Chemical Pathology Flashcards
(231 cards)
1
Q
How do you correct serum calcium level? When might this be necessary?
A
Corrected Ca2+ = serum Ca + 0.02*(40-albumin)
Important to do if the patient has low total Ca but has a possible source of hypoalbuminaemia, eg. liver failure
2
Q
Describe the Ca homeostasis mechanisms when serum Ca decreases.
A
Drop in serum Ca causes PTH to be released from the parathyroid glands. PTH causes the release of Ca by bone, and stimulates the kidneys to increase the absorption of Ca + increase 1a hydroxylase activity + phosphate loss. 1a hydroxylase causes gut absorption of Ca.
These activities lead to an increase in serum Ca, and PTH decreases.
3
Q
Describe the Vitamin D synthesis pathway
A
Vitamin D synthesis starts with 2 pathways-
1) Cholesterol converted to Cholecalciferol (D3) by sun
2) Absorbed from the gut as Vitamin D3 (animal) or D2 (plant- ergocalciferol)
Then, this is converted to 25 hydroxyVitamin D in the liver, then to 1,25 diOHVit D/ calcitriol by the kidneys.
4
Q
A patient has a total calcium of 2.1 and an albumin of 25. What is the corrected calcium? Is this patient hypocalcaemic?
A
Corrected Ca= total Ca + 0.02(40-albumin)
= 2.1 + 0.02( 15) = 2.4 mmol/L
The patient is not hypocalcaemic. They have a low albumin.
5
Q
Which is the active form of Vitamin D? Which the is measured form?
A
Calcitriol (1,25) is the active form, but 25OHD3 is the measured form
6
Q
In which condition may Vitamin D synthesis increase? Why?
A
Sarcoidosis, due to an increase in the 1a hydroxylase enzyme in sarcoid tissue.
7
Q
T/F. PTH works directly on the gut to increase Ca resorption.
A
False. PTH increase 1a hydroxylase activity, which increases gut Ca resorption.
8
Q
What can be used as a marker of bone turnover? Where is it produced?
A
Alkaline phosphatase. Found in osteoblasts.
9
Q
Which mineral is needed for PTH production?
A
Mg2+
10
Q
What is the difference between osteoporosis and osteomalacia?
A
In osteoporosis, there is decreased amount of bone with normal structure.
In osteopenia, there is abnormally structured bone
11
Q
Colle’s fracture would typically occur in which bone disease?
A
Osteoporosis
12
Q
Name some risk factors for the development of osteoporosis.
A
Cushing’s syndrome, early menopause, thyrotoxicosis, anorexia, old age.
13
Q
How is the severity of osteoporosis assessed? What is normal?
A
Measured using DEXA scanning, which assesses the density of bone at 2 sites, the lumbar spine and the ilium.
This gives a T score, which compares the density against the bone density of a young healthy person. A T score of -1 to -2.5 indicates osteopenia, and
14
Q
Name some causes of Vitamin D deficiency.
A
Poor diet, malabsorption, lack of sunlight, liver disease, renal disease, anticonvulsants, phytic acid
15
Q
What is the biochemical picture in Vitamin D deficiency?
A
Low Ca, low Vitamin D (25OH), low phosphate, high alk phos
16
Q
In which patients might you find pseudofractures on Xray? What other name is there?
A
Patients with osteomalacia/Rickets. Also called Looser’s zones.
17
Q
What are the treatments for osteoporosis?
A
Conservative: exercise, good diet w/ Vitamin D and Ca supplementation
Medical: bisphosphonates, teriparatide, strontium, HRT, and SERMs
18
Q
What is the mechanism of action of bisphosphonates? What is an example?
A
Alendronate is an example of a bisphosphonate. They bind to bone and are taken up by osteoclasts, where they cause dysfunction and death, thereby preventing bone resorption.
19
Q
What is the mechanism of teriparatide?
A
Teriparatide is a PTH derivative, and causes increased activity in osteoblats > osteoclasts, resulting in overall bone formation
20
Q
What is an example of a SERM? What is the MoA?
A
Raloxifene. They work by selectively stimulating oestrogen receptors in bone but not in breast, and therefore cause bone formation
21
Q
What are the signs + symptoms of hypercalcaemia?
A
Bones: bone and muscle pain
Stones: Polyuria, polydipsia, kidney stones
Moans: abdo pain, constipation
Groans: depression, psychosis, confusion, seizures
22
Q
Name several causes of hypercalcaemia
A
Primary hyperparathyroidism, malignancy (bony mets, multiple myeloma, small cell lung cancer), sarcoidosis, familial hypocalciuric hypercalcaemia, thyrotoxicosis
23
Q
What is the pathophysiology of familial hypocalciuric hypercalcaemia?
A
The Ca sensing receptor has a higher set point, meaning that PTH isn’t released until Ca is higher than expected. The affected individual is usually asymptomatic.
24
Q
How do you manage hypercalcaemia?
A
Admit if levels very high/severe symptomatic.
IV fluids. Treat the cause eg. IV bisphosphonates, parathyroidectomy
25
What are the signs + symptoms of hypocalcaemia?
```
Convulsions
Arrhythmias (prolonged QT)
Tetany: Chvostek's sign (face)Trousseau's sign (carpo-pedal spasm)
Stridor
Perioral numbness
```
26
How do you manage hypocalcaemia?
Replace Ca and Vitamin D
27
Name some causes of hypocalcaemia.
High PTH: vitamin D deficiency, liver disease, renal disease (renal osteodystrophy), PTH resistance
Low PTH: hypoparathyroidism. Iatrogenic, DiGeorge syndrome, Mg deficiency eg. PPI use
28
What is serum vitamin D in renal osteodystrophy? Why?
Normal. The dysfunction is with the 1a hydroxylase enzyme, but 25OH Vit D is what is measured (this is unaffected)
29
What are the signs + symptoms of Paget's disease of bone?
Bone pain, warmth over the affected bone, deformity, fractures, salt + pepper skull
30
What is the most useful investigation for diagnosing Paget's disease?
Bone scan (radioactive)
31
What is the pathophysiology of pseudohyperparathyroidism?
There is peripheral resistance to PTH, rather than a true PTH deficiency.
32
What is pseudopseudohypoparathyroidism?
Inherited condition caused by a gene defect in the same gene as PHP and appears similar to Type 1 PHP but has NORMAL biochemistry. Not caused by resistance to PTH.
33
What are the 3 purines? What is their function?
Adenosine, guanine, inosine. They are second messengers, make up DNA/RNA and are involved in ATP transfer
34
Describe purine metabolism to uric acid
Purines -> hypoxanthine -> xanthine (by xanthine oxidase) -> urate (also by xanthine oxidase).
