  • euvolemic
  • hypervolemic
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6
Q

Compare clinical features of hypo and hypervolaemia

A

Hypo

  • tachycardic
  • postural hypotension
  • dry mucous membranes
  • reduced skin turgor
  • confusion/drowsiness
  • reduced urine output
  • LOW urine Na+ (<20)

Hyper

  • raised JVP
  • bibasal crackles
  • peripheral oedema
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7
Q

What is the most reliable clinical sign of hypovolaemia?

A

LOW urinary sodium (<20)

Shows the kidney is trying to retain fluid because in hypovolaemia, the body is low in salt AND water

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8
Q

What would alter interpretation of urine sodium?

A

Diuretic use

Urine can be checked 48hrs after stopping drug

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9
Q

Causes of hypovolaemic hyponatraemia

A

GI loss (vomiting and diarrhoea)
Diuretics
Salt losing nephropathy

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10
Q

Causes of euvolaemic hyponatraemia

A

Hypothyroidism
Adrenal insufficiency
SIADH

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11
Q

Causes of hypervolaemic hyponatraemia

A

Cardiac failure
Cirrhosis
Nephrotic syndrome/renal failure

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12
Q

How does SIADH lead to hyponatraemia?

A

SIADH describes a state where excess ADH is released

Results in excess retention of water and pt initially becomes hypervolaemic

However, expanded volume stimulates release of natriuretic peptides

Leads to natriuresis; loss of Na+ via urine and water follows

End volume status is euvolaemia w hyponatramia

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13
Q

Causes of SIADH

A

CNS pathology (tumour, abscess, stroke)
Lung pathology (small cell lung Ca, pneumothorax, PE, chest infection)
Drugs (SSRI, TCA, opiates, PPIs, carbamazepine)
Tumours
Surgery

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14
Q

How is SIADH diagnosed?

A

Diagnosis of exclusion

  • true hyponatraemia (<135)
  • low plasma/serum osmolality (<270)
  • high urine sodium (>20)
  • high urine osmolality (<100) due to natriuresis
  • no adrenal/thyroid/renal dysfunction so normal 9am cortisol and normal TFTs
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15
Q

Why do hypothyroid pts become hyponatraemic?

A

Hypothyroidism leads to reduced cardiac output due to reduced cardiac contractility

Detected by baroreceptors -> ADH release to correct BP

Increased water retention

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16
Q

Why do adrenal insufficient pts become hyponatraemic?

A

Adrenal insufficiency leads to low aldosterone and cortisol

Low aldosterone -> less salt and water retention in kidney

Low cortisol -> excess ADH release and water retention

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17
Q

What happens to urinary sodium in cardiac failure?

A

LOW

Secondary hyperaldosteronism occurs due to activation of renin-angiotensin-aldosterone system to keep BP high

Aldosterone promotes water and sodium retention in kidney

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18
Q

Treatment for hyponatraemia

A

Hypo
- volume replacement with 0.9% saline (NaCl)

Euvo/hyper

  • fluid restriction
  • treat underlying cause
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19
Q

Signs of severe hyponatraemia

A

Nausea and vomiting (<134)
Confusion (<131)
Seizures, non-cardiogenic pulmonary oedema (<125)
Coma (<117) and eventual death

expert help needed

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20
Q

Risks of sodium correction treatment

A

Central pontine myelinolysis if serum sodium corrected faster than 8-10mmol/L in first 24 hours

Water moves too quickly out of cells, affecting CNS gap junctions, inflammatory cells enter via compromised junctions -> osmotic demyelination

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21
Q

Signs of osmotic demyelination

A 
Quadriplegia
Dysarthria
Dysphagia
Seizures
Coma
Death

*manifest a few days after sodium corrected too quickly

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22
Q

What should you do if sodium is administered too quickly?

A

Lower Na+ using 5% dextrose

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23
Q

What drugs are used to treat SIADH?

A

If fluid restriction not enough

  1. Demeclocycline
    - reduce effect of ADH on collecting duct cells
    - monitor U&Es due to nephrotoxicity risk
  2. Tolvaptan
    - V2 receptor antagonist
    - expensive and associated w high risk in serum sodium
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24
Q

What causes hypernatraemia?

A

Hyper Na+ >145mmol/L
- raised urea, albumin and PCV

Caused by unreplaced water loss

  • GI loss
  • Sweat loss
  • Renal loss: osmotic diuresis, diabetes insipidus (reduced ADH release/action)

