Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pathology > Chemical Pathology > Flashcards

Chemical Pathology Flashcards

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What can be used as a marker of bone turnover? Where is it produced?

A

Alkaline phosphatase. Found in osteoblasts.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which mineral is needed for PTH production?

A

Mg2+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Colle’s fracture would typically occur in which bone disease?

A

Osteoporosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Name some risk factors for the development of osteoporosis.

A

Cushing’s syndrome, early menopause, thyrotoxicosis, anorexia, old age.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Name some causes of Vitamin D deficiency.

A

Poor diet, malabsorption, lack of sunlight, liver disease, renal disease, anticonvulsants, phytic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the biochemical picture in Vitamin D deficiency?

A

Low Ca, low Vitamin D (25OH), low phosphate, high alk phos

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Name several causes of hypercalcaemia

A

Primary hyperparathyroidism, malignancy (bony mets, multiple myeloma, small cell lung cancer), sarcoidosis, familial hypocalciuric hypercalcaemia, thyrotoxicosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How do you manage hypercalcaemia?

A

Admit if levels very high/severe symptomatic.

IV fluids. Treat the cause eg. IV bisphosphonates, parathyroidectomy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the signs + symptoms of hypocalcaemia?

A 
Convulsions
Arrhythmias (prolonged QT)
Tetany: Chvostek's sign (face)Trousseau's sign (carpo-pedal spasm)
Stridor
Perioral numbness
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

How do you manage hypocalcaemia?

A

Replace Ca and Vitamin D

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Name some causes of hypocalcaemia.

A

High PTH: vitamin D deficiency, liver disease, renal disease (renal osteodystrophy), PTH resistance
Low PTH: hypoparathyroidism. Iatrogenic, DiGeorge syndrome, Mg deficiency eg. PPI use

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is serum vitamin D in renal osteodystrophy? Why?

A

Normal. The dysfunction is with the 1a hydroxylase enzyme, but 25OH Vit D is what is measured (this is unaffected)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are the signs + symptoms of Paget’s disease of bone?

A

Bone pain, warmth over the affected bone, deformity, fractures, salt + pepper skull

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is the most useful investigation for diagnosing Paget’s disease?

A

Bone scan (radioactive)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is the pathophysiology of pseudohyperparathyroidism?

A

There is peripheral resistance to PTH, rather than a true PTH deficiency.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is pseudopseudohypoparathyroidism?

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What are the 3 purines? What is their function?

A

Adenosine, guanine, inosine. They are second messengers, make up DNA/RNA and are involved in ATP transfer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Describe purine metabolism to uric acid

A

Purines -> hypoxanthine -> xanthine (by xanthine oxidase) -> urate (also by xanthine oxidase).
Urate is then excreted in urine.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Which enzyme involved in purine metabolism do humans lack?

A

Uricase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What are normal urate levels in males and females?

A

M: 0.12-0.42
F: 0.12-0.36

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Where is gout most commonly found? Why?

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Explain the excretion of uric acid

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Describe the formation of nucleotides from purines

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What is the key enzyme in the purine de novo synthesis pathway? What is important about it?

A

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).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What is the key enzyme in the purine salvage pathway? What reaction does it catalyse?

A

HPRT/HGPRT. It converts hypoxanthine and guanine into IMP and GMP respectively.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Which enzyme is deficient in Lesch Nyhan syndrome? Explain the pathophysiology.

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Describe the presentation of Lesch Nyhan syndrome

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Name some causes of hyperuricaemia

A

Increased production: high cell turnover eg. chemotherapy for haem malignancies
Decreased excretion: CKD, thiazide diuretics, lead poisoning

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What are the 2 forms of gout? Where are they found?

A

Acute (podagra) painful joint inflammation

Chronic (tophaceous) nodules deposited in soft tissue eg. ears, elbows

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

How do you manage gout acutely?

A

Decrease inflammation with NSAIDs, colchicine, steroids.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What is the MoA of colchicine?

A

Inhibits tubulin, which prevents neutrophil migration and decreases inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

How do you manage gout after initial acute management?

A

Increase fluids. Allopurinol, probenasid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What is the MoA of allopurinol and probenasid?

A

Allopurinol: xanthine oxidase inhibitor. Decreases uric acid production
Probenasid: uricosuric. Increases renal excretion of uric acid.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

You should not give a patient allopurinol who is already taking ______. Explain.

