Adrenal

Question 1

Does sodium follow water or water follow sodium

Answer 1

WATER ALWAYS FOLLOWS SODIUM

Question 2

How does the ICF compartment compare to that of ECF?
What happens when water is gained or lost from the body?
What is it important to remember re this when thinking about clinical signs of water overload or deficit?

Answer 2

It is important to note that the ICF is double the size of the ECF. This is important, as when water is gained or lost from the body, it is distributed across all body compartments, since water is not confined to any one compartment.
This means that the clinical signs of water overload or deficit are correspondingly muted or ‘diluted’ if you like. So you can for example lose quite a lot of pure water without being obviously dehydrated clinically.

Question 3

How do the concentrations of Na and K differ in the ICF compared to the ECF?
How is this maintained?
How does the body use this to maintain ECF fluid volume?

Answer 3

the normal concentration of sodium in the ICF is much smaller than that in the ECF. Potassium concentration is the opposite – it is much higher in the ICF than the ECF. The plasma membrane has a Na/K pump, which maintains these concentration gradients. The pump confines Na to the ECF compartment. The body uses the fact that Na is confined to the ECF to control the ECF volume.

Question 4

What do your kidneys do if the ECF volume is too high or too low?

Answer 4

if your ECF volume is too high, the kidneys excrete more Na and thus you lose water with it. If the ECF volume is too low, the kidneys ‘hang on’ to Na in an attempt to retain water and restore volume to normal.

Question 5

What are the clinical signs of reduced ECF volume?

Why are these specific?

Answer 5

Dry mucous membranes, postural decrease in blood pressure.

Because Na loss is confined to the ECF

Question 6

If you lose control of Na excretion because of pathology, what happens to sodium?
What does this cause in the fluid compartments of the body?
How does this relate to the clinical signs?

Answer 6

Sodium loss
A reduction in the ECF volume. Because the volume loss is confined to the ECF (since the sodium is lost exclusively from the ECF), the clinical signs are obvious, and develop quickly.

Question 7

What is sodium controlled by?
Which type of hormone regulates this and where are they produced?
What is the main mineralocorticoid hormone?
What does mineralocorticoid activity refer to?

Answer 7

SODIUM is controlled by mineralocorticoid activity.
Steroid hormones produced in the adrenal gland
Aldosterone (also cortisol)
Mineralocorticoid activity refers to sodium retention in exchange for potassium and/or hydrogen ions.

Question 8

What two things does aldosterone cause in the kidney?

Answer 8

Aldosterone causes Na to be reabsorbed from that filtrate in exchange for K or H. You excrete positively charged ions – either K or H. You retain Na, so you retain H2O. You also lose more potassium and hydrogen.

Question 9

What happens if you have too little mineralocorticoid activity?

Answer 9

If you have too little mineralocorticoid activity, you lose sodium, so lose water. Since this is from the ECF, the patient will be dry.

Question 10

What does to much mineralocorticoid activity do to sodium?

Answer 10

Too much mineralocorticoid activity means sodium retention.

Question 11

Where is ADH released from?
What type of stimuli cause this?
What does ADh do to the kidneys?

Answer 11

WATER is controlled by ADH (Anti-Diuretic Hormone).
ADH is released by the posterior pituitary in response to osmotic & non-osmotic stimuli.
The function of ADH on the kidneys is to cause water to be reabsorbed – pee out small amount of concentrated urine.

Question 12

What is the term used when we assess urine concentration?

What does an increase or decrease of ADH to do urine concentration?

Answer 12

Urine osmolality
Increased ADH - concentrated urine - high urine osmolality
Decreased ADH - dilute urine - low urine osmolality

Question 13

What does countercurrent multiplication refer to?

Answer 13

The concept of having a concentration gradient between what’s in the filtrate and whats surrounding the filtrate - you want a big concentration gradient between the two

Question 14

What are the two possible causes of hyponutraemia?

Give two possible causes of each, with examples?

Answer 14

This can be caused by too much water, or too little sodium.
Too much water
- ↓excretion e.g. SIADH – syndrome of inappropriate ADH secretion
- increased intake e.g. compulsive water drinking – very unusual and very obvious
Too little sodium
- ↑ sodium loss - kidneys e.g. Addison’s, gut, skin
- increased sodium intake - rare cause

Question 15

What are the two possible causes of hypernutraemia?