Typically in pts who don’t drink when dehydrated, i.e. elderly, children

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25
What is approximate fluid balance in the body?
60-40-20 60% of total body weight = water 40% of body weight = intracellular 20% of body weigh = extracellular (needs salty water for cells to survive in)
26
Osmolality vs Osmolarity defintions
Osmolality - total no. of particles in solution, measured with an osmometer (mmol/kg) Osmolarity - calculated (mmol/L)
27
Osmolarity equation
2(Na+ + K+) + urea + glucose *anions will roughly equal cations thus cations doubled
28
What are the causes of hyponatraemia based on osmolality?
High osmolality - glucose/mannitol infusion Normal osmolality - spurious result, drip arm sample, pseudohyponatraemia (hyperlipidaemia/paraproteinaemia) Low osmolality - true hyponatraemia
29
What is the difference in causes for hypovolaemic hyponatraemia based on urine sodium?
High urine Na+ (>20) - RENAL - diuretics, addison's, salt-losing nephropathy - kidney fails to reabsorb sodium so water lost as well Low urine Na+ (<20) - NON-RENAL - vomiting, diarrhoea, excess sweat - kidney doing best to hold onto Na
30
Signs of diabetes insipidus
Hypernatraemia (lethargy, thirst, irritability, confusion, coma, fits) Clinically euvolaemic Polyuria and polydipsia Low urine osmolality (<2)
31
Ix for diabetes insipidus
1. Serum glucose (exclude DM) 2. Serum K+ (exclude hypokalaemia) 3. Serum Ca2+ (exclude hypercalcaemia) 4. Plasma and urine osmolality 5. 8-hour water deprivation test; DIAGNOSTIC
32
How is the type of diabetes insipidus confirmed?
8-hour water deprivation test Normal - urine osmolality >600, can concentrate Primary polydipsia - urine concentrates less than normal Cranial DI - Urine osmolality increases >600 ONLY AFTER desmopressin Nephrogenic DI - no increase in urine osmolality even after desmopressin
33
Causes and treatment of diabetes insipidus
Cranial - lack/no ADH - surgery, trauma, craniopharyngioma, autoimmune hypohysitis - mx: desmopressin Nephrogenic - insensitive to ADH - inherited, drugs (lithium, demeclocycline), hypokalaemia, hypercalcaemia - mx: thiazide diuretics
34
What are the three most important buffering systems in the body?
Bicarbonate (ECF< glomerular filtrate) H+ + HCO3- /=/ H2CO3 Haemoglobin (red cells) H+ + Hb- /=/ HHb Phosphate (renal tubular fluid/intracellular) H+ + HPO4- /=/ H2PO4
35
What is the main system H+ is excreted by the body?
H+ excreted into renal tubules in return for Na+ absorption Important for kidneys to excrete H+ and regenerate HCO3- to maintain bicarbonate buffering system (only works in short term as uses up HCO3- quickly)
36
How is HCO3- produced in the body?
From carbonic acid made from CO2 excreted by the lungs (product of metabolism) CO2 + H2O /=/ H2CO3 /=/ H+ + HCO3-
37
What results do ABGs produce?
pO2 = partial pressure of oxygen pCO2 = partial pressure of CO2 pH Analyser does NOT directly measure bicarbonate; calculates it with equation
38
What may cause metabolic acidosis?
Increased H+ production (DKA, lactic acidosis) Decreased H+ excretion (renal tubular acidosis, renal failure) Bicarbonate loss (intestinal fistula)
39
How does the body compensate for metabolic acidosis?
Increases resp rate and blow off more CO2 in an attempt to reduce H+ Compensated metabolic acidosis should have a low pCO2
40
What may cause respiratory acidosis?
Lung pathology that leads to increased CO2 Decreased ventilation, poor lung perfusion, impaired gas exchange
41
How does the body compensate for respiratory acidosis?
Slightly increasing the bicarbonate concentration Kidney scompensate by increasing H+ excretion and HCO3- regeneration but slower than respiratory compensation May see elevated HCO3- and CO2 with normal H+ in compensated respiratory acidosis
42
What do you expect to see in patients with COPD in an ABG? (not an exacerbation)
Chronic respiratory acidosis with chronically high bicarbonate levels
43
What may cause metabolic alkalosis?
H+ loss (pyloric stenosis) Hypokalaemia (K+ main transport agent for H+ exchange - Na/K/ATPase) Ingestion of bicarbonate (overdose of antacids)
44
How does the body compensate for metabolic alkalosis?
If hypokalaemic, cannot excrete H+!! Resp centre will become inhibited leading to a rise in pCO2 for H+ to return to normal
45
What may cause respiratory alkalosis?
Due to hyperventilation Anxiety Artificial ventilation or stimulation of resp centre (rare) Pregnancy Altitude
46
How does the body compensate for respiratory alkalosis?
May see with assisted ventilation - prolonged results in decreased renal H+ and decreased HCO3- generation Compensation only occurs in chronic cases, H+ returns to normal but pCO2 and HCO3- remain low
47
Metabolic acidosis ABG
pH: LOW pCO2: LOW HCO3-: LOW Immediate compsenation: hyperventilation
48
Metabolic alkalosis ABG
pH: HIGH pCO2: HIGH HCO3-: HIGH Immediate compensation: hypoventilation
49
Respiratory acidosis ABG
pH: LOW pCO2: HIGH HCO3-: HIGH (renal delayed compensation) *normal/high pCO2 worrying - ITU RV/vent support needed
50
Respiratory alkalosis ABG
pH: HIGH pCO2: LOW HCO3-: LOW (renal delayed compsensation)
51
Role of anion gap in ABGs
Elevated anion gap in metabolic acidosis, helps determine cause
52
Causes of metabolic acidosis with elevated anion gap
KULT Ketoacidosis (DKA, alcoholic, starvation) Uraemia (renal failure) Lactic acidosis Toxins (ethylene glycol, methanol, paraldehyde, salicylate)
53
What ABG changes may these drugs cause? a) aspirin b) salicylates c) opioids d) loop diuretics
a) Metabolic acidosis (high anion gap) b) Respiratory alkalosis (brainstem stimulation) c) Respiratory acidosis (T2 resp failure) d) Metabolic alkalosis (K+ depletion)
54
Role of osmolar gap in ABGs
Helpful in differentiating caues of elevated anion gap metabolic acidosis Elevation suggestive of presence of abnormal solute (alcohol, mannitol, ketones, lactate)
55
Which hormones regular potassium and where do they come from?
Angiotensin II Aldosterone *Angiotensinogen (liver) via renin -> angiotensin I via ACE in lungs -> angiotensin II STIMULATES aldosterone release (adrenals/zona glomerulosa)
56
What does aldosterone do?
Stimulate Na+ reabsorption (water retention) and K+ excretion Acts on cortical collecting duct on mineralocorticoid receptor Na+ channels increase on luminal membrane, more Na+ reabsorbed, lumen electronegative therefore K+ moves down electrogradient and SECRETED
57
What is normal serum concentration for K+?
3. 5-5.0 mmol/L | * K+ most abundant intracellular cation*
58
ECG changes seen with hyperkalaemia
Loss of P waves Tall, tented T waves Broad QRS complexes (late change) ECG is 'pulled apart' to create a 'sine wave' if severe/untreated
59
Mx of hyperkalaemia