A

Azathioprine. Allopurinol will increase levels of mercaptopurine, which is toxic to bone marrow.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

How would you differentiate between gout and other types of painful joint swelling?

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What is the Guthrie test and when is it done? Which conditions are tested for?

A

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).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Describe the pathophysiology of PKU. What is the treatment?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Describe the pathophysiology of MCADD. What is measured on the Guthrie test?

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Describe the process of screening for CF.

A

Guthrie spot measuring immune reactive trypsinogen -> DNA mutation testing (for 4 mutations) if +ve

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Describe the main defect in homocystinuria and the classic features.

A

No re-methylation of homocysteine. Causes lens dislocation, mental retardation, VTE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What is the point of the urea cycle? What happens when there are defects?

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

What are investigations for urea cycle defects? Treatments?

A

-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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

What is the biochemical hallmark of organic acidurias? Why do these occur?

A

High ammonia with metabolic acidosis and high anion gap.

Defect in the breakdown of complex amino acids eg. isovaleryl-CoA dehydrogenase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

What syndrome can organic acidurias present like? this happen and what are the classic features?

A

Reye’s syndrome. Can be a feature of IMD or triggered by salicylates (aspirin), antiemetics, valproate.
Vomiting, lethargy, confusion, seizures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Name some features (biochemical + physical) of defects in the B oxidation pathway.

A

Hypoketotic hypoglycaemia.

Hepatomegaly and cardiomegaly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Name 2 main carbohydrate disorders and describe their mechanisms + presentations

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

What is a key feature of mitochondrial diseases that explains why they can present at any age in any organ?

A

Heteroplasmy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Which organs are typically affected in mitochondrial diseases and why?

A

Brain, kidneys, muscle, retina, endocrine organs. They have a high energy requirement.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

What is MELAS?

A

Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

What are some investigations used to diagnose mitochondrial disorders?

A

Lactate (high), CSF lactate and pyruvate, CK (high), muscle biopsy, mitochondrial DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

For which IMDs what you measure urine mucooligopolysaccharides?

A

Lysosomal storage diseases eg. Tay Sachs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

At what age is renal function in children fully developed?

A

2 years. Before this time, GFR is low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

Name 3 differences between adult and child renal function

A

Infants have

  • Lower GFR:surface area
  • Persistent sodium loss
  • Less reabsorption and concentrating ability
  • More susceptible to acidosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

Name some causes of neonatal hyperbilirubinaemia

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

What level of conjugated bilirubin is always pathological in neonates? Name 2-3 causes.

A

> 20umol/L

Biliary atresia, IMDs eg. galactosaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

What are the biochemical features of osteopenia of prematurity?

A

Normal Ca
Low Phosphate (<1 mmol/L)
Very high alkaline phosphatase (>1200U/L)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

What are the fat soluble vitamins and what results when these are deficient?

A

A: colour blindness
D: osteomalacia/Ricket’s.
E: anaemia, neuropathy
K: defective clotting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

What are the different B vitamins and what results when these are deficient?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

How do you measure B1 and B2 levels?

A

RBC transketolase for B1, RBC glutathione reductase for B2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

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.

A

Iron
Iodine
Copper

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

What are some conditions that can result in malnutrition?

A

GI conditions: coeliac, Crohn’s
Chronic liver disease and kidney disease
Pancreatic insufficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

What is Marasmus? What is Kwashiorkor?

A

Marasmus: generalised poor nutrition. Thin and emaciated.
Kwashiorkor: protein deficient. Muscle wasting, oedematous, fatty liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

What is normal serum sodium? What are the 2 main physiological systems controlling sodium + fluid balance and how do they work?

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

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

a) Serum osmolarity = 2 (Na + K) +glucose + urea

b) 298.5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

a) What is the serum osmolality in true hyponatraemia? b) What are the 3 main types of hyponatraemia? Name several causes of each.

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

How can urine sodium be useful in determining the cause of hyponatraemia?

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

Why do liver failure and heart failure cause hyponatraemia?

A

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).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

How do you treat hyponatraemia?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

How should you fluid replace a patient with hyponatraemia? What is the significant complication to avoid?

A

Slowly! Aim for increase in sodium of 8-10 mmol over 24 hours.
Must avoid central pontine myelinolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

How would you diagnose SIADH?