Give two possible causes of each, with examples?

Answer 15

This can be cause by too little water, or too much sodium.
Too little water
- ↑ water loss - diabetes insipidus (problem with ADH secretion or action)
- decreased water intake e.g. very young, elderly patients (insensible water loss continues)
Too much sodium - rare – may not be suspected
- Some IV medications are given as sodium salts
- Near-drowning in sea
- Infants given high-salt feeds

Question 16

Is hyper or hyponutraemia more common?

Answer 16

Hyponutraemia

Question 17

Is it more common to have problems with sodium balance or water balance?

Answer 17

In general it’s much more common to have problems with water balance rather than sodium.

Question 18

A 24 year-old student presents with a six month history of malaise, tiredness, poor appetite and one stone weight loss. She has developed a craving for salty foods – crisps in particular. She has had a number of dizzy spells particularly while in warm places.
She is thin. She has low BP which falls further on standing. You have the impression that she is tanned, and you find increased pigmentation in her mouth and hand creases.
Her bloods show a low sodium [122] and a high potassium [5.8].
What is this a typical history of?

Answer 18

Addison’s disease

Question 19

Addison’s disease

• What is the basic problem?
• What does this do to Na in the kidneys?
• What does this do to the patient clinically?
• What causes the excess pigmentation?

Answer 19

Basic problem is adrenal insufficiency – Addison means primary adrenal insufficiency
- So can’t make enough steroids
- So doesn’t have enough mineralocorticoid activity
- So can’t retain enough sodium in the kidneys – losing Na and water, and retaining K and H
So loses sodium (and water with it) from ECF
There is decreased ECF volume meaning patient is clinically dehydrated
Symptoms of dizziness etc reflect hypotension from decreased ECF
Excess pigmentation reflects excess ACTH from pituitary

Question 20

• Patient often in hospital with other illness
• Routine biochemistry shows decreased [Na]
• On examination, volume status usually unremarkable
• Patient usually has no symptoms specifically due to low sodium
• Investigations for causes of sodium loss e.g. Addison’s negative
• Patient presumed to have too much water
• Most of these patients have ‘inappropriate’ ADH secretion
  What is this a classic history of?

Answer 20

SIAD: syndrome of inappropriate antidiuresis (inappropriate’ means inappropriate for the osmolal state).

Question 21

What are the two types of stimuli for ADH release?

Which occurs in health and which in disease?

Answer 21

1. Osmotic (in health)

2. Non-osmotic (in disease) – very common, especially in hospital

Question 22

What are three examples of non-osmotic simuli for ADH release?

Answer 22

1. Hypovolaemia/hypotension
2. Pain
3. Nausea/vomiting

Question 23

Syndrome of inappropriate antidiuresis

• What is the basic problem?
• What does this do to water?
• Timeline of disease?
• What does this do to the patients clinical volume status?
• When does it usually come to your attention?
• What is presumed to be the problem?
• How is the diagnosis made?

Answer 23

Basic problem is ADH secreted in response to a non-osmotic stimulus
This causes water retention. This often occurs slowly and the retained water is distributed over all body compartments (ICF as well as ECF) – so patient’s volume status clinically may be unremarkable.
- It first comes to attention when U&E done and [Na] found to be low.
- Clinicians often aren’t sure why [Na] is low and investigate to exclude the other main mechanism of [Na] – i.e. too little sodium
- Diagnosis of water excess as the mechanism is often by exclusion – once adrenal insufficiency (and other sources of sodium loss) excluded, you start to think about water

Question 24

A 29 year-old man is admitted to ITU following a cycling accident in which he sustained a severe head injury. During his ITU stay his urine output is in excess of 12 litres daily; his IV fluid requirement is correspondingly large.
Serum sodium is 167 mmol/L on admission to ITU and slowly falls as fluid replacement ‘catches up’. He is in addition commenced on desmopressin (exogenous ADH) which produces a sharper fall in sodium.
What is this a typical presentation of?

Answer 24

Diabetes insipidus
He has transected his pituitary stalk – no longer secreting ADH from posterior pituitary. He is not reabsorbing water in the usual way, so he pees out lots of diluted urine.

Question 25

Diabetes insipudus - What is the basic problem? - What does this do to urine osmolality? - What does this do to [Na]? - How is it treated?