Repeat sampling - may be spurious result due to haemolysis - repeat if >7 ECG - check if any changes/arrhythmia K+ >5.5 w ECG OR K+ >6.5 regardless of ECG triggers: 10ml of 10% calcium gluconate - stabilise myocardium, prevent arrhythmia 100-200ml of 10-20% dextrose + 10 units of insulin - drive K+ into cells - dextrose avoid hypoglycaemia - note: 50ml 50% dextrose old mx, very irritant Nebulised salbutamol - drive K+ into cells Consider calcium resonium 15g PO or 60g PR - bind K+ in gut Treat underlying cause
60
Causes of hyperkalaemia
Artefact - spurious result due to haemolysis/EDTA contamination in FBC bottle Renal impairment - renal failure as reduced GFR so reduced K+ secretion - happens late due to compensatory mechanisms Reduced renin activity - RARE cause: type 4 renal tubular acidosis - NSAIDs Drugs - ACEi -> less aldosterone - ARBs -> less angiotensin II, less aldosterone - spironolactone -> aldosterone antagonists Low aldosterone - Addison's (damaged adrenal cortex) - Type 4 renal tubular acidosis (low renin) K+ release from cells - Rhabdomyolysis - Acidosis (high H+, K+ leaves cells to take H+ in to normalise pH and maintain gradient)
61
What care should be taken for patients on digoxin when administrating calcium?
Cardiac monitoring should be performed IV Ca2+ can precipitate arrhythmias
62
Causes of hypokalaemia
GI loss - D&V Renal loss - Hyperaldosteronism (Conn's), Cushing's (excess cortisol) -> act on MR - Increased Na+ to distal nephron; drugs, Bartter/Gitelman syndromes - osmotic diuresis Redistribution into cells - insulin - beta agonists - alkalosis; opposite mechanism of acidosis (H+ leave cell, K+ enters) Rare - renal tubular acidosis type 1 and 2 - hypomagnesaemia
63
Which drugs and syndromes cause hypokalaemia and why?
Loop diuretics + Bartter syndrome - blocks triple transporter (Na+/K+/Cl-) in ascending limb of loop of Henle - Na+ not absorbed loop of Henle so MORE deliver to distal nephron and K+ lost via voltage gradient in exchange Thiazide diuretics + Gitelman syndrome - blocks Na+ and Cl- reabsorption in distal convoluting tubule - more Na+ delivered to distal nephron so K+ lost via voltage gradient in exchange
64
Clinical features of hypokalaemia
MAP Muscle weakness Arrhythmias Polyuria and polydipsia (low K+ -> nephrogenic DI)
65
Screening ix to order if pt hypokalaemic + hypertensive
Aldosterone:renin ratio - 1o hyperaldosteronism; high ratio as renin supressed - think Conn's
66
Can cardiac failure cause hypokalaemia?
Two things happening 1. 2o hyperaldosteronism due to excess activation of RAAS -> increase K+ excretion 2. Renal hypoperfusion meaning reduced GFR -> reduce K+ excretion Therefore net clinical effect may not be hypokalaemia; difficult to predict K+ levels in these patients
67
Can cardiac failure cause hyponatraemia?
Low cardiac output -> baroreceptors detected -> stimulate ADH -> retains water -> dilutes osmolality -> hyponatraemia
68
Mx of hypokalaemia
K+ 3.0-3.5 - oral KCl (2 SandoK tablets for 48 horus) - re-check level K+ <3.0 - IV KCl - max. rate 10mmol/hour - highly irritant Treat underlying cause
69
How can renal tubular acidosis affect K+?
Type 1 - most severe - distal failure of H+ excretion and subsequent acidosis - HYPOKALAEMIA Type 2 - milder - failure to reabsorb HCO3- leads to acidosis - HYPOKALAEMIA Type 3 irrelevant lol Type 4 - leads to acidosis HOWEVER aldosterone deficiency/resistance so HYPERKALAEMIA
70
A 67-year-old man was started on Bendroflumethiazide for hypertension 2 weeks ago. He has had diarrhoea and vomiting for two days. He has dry mucous membranes and reduced skin turgor. - Sodium: 129 mmol/l - Potassium: 3.5 mmol/l - Urea: 8.0 mmol/l - Creatinine: 100 micromoles/l Mx plan?
This patient is showing signs of hypovolaemia. He is also hyponatraemic. Causes of hypovolaemic hyponatraemia include D&V, diuretics and salt-losing nephropathy. Treatment: 0.9% sodium chloride.
71
A 57-year-old woman has breathlessness, worsened on lying flat. Her past medical history includes an NSTEMI. She is taking ramipril, bisoprolol, aspiring and simvastatin. She has an elevated JVP, Bibasal crackles and bilateral leg oedema. - Sodium: 128 mmol/l - Potassium: 4.5 mmol/l - Urea: 8.0 mmol/l - Creatinine: 100 micromoles/l Mx plan?
o Increased urea can suggest reduced GFR aka renal impairment o Reduced urea can suggest alcoholism This patient is showing signs of hypervolaemia (clinically). Causes of hypervolaemic hyponatraemia include cardiac failure (likely here), cirrhosis and nephrotic syndrome. Treatment: fluid restriction, treat the underlying cause.
72
A 55-year-old man has jaundice. He has a past history of excessive alcohol intake. He has multiple spider naevi, shifting dullness and splenomegaly. - Sodium: 122 mmol/l - Potassium: 3.5 mmol/l - Urea: 2.0 mmol/l - Creatinine: 80 micromoles/l Mx plan?
The diagnosis is cirrhosis. Cirrhosis can cause hyponatraemia due to a release in excess nitric oxide. Portal hypertension is associated with a systemic vasodilation due to release of NO – the resulting reduced blood pressure is detected, causing a release in ADH. Treatment: fluid restriction, treat the underlying cause.
73
A 40-year-old woman presents with fatigue, weight gain, dry skin and cold intolerance. On examination, she looks pale. - Sodium: 130 mmol/l - Potassium: 4.2 mmol/l - Urea: 5.0 mmol/l - Creatinine: 65 micromoles/l Next ix and mx?
This sounds like a diagnosis of hypothyroidism. Reduced cardiac contractility results in a reduced blood pressure, which is sensed by baroreceptors. There is a subsequent release in ADH, and more water absorbed (and hyponatraemia). The patient is euvolaemic. We need to check TFTS. Treatment: Treat the underlying cause (thyroxine replacement)
74
A 45-year-old woman presents with dizziness and nausea. On examination, she looks tanned and has postural hypotension. - Sodium: 128 mmol/l - Potassium: 5.5 mmol/l - Urea: 9.0 mmol/l - Creatinine: 110 micromoles/l Next ix and mx?
This sounds like adrenal insufficiency; hyponatraemia and hyperkalaemia make us think of hypoadrenalism. The patient is euvolaemic. We should perform a short synACTHen test (in a healthy person, cortisol will shoot up, but in adrenal insufficiency, it won’t). Treatment: Hydrocortisone and Fludrocortisone (both glucocorticoid and mineralocorticoid replacement).
75
A 62-year-old man has chest pain, cough and weight loss. He looks cachectic. He has a 30-pack year smoking history. - Sodium: 125 mmol/l - Potassium: 3.5 mmol/l - Urea: 7.0 mmol/l - Creatinine: 85 micromoles/l Next ix?