Urate is then excreted in urine.
35
Which enzyme involved in purine metabolism do humans lack?
Uricase
36
What are normal urate levels in males and females?
M: 0.12-0.42
F: 0.12-0.36
37
Where is gout most commonly found? Why?
The feet, specifically the 1st MTP joint. This is because the solubility of uric acid is 0.40 at 37˚ but only 0.27 at 30˚, so it is more likely to precipitate at the extremities.
38
Explain the excretion of uric acid
Freely filtered at the glomerulus, then reabsorbed + secreted. By the end 10% is left in urine, this is called the fractional excretion of uric acid (FEUA)
39
Describe the formation of nucleotides from purines
Two pathways:
1) de novo synthesis: completely formed from scratch
2) Salvage pathway from purines by the HPRT/HGPRT enzyme. Preferred method except in bone marrow
40
What is the key enzyme in the purine de novo synthesis pathway? What is important about it?
PAT. It is the enzyme that controls the rate-limiting step of the de novo synthesis pathway.
It is under negative feedback from GMP and AMP (the end products).
41
What is the key enzyme in the purine salvage pathway? What reaction does it catalyse?
HPRT/HGPRT. It converts hypoxanthine and guanine into IMP and GMP respectively.
42
Which enzyme is deficient in Lesch Nyhan syndrome? Explain the pathophysiology.
HPRT. This leads to a decrease in IMP/GMP, so there is reduced negative feedback on PAT and an increase in the de novo synthesis pathway, leading to high levels of uric acid.
43
Describe the presentation of Lesch Nyhan syndrome
Affected individuals are normal at birth, but have developmental delay by 6 months, and choreiform movements at 1 year. There is also spasticity, UMN pathology, mental retardation, self mutilation and hyperuricaemia and gout.
44
Name some causes of hyperuricaemia
Increased production: high cell turnover eg. chemotherapy for haem malignancies
Decreased excretion: CKD, thiazide diuretics, lead poisoning
45
What are the 2 forms of gout? Where are they found?
Acute (podagra) painful joint inflammation
| Chronic (tophaceous) nodules deposited in soft tissue eg. ears, elbows
46
How do you manage gout acutely?
Decrease inflammation with NSAIDs, colchicine, steroids.
47
What is the MoA of colchicine?
Inhibits tubulin, which prevents neutrophil migration and decreases inflammation
48
How do you manage gout after initial acute management?
Increase fluids. Allopurinol, probenasid
49
What is the MoA of allopurinol and probenasid?
Allopurinol: xanthine oxidase inhibitor. Decreases uric acid production
Probenasid: uricosuric. Increases renal excretion of uric acid.
50
You should not give a patient allopurinol who is already taking ______. Explain.
Azathioprine. Allopurinol will increase levels of mercaptopurine, which is toxic to bone marrow.
51
How would you differentiate between gout and other types of painful joint swelling?
Joint effusion aspirate. View under polarised light with a red filter, and monosodium urate crystals will be negatively birefringent (blue perpendicular to axis). Pyrophosphate crystals (pseudogout) will be positively birefringent.
52
What is the Guthrie test and when is it done? Which conditions are tested for?
Newborn screening test for congenital diseases. Done at 5-8 days old.
CF, hypothyroidism, sickle cell disease, phenylketonuria, MCADD, homocystinuria, maple syrup urine disease (MSUD), isovaleric acidaemia, glutaric aciduria Type 1 (GA1).
53
Describe the pathophysiology of PKU. What is the treatment?
Normally, phenylalanine is converted to tyrosine by phenylalanine hydroxylase. This enzyme is deficient in PKU, causing phenylalanine to build up (and phenylpyruvate + phenylacetic acid). This is toxic and causes low IQ.
Treatment is low phenylalanine diet
54
Describe the pathophysiology of MCADD. What is measured on the Guthrie test?
There is deficiency in the median chain acyl-CoA enzyme, which is part of the fatty acid B oxidation pathway. This prevents the utilisation of fatty acids (ketogenesis) and causes hypoglycaemia during periods of fasting.
To test, measure acylcarnitine.
55
Describe the process of screening for CF.
Guthrie spot measuring immune reactive trypsinogen -> DNA mutation testing (for 4 mutations) if +ve
56
Describe the main defect in homocystinuria and the classic features.
No re-methylation of homocysteine. Causes lens dislocation, mental retardation, VTE
57
What is the point of the urea cycle? What happens when there are defects?
To metabolise ammonia to urea for excretion in the urine. Defects in the pathway (7 enzymes + 3 others) lead to respiratory alkalosis, vomiting, encephalopathy, psychiatric symptoms, coma.
58
What are investigations for urea cycle defects? Treatments?
-Ammonia levels (High)
-Glutamine (High, because ammonia attached to glutamate)
-Amino acids in the urea cycle (High or absent, depending where the defect one)
Treatment: decrease production (low protein diet), remove ammonia (Na benzoate, phenoacetate)
59
What is the biochemical hallmark of organic acidurias? Why do these occur?
High ammonia with metabolic acidosis and high anion gap.
| Defect in the breakdown of complex amino acids eg. isovaleryl-CoA dehydrogenase
60
What syndrome can organic acidurias present like? this happen and what are the classic features?
Reye's syndrome. Can be a feature of IMD or triggered by salicylates (aspirin), antiemetics, valproate.
Vomiting, lethargy, confusion, seizures
61
Name some features (biochemical + physical) of defects in the B oxidation pathway.
Hypoketotic hypoglycaemia.
| Hepatomegaly and cardiomegaly
62
Name 2 main carbohydrate disorders and describe their mechanisms + presentations
Galactosaemia (Gal-1-PUT): galactose-1-phosphate builds up because of enzyme deficiency. D+V, conjugated hyperbilirubinaemia, hypoglycaemia, sepsis, hepatomegaly
Glycogen storage disorder type 1 (von Gierke): glycogen cannot be broken down because of phosphatase deficiency and builds up in the liver. Hepatomegaly, hypoglyacemia, lactic acidosis
63
What is a key feature of mitochondrial diseases that explains why they can present at any age in any organ?
Heteroplasmy
64
Which organs are typically affected in mitochondrial diseases and why?
Brain, kidneys, muscle, retina, endocrine organs. They have a high energy requirement.
65
What is MELAS?
Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes
66
What are some investigations used to diagnose mitochondrial disorders?