A

Plasma sodium + osmolality (LOW Na, LOW osm)
Urine sodium + osmolality (HIGH Na, HIGH osm >100)
Rule out other endocrine causes eg. hypothyroidism, adrenal failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

What are the signs/symptoms of hyponatraemia?

A

Nausea and vomiting –> confusion –> seizures –> coma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

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?

A

The patient has pseudo-hyponatraemia. This may be caused by conditions that increase plasma lipids/proteins eg. hypertriglyceridaemia or MM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

What are some causes of SIADH?

A
  • Intracranial pathology eg. infection, tumours
  • Lung pathology eg. cancer, TB, infection
  • Drugs eg. SSRI, TCA, opiates, PPIs, carbamazepine
  • Surgery
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

What is the management of SIADH?

A
  • Fluid restriction
  • Demeclocycline (reduces ADH responsiveness in the tubules). Must monitor U&Es
  • Vaptans eg. tolvaptan (V2R antagonist)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

Name some causes of hypernatraemia

A

Caused by unreplaced water loss eg. D&V in elderly, renal losses (osmotic diuresis), diabetes insipidus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

How would you investigate hypernatraemia?

A
  • 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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

Describe the management of hypernatraemia

A

Fluid replacement with 5% dextrose (to avoid extra salt)

94
Q

Define a porphyria. What is the mechanism by which this causes disease?

A

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
Q

Describe the structure of haem. Where is it produced?

A

Haem is comprised of tetrapyrrole rings surrounding an Fe2+ ion. It is produced in all cells of the body

96
Q

Describe the haem synthesis pathway

A

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
Q

Describe the classification of porphyrias

A 
Classified by the type of presentation 
1. Neurovisceral symptoms (ophthalmoplegia, quadraparesis)
2. Blistering cutaneous 
3. Non-blistering cutaneous
Also by acute/non-acute.
98
Q

Which is highly coloured, porphyrinogens or porphyrins?

A

Porphyrins. Uroporphyrins (early in the pathway) are excreted in urine, while coproporphyrins (late in the pathway) are excreted in the faeces

99
Q

T/F: There are 8 enzymes in the haem synthesis pathway, with 8 corresponding porphyrias

A

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
Q

What are the names of the different porphyrias, and which enzyme deficiency are they caused by?

A
  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
Q

Which porphyrias are acute?

For each: Which enzyme is deficiency? What builds up? What is their presentation? +treatment if known

A
  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
Q

How would you differentiate between the types of acute porphyrias?

A
  • 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
Q

Which porphyrias are non-acute?

For each: Which enzyme is deficiency? What builds up? What is their presentation? +treatment if known

A
  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
Q

How would you investigate the different presentations of porphyria?

A

If neurovisceral symptoms: send urine PBG
If blistering cutaneous: send urine/faeces porphyrins
If photosensitivity: send RBC protoporphyrin

105
Q

Is potassium in higher concentration inside or outside of cells?
What is normal serum K+?

A

Higher intracellularly.

Normal serum K+ 3.5-5.0 mmol/L

106
Q

Describe the process of renin and aldosterone release.

A

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
Q

How does aldosterone work?

A

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
Q

Name some causes of hyperkalaemia.

A

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
Q

Describe how you would manage hyperkalaemia.

A

-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
Q

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?

A 
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
Q

Name some causes of hypokalaemia.

A

-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
Q

Explain why loop and thiazide diuretics cause hypokalaemia.

A

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
Q

Name some features of hypokalaemia.

A
  • Muscle weakness
  • Arrhythmia
  • Nephrogenic DI (polyuria, polydipsia)
114
Q

When would you see a high aldosterone: renin ratio?

A

In Conn’s (primary hyperaldosteronism). Raised aldosterone would inhibit renin release.

115
Q

How would you manage hypokalaemia?

A

Treat the underlying cause.
K+ 3.0-3.5 mmol/L: give oral KCl (Sando K)
K+ <3: IV KCl

116
Q

What are the functions of the liver? What happens when the liver fails?

A
  • 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
Q

Name the different liver function tests and what they indicate

A
  • 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
Q

Where are AST and ALT found? What does it mean when they are raised?

A

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
Q

Where is ALP found? What does it mean when it is raised?

A

Bile ducts, bone, placenta

High levels may indicate cholestasis (eg PBC, PSC), bone turnover (MM, mets, hyperparathyroid), pregnancy

120
Q

What can cause a low albumin?