Answer 25

Basic problem is disruption of pituitary or pituitary stalk – so patient can’t secrete ADH from posterior pituitary So there’s no ADH to act on kidneys to cause water to be reabsorbed So LOTS of (pure) water is lost in urine So patient’s [Na] is high, reflecting the water deficit If the pituitary can’t make/release ADH, then we can give exogenous ADH (desmopressin) to replace it

Question 26

What is the most important clinical information in assessing Na and water balance?

Answer 26

Volume status

Question 27

If you get low water volume in a patient with low Na, then what is the problem?

Answer 27

Too little Na

Question 28

If the balance between capillary and ICF is altered so there is more water in the ICF then what happens to circulating volume? What two things does the body do in response to this? What does this do to the interstitial fluid?

Answer 28

Reduced circulating volume 1. Switches on aldosterone (secondary hyperaldosteronism), which causes Na to be reabsorbed in exchange for K and H, so you also reabsorb water 2. You also secrete ADH to try and restore blood volume back to normal This goes some way to restoring the circulating volume, but some of the reabsorbed water goes back into the interstitial fluid.

Question 29

What does oedema tell you about water compartments?

Answer 29

Oedema tells you that the water is in the wrong place, not that there is too much of it. You are likely to have too much sodium, in the wrong place. Basically, oedema signifies effective circulating volume depletion. Compensation for that (ADH & aldosterone to restore volume) produces a vicious circle.

Question 30

How can you tell if hypo or hypernutraemia is serious? What symptoms might this cause? What about if there has been a rapid change in [Na]?

Answer 30

[Na] itself is helpful. If very low (<120 mmol/L) or very high (>155 mmol/L), then YES it is serious If [Na] is very low or high the patient may develop symptoms due to the abnormal [Na] e.g. altered consciousness, confusion, nausea. If the patient has these symptoms in context of very low or high [Na], then YES it is VERY serious. If [Na] has fallen or risen rapidly to current level, that may be serious.

Question 31

A patient has low [Na] - What are the two possible causes? - what is the most helpful investigation? - What are the two possible causes of the Na problem? - What should you do if you suspect adrenal insufficiency? - What should you consider if the patient isn't dry?

Answer 31

Has to be either too little sodium or too much water Most helpful info is patient’s volume status - If dry → too little sodium - If not dry → too much water If too little sodium then has to be either decreased intake or increased loss, either from gut, skin or kidney. Decreased intake uncommon. Gut/skin loss usually obvious 4If suspect adrenal insufficiency, then measure cortisol and ACTH, but if patient unwell DON’T wait – give patient sodium replacement. If not dry, and adrenal insufficiency excluded, must be water excess.

Question 32

How should you treat a patient with the following problems? - Too little sodium - Too much water - Too little water - Too much sodium

Answer 32

Too little sodium → give sodium Too much water → fluid restrict Too little water → give water Too much sodium → get rid of excess sodium e.g. diuretics to induce natriuresis, and then replace just the water

Question 33

Name the three zones that the adrenal cortex can be divided into and the hormones that each produces

Answer 33

``` Zona Glomerulosa – - Mineralocorticoids - Aldosterone Zona Fasciculata – - Glucocorticoids - Cortisol Zona Reticularis – - Sex Steroids - Glucocorticoids ```

Question 34

Adrenal Cortex Pathology - Give three causes of hyperfunction - Give two types of hypofunction and an example of each

Answer 34

``` Hyperfunction - Hyperplasia - Tumour - Carcinoma Hypofunction - Acute – Waterhouse-Friderichsen - Chronic – Addison’s disease ```

Question 35

Congenital adrenocortical hyperplasia - What type of disorder? - What does this cause? - Symptoms? - Basic pathology?

Answer 35

Group of autosomal recessive disorders. Deficiency / lack of enzyme required for steroid biosynthesis. Altered biosynthesis leads to increased androgen production - Masculinisation - Precocious puberty Reduced cortisol stimulates ACTH release and cortical hyperplasia (10-15x normal weight).

Question 36

Acquired adrenocortical hyperplasia - What hormone is produced and what does this cause? - What are the two types and what is the difference between them?