Lactate (high), CSF lactate and pyruvate, CK (high), muscle biopsy, mitochondrial DNA
67
For which IMDs what you measure urine mucooligopolysaccharides?
Lysosomal storage diseases eg. Tay Sachs
68
At what age is renal function in children fully developed?
2 years. Before this time, GFR is low
69
Name 3 differences between adult and child renal function
Infants have
- Lower GFR:surface area
- Persistent sodium loss
- Less reabsorption and concentrating ability
- More susceptible to acidosis
70
Name some causes of neonatal hyperbilirubinaemia
Within the first 24 hours:
Haemolytic disease of the newborn
G6PD deficiency
Crigler-Najjar syndrome
```
Prolonged jaundice:
Congenital infection/sepsis
Congenital hypothyroidism
Breast milk jaundice
Hepatobiliary disease
IMDs
```
71
What level of conjugated bilirubin is always pathological in neonates? Name 2-3 causes.
>20umol/L
| Biliary atresia, IMDs eg. galactosaemia
72
What are the biochemical features of osteopenia of prematurity?
Normal Ca
Low Phosphate (<1 mmol/L)
Very high alkaline phosphatase (>1200U/L)
73
What are the fat soluble vitamins and what results when these are deficient?
A: colour blindness
D: osteomalacia/Ricket's.
E: anaemia, neuropathy
K: defective clotting
74
What are the different B vitamins and what results when these are deficient?
B1 (thiamin): Beri Beri, Wet- heart failure and Dry- Wernicke's encephalopathy (confusion, ataxia, ophthalmoplegia)
B2 (riboflavin): glossitis
B3 (niacin): pellagra (dermatitis, dementia, diarrhoea)
B6 (pyridoxone): dermatitis, anaemia
B12 (cobalamin): pernicious anaemia
75
How do you measure B1 and B2 levels?
RBC transketolase for B1, RBC glutathione reductase for B2
76
Trace elements:
Deficiency of ____ can cause anaemia and excess can cause haemochromatosis.
Deficiency or excess of ____ can cause thyroid problems.
Excess of ____ can cause Wilson's disease.
Iron
Iodine
Copper
77
What are some conditions that can result in malnutrition?
GI conditions: coeliac, Crohn's
Chronic liver disease and kidney disease
Pancreatic insufficiency
78
What is Marasmus? What is Kwashiorkor?
Marasmus: generalised poor nutrition. Thin and emaciated.
Kwashiorkor: protein deficient. Muscle wasting, oedematous, fatty liver
79
What is normal serum sodium? What are the 2 main physiological systems controlling sodium + fluid balance and how do they work?
135-145 mmol/L
1. ADH/vasopressin: released by posterior pituitary in response to increasing osmolality/decreasing BP --> acts on renal collecting duct V2R to increase AQP2 insertion in the luminal membrane --> water resorption --> decrease plasma osmolality
2. Aldosterone: released by the adrenal glomerulosa in response to renin secretion by the kidneys --> binds to MR in renal collecting duct --> Na resorption (and water) --> increase BP
80
a) How do you calculate serum osmolarity?
b) What is the serum osmolarity:
- Na 140, Cl 100, bicarb 18, urea 5, glucose 5.5, K 4
a) Serum osmolarity = 2 (Na + K) +glucose + urea
| b) 298.5
81
a) What is the serum osmolality in true hyponatraemia? b) What are the 3 main types of hyponatraemia? Name several causes of each.
a) Low serum osmolality
b)
1. Hypovolaemic: D+V, diuretics, Na-losing nephropathy
2. Euvolaemic: SIADH, Addison's, hypothyroidism
3. Hypervolaemic: heart/renal/liver failure
82
How can urine sodium be useful in determining the cause of hyponatraemia?
Urine sodium can indicate if the kidneys are functioning properly to absorb sodium. eg:
- If the patient is hypovolaemic, high urine sodium indicates a renal cause eg. diuretics vs low urine sodium indicates lack of overall body sodium eg. D+V
- If the patient is hypervolaemic, high urine sodium indicates a renal cause eg. AKI/CKD vs low urine sodium indicates low overall sodium eg. liver/heart failure
- Urine sodium is high if euvolaemic
83
Why do liver failure and heart failure cause hyponatraemia?
Liver failure: decreased breakdown of vasodilative compounds eg. NO --> decreased BP --> increased ADH to compensate --> increase water volume without increasing sodium --> hypervolaemic hyponatraemia
Heart failure: low CO --> low BP --> ADH release --> water resorption > sodium resorption --> hypervolaemic hyponatraemia
Also have aldosterone secretion leading to increased BP (and some sodium resorption but not enough).
84
How do you treat hyponatraemia?
Management depends on the cause.
Hypovolaemic: give fluids and treat the cause eg. antiemetics
Euvolaemic: endocrine Ix (TFTs, urine osmolality, ACTH, etc). Treat cause eg. levothyroxine, glucocorticoids + fludrocortisone
Hypervolaemic: treat cause. Fluid restriction +/- diuresis
85
How should you fluid replace a patient with hyponatraemia? What is the significant complication to avoid?
Slowly! Aim for increase in sodium of 8-10 mmol over 24 hours.
Must avoid central pontine myelinolysis
86
How would you diagnose SIADH?
Plasma sodium + osmolality (LOW Na, LOW osm)
Urine sodium + osmolality (HIGH Na, HIGH osm >100)
Rule out other endocrine causes eg. hypothyroidism, adrenal failure
87
What are the signs/symptoms of hyponatraemia?
Nausea and vomiting --> confusion --> seizures --> coma
88
A patient has a serum sodium of 130 mmol/L and a plasma osmolality of 290 mOsmol/L. What is the diagnosis and what might be the cause?
The patient has pseudo-hyponatraemia. This may be caused by conditions that increase plasma lipids/proteins eg. hypertriglyceridaemia or MM
89
What are some causes of SIADH?
- Intracranial pathology eg. infection, tumours
- Lung pathology eg. cancer, TB, infection
- Drugs eg. SSRI, TCA, opiates, PPIs, carbamazepine
- Surgery
90
What is the management of SIADH?
- Fluid restriction
- Demeclocycline (reduces ADH responsiveness in the tubules). Must monitor U&Es
- Vaptans eg. tolvaptan (V2R antagonist)
91
Name some causes of hypernatraemia
Caused by unreplaced water loss eg. D&V in elderly, renal losses (osmotic diuresis), diabetes insipidus
92
How would you investigate hypernatraemia?