A
  • Liver disease: cirrhosis, failure
  • Renal loss: CKD, nephrotic syndrome
  • Malnutrition
  • Sepsis (third spacing)
121
Q

T/F. PT and INR are good measures of long term liver function

A

False. The half life of clotting factors is relatively short, so PT and INR reflect acute liver function

122
Q

Elevated alpha fetoprotein can be caused by:

A
  • Hepatocellular carcinoma
  • Germ cell tumours
  • Pregnancy
123
Q

How would you investigate jaundice?

A
  • Serum bilirubin level
  • Raised ALT/AST -> hepatocyte damage
  • Raised ALP -> biliary tree
  • USS -> dilated vs nondilated
  • Urine dip
124
Q

Jaundice and raised ALP can be caused by:

They can be distinguished using:

A

-Obstruction of the biliary tree
-Fibrosis/damage to the biliary tree (PBC or PSC)
Liver USS can differentiate

125
Q

Describe the excretion of bilirubin pathway

A
  • 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
Q

How can a urine dip help to investigate the cause of jaundice?

A
  • 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
Q

List some tests used to investigate liver disease

A
  • 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
Q

What is the Van den Bergh reaction?

A
  • 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
Q

What is GFR? What is a normal GFR?

A

Glomerular filtration rate: the amount of blood filtered by the kidneys per hour.
Normal: 120 ml/hr. Decreases with age

130
Q

Describe the different ways GFR can be calculated

A
  • 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
Q

Where is creatinine produced? What do creatinine levels depend on?

A
  • Muscles

- Depends on age, sex, weight (muscle mass), ethnicity

132
Q

Which test can be used to estimate renal function in low GFR?

A

Cystatin C

133
Q

If a patient has proteinuria, which tests would you consider doing next?

A

Urine protein:creatinine ratio to quantify the amount of protein in the urine.
Or 24hour urine protein collection. Not used often.

134
Q

What kind of tests can be done on urine samples? What can they show?

A
  • 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
Q

What can a urine dipstick show?

A
  • 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
Q

What is an AKI? What are the types? How is it diagnosed?

A

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
Q

Name some causes of pre-renal AKI

A

Reduced renal perfusion:

  • Hypovolaemia, hypotension, oedema
  • Renal artery stenosis
  • NSAIDs, calcineurin inhibitors -> constrict afferent art
  • ACEi/ARBs -> dilate efferent art
  • Diuretics
138
Q

Name some causes of post-renal AKI

A

Obstruction to urine flow:

  • Ureteric obstruction eg. stones
  • Bladder neck obstruction eg. tumours
  • Prostate enlargement eg. BPH, cancer
139
Q

Name some causes of renal AKI

A
  • 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
Q

What is the most common cause of AKI?

A

Pre-renal and ATN

141
Q

What are the stages of CKD?

A

Stage 1: 120-90

2: 89-60
3a: 59-45
3b: 44-30
2: 29-15
1: 14-0

142
Q

What are some common causes of CKD?

A 
Diabetes!!
Hypertension!
Atherosclerotic renal disease
Glomerulonephritis, vasculitis
PKD
143
Q

What are the consequences of CKD?

A

Fluid balance: oedema, hypertension
Electrolytes: hyperkalaemia, hyponatraemia -> VT/VF
Acid-base: metabolic acidosis
Metabolite excretion: uraemia -> encephalopathy, cardiomyopathy
Endocrine: osteodystrophy, anaemia

144
Q

How do you manage anaemia associated with CKD?

A

EPO alpha/beta injections

145
Q

How do you manage renal bone disease?

A

Activated Vitamin D supplements, calcium

146
Q

Why does CKD cause acidosis? How is it managed?

A

No H+ excretion due to failure of renal excretion mechanisms. Give Na bicarb

147
Q

What is the biochemical profile of renal bone disease?

A

High phosphate
Low Ca
Normal Vit D (measured is 25OH)
High PTH/normal PTH

148
Q

Which type of renal replacement therapy is best for patients who want to dialyse at home?

A

Peritoneal dialysis. Haemodialysis must be done in the hospital.

149
Q

What is the normal pH of the body? How is pH regulated?

A

7.35-7.45

Regulated by buffer with bicarb. Kidneys produce bicarb/excrete H+, lungs ventilate to decrease/increase CO2

150
Q

Name some causes of metabolic acidosis. Describe the acid-base results.

