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Pathology > Chemical Pathology- Part 1 (p72-85- Fluid balance, electrolytes, acid-base, LFTs, porphyrias, pituitary + thyroid) > Flashcards

Chemical Pathology- Part 1 (p72-85- Fluid balance, electrolytes, acid-base, LFTs, porphyrias, pituitary + thyroid) Flashcards

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1
Q

What % of body is water?

A

60

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2
Q

What is ratio of intracellular:extracellular fluid?

A

2:1

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3
Q

What does extracellular fluid include (three different things)?

A

Intravascular
Interstitial (between cells- largest component)
Transcellular- epithelial lined spaces e.g. CSF, joint fluid etc

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4
Q

Define osmolality

A

Total number of particles in solution- measured with an osmometer (units- mmol/kg)

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5
Q

Define osmolarity

A

The concentration of a solution- calculated (units mmol/l)

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6
Q

What physiological determinants of osmolality and osmolarity are there in serum/plasma?

A 
Na+
K+
Cl-
HCO3-
Urea
Glucose
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7
Q

What pathological determinants of osmolality and osmolarity are there in serum/plasma?

A

Endogenous (e.g. glucose) or exogenous (e.g. ethanol)

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8
Q

Osmolarity calculation?

A

2(Na+ + K+) + urea + glucose

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9
Q

What is the osmolar gap?

A

The difference between osmolality and osmolarity

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10
Q

Why is the osmolar gap useful in metabolic acidosis?

A

If osmolarity is lower than osmolality we can assume there are extra unmeasured solutes that are dissolved

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11
Q

Normal range for serum osmolality?

A

275-295 mmol/kg

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12
Q

Normal range for Na+?

A

135-145mmol/l

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13
Q

What maintains Na+ as mainly an extracellular cation?

A

Na+/K+ ATPase

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14
Q

What would you see in symptomatic hyponatraemia?

A

N+V (<136mmol/l)
Confusion (<131mmol/l)
Seizures, pulmonary oedema (<125mmol/l)
Coma (<117mmol/l)

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15
Q

How do you determine whether it is a true hyponatraemia?

A

Using serum osmolality:
High-
Glucose/mannitol infusion

Normal-
Spurious
Drip arm sample
Pseudohyponatraemia

Low-
True hyponatraemia

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16
Q

What causes of pseudohyponatraemia are there?

A

Hyperlipidaemia

Paraproteinaemia

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17
Q

What would you be considering aetiology and treatment wise in a hypervolaemic hyponatraemic patient?

A

Three failures- heart, renal and liver

Treatment:
Fluid restrict and treat cause

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18
Q

What would you be considering aetiology and investigation wise in a euvolaemic hyponatraemic patient?

A

Hypothyroidism
Glucocorticoid insufficiency
SIADH

investigations:
TFTs
Short synacthen test
Paired urine and serum osmolality

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19
Q

What would you be considering diagnosis and treatment wise in a hypovolaemic hyponatraemic patient?

A

Diarrhoea
Vomiting
Diuretics
Salt losing nephropathy

Treatment
Fluid restoration with 5% dextrose

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20
Q

How does liver failure cause hyponatraemia?

A

There is poor breakdown of vasodilators like nitric oxide, these cause a low BP and subsequent ADH release causes water retention, which dilutes down sodium

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21
Q

What is the risk when treating hyponatraemia?

A

Rapid correction can lead to central pontine myelinolysis (locked in syndrome) therefore increase Na+ by 1mmol/l/hr

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22
Q

Why is hyponatraemia post surgery common?

A

Over hydration with hypotonic IV fluids

Transient increase in ADH due to stress of surgery

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23
Q

What is the lab criteria for SIADH?

A

True hyponatraemia
Clinically euvolaemic
Inappropriate high urine osmolality and increased renal sodium excretion (>20mmol/l)
Normal 9am cortisol and TFTs (diagnosis of exclusion)

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24
Q

Causes of SIADH?