- Glucose (test for DM- causes osmotic diuresis)
- U&Es (caused by low K+), Ca (high)
- Plasma and urine osmolality (test for DI)
- Water deprivation test (test for DI)
93
Describe the management of hypernatraemia
Fluid replacement with 5% dextrose (to avoid extra salt)
94
Define a porphyria. What is the mechanism by which this causes disease?
A complete or partial deficiency in any of the enzymes in the haem synthesis pathway.
Deficiency in enzymes leads to build up of intermediate porphyrinogens. These become oxidised to porphyrins, which are toxic.
95
Describe the structure of haem. Where is it produced?
Haem is comprised of tetrapyrrole rings surrounding an Fe2+ ion. It is produced in all cells of the body
96
Describe the haem synthesis pathway
8 steps. Basically:
1) ALA synthase produces ALA (in mitochondria)
2) ALA -> PBG by PBG synthase
3) PBG -> HMB by HMB synthase
4) HMB -> uroporphyrinogen III by U. II synthase
5) U. III -> coproporphyrinogen by uroporphyrinogen decarboxylase
6) Coproporphyrinogen -> Protoporphyrinogen IX by coproporphyrinogen oxidase
7) Protoporphyrinogen IX -> Protoporphyrin IX by protoporphyrinogen oxidase
8) Protoporphyrin IX -> Haem by ferrochetalase
97
Describe the classification of porphyrias
```
Classified by the type of presentation
1. Neurovisceral symptoms (ophthalmoplegia, quadraparesis)
2. Blistering cutaneous
3. Non-blistering cutaneous
Also by acute/non-acute.
```
98
Which is highly coloured, porphyrinogens or porphyrins?
Porphyrins. Uroporphyrins (early in the pathway) are excreted in urine, while coproporphyrins (late in the pathway) are excreted in the faeces
99
T/F: There are 8 enzymes in the haem synthesis pathway, with 8 corresponding porphyrias
False. There are 8 enzymes in the pathway, but only 7 porphyrias. Deficiency in ALA synthase (the first enzyme in the pathway) causes sideroblastic anaemia
100
What are the names of the different porphyrias, and which enzyme deficiency are they caused by?
1. Acute porphyria- PBG synthase deficiency
2. Acute intermittent porphyria- HMB synthase deficiency
3. Congenital erythropoietic porphyria- Uroporphyrinogen III synthase deficiency
4. Porphyria cutanea tarda- Uroporphyrinogen III decarboxylase deficiency
5. Hereditary coproporphyria- Coproporphyrinogen oxidase deficiency
6. Variegate porphyria- Protoporphyrinogen IX oxidase deficiency
7. Erythropoietic protoporphyria- Ferrochetalase deficiency deficiency
101
Which porphyrias are acute?
| For each: Which enzyme is deficiency? What builds up? What is their presentation? +treatment if known
1. Acute porphyria (PBG synthase deficiency, ALA excess). Neurovisceral w/ coma, bulbar palsy, motor neuropathy
2. Acute intermittent porphyria (HMB synthase deficiency. ALA + PBG excess). Neurovisceral attacks (abdo pain, neuro, psychiatric symptoms) triggered by drugs, stress, fasting. PBG in urine! Treat with haem arginate, IV carbohydrates
3. Hereditary coproporphyria (Coproporphyria oxidase. Porphyrin + PBG+ ALA excess). Neurovisceral + blistering (after sun exposure).
4. Variegate porphyria (Protoporphyrinogen oxidase. Porphyrin +PBG+ALA excess). Neurovisceral + blistering.
102
How would you differentiate between the types of acute porphyrias?
- Is there skin involvement? Yes: must be HCP or VP, not AIP
- Is there PBG in the urine? Yes: HCP, VP or AIP
- Are there porphyrins in the urine/faeces? Yes: HCP or VP, not AIP
103
Which porphyrias are non-acute?
| For each: Which enzyme is deficiency? What builds up? What is their presentation? +treatment if known
1. Congenital erythropoietic porphyria (uroporphyrinogen synthase. Porphyrin excess). Blistering after sun exposure.
2. Porphyria cutanea tarda (uroporphyrinogen decarboxylase. Uroporphyrin excess). Blistering after sun exposure.
3. Erythropoietic protoporphyria (ferrochetalase). Non-blistering: photosensitivity.
104
How would you investigate the different presentations of porphyria?
If neurovisceral symptoms: send urine PBG
If blistering cutaneous: send urine/faeces porphyrins
If photosensitivity: send RBC protoporphyrin
105
Is potassium in higher concentration inside or outside of cells?
What is normal serum K+?
Higher intracellularly.
| Normal serum K+ 3.5-5.0 mmol/L
106
Describe the process of renin and aldosterone release.
The juxtaglomerular apparatus of the kidneys is stimulated to produce renin in 3 different ways: decreased pressure (BP), decreased sodium (sensed by macula densa), and sympathetic stimulation.
Renin then converts angiotensinogen to angiotensin I, which is converted to angiotensin II by ACE. Angiotensin II then stimulates the zona glomerulosa of the adrenal gland to release aldosterone.
*Aldosterone release can also be stimulated by HIGH K+
107
How does aldosterone work?
Aldosterone binds to the MR in the collecting duct to stimulate ENaC channels in the luminal membrane, and inhibit the degradation of these channels by Nedd4.
The net influx of Na causes water to be absorbed along the gradient, which is then absorbed into the circulation. The movement of Na into the cell causes K+ to move out, into the lumen.
This leads to an increase in water + Na, increasing BP, and also a decrease in K+.
108
Name some causes of hyperkalaemia.
Renal causes: renal failure (late), Type 4 renal tubular acidosis
Addison's
Drugs: ACEi, ARBs, aldosterone antagonists (spironolactone), NSAIDs
Rhabdomyolysis (release of K+ from cells)
Acidosis (compensation for uptake of H+ that occurs to minimise the acidosis)
109
Describe how you would manage hyperkalaemia.
-Identify the cause and treat eg. replacement in Addison's, hold drugs
If >6.5, or ECG changes:
-10 ml 10% Ca gluconate (protect the heart)
-50 ml 50% glucose + 10 units insulin
-Consider salbutamol nebs
110
An 82 year old man is brought to A&E by ambulance after he was found at home with reduced level of consciousness. His neighbour had called emergency services after not seeing him for 5 days.
On examination, he has dry mucous membranes and reduced skin turgor. He has significant bruising on his left hand side, with several superficial ulcers.
You request an ECG.
1) What is the likely diagnosis for this man?
2) What might you see on ECG?
```
This is a case of a long-lie. This man likely has rhabdomyolysis, leading to increased serum K+.
On ECG, you might see:
-Flat p waves
-Prolonged PR interval
-Wide QRS
-Tented T waves
```
111
Name some causes of hypokalaemia.