A
  • Increased H+ production: DKA, sepsis, metformin
  • Decreased H+ loss: renal failure

Low pH, low HCO3, negative BE. Low CO2 in compensation

151
Q

Name some causes of a respiratory acidosis. Describe the acid-base results.

A
  • Decreased ventilation: hypoventilation
  • Impaired gas exchange: COPD, pneumonia
  • Poor lung perfusion: PE

Low pH, high CO2. High bicarb and +ve BE in compensation.

152
Q

Name some causes of metabolic alkalosis. Describe the acid-base results.

A
  • Increased bicarb: antacids
  • Increased H+ loss: vomiting
  • Hypokalaemia

High pH, high bicarb, +ve BE. High CO2 in compensation

153
Q

Name some causes of respiratory alkalosis. Describe the acid-base results.

A

-Increased ventilation: anxiety

High pH, low CO2. Low bicarb in compensation.

154
Q

Which acid-base abnormality is seen in aspirin overdose?

A

Mixed respiratory alkalosis and metabolic acidosis

155
Q

How do you calculate an anion gap? What is a high anion gap and what does it mean?

A

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
Q

Name the hormones produced by the pituitary and what effect they have.

A

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
Q

What are two ways of testing the pituitary hormones

A
  • Hormone level: gives static picture of functioning

- Pituitary function tests: allows assessment of response to stimulation

158
Q

Describe how pituitary function testing is done. What are the contraindications and side effects?

A

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
Q

What is a normal response to combined pituitary function testing?

A 
Increase of:
>10 GH
>550 cortisol 
LH >10 
FSH >2 
> prolactin and TSH
160
Q

What are some causes of hypopituitarism?

A
  • Prolactinoma (causing stalk compression)
  • Other non-functioning adenoma
  • Sheehan’s syndrome
  • Pituitary apoplexy
161
Q

What can be used to replace pituitary hormones?

A
  • TSH: give thyroxine
  • GH: give GH injections SC
  • ACTH: give pred/hydrocort
  • FSH+LH: give oestrogen (unless fertility is the goal)
162
Q

What is the treatment for prolactinoma?

A
  • Microadenoma: watch and wait unless symptomatic

- Macrodenoma/symp: D2R agonist eg. bromocriptine/cabergoline. Surgery.

163
Q

What is the cause of acromegaly? What is the treatment?

A

Caused by a GH-secreting adenoma. Surgery, RDx, octreotide/lanreotide

164
Q

Describe the anatomy of the adrenals and the function of each area

A 
Outer capsule
Cortex:
-Zona glomerulosa: aldosterone
-Zona fasciculata: cortisol
-Zona reticularis: sex hormones
Medulla: catecholamines
165
Q

Primary hypothyroidism and Addison’s indicate ___

A

Schmidt’s syndrome. Autoimmune condition w/ antibodies against thyroid and adrenals.

166
Q

Describe how a SynACTHen test is done and the normal results.

A

Measure cortisol at baseline. Administer 250mcg ACTH IM and measure response at 30mins + 60 mins.
Cortisol should increase by >550nm

167
Q

Name 4 causes of adrenal masses (+1 niche for extra points)

A
  • Non-functioning adenoma
  • Phaeo
  • Conn’s
  • Cortisol producing adenoma
  • TB granuloma
168
Q

How are phaeos diagnosed? What is the management?

A

Dx: clinical + urinary catecholamines, VMA. Imaging. Adrenal vein sampling.

  • Alpha block
  • Beta block
  • Surgery
169
Q

Name some conditions associated with phaeo

A
  • MEN2: parathyroid, thyroid, phaeo
  • von Hippel Lindau: phaeo, renal cell carcinoma, renal cysts
  • Neurofibromatosis 1: Cafe au Lait spots, neurofibromas, phaeo, Lisch nodules
170
Q

How do you interpret the aldosterone: renin ratio?

A

High aldo, low renin is Conn’s (appropriate renin suppression)
High aldo, high renin is RAS (no suppression)

171
Q

Name some causes of Cushing’s syndrome

A
  • Cushing’s disease: pituitary adenoma
  • Adrenal adenoma
  • Steroids
  • Ectopic ACTH eg. SCLC
172
Q

How is Cushing’s diagnosed?