A

Malignancy- small cell lung cancer (most common), pancreas, prostate, lymphoma)
CNS disorders- meningoencephalitis, haemorrhage, abscess
Chest- TB, pneumonia, abscess
Drugs- opiates, SSRIs, carbamazepine, PPIs

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25
Treatment of SIADH?
Fluid restriction and treat cause, demeclocycline and tolvaptan induce a state of diabetes insipidus that may help
26
Symptoms of hypernatraemia?
Thirst -> confusion -> seizures + ataxia -> coma
27
What causes are there of hypovolaemic hypernatraemia?
GI loss- vomiting, diarrhoea Skin loss- excessive sweating, burns Renal loss- loop or osmotic
28
What causes are there of euvolaemic hypernatraemia?
Respiratory (tachypnoea) Skin (sweating + fever) Renal (DI)
29
What causes are there of hypervolaemic hypernatraemia?
``` Mineralocorticoid excess (Conn's syndrome) Hypertonic saline ```
30
What can rapid correction of hypernatraemia lead to?
Cerebral oedema
31
Clinical features of DI?
Hypernatraemia (lethargy, thirst, irritable, confusion, coma, fits) Clinically euvolaemic Polyuria and polydipsia Urine:plasma osmolality <2
32
What is the difference between cranial and nephrogenic DI?
Cranial- lack of ADH | Nephrogenic- receptor defect (insensitivity)
33
Causes of cranial DI?
Surgery, trauma or tumours
34
Causes of nephrogenic DI?
Inherited channelopathies Lithium, democlocycline Hypercalcaemia
35
How is DI diagnosed?
8h fluid deprivation test: Normal- urine conc >600mOsmol/kg Primary polydipsia- urine conc 400-600 Cranial DI- urine only concentrates after desmopression Nephrogenic- low concentration after desmopressin
36
Normal range of potassium?
3.5-5.5mmol/l
37
Causes of hypokalaemia?
Either depletion or shift into cells- rarely decreased intake GI loss Renal loss- hyperaldosteronism, excess cortisol, diuretics, osmotic diuresis Redistribution into cells Rare tubular acidosis or hypomagnesaemia
38
What are the 3 types of renal tubular acidosis and how are they different?
Type 1- most severe, distal failure of H+ excretion and subsequent acidosis and hypokalaemia (failed hydrogen potassium pumping) Type 2- Milder, proximal failure to reabsorb bicarbonate, leads to acidosis and hyperkalaemia Type 4- aldosterone deficiency or resistance (acidosis and hyperkalaemia)
39
Treatment of hypokalaemia?
Oral SandoK and monitoring potassium levels or if lower than 3.0 consider intravenous potassium chloride
40
Causes of hyperkalaemia?
Excessive intake- oral, parenteral or stored blood transfusion ``` Transcellular movement (ICF>ECF)- acidosis, insulin shortage (DKA) and tissue damage/catabolic state ``` ``` Decreased excretion- Acute renal failure (oliguric phase) CRF K-sparing diuretics (spironolactone) Mineralocorticoid deficiency (Addison's) NSAIDs, ACEi, ARBs ```
41
Treatment of hyperkalaemia?
10ml 10% calcium gluconate, 100mls 20% dextrose and 10 units insulin. Salbutamol useful as well
42
Normal blood pH range?
7.35-7.45
43
Normal blood CO2 range?
4.7-6kPa
44
Normal blood bicarbonate range?
22-30mmol/l
45
Normal blood O2 range?
10-13kPa
46
What are the steps in checking for an acidosis/alkalosis?
Check pH CO2- does it fit with pH Bicarbonate- does it fit with pH Compensation- Any? Partial? Complete?
47
What would you see in a metabolic acidosis?
pH low, bicarb low, CO2 normal or low if compensated
48
Causes of metabolic acidosis?
Lactate build up in DKA Renal tubular acidosis Intestinal fistula
49
What would you see in a metabolic alkalosis?
Raised pH and bicarb, CO2 normal or raised if compensated
50
Causes of metabolic alkalosis?
Pyloric stenosis Hypokalaemia Ingestion of bicarb
51
What would you see in a respiratory acidosis?
Low pH, bicarb normal or raised if compensated, high CO2
52
Causes of resp acidosis?
Lung injury- pneumonia COPD Decreased ventilation- Morphine OD
53
What would you see in a resp alkalosis?
Raised pH, bicarb normal or low if compensated, low CO2
54
Causes of resp alkalosis?
Mechanical ventilation | Anxiety/panic attack
55
What is the anion gap?
Difference between total concentration of principal cations and anions - i.e. Concentration of unmeasured anions in plasma
56
Normal range for anion gap?
14-18mmol/l
57
Causes of elevated anion gap metabolic acidosis?
KULT Ketoacidosis- diabetic, alcoholic, starvation Uraemia- renal failure Lactic acidosis Toxins- ethylene glycol, methanol, paraldehyde, salicylate
58
Which LFTs are markers of liver cell damage?
``` ALT AST Alk Phos GGT Bilirubin ```
59
Which LFTs are markers of synthetic function?
Clotting (INR) Albumin Glucose
60
When are the aminotransferases (AST/ALT) raised?
When hepatocytes die
61
What would you see in terms of LFTs in alcoholic liver disease?
AST:ALT = 2:1
62
What would you see in terms of LFTs in viral liver disease?
AST:ALT = <1:1
63
When is ALP raised?
Cholestasis (intrahepatic or extrahepatic) and bone disease, very high in pregnancy
64
When is gamma GT (GGT) raised?
In chronic alcohol use Bile duct disease Metastases Also used to confirm hepatic source of raised ALP
65
What are porphyrias?
Disorders caused by deficiency in enzymes, involved in haem biosynthesis, leading to build up of toxic haem precursors
66
What is the inheritance pattern of acute intermittent porphyria (AIP)?
Autosomal dominant
67
What causes AIP?
HMB (hydroxmethylbilane) synthase deficiency
68
Symptoms of AIP?
Neurovisceral- Abdo pain, seizures, psych, N+V, tachycardia, HTN, sensory loss, muscle weakness, constipation, incontinence, NO cutaneous manifestations
69
How is AIP diagnosed?
ALA + PBG in urine ('Port wine urine')
70
How do you treat AIP?
Avoid precipitating factors, analgesia, IV carbohydrate/haem arginate
71
What are the two types of acute poryphrias with skin lesions?
``` Hereditary coproporphyria (HCP) + Varegiate poryphria (VP) Same neurovisceral lesions with skin lesions ```
72
How do non-acute porphyrias present and what are the three types?
``` Skin lesions ONLY e.g. Congenital Erythopoietic porphyria (CEP) Erythropoietic protoporphyria (EPP) Porphyria Cutanea Tarda (PCT) ```
73
What is a typical feature of erythropoietic protoporphyria (EPP)?
Photosensitivity Burning Itching oedema following sun exposure
74
What causes PCT?
Uroporphyrinogen decarboxylase deficiency
75
Symptoms of PCT?
Cutaneous- vesicles (crusting, pigmented, superficial scarring) on sun exposed sites
76
How is PCT diagnosed?
Increased urinary uroporphyrins + coproporphyrins + ferritin
77
How is PCT treated?
Avoid precipitants (alcohol, hepatic compromise), phlebotomy
78
Name 5 hormones released by the hypothalamus?
``` GHRH GnRH TRH Dopamine CRH ```
79
What action does GHRH have on pituitary hormones?
Stimulates GH
80
What action does GnRH have on pituitary hormones?
Stimulates LH/FSH
81
What action does TRH have on pituitary hormones?
Stimulates TSH and prolactin
82
What action does dopamine have on pituitary hormones?
Inhibits prolactin
83
What action does CRH have on pituitary hormones?
Stimulates ACTH
84
What does a combined pituitary function test (CPFT) involve?
Administration of LHRH, TRH and insulin then measurement at 0, 30, 60, 90 and 120 minute levels of pituitary hormones
85
When is a CPFT indicated?
Assessment of all components of anterior pituitary function used particularly in pituitary tumours or following tumour treatment
86
When is a CPFT contraindicated?
IHD Epilepsy Untreated hypothyroidism
87
What is an easy way to assess whether a pituitary adenoma is likely to be benign or aggressive?
Size Microadenoma <10mm usually benign Macroadenoma >10mm usually aggressive
88
What can a pituitary adenoma compress and subsequently lead to?
Optic chiasm -> bitemporal hemianopia
89
Which hormones are released from the neurohypophysis (posterior pituitary gland)?
ADH | Oxytocin
90
What are the causes of excess ADH?
Lung paraneoplasia- SCC, pneumonia Brain- traumatic injury, meningitis, primary or secondary tumours Iatrogenic- SSRIs, amitryptilline, carbamazepine, PPIs
91
What is diabetes insipidus?
Increased diuresis due to either failure of production (neurogenic) or insensitivity (nephrogenic) to ADH, leading to decreased urine osmolality and increased serum osmolality
92
What would you suspect if TFTs showed a raised TSH and low T4?
Hypothyroidism
93
What would you suspect if TFTs showed a raised TSH and normal T4?
Treated hypothyroidism or sub-clinical
94
What would you suspect if TFTs showed a raised TSH and T4?
TSH secreting tumour or thyroid hormone resistance
95
What would you suspect if TFTs showed a low TSH and high T3 and T4?
Hyperthyroidism
96
What would you suspect if TFTs showed a low TSH and normal T3 and T4?
Subclinical hyperthyroidism
97
What would you suspect if TFTs showed a low TSH and low T4?
Central hypothyroidism (hypothalamic/pituitary disorder)
98
What would you suspect if TFTs showed a raised (then later decreased) TSH and low T3 and T4?
Sick euthyroidism. Body tries to shut down metabolism as thyroid gland has reduced output
99
What causes of high uptake hyperthyroidism are there?
Graves disease Toxic multinodular goitre Toxic adenoma (hot nodule on isotope scan)
100
What is F:M ratio of Graves?
9:1
101
What causes of low uptake hyperthyroidism are there?
Subacute De Quervains thyroiditis (self-limiting post-viral painful goitre)- initially hyper then hypo Postpartum thyroiditis
102
What autoimmune causes of hypothyroidism are there?
Primary atrophic hypoT | Hashimotos
103
What non immune causes are there of hypothyroidism?
Iodine deficiency (mr. Worldwide) Post-thyroidectomy/radioiodine Drug-induced- antithyroid drugs, lithium, amiodarone
104
How does primary atrophic hypothyroidism differ from Hashimotos?
Primary atrophic- diffuse lymphocyte infiltration + atrophy. No goitre so small thyroid. No known antibodies Hashimotos- Plasma cell infiltration + goitre, elderly females, initial hashitoxicosis, auto-antibody titres raised
105
Treatment of hyperthyroidism?
Depends on aetiology. Low uptake- symptomatic with beta blockers, NSAIDs for De Quervains High uptake- BB + antithyroid therapy (carbimazole/propylthiouracil) Can also use radioiodine or surgery
106
Why is propylthiouracil rarely used nowadays?
Risk of aplastic anaemia
107
Treatment of hypothyroidism?
Thyroid replacement therapy
108
Most common type of thyroid neoplasia?
Papillary
109
5 subtypes of thyroid neoplasia?
``` Papillary- >60% Follicular- 25% Medullary- 5% Lymphoma- 5% Anaplastic- Rare ```
110
Treatment of papillary thyroid neoplasia?
Surgery +/- radioiodine and thyroxine to decrease TSH
111
What might you see on histology of papillary thyroid neoplasia?
Psammoma bodies
112
What is medullary thyroid neoplasia linked to?
MEN2 (they also produce calcitonin)
113
What are the three different types of multiple endocrine neoplasia?
MEN1 (3Ps)- Pituitary, pancreas (insuloma), parathyroid MEN2a (2Ps1M)- Parathyroid, phaeochromocytoma, medullary (thyroid) MEN2b (1P, 2Ms)- Phaeochromocytoma, medullary thyroid, mucocutaneous neuromas (+ marfanoid)

Pathology (13 decks)

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