-GI loss: vomiting, diarrhoea
-Renal loss: osmotic diuresis
-Drugs: diuretics (loop, thiazides), insulin, beta-agonists
-Conn's syndrome, Cushing's syndrome
-Alkalosis (H+ moves out of cells, K+ moves in)
Rarely:
-Renal tubular acidosis Type 1+2
-Low Mg
-Barter syndrome
-Gitelman syndrome
112
Explain why loop and thiazide diuretics cause hypokalaemia.
Loop diuretics prevent the resorption of Na+ in the ascending loop of Henle.
Thiazide diuretics prevent the resorption of Na+ in the distal tubule.
In both situations, more Na+ reaches the collecting duct. Therefore, more is absorbed. Because of this gradient, K+ must leave the cell into the lumen, leading to hypokalaemia.
Note: Barter syndrome mimics loops, Gitelman syndrome mimics thiazides.
113
Name some features of hypokalaemia.
- Muscle weakness
- Arrhythmia
- Nephrogenic DI (polyuria, polydipsia)
114
When would you see a high aldosterone: renin ratio?
In Conn's (primary hyperaldosteronism). Raised aldosterone would inhibit renin release.
115
How would you manage hypokalaemia?
Treat the underlying cause.
K+ 3.0-3.5 mmol/L: give oral KCl (Sando K)
K+ <3: IV KCl
116
What are the functions of the liver? What happens when the liver fails?
- Metabolism: carbohydrates, fatty acids, amino acids
- Waste removal: ammonia, etc
- Synthesis: clotting factors, proteins
- Bilirubin metabolism
- Hormone metabolism
Failure: hypoglycaemia, high ammonia, lactic acidosis, coagulopathy, low albumin, hyperbilirubinaemia + jaundice, Vit D deficiency
117
Name the different liver function tests and what they indicate
- Alanine aminotransferase (ALT): hepatocyte damage
- Aspartate aminotransferase (AST): hepatocyte damage
- Gamma GT: damage to the hepatocytes/small bile ducts
- Alkaline phosphatase: damage to the biliary tree
- Bilirubin: obstruction, impaired conjugation
- Clotting factors: synthetic function
- Albumin: synthetic function
118
Where are AST and ALT found? What does it mean when they are raised?
ALT: mostly in the liver (aLt - Liver). More specific
AST: liver, muscles, heart, kidney, brain
-High levels indicate hepatocyte damage
-AST:ALT ratio of 2 indicates alcoholic hepatitis
119
Where is ALP found? What does it mean when it is raised?
Bile ducts, bone, placenta
| High levels may indicate cholestasis (eg PBC, PSC), bone turnover (MM, mets, hyperparathyroid), pregnancy
120
What can cause a low albumin?
- Liver disease: cirrhosis, failure
- Renal loss: CKD, nephrotic syndrome
- Malnutrition
- Sepsis (third spacing)
121
T/F. PT and INR are good measures of long term liver function
False. The half life of clotting factors is relatively short, so PT and INR reflect acute liver function
122
Elevated alpha fetoprotein can be caused by:
- Hepatocellular carcinoma
- Germ cell tumours
- Pregnancy
123
How would you investigate jaundice?
- Serum bilirubin level
- Raised ALT/AST -> hepatocyte damage
- Raised ALP -> biliary tree
- USS -> dilated vs nondilated
- Urine dip
124
Jaundice and raised ALP can be caused by:
| They can be distinguished using:
-Obstruction of the biliary tree
-Fibrosis/damage to the biliary tree (PBC or PSC)
Liver USS can differentiate
125
Describe the excretion of bilirubin pathway
- Haem -> bilirubin
- Bilirubin conjugated in hepatocytes with glutathione and secreted in bile into GI tract
- Metabolised to urobilinogen
- Some urobilinogen is reabsorbed and excreted in urine as urobilin
- Some passes through the GI tract and converted to stercobilinogen -> stercobilin
126
How can a urine dip help to investigate the cause of jaundice?
- There should be no bilirubin in urine, only urobilin
- +ve bilirubin indicates high conjugated levels (obstructive)
- Absent urobilin: obstructive jaundice (no bile in the GI tract to be reabsorbed as urobilinogen)
- High urobilin: haemolysis, hepatitis, sepsis
127
List some tests used to investigate liver disease
- Enzymes and synthetic function tests
- FBC, film, DAT, LDH, haptoglobins: haemolysis
- Tumours markers (AFP)
- Hepatitis serology, caeruloplasmin, A1 antitrypsin, antibodies (AMA), ferritin
- CT, MRI, MRCP, USS, fibroscan
128
What is the Van den Bergh reaction?
- Used to measure serum bilirubin
- Direct reaction (without methanol) will cause conjugated bilirubin to precipitate
- Indirect reaction (with methanol) will cause both conj and unconj to precipitate eg. total bilirubin
- Can calculate unconj + conj based on this
129
What is GFR? What is a normal GFR?
Glomerular filtration rate: the amount of blood filtered by the kidneys per hour.
Normal: 120 ml/hr. Decreases with age
130
Describe the different ways GFR can be calculated
- Calculate clearance. Need a substance that is freely filtered at the glomerulus, not reabsorbed/secreted eg. *INULIN*, Cr-EDTA, or iohexol. Difficult and time intensive
- Cockroft Gault: estimates creatinine clearance based on plasma creatinine, takes into account factors affecting clearance. NOT GFR
- MDRD: equation for eGFR, derived from cohort studies. Takes into account age, sex, weight, ethnicity
- CKD-EPI: basically an upgraded MDRD. The currently used equation
131
Where is creatinine produced? What do creatinine levels depend on?
- Muscles
| - Depends on age, sex, weight (muscle mass), ethnicity
132
Which test can be used to estimate renal function in low GFR?
Cystatin C
133
If a patient has proteinuria, which tests would you consider doing next?
Urine protein:creatinine ratio to quantify the amount of protein in the urine.
Or 24hour urine protein collection. Not used often.
134
What kind of tests can be done on urine samples? What can they show?
- Urinalysis-dipstick (screen for CVD, infection, DM, renal disease)
- MC&S (white cells, red cell casts, crystals, bacteria)
- PCR (quantify protein)
- 24 hour collection (protein, electrolytes, metabolites)
135
What can a urine dipstick show?
- pH (sign of kidney function eg. ability to acidify urine)
- Specific gravity
- Protein (CVD or renal disease)
- Blood (renal disease, infection, tumours)
- Glucose (DM, pregnancy)
- Ketones (DM)
- Nitrites (infection- reductase bacteria eg. E coli)
- Leukocytes (infection, inflammation)
136
What is an AKI? What are the types? How is it diagnosed?
AKI - acute kidney injury- occurs when there is a rapid decline in renal function affecting fluid balance, electrolytes, and acid base.
Can be classified as pre-renal, renal, or post-renal depending on cause
Diagnosis:
-Increase in creatinine in 48hours:
1) +26 or 1.-1.9x baseline
2) 2.0-2.9xbaseline 3) >3x or +354umol/L baseline
-Decrease in urine output: <0.5ml/kg/hour in <12 hours
137
Name some causes of pre-renal AKI
Reduced renal perfusion:
- Hypovolaemia, hypotension, oedema
- Renal artery stenosis
- NSAIDs, calcineurin inhibitors -> constrict afferent art
- ACEi/ARBs -> dilate efferent art
- Diuretics
138
Name some causes of post-renal AKI
Obstruction to urine flow:
- Ureteric obstruction eg. stones
- Bladder neck obstruction eg. tumours
- Prostate enlargement eg. BPH, cancer
139
Name some causes of renal AKI
- ATN (as a result of pre-renal AKI)
- Tubular injury: ischaemia, toxins, contrast, drugs (aminoglycosides, amphotericin, aciclovir)
- Immune dysfunction: glomerulonephritis, vasculitis
- Infiltrative disease: amyloidosis, myeloma
140
What is the most common cause of AKI?
Pre-renal and ATN
141
What are the stages of CKD?
Stage 1: 120-90
2: 89-60
3a: 59-45
3b: 44-30
2: 29-15
1: 14-0
142
What are some common causes of CKD?
```
Diabetes!!
Hypertension!
Atherosclerotic renal disease
Glomerulonephritis, vasculitis
PKD
```
143
What are the consequences of CKD?
Fluid balance: oedema, hypertension
Electrolytes: hyperkalaemia, hyponatraemia -> VT/VF
Acid-base: metabolic acidosis
Metabolite excretion: uraemia -> encephalopathy, cardiomyopathy
Endocrine: osteodystrophy, anaemia
144
How do you manage anaemia associated with CKD?
EPO alpha/beta injections
145
How do you manage renal bone disease?
Activated Vitamin D supplements, calcium
146
Why does CKD cause acidosis? How is it managed?
No H+ excretion due to failure of renal excretion mechanisms. Give Na bicarb
147
What is the biochemical profile of renal bone disease?
High phosphate
Low Ca
Normal Vit D (measured is 25OH)
High PTH/normal PTH
148
Which type of renal replacement therapy is best for patients who want to dialyse at home?
Peritoneal dialysis. Haemodialysis must be done in the hospital.
149
What is the normal pH of the body? How is pH regulated?
7.35-7.45
| Regulated by buffer with bicarb. Kidneys produce bicarb/excrete H+, lungs ventilate to decrease/increase CO2
150
Name some causes of metabolic acidosis. Describe the acid-base results.
- Increased H+ production: DKA, sepsis, metformin
- Decreased H+ loss: renal failure
Low pH, low HCO3, negative BE. Low CO2 in compensation
151
Name some causes of a respiratory acidosis. Describe the acid-base results.
- Decreased ventilation: hypoventilation
- Impaired gas exchange: COPD, pneumonia
- Poor lung perfusion: PE
Low pH, high CO2. High bicarb and +ve BE in compensation.
152
Name some causes of metabolic alkalosis. Describe the acid-base results.
- Increased bicarb: antacids
- Increased H+ loss: vomiting
- Hypokalaemia
High pH, high bicarb, +ve BE. High CO2 in compensation
153
Name some causes of respiratory alkalosis. Describe the acid-base results.
-Increased ventilation: anxiety
High pH, low CO2. Low bicarb in compensation.
154
Which acid-base abnormality is seen in aspirin overdose?
Mixed respiratory alkalosis and metabolic acidosis
155
How do you calculate an anion gap? What is a high anion gap and what does it mean?
Positive ions - negative ions
(Na + K) - (Cl + bicarb)
Normal anion gap: 14-18. A high anion gap means there must be other negative ions in the blood eg. lactic acid, uraemia, ketoacidosis, toxins.
156
Name the hormones produced by the pituitary and what effect they have.
TSH: stimulates T4 production
ACTH: stimulates cortisol production
GH: stimulates IGF-1 production and proliferation
FSH+ LH: stimulates oogenesis/spermatogenesis and sex hormone production
Prolactin: stimulates proliferation of lactiferous glands
157
What are two ways of testing the pituitary hormones
- Hormone level: gives static picture of functioning
| - Pituitary function tests: allows assessment of response to stimulation
158
Describe how pituitary function testing is done. What are the contraindications and side effects?
Combined PFT: give GnRH (100mcg), TRH (200mcg) and insulin (0.15units/kg) IV
-Measure the levels of all 5 hormones + glucose at baseline + again after stimulation (30, 60, 90, 120 mins)
Not for those with Hx of cardiac problem or epilepsy
SE: sweating, palpitations, flushing, nausea
159
What is a normal response to combined pituitary function testing?
```
Increase of:
>10 GH
>550 cortisol
LH >10
FSH >2
> prolactin and TSH
```
160
What are some causes of hypopituitarism?
- Prolactinoma (causing stalk compression)
- Other non-functioning adenoma
- Sheehan's syndrome
- Pituitary apoplexy
161
What can be used to replace pituitary hormones?
- TSH: give thyroxine
- GH: give GH injections SC
- ACTH: give pred/hydrocort
- FSH+LH: give oestrogen (unless fertility is the goal)
162
What is the treatment for prolactinoma?
- Microadenoma: watch and wait unless symptomatic
| - Macrodenoma/symp: D2R agonist eg. bromocriptine/cabergoline. Surgery.
163
What is the cause of acromegaly? What is the treatment?
Caused by a GH-secreting adenoma. Surgery, RDx, octreotide/lanreotide
164
Describe the anatomy of the adrenals and the function of each area
```
Outer capsule
Cortex:
-Zona glomerulosa: aldosterone
-Zona fasciculata: cortisol
-Zona reticularis: sex hormones
Medulla: catecholamines
```
165
Primary hypothyroidism and Addison's indicate ___
Schmidt's syndrome. Autoimmune condition w/ antibodies against thyroid and adrenals.
166
Describe how a SynACTHen test is done and the normal results.
Measure cortisol at baseline. Administer 250mcg ACTH IM and measure response at 30mins + 60 mins.
Cortisol should increase by >550nm
167
Name 4 causes of adrenal masses (+1 niche for extra points)
- Non-functioning adenoma
- Phaeo
- Conn's
- Cortisol producing adenoma
- TB granuloma
168
How are phaeos diagnosed? What is the management?
Dx: clinical + urinary catecholamines, VMA. Imaging. Adrenal vein sampling.
- Alpha block
- Beta block
- Surgery
169
Name some conditions associated with phaeo
- MEN2: parathyroid, thyroid, phaeo
- von Hippel Lindau: phaeo, renal cell carcinoma, renal cysts
- Neurofibromatosis 1: Cafe au Lait spots, neurofibromas, phaeo, Lisch nodules
170
How do you interpret the aldosterone: renin ratio?
High aldo, low renin is Conn's (appropriate renin suppression)
High aldo, high renin is RAS (no suppression)
171
Name some causes of Cushing's syndrome
- Cushing's disease: pituitary adenoma
- Adrenal adenoma
- Steroids
- Ectopic ACTH eg. SCLC
172
How is Cushing's diagnosed?
High midnight cortisol + high 9 am cortisol
Dexamethasone suppression test:
-0.5mg dex every 6 hours for 2 days
-Test cortisol after 2 days
-Reduction <50 normal. No reduction: Cushing's
Petrosal sinus sampling: to check if pituitary adenoma
173
Describe the formation of thyroxine
Iodide is absorbed by the thyroid cells and transported into the colloid
In the colloid, iodide is converted to iodine by thyroid peroxidase and then thyroglobulin is iodinated to form T4 and T3.
Then transported through the cell into the blood where it binds to thyroid binding globulin (TBG) + others
174
Name some causes of hypothyroidism
```
Primary hypothyroidism:
-Hashimoto's
-Viral thyroiditis
-Iodine deficiency
-Amiodarone, lithium
Secondary hypothyroidism:
-Pituitary failure eg. Sheehan's, apoplexy, tumour, RDx
```
175
What is the thyroid picture in primary and secondary hypothyroidism?
Primary: low T4, high TSH
Secondary: low T4, low TSH
176
How is hypothyroidism managed?
Levothyroxine. Start 50mcg -> 200/day. Titrate to normal TSH levels
177
What is subclinical hypothyroidism? What are the implications?
Normal T4 but with high TSH
| Some patients will go on to develop hypothyroidism. Can check for antibodies (anti-TPO)
178
What is sick euthyroid?
A condition in which the patient has abnormal TFTs due to severe non-thyroidal illness
Low T4/T3 with high TSH.
Basically, giving thyroxine does not improve symptoms.
179
Name some causes of hyperthyroidism.
Primary: Graves disease, viral thyroiditis (de Quervain's), toxic multinodular goitre, thyroid adenoma, iodine excess, amiodarone, post-partum thyroiditis
Secondary: pituitary adenoma
180
Describe the TFTs in primary and secondary hyperthyroidism. What other tests would you consider?
```
Primary: high T4/3, low TSH
Secondary: high T4/3, high TSH
-Thyroid antibodies
-Technitium scan/radiouptake: high uptake in Graves, toxic multinodular goitre, and adenoma. Low uptake in post-partum and viral
-ECG
```
181
Describe the management of hyperthyroidism. What are the important things to be aware of?
- Beta blockers
- Carbimazole: can cause agranulocytosis.
- PTU: best for pregnancy
* *Block and replace
- Radio-iodine: not if pregnant, breastfeeding
- Surgery
182
How is T2DM diagnosed?
```
Symptoms plus:
1. Fasting BG >7.0 mM
2. HbA1c >48 mmol/L
3. Random BG >11.1 mM with symptoms of DM
Or no symptoms and 2 of the above.
```
183
What are some complications of T1DM?
DKA
Hypos
Macrovascular disease: MI, stroke/TIA, PVD
Microvascular disease: nephropathy, retinopathy, neuropathy
184
Name some causes of hyperglycaemia
- T1DM, T2DM
- Cushing's
- Acromegaly
- Sepsis
- Trauma
185
Define HHS
Hyperosmolar hyperglycaemic state. A complication of T2DM characterised by confusion and dehydration.
- Plasma osm >320
- Plasma glucose >30
- pH >7.3
186
What is the management of HHS?
Fluid replacement!!
Slowly reduce glucose and Na
Frequent monitoring of U+Es
187
Define DKA
Diabetic ketoacidosis. A complication of T1DM characterised by ketosis and metabolic acidosis.
pH <7.3, glucose >11 mM, ketones >3 mM
188
How should you correct hypoglycaemia?
If conscious: oral glucose- both fast and slow release
If drowsy: buccal glucose
If unconscious: IV 50 ml 50% or 100 ml 20% glucose
189
Define hypoglycaemia. Name some causes
```
Usually considered as <4 mM but varies. Different levels cause adrenergic effects -> neuroglycopenic
Causes:
-Insulin use
-Other diabetes meds: SUs, GLP-1 agonists
-Anorexia
-Adrenal failure
-Liver failure
-Insulinoma
-Neonates: IMDs, prematurity
```
190
How do you investigate suspected hypoglycaemia?
- Blood glucose: grey top bottle
- Blood ketones: raised indicates low insulin
- Insulin level
- C peptide level
- Drugs
- Cortisol, GH
191
Name some different ketones
3-hydroxybutyrate
Acetone
Acetoacetate
192
What biochemical abnormalities would you expect to see in a neonate with an IMD affecting beta oxidation? Why?
-Hypoglycaemia
-Low insulin
-Low ketones
Hypoinsulinaemia Hypoglycaemic is the correct response. There is no ketone formation because beta ox defect.
193
A differential for insulinoma is ___
Sulphonylurea OD
194
In hypoglycaemia, FFAs should be ___
High. In hypos -> low insulin -> increased FFA
195
Why is cholesterol implicated in disease?
High levels of circulating cholesterol contribute to the formation of atherosclerotic plaques:
Inflammation -> foam cells -> necrosis -> plaque
Cholesterol esters in foam cells, crystals in necrotic core
196
Name the different types of lipoproteins and their roles
- Chylomicrons: biggest. Transport from gut to liver. High in triglycerides.
- VLDL: bad. High in triglycerides.
- LDL: bad. Circulating cholesterol.
- HDL: good. Bring cholesterol to the liver.