A

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
Q

Describe the formation of thyroxine

A

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
Q

Name some causes of hypothyroidism

A 
Primary hypothyroidism: 
-Hashimoto's
-Viral thyroiditis
-Iodine deficiency
-Amiodarone, lithium
Secondary hypothyroidism:
-Pituitary failure eg. Sheehan's, apoplexy, tumour, RDx
175
Q

What is the thyroid picture in primary and secondary hypothyroidism?

A

Primary: low T4, high TSH
Secondary: low T4, low TSH

176
Q

How is hypothyroidism managed?

A

Levothyroxine. Start 50mcg -> 200/day. Titrate to normal TSH levels

177
Q

What is subclinical hypothyroidism? What are the implications?

A

Normal T4 but with high TSH

Some patients will go on to develop hypothyroidism. Can check for antibodies (anti-TPO)

178
Q

What is sick euthyroid?

A

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
Q

Name some causes of hyperthyroidism.

A

Primary: Graves disease, viral thyroiditis (de Quervain’s), toxic multinodular goitre, thyroid adenoma, iodine excess, amiodarone, post-partum thyroiditis
Secondary: pituitary adenoma

180
Q

Describe the TFTs in primary and secondary hyperthyroidism. What other tests would you consider?

A 
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
Q

Describe the management of hyperthyroidism. What are the important things to be aware of?

A
  • Beta blockers
  • Carbimazole: can cause agranulocytosis.
  • PTU: best for pregnancy
  • *Block and replace
  • Radio-iodine: not if pregnant, breastfeeding
  • Surgery
182
Q

How is T2DM diagnosed?

A 
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
Q

What are some complications of T1DM?

A

DKA
Hypos
Macrovascular disease: MI, stroke/TIA, PVD
Microvascular disease: nephropathy, retinopathy, neuropathy

184
Q

Name some causes of hyperglycaemia

A
  • T1DM, T2DM
  • Cushing’s
  • Acromegaly
  • Sepsis
  • Trauma
185
Q

Define HHS

A

Hyperosmolar hyperglycaemic state. A complication of T2DM characterised by confusion and dehydration.

  • Plasma osm >320
  • Plasma glucose >30
  • pH >7.3
186
Q

What is the management of HHS?

A

Fluid replacement!!
Slowly reduce glucose and Na
Frequent monitoring of U+Es

187
Q

Define DKA

A

Diabetic ketoacidosis. A complication of T1DM characterised by ketosis and metabolic acidosis.
pH <7.3, glucose >11 mM, ketones >3 mM

188
Q

How should you correct hypoglycaemia?

A

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
Q

Define hypoglycaemia. Name some causes

A 
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
Q

How do you investigate suspected hypoglycaemia?

A
  • Blood glucose: grey top bottle
  • Blood ketones: raised indicates low insulin
  • Insulin level
  • C peptide level
  • Drugs
  • Cortisol, GH
191
Q

Name some different ketones

A

3-hydroxybutyrate
Acetone
Acetoacetate

192
Q

What biochemical abnormalities would you expect to see in a neonate with an IMD affecting beta oxidation? Why?

A

-Hypoglycaemia
-Low insulin
-Low ketones
Hypoinsulinaemia Hypoglycaemic is the correct response. There is no ketone formation because beta ox defect.

193
Q

A differential for insulinoma is ___

A

Sulphonylurea OD

194
Q

In hypoglycaemia, FFAs should be ___

A

High. In hypos -> low insulin -> increased FFA

195
Q

Why is cholesterol implicated in disease?

A

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
Q

Name the different types of lipoproteins and their roles

A
  • 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
Q

Describe cholesterol metabolism

A
  • 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
Q

Explain what happens when triglycerides are absorbed

A
  • Triglycerides in diet -> chylomicrons -> broken into FFAs by lipoprotein lipase
  • FFAs taken up by liver and packed into VLDLs
199
Q

Name several inherited conditions affecting lipid metabolism

A
  • Primary hypercholesterolaemia: eg. familial type II
  • Primary hypertriglyceridaemia: eg. familial type I, IV, V
  • Primary mixed hyperlipidaemia
  • Hypolipidaemia: eg. Ab-lipoproteinaemia, Tangier disease
200
Q

Familial hypercholesterolaemia is caused by which mutations? How does it present?

A 
AD condition. Mutations in LDLR, apoB, PCSK9
Very common (1:500 heterozygotes). High LDL, premature atherosclerosis, corneal arcus, xanthelasma
201
Q

What is the function of PCSK9? What do mutations do?