This sounds like a potential case of lung cancer; the patient may have SIADH as a result (excess ADH released ectopically and inappropriately from the lung tumour). The patient will be euvolaemic. The next thing to do is check plasma and urine osmolality (plasma osmolality low, urine osmolality high). The diagnosis of SIADH: - No hypovolaemia - No hypothyroidism - No adrenal insufficiency - Reduced plasma osmolality AND increased urine osmolality (>100) Causes of SIADH include CNS pathology, lung pathology, drugs (SSRI, TCA, opiates, PPIs), tumours and surgery.
76
A 20-year-old man presents with polyuria and polydipsia. On examination, he has bitemporal hemianopia. - Sodium: 150 mmol/l - Potassium: 4.0 mmol/l - Urea: 5.0 mmol/l - Creatinine: 70 micromoles/l Next ix?
This patient has hypernatraemia. Causes of hypernatraemia include unreplaced water loss (GI losses, sweat loss, renal losses e.g. osmotic diuresis, reduced ADH release/action) in association with the patient not being able to control water intake (children, elderly). Investigations for suspected diabetes insipidus: - Serum glucose (exclude diabetes mellitus) - Serum potassium (exclude hypokalaemia) - Serum calcium (exclude hypercalcaemia) - Plasma and urine osmolality - Water deprivation test
77
A 65-year-old man with type 2 diabetes mellitus and hypertension presents malaise and drowsiness. He is on a basal bolus insulin regimen, ramipril, amlodipine, simvastatin and aspirin. - Sodium: 125 mmol/l - Potassium: 6.5 mmol/l - Urea: 18.0 mmol/l - Creatinine: 250 micromoles/l Mx plan?
This patient is hyperkalaemic. They are on ACE inhibitors. The creatinine and urea are also very high, which prompts us to think that the hyperkalaemia is being caused by renal failure (reduced GFR and reduced filtration). We would advise the patient to hold off of Ramipril (less ACE à less aldosterone à less potassium excretion).
78
A 50-year-old man is referred with hypertension, that has been difficult to control despite maximum doses of amlodipine, ramipril and bisoprolol. - Sodium: 140 mmol/l - Potassium: 3.0 mmol/l - Urea: 4.0 mmol/l - Creatinine: 70 micromoles/l Next step?
The hypernatraemia and hypokalaemia prompt us to want to measure the aldosterone:renin ratio.
79
What is a porphyria?
Group of disorders caused by deficiencies in enzymes of haem biosynthetic pathway
80
Why is haem vital for erythroid and liver cells?
Creates cytochrome, needed for electron transfer chain in mitochondria
81
What is one of the key enzymes in the haem synthesis pathway?
ALA synthase (aminolevulinic acid) Starts of pathway by generated 5-ALA from succinyl CoA + glycine The rest of the pathway relies on enzymes to change 5-ALA into haem
82
How may porphyrias be classified?
Site of enzyme deficiency - erythroid - hepatic Clinical presentation - acute = neurovisceral - non-acute cutaneous
83
What causes neurovisceral signs in porphyrias?
Accumulation of 5-ALA | Typically acute presentation
84
What causes cutaneous signs in porphyrias?
Porphyrin precursors accumulate in skin, become oxidised into porphyrins then into toxic, activated porphyrins by UV light that can cause blistering/non-blistering skin lesions
85
Porphyrinogens vs porphyrins
Porphyrinogens - RAISED in porphyria; precursor to porphyrins - colourless as no double bond - unstable so will readily oxidise when sample reaches lab Porphyrins - highly coloured as double bonds present - will show up as deep red/purple when urine sample left to oxidise (porphyrinogens -> porphyrins)
86
Name the acute porphyrias and the enzymes affected
Acute porphyria: - PBG synthase/ALA dehydratase deficiency - RARE Acute intermittent porphyria: - HMB synthase/PBG deaminase deficiency Acute porphyrias w skin lesions: - hereditary coproporphyria (HCP) due to coproporphyrinogen oxidase deficiency - variegate porphyria (VCP) due to protoporphyrinogen oxidase deficiency
87
How can you differentiate between the acute prophyrias?
AIP: NO skin lesions HCP and VP: skin lesions Send urine sample - PBG raise in ALL three Check total porphyrins in urine (protect from light) and stool sample - HIGH in HCP and VP - not high in AIP
88
Name the non-acute porphyrias and the enzymes affected
Porphyria cutaenea tarda (most common) - uroporphyrinogen decarboxylase deficiency Erythropoietic protoporphyria - ferrochetelase deficiency Congenital erythropoietic porphyria - uroporphyrinogen III synthase deficiency
89
Which porphyrias are associated with myelodysplastic syndromes?
Erythropoietic porphyria Congenital erythropoietic porphyria
90
Which sx are seen in acute porphyrias and in which ones?
Neurovisceral: - Painful abdomen - Seizures - Peripheral neuropathy - Psychosis - Port urine - Muscle weakness - Constipation - Urinary incontinence => AIP, HCP, VP Skin lesions: - blistering - skin fragility - affects back of hands and back of neck (sun exposed) => HCP, VP
91
Mx of acute porphyrias
Conservative - avoid precipitating factors (infection, pre-empt if surgery, ALA synthase inducers) - adequate nutrition and analgesia Acute attack - treat underlying infection/illness - IV haem arginate - IV carbohydrate
92
Which sx are seen in non-acute porphyrias and in which ones?
NO neurovisceral, ONLY skin lesions PCT - vesicles on sun-exposed areas - skin crusting - superficial scarring and pigmentation EPP + CEP - NON-blistering - photosensitivity; burning, itching, oedema after sun exposure
93
Mx of non-acute porphyrias
PCT - avoid precipitants (alcohol, liver disease) - chloroquine EPP, CEP - avoid sun exposure
94
How do you differentiate between the cutaenous porphyrias?
PCT - increased urinary uroporphyrins and coproporphyrins - increased ferritin - abnormal LFTs EPP - RBC protoporphyrin levels elevated
95
What carcinogen can trigger PCT-like syndrome?
Hexachlorobenzene
96
What would you expect to see in urine sample if AIP vs PCT?
AIP - Increased urinary porphobilinogen and aminolaevulinic acid PCT - increased urinary uroporphyrins and coproporpyrins
97
Why may you see hyponatraemia associated with AIP?
Due to SIADH
98
Which LFTs are indicative of liver cell damage?
``` ALT AST ALP (alk phos) GGT Bilirubin ```
99
Which LFTs are indicative of synthetic function?
Clotting (INR) Albumin Glucose
100
What is the best marker of liver function in acute liver injury?
Prothrombin time
101
LFT shows ALT and AST > 1000 Ddx?
Acute viral hepatitis Toxin i.e. paracetamol Ischaemic hit
102
What would you suspect with the following LFT findings? a) AST:ALT 2:1 b) AST:ALT 1:1 c) ALT > AST d) ALT + AST > 1000
a) EtOH liver disease b) viral hepatitis c) chronic liver disease d) acute viral hep, paracetamol OD, ischaemic hit
103
What LFTs would you see in a cholestatic/obstructive picture?
Raised GGT and ALP
104
Why may you see an isolated raised ALP?
Physiological - pregnancy, childhood Bone issues - x5 = Paget's, osteomalacia -
105
Why is ALP normal in myeloma?
Plasma cells suppress osteoblasts