197
Describe cholesterol metabolism
- Diet/bile acids: absorbed in the small intestine -> chylomicrons to the liver
- de novo synthesis: HMG co-A reductase
- Packaged into LDLs and VLDLs as esters/made into bile acids
- HDL returns cholesterol to the liver
198
Explain what happens when triglycerides are absorbed
- Triglycerides in diet -> chylomicrons -> broken into FFAs by lipoprotein lipase
- FFAs taken up by liver and packed into VLDLs
199
Name several inherited conditions affecting lipid metabolism
- Primary hypercholesterolaemia: eg. familial type II
- Primary hypertriglyceridaemia: eg. familial type I, IV, V
- Primary mixed hyperlipidaemia
- Hypolipidaemia: eg. Ab-lipoproteinaemia, Tangier disease
200
Familial hypercholesterolaemia is caused by which mutations? How does it present?
```
AD condition. Mutations in LDLR, apoB, PCSK9
Very common (1:500 heterozygotes). High LDL, premature atherosclerosis, corneal arcus, xanthelasma
```
201
What is the function of PCSK9? What do mutations do?
PCSK9 is responsible for causing breakdown of the LDLR.
Gain of function (eg. more activity) -> increased breakdown -> increased LDL in the blood
Loss of function (eg. less activity) -> decreased breakdown -> decreased LDL in the blood
202
Familial hypertriglyceridaemia is caused by which mutations? Which lipoprotein is in excess?
Mutations in lipoprotein lipase, apoC, apoA
Type I: increased chylomicrons
Type IV/V: VLDL
203
What are some secondary causes of hyperlipidaemia?
```
Pregnancy
Hypothyroidism
Alcoholism
Anorexia
Nephrotic syndrome
```
204
What are some treatments for hyperlipidaemia? Describe their MoA
- Statins: inhibit HMG CoA reductase, decrease cholesterol synthesis
- Ezetimibe: blocks cholesterol absorption by NPC1L1. Often used in statin intolerance
- PCSK9 inhibitors: reduce LDLR breakdown, decrease LDL levels
- Cholestyramine: resin, blocks bile acid resorption
- Orlistat: lipase inhibitor, prevents fat absorption
- Fibrates: lower TGs
205
What was the main finding of the SPRINT trial? UKPDS? DCCT?
SPRINT: showed that aggressive management of BP decreases mortality (specifically w/ thiazides)
UKPDS: in T2DM, early tight glucose control has a legacy effect of reduced mortality + problems
DCCT: in T1DM, tight control improves outcomes
206
Name some different types of medications used in diabetes and their MoA + indications
Metformin: biguanide, increases insulin sensitivity in periphery. First line in T2DM
SGLT2i eg empagliflozin: increases glucose excretion in urine. Good for weight loss, BP, CVD
Thiazolidinedione eg. pioglitazone: PPARy stimulation -> increase insulin sensitivity
GLP-1 agonists -glutides eg liraglutide, exanatide: increases incretin/insulin release. Can cause hypos.
Sulphonylureas eg gliclazide: stimlate insulin production. Can cause hypos.
DPP4 inhibitors -gliptins eg sitagliptin: inhibits GLP-1 breakdown, increases insulin. Can cause hypos.
207
Gliclazide is an example of ---?
Sulphonylurea
208
Sitagliptin is an example of ---?
DPP4 inhibitor
209
Exanatide is an example of ---?
GLP-1 agonist
210
Empagliflozin is an example of ---?
SGLT2 inhibitor
211
Pioglitazone is an example of ---?
Thiazolidinedione
212
Elevated enzyme levels indicates what?
Primarily: Tissue damage
Also: increased synthesis, decreased breakdown
213
ALP is produced by .....
| Raised ALP is caused by:
```
Bile ducts
Bone (from osteoblasts)
Placenta, germ cell tumours
Intestines
Raised: pregnancy, bone turnover (Paget's, osteomalacia, mets), liver disease (cholestasis, cirrhosis)
```
214
A patient has a raised ALP. What tests would you do next and why?
```
LFTs - raised enzymes would indicate liver cause
Bone profile (Vit D, Ca, PTH)- may indicate breakdown
```
215
ALT is produced by ...
AST is produced by...
Raised levels indicate:
ALT: hepatocytes mostly. Also kidney, pancreas, heart
AST: many organs. Heart, liver, muscle, kidneys, etc
Both: hepatitis. AST> ALT in alcoholic. AST also MI
216
GGT is produced by...
| Raised levels indicate:
Biliary tree and hepatocytes, kidney, pancreas
| Increased in alcohol use, enzyme inducing drugs
217
What are some markers of pancreatitis? Which is the most specific?
Amylase. Also raised in other causes of acute abdo and parotitis.
Pancreatic lipase. More specific.
218
What are the types of CK and where are they produced?
| Raised CK is indicative of ....
CK-MM: skeletal muscle
CK-MB: cardiac muscle
CK-BB: brain
Muscle damage
219
What are some causes of a raised CK?
- Muscle injury: rhabdomyolysis, exercise, muscular dystrophy, myositis, statin myopathy
- Cardiac injury: MI, cardiomyopathy
220
Which enzymes are raised after MI?
CK, AST, LDH, myoglobin: not routinely measured
| Troponins I and T: I is best
221
When should you measure troponins in MI?
At 6 hours and again at 12 hours
222
What are some markers of cardiac failure? What causes their release?
BNP, ANP
| BNP: ventricular stretch
223
What troponins are there and where are they produced?
I, T, C
I +T, some C: cardiac
C: skeletal
224
Where is LDH produced? What do raised LDH levels indicate?
Muscle, liver, kidneys, blood cells, heart. Placenta + germ cell tumours.
Raised LDH: muscle injury (myositis, rhabdo), hepatitis, haemolytic anaemia, leukemia, MI
225
What triad of symptoms/signs should make you think of porphyria?
Neuro signs
Abdo pain
Psychiatric symptoms
226
Where does a blood sample have to be taken for drug screening in post-mortems?
Femoral vein
227
How does cocaine affect the body? How can it cause death?
```
Happy/elated
Decreased appetite and need for sleep
Increased HR, BP, temp
Dilated pupils
Irritability, anxiety
Death via cardiac arrhythmia, vasospasm (MI)
```
228
How do opioids affect the body? How does withdrawal present?
```
Respiratory depression (cause of death)
Constricted pupils
Constipation
Flushing, itching
Decreased HR and RR
Withdrawal: goosebumps, diarrhoea, restlessness
```
229
When can drugs be detected in different samples?
Blood: within 12 hours
Urine: within 2-3 days
Hair: several months
230
Tinnitus, deafness and nystagmus are signs of toxicity of which drug?
Gentamicin
231
Digoxin toxicity presents with...
Arrhythmia, heart block, confusion, seeing yellow