Answer 36

``` Endogenous ACTH production - Pituitary adenoma (Cushing’s disease) - Ectopic ACTH - Paraneoplastic syndrome (small cell lung carcinoma) Diffuse or Nodular - Diffuse – ACTH driven - Nodular usually ACTH independent ```

Question 37

Adrenocortical tumours - Who gets them? - M:F? - Presentation?

Answer 37

Mainly adults - can occur in younger patients (?Li-Fraumeni syndrome). Males and females are equally affected. Presentation - Incidental finding (radiology, autopsy) - Hormonal effects - Mass lesion - Carcinomas with necrosis can cause fever

Question 38

Adrenocortical adenoma - Describe the lesion itself - What does it resemble histologically? - Functional or not? - How are they usually found?

Answer 38

Well circumscribed, encapsulated lesions Usually small – up to 2 to 3cm Yellow / brown cut surface (lipid) – this is very characteristic of the adrenal cortex itself – because of the abundance of lipids present in the cells Composed of cells resembling adrenocortical cells Well differentiated, small nuclei, rare mitoses -> i.e. lack the usual histological features of malignancy Can be functional, but more likely not There are usually incidentally found.

Question 39

Adrenocortical carcinoma - Common or rare? - What do they resemble? - Where do they spread to? - Prognosis?

Answer 39

These are rare. More likely to be functional - virilising tumours usually malignant Can closely resemble adenoma - adenoma and carcinoma form a spectrum. Spread of carcinoma - Local invasion – retroperitoneum, kidney - Metastasis – usually vascular (liver, lung and bone) - Peritoneum and pleura - Regional lymph nodes 5 year survival 20-35%, 50% dead in two years.

Question 40

Distinction between benign and malignant can be difficult. | Give five features suggesting adrenocortical carcinoma

Answer 40

``` Large size (>50g, often >20cm) Haemorrhage and necrosis Frequent mitoses, atypical mitoses Lack of clear cells Capsular or vascular invasion ```

Question 41

Give three causes of Conn's syndrome (primary hyperaldosteronism) in relation to adrenocortical tumours

Answer 41

1. Usually (60%) associated with diffuse or nodular hyperplasia of both adrenal glands 2. Adenoma (35%) – rarely carcinoma - Solitary, small, bright yellow and buried within the gland – do not cause a mass lesion - Spironolactone bodies - Do not suppress ACTH so adjacent & contralateral adrenal tissue is not atrophic 3. Glucocorticoid remediable - Uncommon genetic disorder with production of hybrid steroids, cortisol and aldosterone - Under the influence of ACTH

Question 42

Which tumour produces spironolactone bodies?

Answer 42

Adrenocortial adenoma

Question 43

Give two causes of secondary hyperaldosteronism

Answer 43

Increased renin | Decreased renal perfusion, hypovolaemia, pregnancy

Question 44

What are the two tumours associated with the adrenal medulla?

Answer 44

Neuroblastoma | Phaeochromocytoma

Question 45

Neuroblastoma - When is it usually diagnosed? - Where does it arise from? - What is it composed of?

Answer 45

Usually diagnosed 18 months, 40% diagnosed in infancy. 40% arise in the adrenal medulla – the remainder mostly along the sympathetic chain. Composed of primitive appearing cells but can show maturation and differentiation towards ganglion cells.

Question 46

Phaeochromocytoma - Derived from? - What might it cause? - What is laboratory diagnosis based on? - Describe the pathology - Where might it metastasize to?

Answer 46

This is a neoplasm derived from chromaffin cells of the adrenal medulla, which secretes catecholamines. Rare cause of secondary hypertension. Laboratory diagnosis - detection of urinary excretion of catecholamines and metabolites Pathology – Range from small to large necrotic tumour masses – 1g to >2kg described, average 100g – May see adrenal remnants on the surface – Yellow, red/brown to haemorrhagic and necrotic Skeletal

Question 47

Phaeochromocytoma is a feature of which endocrine disease? What are the two types? Briefly describe each.

Answer 47

Multiple Endocrine Neoplasma (MEN) 1. MEN2A (sipple syndrome) – Phaeochromocytoma (40-50%), Medullary thyroid carcinoma (100%), parathyroid hyperplasia (10-20%) MEN2B – Phaeochromocytoma, Medullary thyroid carcinoma, neuromas or ganglioneuromas, marfanoid habitus