106
Which conditions may you see low albumin in?
``` Chronic liver disease Malnutrition Protein-losing enteropathy Nephrotic syndrome Sepsis (3rd spacing) ```
107
Which conditions may you see low urea in?
Severe liver disease Malnutrition Pregnancy
108
Which conditions may you see raised urea (x10) in?
Upper GI bleed Large protein meal Dehydration AKI
109
What clinical findings would you expect to see in prehepatic jaundice?
Normal/increased - unconjugated bilirubin - urobilinogen Normal - urine colour - stool colour - AST/ALT - ALP Splenomegaly present Absent - conjugated bilirubin - urine bilirubin - conjugated bilirubin in urine
110
What clinical findings would you expect to see in hepatic jaundice?
Increased - conjugated bilirubin (in urine) - unconjugated bilirubin - urobilinogen (in urine) - AST/ALT - ALP (could be normal) Urine colour dark Stool colour normal/pale Splenomegaly present
111
What clinical findings would you expect to see in post-hepatic jaundice?
Increased - conjugated bilirubin (in urine) - ALP - AST/ALT - urine bilirubin present Urine colour dark Stool colour pale Absent - splenomegaly - urobilinogen (or decreased)
112
Why don't you get urine bilirubin in prehepatic jaundice?
Uncojugated BR from haem breakdown by macrophages in spleen are tightly bound to albumin thus unable to pass through glomerulus
113
Why do you get dark urine and pale stools in post-hepatic jaundice?
Increase in urobilinogen/conjugated BR (lots absorbed by blood), pale stool = low levels of stercobilinogen + dark urine
114
Hepatomegaly with a smooth margin is indicative of which conditions?
Viral hepatitis Biliary tract obstruction Hepatic congestion secondary to HF (Budd Chiari)
115
Hepatomegaly with a craggy border is indicative of which conditions?
Hepatic metastatic disease Polycystic disease Cirrhosis (shrinks)
116
Causes of prehepatic jaundice
1. Haemolytic anaemia 2. Ineffective erythropoiesis i.e. thalassaemia 3. Congestive cardiac failure
117
Causes of hepatic jaundice
1. Hepatocellular dysfunction (viral, alcohol hep) | 2. Impaired conjugation, BR excretion, BR uptake (Gilbert syndrome, Crigler Najjar syndrome)
118
Causes of post-hepatic jaundice
Obstruction of biliary tree 1. Intraluminal (stones, strictures) 2. Luminal (mass/neoplasm, inflammation - PSC, PBC) 3. Extra-luminal (Ca pancreas, cholangio Ca)
119
What are common problems in LBW babies?
Respiratory distress syndrome Retinopathy of prematurity (due to oxygen hypertoxicity) Intraventricular haemorrhage Patent ductus arteriosus Necrotising enterocolitis (inflammation bowel wall - necrosis + perforation)
120
What is NEC?
Necrotising enterocolitis - inflammation of bowel wall progressing to necrosis and perforation - bloody stools - abdominal distention - intramural air (pneumatosis intestinalis) on X ray
121
Compare newborn renal function to adults
Low GFR for surface area Less reabsorption as short proximal tubule Reduced concentrating ability as short loops of Henle and distal collecting ducts Persistent sodium loss due to distal tubule being relatively aldosterone-insensitive
122
Why do newborns have a high insensible water loss?
High surface area to body weight ratio Skin blood flow increased Metabolic/respiratory rate higher than adults Transepidermal fluid loss (skin not as good barrier/skin not keratinised in prems)
123
When would you see hypernatraemia in a baby?
Common in first two weeks of term baby/common prems Associated with dehydration or overly concentrated milk formula
124
When would you see hyponatraemia in a baby?
Relatively rare Causes include - excessive intake > total body water (first 4-5 days life) - loss of Na loss due to immature tubular function in pts on diuresis (after 4-5 days life) - factitious (hyperglycaemia) - congenital adrenal hyperplasia (21-hydroxylase deficiency)
125
Clinical features of congenital adrenal hyperplasia when presenting as a child
Hyponatraemia/hyperkalaemia with volume depletion Hypoglycaemia (lack of cortisol) Ambiguous genitalia in perceived female neonates - believed male neonates more likely to present w salt-losing crisis Growth acceleration due to excess androgens (rare complaint in children)
126
What presentation of jaundice is always pathological in a neonate?
Jaundice <24 hours of life - acute haemolysis - sepsis Jaundice > 2 weeks of life - hepatobiliary failure Conjugated hyperbilirubinemia at any stage of infancy - biliary atresia - ascending cholangitis in TPN
127
Typical changes seen in hepatic markers due to pre hepatic jaundice
``` Unconjugated BR: ++ Conjugated BR: normal ALT/AST: normal ALP: normal/++ GGT: normal/++ ```
128
Typical changes seen in hepatic markers due to hepatic jaundice
``` Unconjugated BR: normal Conjugated BR: ++ ALT/AST: ++ ALP: + GGT: + ```
129
Typical changes seen in hepatic markers due to post hepatic jaundice
``` Unconjugated BR: normal Conjugated BR: ++ ALT/AST: + ALP: ++ GGT: ++ ```
130
Fat soluble vitamins
A, D, E, K
131
Water soluble vitamins
B1, B2, B3, B6, B12, C, folate
132
Vit A deficiency results in
Colour blindness
133
Vit A excess results in
Exfoliation | Hepatitis
134
Vit D deficiency results in
Osteomalacia | Rickets
135
Vit D excess results in
Hypercalcaemia
136
Vit E deficiency results in
Anaemia/neuropathy | ?Malignancy/IHD
137
Vit K deficiency results in
Defective clotting
138
How do you test for fat soluble vitamin levels?
A, D, E = serum | K = PTT
139
What are the other names for the following vitamins? a) B1 b) B2 c) B3 d) B6 e) B12
a) thiamine b) riboflavin c) niacin d) pyridoxine e) cobalamin
140
B1 deficiency results in
Beri-beri Neuropathy Wernicke's
141
B2 deficiency results in
Glossitis
142
B3 deficiency results in
Pellagra (3Ds) - dementia - dermatitis - diarrhoea
143
B6 deficiency result sin
Dermatitis | Anaemia
144
B12 deficiency results in
Pernicious anaemia
145
B6 excess results in
Neuropathy
146
Vit C deficiency results in
Scurvy
147
Vit C excess results in
Renal stones
148
Folate deficiency results in
Megaloblastic anaemia | Neural tube defects
149
How do you test for water soluble vitamin levels?
``` B1 = RBC transketolase B2 = RBC glutathione reductase B6 = RBC AST activation B12 = serum B12 Vit C = plasma levels Folate = RBC folate ```
150
Iron deficiency results in
Hypochromic anaemia
151
Iodine deficiency results in
Goitre | Hypothyroidism
152
Zinc deficiency results in
Dermatitis
153
Copper deficiency results in
Anaemia
154
Fluoride deficiency results in
Dental caries
155
Copper excess results in
Wilson's disease
156
Fluoride excess results in
Fluorosis
157
What are caeruloplasmin levels in Wilson's disease?
Low | - caeruloplasmin is a copper-binding protein so all used up in Wilson's
158
What deficiencies are seen in Crohn's?
ADEK B12 Foalte Calcium, phosphate, magnesium, zinc deranged if high output/chronic diarrhoea
159
What deficiencies are seen in coeliac?
Iron ADEK B1 B6
160
What deficiencies are seen in chronic liver disease?
``` ADEK B12 Selenium Magnesium Zinc Folate ```
161
What is seen in chronic kidney disease?
Protein energy wasting syndrome
162
What deficiencies are seen in pancreatic insufficiency?
ADEK
163
Causes of hyperinsulinaemic hypoglycaemia
Insulin overdose Sulfonylurea excess Insulinoma Anorexia nervosa
164
Causes of hypoinsulinaemic hypoglycaemia with +ve ketones
``` Alcohol binge with no food Pituitary insufficiency Addison's Liver failure Anorexia nervosa ```
165
Causes of hypoinsulinaemic hypoglycaemia with -ve ketones
Non pancreatic neoplasms - fibrosarcomata - fibromata
166
Triad of hypoglycaemia
Low glucose (varies for different patient populations) Symptoms (adrenergic, neuroglycopenic, but could be no symptoms) Relief of symptoms on administration of glucose
167
Sx seen in hypoglycaemia
Adrenergic: tremors, palpitations, sweating, hunger Neuroglycopaenic: somnolence, confusion, incoordination, seizures, coma Asymptomatic in individuals who have frequent hypos
168
Hyperglycaemic hypoglycaemic with low C-peptide What is this a result of?
Exogenous insulin overdose - patient education to ensure correct insulin delivery method - may have been intentional so consider psych review
169
What is seen in non-islet tumour hypoglycaemia?
Low glucose, insulin, C-peptide, FFA and ketones Result of paraneoplastic syndrome secreting IGF-2, binding to IGF-1 and insulin receptor
170
Drugs that cause hypoglycaemia
Oral hypoglycaemics - sulphonylureas - GLP-1 agents Insulin Other drugs - beta-blockers - salicylates - alcohol (inhibits lipolysis)
171
Calicum range
2.2-2.6 mmol/l
172
Which two hormones are involved with calcium metabolism?
PTH | Calcitriol (1, 24 (OH)2D)
173
What does PTH do?
Increases tubular 1-alpha hydroxylation of vit D (25(OH)D) Mobilises calcium from bone Increases renal calcium reabsorption Increases renal phosphate excretion (phosphate trashing hormone)
174
What does calcitriol do?
Increases calcium and phosphate absorption from the gut Bone remodelling
175
Primary hyperparathyroidism causes
Parathyroid nodule (80%) Hyperplasia and multiple adenomas (15%) Carcinomas (0.5%) MEN1 and MEN2
176
Secondary hyperparathryoidism causes
CKD | Vit D deficiency
177
Tertiary hyperparathryoidism causes
Prolonged secondary hyperPTHism causing unregulat secretion of PTH Kidney transplant
178
Hypoparathyroidism causes
``` Postsurgical (most common) Postradiation Autoimmune Iron deposition in people with thalassaemia Hypo/hypermagnaseamia PseduohypoPTH (resistant to PTH) DiGeorge Syndrome ```
179
``` Calcium: high Phosphate: low PTH: high/normal ALP: high/normal Vit D: normal ``` Dx?
Primary hyperparathyroidism | => intrinsic problem with parathyroid gland causing increased PTH
180
``` Calcium: low/normal Phosphate: high PTH: high ALP: high Vit D: normal ``` Dx?
Secondary hyperparathyroidism | => stimulation of parathyroid gland to produce more PTH
181
``` Calcium: high Phosphate: low PTH: high/normal ALP: high/normal Vit D: normal ``` Dx?
Tertiary hyperparathyroidism | => autonomous PTH secretion
182
``` Calcium: low Phosphate: high PTH: low ALP: low/normal Vit D: normal ``` Dx?
Hypoparathyroidism
183
``` Calcium: low Phosphate: low PTH: high ALP: high Vit D: low ``` Dx?
Osteomalacia/Ricket's in children
184
``` Calcium: normal Phosphate: normal PTH: normal ALP: high Vit D: normal ``` Dx?
Paget's disease | => re-modelling of bone, very rare
185
``` Calcium: normal Phosphate: normal PTH: normal ALP: normal Vit D: normal ``` Dx if pt has bone pain?
Osteoporosis | => bone loss as result of wear and tear
186
Risk factors for Vit D deficiency
Lack of sunlight Dark skin Dietary changes Gut malabsorption (i.e. coeliac)
187
Hypercalcaemia definition
>/= 2.6 mmol/L
188
Hypercalcaemia sx
Stones (renal) Bones (pain) Groans (psych) Moans (abdo pain) - constipation Polyuria - it is an osmotic diuretic Neuro - muscle weakness - confusion - seizures - coma
189
Hypercalcaemia treatment
Double check it is genuine result (repeat if in doubt) Rehydrate, fluids! Bisphosphonates IV - zolendronic acid - pamidronate Treat the underlying cause (check PTH levels)
190
Causes of hypercalcaemia
``` Dehydration Hyperparathyroidism Cancer Sarcoidosis Milk alkali syndrome Thyrotoxicosis Hypervitaminosis D ```
191
What can PTH tell us about the cause of hypercalcaemia?
Appropriate response - PTH suppressed - malignancy most likely - sarcoid, vit D excess, thyrotoxicosis, milk alkali syndrome Inappropriate response - PTH not suppressed (raised/normal) - primary hyperparathyroidism most likely - familial hypocalciuric hypercalcaemia (rare)
192
Hypocalcaemia sx
Increased reflexes Stridor Perioral paraesthesia Chvostek's sign (twitching when you tap face) Trousseau's sign (carpopedal spasm with BP cuff)
193
Why does malignancy result in hypercalcaemia?
Ectopic PTH-related peptide released by tumour - squamous cell lung cancer Bone mets resulting in local bone osteolysis - breast cancer Haematological malignancy releases cytokines causing bone breakdown - myeloma
194
Hypocalcaemia treatment
Repeat result and adjust for albumin (corrected calcium) to confirm if unsure Symptomatic or Ca2+ < 1.875 mmol/L -> 10% calcium gluconate IV Asx/chronic/milk - Oral calcium supplementation (not at mealtime); SandoCal - vit D if low PTH or vit D
195
Hypocalcaemia causes with high phosphate
High phosphate - CKD - hypoparathyroidism - post thyroid surgery - pseudohypoparathyroidism - hypomagnesaemia
196
Hypocalcaemia misreading due to
Artefact | - hypoalbuminaemia
197
Hypocalcaemia causes with low phosphate
Low phosphate - osteomalacia - acute pancreatitis - overhydration - respiratory alkalosis (decreased ionised/active Ca2+)
198
Risk factors for renal stones
Dehydration Abnormal urine pH (meat intake, renal tubular acidosis) Increased excretion of stone constituents Urine infection Anatomical abnormalities
199
Renal stones that are radio-opaque
Calcium mixed Calcium oxalate Calcium phosphate Triple phosphate "Struvite" (staghorn appearance)
200
Renal stones that are radiolucent
Uric acid | Cysteine
201
Preventative mx of renal stones
``` Good hydration Reduce oxalate intake Maintain normal Ca intake Thiazide-induced hypocalciuria Citrate to alkalinise urine ```
202
Ix for recurrent renal stones
Serum: Cr, bicarb, Ca, phosphate, urate, PTH Stone analysis Spot urine: pH, MCS, amino acids, albumin 24 hr urine: volumte (>2.5l), Ca, oxalate, urate, citrate
203
Best measure of kidney function
Glomerular filtration rate = 120ml/hr = age-related decline approx. 1ml/hr/yr
204
What does the presence of proteinuria on dipstick suggest?
Abnormal excretion of protein (usually albumin) due to leaky glomeruli or inability of tubules to reabsorb protein
205
What are the key differences between AKI and CKD?
AKI - abrupt decline in GFR - potentially reversible - treatment targeted to precise diagnosis and reversal of disease CKD - longstanding decline in GFR - irreversible - treatment targeted to prevention of complications of CKD and limitation of progression
206
What do we measure to assess severity of an AKI?
Serum creatinine | Urine output
207
What makes a good marker for GFR?
Clearance of marker = GFR if: - not bound to serum proteins - freely filtered by glomerulus - not secreted/reabsorbed by tubular cells
208
What GFR marker do we use in clinical practice?
Creatinine - endogenous marker - higher in muscular individuals as by-product of muscle turnover - important to know baseline to FOLLOW TREND
209
Define AKI
1. Rise in serum Cr over 26 within 48 hours 2. 50% or greater rise in serum Cr known or presumed to have occurred within the past 7 days 3. Fall in urine output to less than 0.5ml/kg/hour for more than 6 hours
210
Indications for emergency dialysis
A E I O U 1. Acidosis 2. Electrolyte disturbance (refractory hyperkalaemia) 3. Intoxication (lithium, aspirin) 4. Overload (pulmonary oedema) 5. Uraemic encephalopathy
211
CKD Staging
Stage 1 - kidney damage with normal GFR (90+) Stage 2 - Mild GFR (60-89) Stage 3 - Moderate GFR (30-59) Stage 4 - Severe GFR (15-29) Stage 5 - End-stage kidney failure (< 15/dialysis)
212
Common causes of CKD
``` Diabetes Atherosclerotic renal disease Hypertension Chronic glomerulonephritis Infective or obstructive uropathy Polycystic kidney disease ```
213
Complications of CDK
Failing homeostatic function - acidosis, hyperkalaemia Failing hormonal function - anaemia (no EPO), renal bone disease (low vit D) CVD - vascular calcification, uraemic cardiomyopathy Uraemia and death
214
How is haemodialysis done?
Tunneled central line (Tessio line) OR Arteriovenous fistula
215
How is peritoneal dialysis done?
Via a Tenckoff catherer where peritoneum used as dialysis membrane
216
Aldosterone action
Sodium IN | Potassium OUT
217
What do the following hypothalamic hormones trigger production of in the pituitary? a) GHRH b) GnRH c) TRH d) Dopamine e) CRH
a) GH b) LH/FSH c) TSH, prolactin d) Prolactin e) ACTH * remember this is hypothalamo-pituitary axis
218
Contraindications of combined pituitary function test
Ischaemic heart disease Epilepsy Untreated hypothyroidism (impairs GH and cortisol response)
219
Side effects of combined pituitary function test
Adrenergic effects of hypoglycaemia - sweating, palpitations, LOC. convulsions (RARE) Metallic taste in mouth, flushing and nausea
220
What is in combined pituitary function test?
LHRH (GnRH), TRH and insulin
221
Pituitary tumour classifications
Microadenoma < 10mm (usually benign) Macroadenoma > 10mm (aggressive bb) Non-functioning adenoma (crushes stalk...)
222
What visual changes may you see with a pituitary adenoma?
Bitemporal hemianopia due to optic chiasm compression
223
Macroprolactinaemia
> 5000 miu/l prolactin lol
224
Mx of prolactinoma
1st line: Replacement - hydrocortisone, T4, oestrogen, GH - DA antagonists (cabergoline, bromocriptine) 2nd line: Transphenoidal excision
225
Mx of non-functioning pituitary adenoma
Cabergoline/bromocriptine - watch and wait if asx - if no sx just leave it alone bb
226
Diagnosis of acromegaly
OGTT (gold standard) IGF-1 Signs: high glucose, Ca, phosphate
227
Mx of acromegaly
1. Transphenoidal surgery 2. Pituitary radiotherapy if surgery fails 3. Cabergoline 4. Octreotide - somatostatin analogue (expensive bad boi and cannot stop once started) 5. GH antagonist - pegvisomant
228
High TSH Low T4 Diagnosis?
Hypothyroidism - atrophic - Hashimoto's - subacute (De Quervain's) - postparum - Riedal thyroiditis
229
High TSH Normal T4 Diagnosis?
Treated hypothyroidism or subclinical hypothyroidism - look out for associated hypercholesterolaemia seen in hypothyroid pts
230
High TSH High T4 Diagnosis?
TSH secreting tumour Thyroid hormone resistance
231
Low TSH High T4/3 Diagnosis?
Hyperthyroidism - Grave's - toxic multinodular goitre (Plummer's) - toxic adenoma - drugs (thyroxine, amiodarone) - ectopic (trophoblastic tumour, struma ovarii)
232
Low TSH Normal T4/3 Diagnosis?
Subclinical hyperthyroidism | - may progress to 1o hypothyroidism if pt is anti-TPO antibody +ve
233
Low TSH Low T4 Diagnosis?
Secondary hypothyroidism | - hypothalamic/pituitary disorder
234
High TSH followed by low TSH Low T3/4 Diagnosis?
Sick euthyroidism with any severe illness | - body shuts down metabolism as thyroid gland reduced output
235
Normal TSH Abnormal T4 Diagnosis?
?Assay interference Changes in TBG Amiodarone
236
Hyperthyroid tx
Sx relief - beta blockers - topical steroids for dermopathy - eye drops in Graves Medical - carbimazole (agranulocytosis risk, rashes common) Radio-iodine - risk of permanent hypothyroidism - CI in pregnancy and lactating women Surgical - hemi/total thyroidectomy
237
Indications for surgical thyroidectomy
Women intending to become pregnant in next 6/12 Local compression 2o to thyroid goitre (oesophageal/tracheal) Cosmetic Suspected cancer Co-existing hyperparathyroidism Refractory to medical tx
238
Thyroid storm tx
``` HDU/ITU support Cooling required High dose anty-thyroid medication Corticosteroids Circulatory and respiratory support ```
239
How could a pt present in thyroid storm?
Shock Pyrexia Confusion Vomiting
240
anti-TSH receptor abs Which thyroid problem?
Graves disease | - hyper, high uptake on isotope (Tc99)
241
anti-TPO/TG abs Which thyroid problem?
Hashimotos thyroiditis
242
Hurthle cells What's wrong with thyroid?
Hashimotos thyroiditis
243
Higher risk of thyroid neoplasm
``` Solitary Solid Young Male Cold nodules ```
244
Psammoma bodies and empty-appearing nuclei with central clearing Which thyroid neoplasia?
Papillary - women - associated with irradiation - good prognosis empty nuclei = Orphan Annie eyes
245
What do follicular thyroid neoplasias spread to first?
Blood >> lungs, bone, liver, breast, adrenals
246
Parafollicular C cells secreting calcitonin Which thyroid neoplasia?
Medullary | - sporadic 80%, MEN2 20% cases
247
What should you screen for with medullary thyroid neoplasia?
Phaeochromocytoma | - MEN2 mutation
248
What is MALToma associated with?
Chronic Hashimoto's
249
Undifferentiated follicular, large pleomorphic giant cells with spindle cells Which thyroid neoplasia?
Anaplastic - elderly - die within a year :(
250
MEN1 disorders
Pituitary Pancreatic (insulinoma) Parathyroid (hyper) *3Ps
251
MEN2a disorders
Parathyroid Phaeochromocytoma Medullary thyroid *2Ps, 1M
252
MEN2b disorders
Phaeochromocytoma Medullary thyroid Mucocutaneous neuromas (& marfanoid) *1P, 2Ms
253
``` High K+ Low Na+ Low glucose 90/50 BP upon standing Skin pigmentation noted in mouth ``` What ix would confirm diagnosis?
SynACTHen test | - Addison's
254
``` High K+ Low Na+ Low glucose 90/50 BP upon standing Skin pigmentation noted in mouth ``` What tx needed?
Hydrocortisone and fludrocortisone if primary adrenal lesion present - Addison's
255
Ix for Cushing's
Overnight dexamethasone suppression test OR 24hr urinary free cortisol Ideal now is inferior pituitary petrosal sinus sampling however not always available
256
ACTH dependent Cushing's
``` Pituitary tumour (Cushing's disease x) Ectopic ACTH-producing tumour (small cell Ca, carcinoid tumour) ```
257
ACTH independent Cushing's
Adrenal adenoma/cancer Adrenal nodular hyperplasia Iatrogenic steroid use lol
258
Low K+ High Na+ 156/100 BP not responding to tx What ix would confirm diagnosis?
Aldosterone:renin ratio | - RAISED in Conn's
259
Low K+ High Na+ 156/100 BP not responding to tx What tx needed?
Aldosterone antagonists/K+ sparing diuretics for Conn's - spironolactone - eplerenone - amiloride
260
Phaeo tx
1. Alpha blockade 2. Beta blockade 3. Surgery when BP well controlled
261
Phaeo ix
Plasma and 24h urinary metadrenaline measurement/catecholamines & VMA (metabolite of adrenaline)
262
Phenytoin toxicity
Ataxia | Nystagmus
263
Digoxin toxicity
Arrhythmias Heart block Confusion Xanthopsia
264
Lithium toxicity
``` Tremor (early) Lethargy Fits Arrhythmia Renal failure ```
265
Aminoglycosides toxicity
Tinnitus Deafness Nystagmus Renal failure
266
Theophylline and aminophylline toxicity
Arrhythmias Convulsions Anxiety Tremor
267
Which enzymes are raised in acute pancreatitis?
Amylase (>10x upper limit normal) | Lipase (>3 upper reference)
268
Pathological raised levels of CK
Duchenne Muscular Dystrophy Myocardial infarction Rhabdomyolysis Statin related myopathy
269
How do we differentiate ALP raised due to bone of liver problems?
We can differentiate liver from bone ALP either by seeing if there is a rise in gamma-GT (liver ALP rises with this), by performing electrophoresis, or by ordering a bone-specific assay of ALP
270
Physiological causes of raised ALP
Pregnancy (3rd trimester) | Childhood (during growth spurt)
271
Pathological causes of raised ALP
>5x ULN - Bone = Paget's, osteomalacia - Liver = cholestasis, cirrhosis <5x ULN - Bone = tumours, fractures, osteomyelitis - Liver = infiltrative disease, hepatitis
272
When is BNP released?
In response to ventricular stretch Highly sensitive for heart failure when levels > 400 Highly specific for excluding HF when levels < 100
273
What is troponin?
Myocardial injury biomarker NOT an enzyme b
274
When is troponin measured for MI?
Measure at 6 hours then 12 hours post onset of pain Remains elevated for 3-10 days
275
When is troponin raised?
``` Coronary spasm Coronary dissection PCI Myocarditis PE HF Cardiomyopathies Sepsis Cardiac surgery Chest trauma Defibrillation ```
276
Types of lipoprotein metabolism disorders
Primary hypercholesteraemia Primary hypertriglyceridaemia Primary mixed hyperlipidaemia Hypolipidaemia
277
How do statins work?
HMG-CoA reductase inhibitor - reduces intrinsic synthesis of cholesterol in lover - SE: myopathy, rhabdomyolysis, fatigue
278
Lipoproteins in order of density
Chylomicron < FFA < VLDL < IDL < LDL < HDL
279
What does Guthrie blood spot test for at 6 days of age?
Phenylketonuria, congenital hypothyroidism, cystic fibrosis, sickle cell disease, MCAD (medium chain acylCoA dehydrogenase) deficiency *The newborn screening programme measures chemicals in the blood spot, it doesn’t involve any genetics. An abnormal chemical level doesn’t always mean that there is a genetic disorder!
280
What does specificity mean?
Probability that someone without the disease will correctly test negative o TN/(FP+TN) o 85 people without CF in total, and 80 actually test negative. Specificity is 80/85=94%
281
What does sensitivity mean?
Probability that someone with the disease will correctly test positive o TP/(TP+FN) o 100 people with CF in total, and 90 actually test positive. Sensitivity is 90/100=90%
282
What does positive predictive value mean?
Probability that someone who tests positive actually has the disease o TP/(TP+FP) o 95 people tested positive, of which 90 had the disease. PPV=90/95=95%
283
What does negative predictive value mean?
Probability that someone who tests negative actually doesn’t have the disease o TN/(TN+FN) o 90 people tested negative, of which 80 didn’t have the disease, NPV=80/90=89%
284
Metabolic conditions that result in accumulation of toxins
Organic acidaemias - propionic acideamia Urea cycle disorders Aminoacidopathies - PKU - Maple syrup urine disease
285
Metabolic conditions that result in reduced energy stores
Glycogen storage disorders - Von Gierke;s Galactossaemia Fatty acid oxidation disorders - MCADD
286
Metabolic conditions that result in large molecule synthethesis
Peroxisomal disorders | Glycosylation disorders
287
Metabolic conditions that result in defects in large molecule metabolism
Lysosomal disorders | - Tay Sachs disease
288
Metabolic conditions that affect the mitochondria
MELAS Kearn's Sayre POEMS
289
Diabetes mellitus type 2 diagnosis
HbA1C >48 Fasting glucose >7 Random glucose >11.1 IGTT >11.1
290
IGTT > 7.8 but < 11.1 Diagnosis?
Impaired glucose tolerance
291
Fasting glucose > 6.1 but < 7.0 Diagnosis?
Impaired fasting glucose
292
DKA criteria
pH < 7.3, Plasma Glucose >11mM, Blood Ketones>3mM (2+ in urine). Rapid onset Medical emergency
293
DKA presentation
Symptoms: confusion, Kussmaul breathing, abdominal pain, nausea, vomiting Precipitants include infection, surgery, missed insulin doses, trauma
294
DKA mx
A-E, senior help Fluid = 0.9% saline Insulin = AFTER fluids, ensure K+ fine, 0.1u/kg/h fixed rate Early senior review +/- ITU involvement Monitor glucose and K+ hourly Catheter to monitor UO
295
HHS criteria
pH > 7.3, Osmolarity > 320mOsm, Blood Glucose > 30mM HHS develops over few days Patients present acutely unwell with confusion and clinical dehydration
296
HHS mx
A-E Fluids = 0.9% saline over 1hr IV insulin = only if > 1 mmol/L ketones, 0.05u/kg/hr fixed rate Monitor = serial U&Es, glucose reading
297
When is DKA resolved?
When ketones < 0.6 and pH > 7.3
298
Causes of a raised 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
299
Causes of a 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)
300
An unexplained metabolic acidosis (usually in the context of overdose) with a raised anion and raised osmolar gap could be caused by?
Glycol, ethanol, mannitol or methanol poisoning

Year 5 Pathology (6 decks)

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