A

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
Q

Familial hypertriglyceridaemia is caused by which mutations? Which lipoprotein is in excess?

A

Mutations in lipoprotein lipase, apoC, apoA
Type I: increased chylomicrons
Type IV/V: VLDL

203
Q

What are some secondary causes of hyperlipidaemia?

A 
Pregnancy
Hypothyroidism
Alcoholism
Anorexia
Nephrotic syndrome
204
Q

What are some treatments for hyperlipidaemia? Describe their MoA

A
  • 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
Q

What was the main finding of the SPRINT trial? UKPDS? DCCT?

A

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
Q

Name some different types of medications used in diabetes and their MoA + indications

A

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
Q

Gliclazide is an example of —?

A

Sulphonylurea

208
Q

Sitagliptin is an example of —?

A

DPP4 inhibitor

209
Q

Exanatide is an example of —?

A

GLP-1 agonist

210
Q

Empagliflozin is an example of —?

A

SGLT2 inhibitor

211
Q

Pioglitazone is an example of —?

A

Thiazolidinedione

212
Q

Elevated enzyme levels indicates what?

A

Primarily: Tissue damage
Also: increased synthesis, decreased breakdown

213
Q

ALP is produced by …..

Raised ALP is caused by:

A 
Bile ducts
Bone (from osteoblasts)
Placenta, germ cell tumours
Intestines
Raised: pregnancy, bone turnover (Paget's, osteomalacia, mets), liver disease (cholestasis, cirrhosis)
214
Q

A patient has a raised ALP. What tests would you do next and why?

A 
LFTs - raised enzymes would indicate liver cause
Bone profile (Vit D, Ca, PTH)- may indicate breakdown
215
Q

ALT is produced by …
AST is produced by…
Raised levels indicate:

A

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
Q

GGT is produced by…

Raised levels indicate:

A

Biliary tree and hepatocytes, kidney, pancreas

Increased in alcohol use, enzyme inducing drugs

217
Q

What are some markers of pancreatitis? Which is the most specific?

A

Amylase. Also raised in other causes of acute abdo and parotitis.
Pancreatic lipase. More specific.

218
Q

What are the types of CK and where are they produced?

Raised CK is indicative of ….

A

CK-MM: skeletal muscle
CK-MB: cardiac muscle
CK-BB: brain
Muscle damage

219
Q

What are some causes of a raised CK?

A
  • Muscle injury: rhabdomyolysis, exercise, muscular dystrophy, myositis, statin myopathy
  • Cardiac injury: MI, cardiomyopathy
220
Q

Which enzymes are raised after MI?

A

CK, AST, LDH, myoglobin: not routinely measured

Troponins I and T: I is best

221
Q

When should you measure troponins in MI?

A

At 6 hours and again at 12 hours

222
Q

What are some markers of cardiac failure? What causes their release?

A

BNP, ANP

BNP: ventricular stretch

223
Q

What troponins are there and where are they produced?

A

I, T, C
I +T, some C: cardiac
C: skeletal

224
Q

Where is LDH produced? What do raised LDH levels indicate?

A

Muscle, liver, kidneys, blood cells, heart. Placenta + germ cell tumours.
Raised LDH: muscle injury (myositis, rhabdo), hepatitis, haemolytic anaemia, leukemia, MI

225
Q

What triad of symptoms/signs should make you think of porphyria?

A

Neuro signs
Abdo pain
Psychiatric symptoms

226
Q

Where does a blood sample have to be taken for drug screening in post-mortems?

A

Femoral vein

227
Q

How does cocaine affect the body? How can it cause death?

A 
Happy/elated
Decreased appetite and need for sleep
Increased HR, BP, temp
Dilated pupils
Irritability, anxiety
Death via cardiac arrhythmia, vasospasm (MI)
228
Q

How do opioids affect the body? How does withdrawal present?

A 
Respiratory depression (cause of death)
Constricted pupils
Constipation
Flushing, itching
Decreased HR and RR
Withdrawal: goosebumps, diarrhoea, restlessness
229
Q

When can drugs be detected in different samples?

A

Blood: within 12 hours
Urine: within 2-3 days
Hair: several months

230
Q

Tinnitus, deafness and nystagmus are signs of toxicity of which drug?

A

Gentamicin

231
Q

Digoxin toxicity presents with…

A

Arrhythmia, heart block, confusion, seeing yellow

Pathology (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions