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Clinical Biochemistry > Year 3 > Flashcards

Year 3 Flashcards

1
Q

What is clinical biochemistry?

A

• Study of the chemical processes of the body in health and disease
Or
• Measurement of chemicals in the body to aid diagnosis, monitoring and treatment of disease

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2
Q

What level does imaging allow you to see?

A

Macro

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3
Q

What are some examples of external body imaging?

A
  • MRI
  • X-ray
  • CT scans
  • Whole body imaging
  • Bone scan
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4
Q

When is imaging not useful?

A
  • When there is no physical abnormality

* When it is at the molecular level

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5
Q

What does diagnostic tests inform us?

A

Identification of disease when patients simply feel “unwell”

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6
Q

What does prognostic tests inform us?

A
  • Disease progression

* Possible treatment

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7
Q

What does monitoring tests inform us?

A
  • How they are responding to treatment

* Informs on any changes necessary

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8
Q

What does screen tests inform us?

A

• If it is a condition that is present sub-clinically by the use of biomarkers

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9
Q

Why are emergency tests important?

A

Patients rushed to hospital with unknown cause requires emergency diagnosis

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10
Q

What do biomarkers do?

A

Inform clinicians on diagnosis and how to proceed with treatment and monitoring of patients

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11
Q

What are some examples of requested samples?

A
  • Blood
  • Urine
  • Ascitic fluid (in abdomen)
  • Gastric fluid
  • Amniotic fluid
  • Cerebrospinal fluid
  • Sweat
  • Saliva (limited use)
  • Faecal material
  • Solid tissues (tumour)
  • Analytes
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12
Q

What are analytes?

A

Substance whose nature and/or concentration is determined by a clinical test

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13
Q

What are the specific conditions that need to be taken into account when collecting a sample?

A
  • Time sample was taken
  • Volume collected
  • Specific diet
  • Fasting/not fasting
  • How is it preserved?
  • How is it transported?
  • Is it immediately analysed or is it stored first?
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14
Q

Why do we need to be aware of how the sample was collected?

A

Can affect biochemistry

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15
Q

What needs to be on the label of a sample?

A
  • Name
  • Date
  • Time of sampling
  • Patient identifier
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16
Q

What does a plasma sample contain?

A
  • Yellow liquid that blood cells are suspended in
  • Contains dissolved proteins (serum albumins, globulins and fibrinogen)
  • Glucose
  • Clotting factors
  • Electrolytes (Na+, Ca2+, Mg2+, HCO3-, Cl- etc)
  • Hormones
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17
Q

What does serum contain?

A

The same as plasma but without the clotting factors (and blood cells)

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18
Q

What are the advantages of simple laboratory tests?

A

• Highly reproducible
• Easy to replicate
• Reduces false positives and false negatives
• Can be done by automation
High throughput – does lots of samples at once (but can be limited when reading low concentration samples)

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19
Q

What test detects samples with low concentrations?

A

Immunoassay analysers

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20
Q

What is the workflow of a chemistry analyser?

A
  • Sample pipetted into cuvette
  • Reagent pipetted into cuvette
  • Reaction mixture mixed and incubated
  • Absorbance monitored
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21
Q

What do general chemistry analysers do?

A

initiate and measure defined reactions

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22
Q

What are the advantages of general chemistry analysers?

A
  • Larger machines can process thousands of samples per hour (may have to wait in queues)
  • Can analyse the same sample 7-10 times
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23
Q

Which general chemistry analysers are typically used?

A
  • Spectrophotometry
  • Potentiometry (ion specific electrodes)
  • Immune-assays
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24
Q

What level of training is required for point of care testing?

A
  • For sophisticated analysers in diabetes or epilepsy clinics there needs to be trained lab staff
  • For glucose testing, blood gases, ITU and GP clinic there needs to be a nurse or medical staff
  • For blood or urine (diabetes) the patient can do it (no training)
  • For glucose, cholesterol, PSA it can be done in pharmacies, supermarkets or internet vendors
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25
Q

How can a clinical biochemistry lab be standardised?

A
  • Standard Operating Procedures (SOPs) – validated protocol followed every time
  • Training Log Books – staff training procedures
  • Analyser Maintenance – machines routinely serviced
  • Reagent logs – storage temp/in-date/batch ID
  • Calibration Log – machines calibrated, analyte controls
  • Serum Indices
  • Quality Control Management System(s)
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26
Q

What are the tests done for a urea and electrolyte profile?

A
  • Sodium
  • Potassium
  • Chloride
  • Bicarbonate
  • Urea
  • Creatinine
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27
Q

What are the tests done for a liver function test profile?

A
  • Aspartate transferase (AST)
  • Alanine aminotransferase
  • Alkaline phosphatase (ALP)
  • Gamma glutamyl transferase (GGT)
  • Bilirubin
  • Total protein
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28
Q

What are the tests done for a bone profile?

A
  • Calcium
  • Phosphate
  • Alkaline phosphatase
  • Albumin
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29
Q

What are the tests done for thyroid function test profile?

A
  • Thyroid simulating hormone

* “free” T4

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30
Q

What are some examples of disease influencing electrolyte imbalances?

A
  • Hypernatremia
  • Hyperkalaemia
  • Diabetes insipidus
  • Conn’s disease (involved in excess production of aldosterone)
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31
Q

What does a urea and electrolyte profile give an indication of?

A
  • Kidney function
  • Overall health
  • Useful in diagnosing many diseases
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32
Q

In a 70kg male with 42L of water (60% of the body is water) how much would the intra and extracellular fluid have?

A

• 66% ICF – 28L (fluid in tissues)
• 33% ECF – 14L
o 3.5L intravascular fluid – blood plasma
o 10.5L interstitial fluid – pleural, pericardial, peritoneal, cerebrospinal and GI fluid

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33
Q

What can cause the water levels to fluctuate?

A
  • Eating
  • Drinking
  • Exercise
  • Passing urine/faeces
  • Sweating
  • Chemical reactions liberating water
  • Diuretics
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34
Q

What treatment uses water balance on the ward?

A

IV drip

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35
Q

What are the features of dehydration?

A
  • Increased pulse
  • Decreased blood pressure
  • Decreased skin turgor
  • Soft/sunken eyeballs
  • Dry mucus membranes
  • Decreased urine output
  • Decreased consciousness
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36
Q

What are the features of over-hydration

A
  • Normal pulse
  • Normal to increased blood pressure
  • Increased skin turgor
  • Normal eyeballs
  • Normal mucus membranes
  • Normal urine output
  • Decreased consciousness
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37
Q

What does dehydration do to osmolality of plasma?

A
  • Increases
  • Less water = increased salt concentration
  • Increased salts initiates mechanisms to control water and salt levels
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38
Q

What usually causes over-hydration?

A

Problems with excretion by the kidneys

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39
Q

What is over-hydration typically not caused by?

A

Excessive intake, except if compulsive drinking disorder

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40
Q

What is osmolality?

A

It is the measure of osmotically active particles in solution

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41
Q

What are the units of osmolality?

A

mOsm/kg

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42
Q

What is the osmolality of a healthy person?

A

285-295 mOsm/kg

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43
Q

How is the osmolality of different body compartments (ICF/ECF) kept equal?

A

• The movement of water across semipermeable membranes in response to concentration changes (except in water controlling cells such as nephrons and sweat glands)

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44
Q

What does osmolality affect in solution?

A

The freezing point which is used to measure osmolality

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45
Q

How do you calculate the calculated plasma osmolality?

A

Calculated Plasma osmolality = 2x [Na+] + 2x [K+] + [urea] + [glucose]

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46
Q

What is the difference between plasma osmolality and urine osmolality?

A

Plasma osmolality remains constant, urine osmolality dramatically changes

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47
Q

Why does urine osmolality change?

A

Absorption or excretion of excess electrolytes

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48
Q

What is the osmolar gap?

A

This is the difference between measured and calculated osmolality

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49
Q

How do you calculate the osmolar gap?

A

Osmolar gap = measured osmolality – calculated osmolality

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50
Q

What does an osmolar gap greater than 10 indicate?

A
  • It is considered abnormal

* Caused by toxins/poisons such as ethanol, methanol, ethylene glycol (antifreeze) as they supress the freezing point

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51
Q

When is the osmolar gap test extremely useful?

A

When the patient is unconscious

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52
Q

How does water deprivation affect plasma osmolality?

A

Increases

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53
Q

How is raised plasma osmolality due to water deprivation corrected?

A

Either by drinking more or urinating less

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54
Q

What is the flow of drinking more occur from the detection of raised plasma osmolality in water deprivation?

A
  • Stimulating thirst
  • Increasing liquid consumption
  • Increased total body volume
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55
Q

What is the flow of urinating less occur from the detection of raised plasma osmolality in water deprivation?

A
  • ADH release
  • Water retention
  • Reduced urine output
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56
Q

How is water deprivation detected?

A

Raised plasma osmolality

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57
Q

What does antidiuretic hormone (ADH) activate in kidney function?

A
  • Renal collecting ducts
  • Permits water reabsorption back into the body and urine concentration
  • At high levels leads to vasoconstriction= increased blood pressure and increased blood volume
  • Also controlled by the renin angiotensin-aldosterone system (RAA system)
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58
Q

What causes ADH increase?

A
  • High ECF osmolality
  • Dehydration/fever
  • Exercise
  • Drugs
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59
Q

What causes ADH decrease?

A
  • Low ECF osmolality
  • Overhydration
  • Alcohol
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60
Q

What occurs if cells are not water balanced?

A
  • Water will move out/move in

* The cell will either swell and rupture or shrink

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61
Q

What are electrolytes?

A

Electrolytes are substances that dissociate into ions in solution and so acquire the ability to conduct electricity

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62
Q

What is the normal amount of sodium within the cellular fluid?

A
  • In plasma (ECF) 142mmol/kg
  • In interstitial fluid (ECF) 145mm/kg
  • In ICF 12mmol/kg
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63
Q

What is the normal amount of potassium within the cellular fluid?

A
  • In plasma (ECF) 4mmol/kg
  • In interstitial fluid (ECF) 4mmol/kg
  • In ICF 156mmol/kg
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64
Q

What are the most requested biochemical profiles?

A
  • Serum sodium
  • Potassium
  • Chloride
  • Urea
  • Creatinine
  • Bicarbonate
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65
Q

What is the major mechanism of transport for sodium and potassium?

A

Na/K pump

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66
Q

What are the functions of sodium?

A
  • Establishes osmotic gradients/fluid balance (hydration of the body in vessels and cells)
  • Blood pressure regulation (hydration of vessels)
  • Aid movement of solutes/nutrients in/out of cells (hydration in cells)
  • Muscle/nerve contractions
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67
Q

What colour blood tube is lithium heparin?

A

Green

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68
Q

Why must blood not be collected from the same arm that has IV drip saline (150 mm NaCl)?

A
  • Artefact

* Can disturb the results

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69
Q

How does temperature affect potassium in a blood sample?

A

Potassium moves out of the cells creating an artificial rise in potassium in ECF

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70
Q

How much sodium should be in a lithium heparin tube?

A

140 mmol/kg

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71
Q

How much potassium should be in a lithium heparin tube?

A

4 mmol/kg

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72
Q

How are electrolytes measured?

A

Either direct (undiluted sample) or indirect (diluted sample) ion-selective electrodes (ISE)

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73
Q

What can be a problem of a diluted sample when conducting indirect ISE?

A

Can result in false values

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74
Q

What does hypovolaemia (low body water) lead to?

A

Decreased blood pressure

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75
Q

What does hypovolaemia activate?

A

Activates mechanism such as renin angiotensin-aldosterone system (RAA system) to regulate water/electrolytes

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76
Q

What is the overview of the RAA system?

A

• Hypovolaemia detected by kidneys in the Juxtaglomerular apparatus
• Release of Renin converts angiotensinogen -> angiotensin I
• Angiotensin Converting Enzyme converts angiotensin I -> angiotensin II
• Stimulates Adrenal cortex
• Aldosterone release
o Kidneys re-absorb sodium and water
o Blood pressure rises
o Potassium is excreted (to balance the sodium increase)

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77
Q

What is aldosterone?

A

A steroid hormone produced by the Adrenal cortex in response to a drop in blood volume (ECF) and a drop in pressure detected in renal juxtaglomerular

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78
Q

What does aldosterone act on?

A
  • Nuclear mineralocorticoid receptors (MR) within the principal cells of the renal distal tubule activating Na/K pump
  • Action is to decrease urinary sodium excretion (exchanging Na with K)
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79
Q

How does aldosterone affect Conn’s disease?

A
  • Primary hyperaldosteronism

* Low renin, high aldosterone

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80
Q

How does aldosterone affect Addision’s disease?

A
  • Hypoaldosteronism

* Low aldosterone

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81
Q

What is atrial natriuretic peptide (ANP)?

A

A powerful vasodilator

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82
Q

Where is atrial natriuretic peptide (ANP) synthesised and released?

A

The heart

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83
Q

What is the purpose of atrial natriuretic peptide (ANP)?

A
  • To oppose the RAA system

* Inhibits production of aldosterone and renin (reduces Na reabsorption – more in the urine)

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84
Q

What affect does atrial natiuretic peptide (ANP) on the body?

A
  • Reduced blood pressure

* Reduced blood volume

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85
Q

What does aldosterone stimulate?

A

Reabsorption of potassium

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86
Q

What is the dietary intake of potassium per day?

A

Approximately 75-150 mmol/day

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87
Q

Where is potassium secreted?

A
  • Kidney and lesser by the gastrointestinal tract
  • At distal nephron in exchange from sodium using the sodium potassium pump, controlled by aldosterone – triggering the secretion of potassium
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88
Q

What does potassium imbalance refer to?

A

Localisation as well as overall concentration

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89
Q

What is hyponatraemia?

A
  • Low sodium serum

* Both low sodium or high water

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90
Q

What are the symptoms of hyponatraemia?

A
  • Mild confusion
  • Fatigue
  • Muscle cramps
  • Oedema
  • Death
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91
Q

When dealing with electrolytes what must be considered?

A

The hydration status of the patient

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92
Q

What are the three categories of blood volume tests depending upon total body fluid that help diagnose disease?

A
  • Low fluid = hypovolaemia
  • Normal fluid = normovolaemia
  • High fluid = hypervolaemia
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93
Q

If blood sodium is low (hyponatraemia) where should be checked?

A

Urine

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94
Q

What does concentrated urine (polyuria) suggest with regards to sodium?

A

It suggests that the cause is due to osmotic diuretic or may also indicate renal failure

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95
Q

What does dilute urine suggest with regards to sodium?

A

Polydipsia (excess thirst) which can lead to hypovolaemia or diabetes insipidus

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96
Q

If sodium levels in urine are still low after fluid replacement what should be examined for?

A
  • Congestive cardiac failure
  • Liver disease
  • Cushing’s syndrome
  • Conn syndrome
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97
Q

What concentration is classed high urine [Na+]?

A

> 20 mmol/L

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98
Q

What are conditions with high urine [Na+]?

A
  • Acute renal failure (no longer absorbing Na+)
  • Addison’s disease (normal renal function but altered hypothalamus/pituitary/adrenal axis
  • SIADH
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99
Q

How should hyponatraemia be examined?

A
  • Blood sodium
  • ECF volume
  • Urine sodium
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100
Q

What is the cause of hyponatraemia?

A

Due to reduced water in the body rather than increased sodium intake (dehydration) although there can be cases of sodium overdose (in children)

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101
Q

What is an example of disease with hypernatraemia?

A
  • Conn’s syndrome (excess aldosterone = sodium retention)

* Diabetes insipidus (production of high volumes of dilute urine caused by either cranial or nephrogenic)

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102
Q

What are the main causes of diabetes insipidus?

A

• Cranial
o Failure to secrete ADH from pituitary gland
o Congenital, following head injury or tumour
• Nephrogenic
o Kidneys fail to respond to ADH

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103
Q

What are the symptoms of diabetes insipidus?

A
  • Polyuria (excess urine output)
  • Polydipsia (excessive thirst)
  • Don’t always develop hypernatraemia if water intake matches loss
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104
Q

What are the possible ways of artefact measurement of sodium?

A
  • Artefact hyponatraemia – blood taken too close to vein with IV fluid
  • Surgical patients – increased ADH (stress), opiate analgesics, IV fluids
  • Dilutional hyponatraemia – significant water retention
  • Syndrome of inappropriate antidiuretic hormone (SIAD)
  • Sick cell syndrome – possible faulty Na+ pump
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105
Q

What is pseudohyponatraemia caused by?

A
  • Incorrect sampling
  • Occurs due to increased protein or lipid concentration in original plasma leading to an erroneously low sodium concentration if diluted – less water and sodium in initial sample
  • Occurs in diluted ISE with a non-genuine sodium measurement of <135-145mmol/L
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106
Q

When is the general term syndrome of inappropriate antidiuretic hormone (SIADH)

A

• When cause of hyponatraemia is not immediately apparent
o Common in elderly, ADH production continues for no reason
o Water retention with multiple causes – ADH secreting tumours, pulmonary disease, CNS, drug side effects ->SIAD OR high water in ECF -> hyponatraemia

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107
Q

What is the diagnosis of SIADH?

A
  • Lack of disease-causing renal leakage of sodium into urine
  • Low plasma osmolality but still producing ADH
  • Loss of sodium in urine
  • Normal renal function
  • Exclusive thyroid, pituitary, adrenal, renal disease or taking diuretics
  • So called as “inappropriate” levels of ADH in blood for water and electrolyte levels
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108
Q

How is sodium imbalance treated?

A
  • Isotonic fluid replacement (increase salts)
  • Reduced fluid intake to reduce water overload
  • Treat primary cause if more serious underlying problem (liver/kidneys/heart)
  • Diuretics
  • Kidney dialysis
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109
Q

What is hypokalaemia?

A 
•	Low potassium in serum
•	Not just K+ depletion (slow) but also relates to K+ relocalisation (fast)
o	Depleted intake
o	Drugs
o	Loss through gut or kidneys
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110
Q

What is the clinical reference range of hypokalaemia?

A

3.3-4.7 mmol/L

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111
Q

What is the acute shift of K+ into cells in hypokalaemia?

A
  • Insulin in high doses (cardiac arrest patients) induces hypokalaemia
  • Adrenaline
  • Cellular incorporation of potassium
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112
Q

What are the principle causes of hypokalaemia?

A
  • Decreased potassium intake
  • Transcellular potassium movement
  • Increased potassium excretion
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113
Q

What are the clinical features of hypokalaemia?

A
  • Even severe hypokalaemia can be asymptomatic
  • Muscle weakness
  • Depression
  • Constipation
  • Paralytic ileus (blocked intestine due to nerves/muscle NOT actual blockage)
  • Cardiac arrythmias
  • Polydipsia/polyuria
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114
Q

What is the management of hypokalaemia?

A
  • Locate the cause
  • Careful with IV potassium fluid replacement therapy
  • Remember potassium enters ECF prior to ICF
  • ECG monitoring
  • Can induce hyperkalaemia (far worse clinical outcome)
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115
Q

What is hyperkalaemia?

A
  • Potassium excess by increased intake, decreased excretion (renal failure), drugs and spurious
  • Defined as potassium excess and localisation
  • More serious than hypokalaemia
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116
Q

What does hyperkalaemia do to cardiac tissue?

A

Lowers membrane potential in cardiac tissue and shortens cardiac potential

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117
Q

What are the symptoms of hyperkalaemia?

A

Slow ventricular fibrillation or cardiac arrest

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118
Q

What is the clinical reference for significant risk of cardiac arrest with hyperkalaemia?

A

6.5 mmol/L

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119
Q

What is the clinical reference for an emergency of a cardiac arrest with hyperkalaemia?

A

> 7 mmol/L

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120
Q

What is the treatment of hyperkalaemia?

A
  • Calcium gluconate competes with potassium giving some protection
  • Glucose and insulin will initiate potassium uptake into cells
  • If kidney failure – requires kidney treatment strategy
  • ECG monitoring
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121
Q

What is the most advantageous of point of care testing?

A

Shortened turn-around time

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122
Q

How is osmolality measured?

A

By freezing it

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123
Q

Where is ADH released from?

A

Pituitray gland

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124
Q

Where is ADH produced from ?

A

Hypothalamus

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125
Q

What is the impact of exercise training on ADH?

A

Decreases

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126
Q

What is a common poison that makes people drunk, which is often responsible for changes in the osmolar gap?

A

Ethanol

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127
Q

What is a false biochemical change caused by an error in sampling or analysis?

A

Artefact

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128
Q

What is a disorder characterised by reduced body fluid?

A

Dehydration

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129
Q

What is a part of the brain known as the thirst centre containing osmoreceptors?

A

Hypothalamus

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130
Q

What is a hormone released in response to hypertonicity of the extracellular fluid (aka antidiuretic hormon)?

A

Vasopressin

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131
Q

What is the difference in osmotic potential across a membrane?

A

Tonicity

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132
Q

What does arterial blood gases (ABG) enable the measurement of?

A

Measurement of effectiveness of blood exchange of oxygen and carbon dioxide

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133
Q

What is Dalton’s law of partial pressure?

A
  • Dalton’s law states that the total pressure of a mixture of gases is the sum of the partial pressures of its components
  • P total = Pgas1 + Pgas2 + Pgas3
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134
Q

How do gases move in pressure?

A

Gases move from areas of high pressure to areas of low pressure

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135
Q

What is the main waste product from respiration?

A

Carbon dioxide

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136
Q

What does carbon dioxide in the blood relate to?

A
  • Acidity
  • High CO2 = acidity
  • Low CO2 = basic
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137
Q

What is PCO2?

A

Partial pressure of carbon dioxide

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138
Q

What is PaCO2?

A

Partial pressure of carbon dioxide in arterial blood

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139
Q

What can the brainstem detect with its respiratory centre?

A

Acidity

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140
Q

What is the role of the respiratory centre in the brainstem?

A
  • System initiates diaphragm and ribs to increase ventilation
  • Removal of CO2 when detect too acidic environment
  • Once rise in PCO2 is detected the equilibrium shifts to the right favouring bicarbonate buffer
  • HCO3 moves to the central chemoreceptor to the respiratory control centre to increase ventilation
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141
Q

How does increased ventilation affect PaCO2?

A

PaCO2 increased

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142
Q

How does decreased ventilation affect PaCO2?

A

PaCO2 decreased

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143
Q

What is PO2?

A

Partial pressure of oxygen

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144
Q

What is PaO2?

A

Partial pressure of oxygen in arterial blood

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145
Q

What is sO2?

A

Oxygen saturation of Hb

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146
Q

What SaO2?

A

Oxygen saturation of Hb in arterial blood

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147
Q

How can SaO2 be simply measured?

A

Using a finger probe called a pulse oximeter

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148
Q

What is hypoxaemia?

A

Oxygen content in arterial blood is reduced

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149
Q

What does hypoxaemia cause?

A
  • Impaired oxygenation
  • Low Hb (anaemia)
  • Reduced affinity of Hb to O2 (CO poisoning)
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150
Q

What is hypoxia?

A

Tissues receive inadequate supply of O2 to support aerobic respiration

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151
Q

What does hypoxia cause?

A
  • Impaired oxygenation
  • Low Hb (anaemia)
  • Reduced affinity of Hb to O2 (CO poisoning)
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152
Q

What is hypoxia often associated with?

A
  • Lactic acidosis

* Cells resorting to anaerobic respiration

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153
Q

What are the types of respiratory impairments?

A
  • Type 1
  • Type 2 acute
  • Type 2 chronic
  • Hyperventilation
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154
Q

What are the features of type 1 respiratory impairment?

A
  • Defective oxygenation

* Normal ventilation

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155
Q

What are the features of type 2 acute and chronic respiratory impairment?

A

Defective ventilation

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156
Q

What are the gas levels associated with type 1 respiratory impairment?

A
  • Low PaO2

* Normal/low PaCO2

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157
Q

What are the gas levels associated with type 2 acute respiratory impairment?

A
  • Low PaO2

* High PaCO2

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158
Q

What are the gas levels associated with type 2 chronic respiratory impairment?

A
  • Low PaO2
  • High PaCO2
  • High HCO3
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159
Q

What are the gas levels associated with hyperventilation respiratory impairment?

A
  • Normal PaO2

* Low PaCO2

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160
Q

What are the causes of type 1 respiratory impairment?

A
  • Acute asthma
  • Pneumonia
  • Alveolitis
  • COPD
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161
Q

What are the causes of type 2 acute respiratory impairment?

A
  • Inhaled foreign body
  • Benzodiazepine toxicity
  • Exhaustion
  • COPD
  • Neuromuscular disorder
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162
Q

What are the causes of type 2 chronic respiratory impairment?

A

When chronic disease, HCO3 will compensate high PCO2

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163
Q

What are the causes of hyperventilation respiratory impairment?

A
  • Anxiety
  • Fear
  • Pain
  • Acidosis
  • Drug toxicity
  • Central nervous system
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164
Q

What processes is H+ critical for to maintain concentration/function of?

A
  • Mitochondria – oxidative phosphorylation
  • Protein conformation
  • Ionisation of weak acids-bases
  • Enzymatic function
  • Chemical reactions
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165
Q

What is the [H+] of a healthy individual?

A

35-46 nmol/L

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166
Q

What can acid-base disorders lead to?

A

Impaired tissue oxygenation

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167
Q

What is an acid?

A

Produces H+ in solution

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168
Q

What is a base?

A

Compound which combined with H+ in solution

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169
Q

What is a buffer?

A

A weak acid (HA) in solution combined with its conjugate base (A)

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170
Q

What is the acid-base equation of Bronsted and Lowery?

A

HA H+ + A-

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171
Q

What is the equation of the Henderson-Hasselbach equation?

A

pH = pKa + log [base]/[acid] –> pH = pKa + log [A- ]/[HA]

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172
Q

What does pKa indicate about an acid?

A

Strength

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173
Q

What is pKa?

A

A dissociation constant

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174
Q

What can H+ be produced by?

A
  • Metabolic acids

* Respiratory acids

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175
Q

What metabolic acids can H+ be produced by?

A
  • Anaerobic metabolism of glucose to lactate and pyruvate
  • Anaerobic metabolism of fatty acids
  • Oxidation of sulphur containing amino acids (cysteine and methionine)
  • Diets rich in protein often give rise to acidic urine
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176
Q

What respiratory acids can H+ be produced by?

A

Carbon dioxide generated by respiration

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177
Q

What does the bicarbonate buffer equation look like if acidic conditions are promoted?

A

CO2 + H2O –> H2CO3 (carbonic acid) –> HCO3

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178
Q

What promotes acidic conditions in the bicarbonate buffer equation?

A

Increased CO2

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179
Q

What does the bicarbonate buffer equation look like if alkaline conditions are promoted?

A

HCO3 –> H2CO3 (carbonic acid) –> CO2 + H20

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180
Q

What promotes alkaline conditions in the bicarbonate buffer equation?

A

Increased bicarbonate

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181
Q

What are the main mechanisms of acid excretion?

A
  • Bicarbonate (buffer)
  • Ammonia (buffer)
  • Phosphate (buffer)
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182
Q

Where is ammonia generated?

A

NH4+ generated in the renal tubular cells

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183
Q

What pH is favoured for ammonia buffer?

A

7.4

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184
Q

What is the equation of ammonia buffer?

A

NH4 + NH3 + H+ pH = 9.2 + Log [NH3] / [NH4 +]

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185
Q

At which pH does phosphate exist as the mono form (HPO4)2-?

A

7.4

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186
Q

At which pH is phosphate buffer effective at?

A
  • 6.8

* Low concentration in ECF, high in bone and ICF

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187
Q

What is the equation of phosphate buffer?

A

• H2PO4 - HPO4 2- + H+ pH = 6.8 + log [HPO4 2- ] / [H2PO4 -]

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188
Q

What is the reference range for pH in urine?

A

4.8-7.8

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189
Q

What does a blood gas analyser measure?

A
  • pH
  • PCO2
  • HCO3
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190
Q

What must the blood be like to be used as a sample in a blood gas analyser?

A
  • Arterial blood
  • Heparinised (prevents clotting)
  • Free of bubbles (effects PCO2)
  • Chilled (reduces glycolysis/lactate)
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191
Q

What is the reference range of pH in blood gas analysis?

A

7.35-7.45

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192
Q

What is the reference range of [H+] in blood gas analysis?

A

35-45 nmol/L

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193
Q

What is the reference range of PCO2 in blood gas analysis?

A

35-45 mmHg

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194
Q

What is the reference range of PO2 in blood gas analysis?

A

12-14.6 kPa

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195
Q

What is the reference range of serum [HCO3-} in blood gas analysis?

A

24-29 mmol/L

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196
Q

In acid-base disorders, what does an increased PCO2 mean ?

A

Respiratory acidosis

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197
Q

In acid-base disorders, what does a decrese in PCO2 mean?

A

Respiratory alkalosis

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198
Q

In acid-base disorders, what does a decrease in [HCO3] mean?

A

Metabolic acidosis

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199
Q

In acid-base disorders, what does an increase in [HCO3] mean?

A

Metabolic alkalosis

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200
Q

What is the equation for the anion gap?

A

Anion Gap = [Na+] + [K+] – [Cl- ] – [HCO3 - ] = 10-18mmol/L

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201
Q

What happens to the anion gap if there is an increase in H+?

A
  • We see a decrease in [HCO3-]

* Anion gap increases

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202
Q

What other “unmeasured” anions are present in the solution making it electroneutral in the anion gap?

A
  • Lactate anion (lactate acidosis)

* Acetoacetate and hydroxybutyrate (Diabetic ketoacidosis)

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203
Q

What may simple electrolyte tests indicate?

A

Metabolic acidosis

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204
Q

What is acid-base compensation?

A

Physiological mechanisms which try to return disordered [H+] (hence pH) back to normal

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205
Q

What type of acid-base compensation is there?

A
  • Plasma buffer compensation
  • Renal compensation
  • Respiratory compensation
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206
Q

How fast is plasma buffer compensation?

A

Immediate response

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207
Q

How fast is renal compensation?

A

Slow response (12-24 hrs)

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208
Q

How fast is respiratory compensation?

A

Quick response (minutes)

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209
Q

What does renal compensation compensate?

A

Impaired lung function

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210
Q

What does respiratory compensation compensate?

A

Metabolic disorders

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211
Q

What is the difference between acute and chronic disorders with regards to how they effect HCO3?

A
  • Acute disorders do not have time to effect HCO3

* Chronic disorders do have time to effect HCO3

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212
Q

What is the pH level in metabolic acidosis?

A

Low (acidic)

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213
Q

What is the pH level in metabolic alkalosis?

A

High (basic)

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214
Q

What is the pH level in respiratory acidosis?

A

Low (acidic)

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215
Q

What is the pH level in respiratory alkalosis?

A

High (basic)

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216
Q

What is the primary change in metabolic acidosis?

A

Decreased HCO3 (acidic)

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217
Q

What is the primary change in metabolic alkalosis?

A

Increased HCO3 (basic)

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218
Q

What is the primary change in respiratory acidosis?

A

Increased PCO2 (acidic)

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219
Q

What is the primary change in respiratory alkalosis?

A

Decreased PCO2 (basic)

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220
Q

What is the compensation in metabolic acidosis?

A

Decreased PCO2 (basic)

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221
Q

What is the compensation in metabolic alkalosis?

A

Increased PCO2 (acidic)

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222
Q

What is the compensation in respiratory acidosis?

A

Increased HCO3 (basic)

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223
Q

What is the compensation in respiratory alkalosis?

A

Decreased HCO3 (acidic)

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224
Q

What are some clinical causes of respiratory acidosis?

A
  • Lung disease, COAD (hypoventilation) = increased [PCO2]
  • Neuromuscular disease e.g. polio, Guillian Barre = chronic breathing problems
  • Drugs = decrease lungs ability to eliminate CO2
  • H+ retained and K+ secreted at kidneys so can present as hypokalaemia
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225
Q

What are some features of the compensation mechanism for respiratory acidosis?

A
  • Buffered by carbonic acid system initially
  • Hyperventilation (main compensation) – decreased [PCO2] but lung function typically impaired
  • Renal system will increase recycling/reclamation of HCO3-
  • Critically requires functioning renal system, urinary system (to accept H+) and no renal tubular acidosis
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226
Q

What are the symptoms of mild to moderate respiratory acidosis?

A
  • Cardiovascular effects, arrhythmia, warm skin, sweating

* CNS depression

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227
Q

What are the symptoms of severe respiratory acidosis?

A
  • Seizures

* Coma

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228
Q

What is the treatment of respiratory acidosis?

A
  • Determine underlying cause

* Correct ventilation

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229
Q

What can be used to determine the underlying cause of respiratory acidosis?

A
  • Sodium, potassium, urea, albumin, calcium and creatinine

* Hydration, electrolytes, calcium levels, kidneys

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230
Q

What can be used to correct ventilation for patients with respiratory acidosis?

A
  • Drug therapy

* Medical oxygen

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231
Q

What are some clinical causes of metabolic acidosis?

A
  • Renal disease – [H+] retained
  • Chronic diarrhoea/intestinal fistula – fluid loss [HCO3-]
  • Renal tubular acidosis – tubular cells cannot excrete [H+] but are losing [HCO3-]
  • Overdose/poisoning – acid metabolites product – e.g. salicylate poisoning
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232
Q

What are some features of the compensation mechanism for metabolic acidosis?

A
  • Buffered by carbonic acid system initially
  • Hyperventilation (main compensation): reduces pCO2, which reduces [H+]
  • Renal system will slowly increase [HCO3-] to bind H+ and push equilibrium to the left
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233
Q

What are some common causes of metabolic acidosis?

A
  • Lactic acidosis (most common)

* Diabetic ketoacidosis

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234
Q

What are some features of lactic acidosis causing metabolic acidosis?

A
  • Low HCO3 and high lactic acid due to low O2 delivered to tissues
  • Leads to anaerobic respiration
  • Blood supply, cardiac, shock/blood pressure
  • Serum lactate is significant predictor of death
  • Can be life threatening
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235
Q

What are some features of diabetic ketoacidosis causing metabolic acidosis?

A
  • Caused by insulin deficiency, no glucose metabolism -> metabolism of fats
  • Fat metabolism generates ketones (organic acids) -> acidosis
  • Diagnosis = high plasma glucose, ketones, anion gap
  • Can be life threatening
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236
Q

What are the symptoms of mild to moderate metabolic acidosis?

A
  • H+ secreted not K+ at kidneys so presented as acidosis and hyperkalaemia
  • May result in release of catacholamines, neuromuscular irritability, arrythmia and tachycardia
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237
Q

What are the symptoms of severe metabolic acidosis?

A
  • Decreased blood pressure, loss of consciousness, coma

* Movement of potassium from ICF to ECF – cardiac arrest (acute hyperkalaemia)

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238
Q

What treatment is given for a patient with metabolic acidosis?

A
  • Determine underlying cause

* I.V. sodium bicarbonate – in life threatening cases

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239
Q

What can be used to determine the underlying cause of metabolic acidosis?

A
  • Blood glucose (diabetes)
  • Blood lactate (acidosis)
  • Urea and creatinine (renal failure)
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240
Q

What are some clinical causes of respiratory alkalosis?

A
  • Hyperventilation, anxiety
  • Pain, sepsis, stroke, meningitis, pulmonary embolism
  • Excess mechanical ventilation
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241
Q

What are features of the compensation mechanism against respiratory alkalosis?

A
  • Buffered by carbonic acid system initially
  • Renal system will decrease ammonia – formation and decrease H+/sodium exchange
  • Decreased reabsorption of HCO3-
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242
Q

What are the symptoms of respiratory alkalosis?

A
  • May cause cardiovascular and neurological symptoms
  • Blood vessels in the brain may constrict
  • Dizziness, confusion, loss of consciousness
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243
Q

What is the treatment for respiratory alkalosis?

A
  • Determine underlying cause

* Correct ventilation

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244
Q

What can be used to determine the underlying cause of respiratory alkalosis?

A

Potassium measurements may indicate hyperkalaemia

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245
Q

What can be used to correct ventilation in a patient with respiratory alkalosis?

A

Rebreathing (paper bag)

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246
Q

What is metabolic alkalosis?

A
  • Increased plasma pH due to loss of H+ or gain of HCO3

* Net result

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247
Q

What are some features of the compensation mechanism of metabolic alkalosis?

A
  • Buffered by carbonic system initially
  • Hypoventilation (main compensation) – increases pCO2, which decreases [HCO3-] (consider lung disease)
  • Renal system will decrease recycling/reclamation of HCO3-
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248
Q

What are some clinical causes of metabolic alkalosis?

A
  • Loss of [H+] in gastric fluid – pyloric stenosis prevents HCO3- rich secretions from duodenum
  • Ingestion of alkali sources – very unlikely cause unless coupled with renal impairment
  • Potassium deficiency – e.g. diuretic therapy
  • Primary adrenal adenoma – excess production of aldosterone
  • Glucocorticoid excess
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249
Q

What are the symptoms of mild to moderate metabolic alkalosis?

A
  • Non-specific symptoms

* Cramps, hypokalaemia -> muscle weakness, confusion, hypovolaemia

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250
Q

What are the symptoms of severe metabolic alkalosis?

A

Severe hypokalaemia, hypocalcaemia, confusion, coma

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251
Q

What treatment is given to a patient with metabolic alkalosis?

A
  • Determine underlying cause
  • Correction of any volume depletion
  • Potassium and chloride depletion management
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252
Q

What is used to determine the underlying cause of metabolic alkalosis?

A
  • Sodium, potassium, urea, albumin, calcium and creatinine

* Hydration, electrolytes, calcium levels, kidneys

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253
Q

What type of cation is calcium?

A

Divalent cation

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254
Q

What percentage of the earth’s crust is calcium?

A

3%

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255
Q

In the body, what is the most abundant fixed form of calcium?

A

• Hydroxyapatite (Ca10(PO4)6(OH)2)

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256
Q

Where is hydroxyapatite most present in the body?

A
  • Bones
  • Teeth
  • Little in the cytoplasm of cells
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257
Q

How much of the body’s calcium is in the bones?

A

Approximately 98%

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258
Q

What other molecules does calcium bind to?

A
  • Albumin

* Globulin

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259
Q

What free form of calcium is in the body?

A
  • Ca++

* Physiologically active found in miniscule portion circulating

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260
Q

What is the dietary intake of calcium per day?

A

25 mmol/day or 10mg/100mL

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261
Q

Where is calcium distributed?

A
  • Bone from the ECF
  • Kidney from plasma
  • GIT from ECF
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262
Q

How is calcium excreted?

A
  • Faeces

* Renal loss

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263
Q

How much calcium is excreted in faeces per day?

A

20 mmol/day

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264
Q

How much calcium is excreted through renal loss per day?

A

5 mmol/day

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265
Q

What is classed as ultra-filterable calcium which is 53% of plasma calcium distribution?

A
  • Complexed calcium (0.13-0.16 mmol/L)

* Ionised calcium (free) (1.03-1.22 mmol/L)

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266
Q

What is classed as protein-bound calcium which is 47% of plasma calcium distribution?

A
  • Albumin bound calcium (0.81 – 0.96 mmol/L)

* Globulin bound calcium (0.22 – 0.26 mmol/L)

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267
Q

How does protein bound calcium affect pH?

A

Protein binding decreases as pH decreases resulting in acidosis

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268
Q

In acidosis, how is calcium effected?

A
  • Decreased calcium binding to protein, increased ionised fraction
  • As pH decreases, [Ca] increases – less calcium is bound to proteins
  • More H+ binds to albumin, displacing calcium, therefore increases ionised Ca
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269
Q

In alkalosis, how is calcium affected?

A
  • Increased calcium binding to protein, decreased ionised fraction
  • As pH increases, [Ca] decreases – more calcium is bound to proteins
  • There are more binding sites available for Ca reducing the ionised calcium
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270
Q

What is the amount that ionised calcium increases by when pH decreases by 0.1?

A

0.05 mmol/L

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271
Q

Does [H+] of acidosis or alkalosis affect the total calcium within the body?

A

No

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272
Q

What do osteoclasts do?

A

Dissolve (resorb) bone material (releasing calcium)

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273
Q

What do osteoblasts do?

A

Reform bone (requires calcium)

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274
Q

What do osteocytes do?

A

Help maintain bone (requires calcium)

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275
Q

What cells cover the surface of the bone?

A

Lining cells

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276
Q

How is calcium regulated?

A

By 3 molecules

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277
Q

What are the molecules controlling calcium regulation?

A
  • Parathyroid hormone (PTH)
  • Vitamin D (calcitriol or 1,25-dihydroxycholeciferol)
  • Calcitonin
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278
Q

What are the principle organs involved with regulation of calcium?

A
  • Gut
  • Kidney
  • Bone
  • Skin, liver and parathyroid glands
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279
Q

How does PTH affect calcium and phosphate?

A
  • Increased calcium

* Decreased phosphate

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280
Q

How does vitamin D affect calcium and phosphate?

A
  • Increased calcium

* Increased phosphate

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281
Q

How does calcitonin affect calcium and phosphate?

A
  • Decreased calcium

* Decreased phosphate

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282
Q

What cells secrete PTH?

A

Chief cells of the parathyroid gland

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283
Q

Where is the parathyroid gland located?

A

4 tiny glands located posteriorly on the thyroid at the back of the neck

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284
Q

When is PTH secreted?

A

In response to decreasing ionised calcium

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285
Q

What does PTH do?

A
  • Causes increased osteoblast maturation and thus increased bone turnover
  • Acts on PTH receptors of target cells of bone and kidney
  • Activate vitamin D to increase calcium absorption
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286
Q

What is the flow order of PTH?

A
  • Low plasma calcium
  • Parathyroid glands
  • Increased PTH to bone and kidney
  • Kidney
  • Increased calcitriol to small intestine (increased absorption of dietary Ca and PO4) and bone (Ca released)
  • Increased plasma calcium
  • Parathyroid
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287
Q

What is PTH?

A

Peptide hormone with activity in the N-terminus

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288
Q

What effect does PTH have on bone?

A
  • Increased reabsorption of Ca

* Osteoclast activity

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289
Q

What effect does PTH have on the renal system?

A
  • Decreased reabsorption of urinary PO4

* Decreased reabsorption of urinary HCO3-

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290
Q

What effect does PTH have on the GIT?

A
  • Increased reabsorption of dietary PO4

* Increased reabsorption of dietary Ca

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291
Q

What does vitamin D do in the intestine?

A
  • Stimulates calbindin-D

* Binds calcium and promotes absorption along with PO4

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292
Q

What does vitamin D do in the bone?

A
  • Mineralisation and reabsorption
  • Increased availability of Ca and PO4
  • Promotes osteoblast activity – osteoclasts do not have a vitamin D receptor
  • Longer term (days) enhance maturation of osteoclasts – osteoblasts release paracrine hormone stimulating osteoclast activity
  • Inhibits calcitonin release
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293
Q

What does vitamin D do in the kidneys?

A

Renal tubular calcium reabsorption

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294
Q

What is the flow order of active vitamin D in calcium regulation?

A
  • Sunlight (UV) to skin
  • 7-dehydrocholestrol (provitamin D)
  • Pre-vitamin D3
  • Cholecalciferol (vitamin D3
  • Liver
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295
Q

What is calcitonin secreted by?

A

Parafollicular or C cells of the thyroid

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296
Q

What is the effect of calcitonin?

A
  • Opposing actions to PTH
  • Reduces Ca reabsorption
  • Reduces renal calcium (and PO4) reabsorption and increases renal excretion
  • Reduces bone reabsorption (supress osteoclast activity)
  • Not clinically relevant other than as a tumour marker
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297
Q

What disease is calcitonin used as a tumour marker for?

A

Medullary thyroid carcinoma (MTC)

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298
Q

How can calcium be measured?

A
  • Spectrophotometry using calcium bound to NMBAPTA shining UV light to get a spectral shift depending on the amount of calcium
  • EDTA is not used as much as it is not specific to calcium
  • Laboratory testing with calcium bund to albumin calculating corrected calcium (<15g/L)
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299
Q

Which sample tubes are used for measuring calcium?

A
  • Lithium heparin (green)
  • Plain serum (red)
  • Serum separator (yellow)
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300
Q

Which sample tubes are not used for measuring calcium and why?

A
  • Sodium citrate (blue) – prevents clotting by binding Ca
  • EDTA (pink) or potassium EDTA (purple) – binds calcium to potassium
  • Fluoride oxalate (grey) – prevents clotting by precipitating Ca and is used more for blood glucose analysis
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301
Q

What type of sample is used to measure calcium?

A
  • Venous
  • Ionised calcium + protein bound + anion bound
  • 2.1-2.6 mmol/L
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302
Q

What occurs to calcium when albumin is low?

A
  • Protein bound calcium will be low

* Ionised calcium is unaffected and remains unchanged

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303
Q

What is the reference range for albumin adjusted in measuring calcium?

A

34-50 g/L

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304
Q

What is the calculation for corrected [Ca] in mmol/L when albumin is <40g/L?

A

Measured total [Ca] (mmol/L) + 0.02 x (40 – serum albumin (g/L))

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305
Q

What is the calculation for corrected [Ca] in mmol/L when albumin is >45g/L?

A

Measured total [Ca] (mmol/L) – 0.02x (serum albumin (g/L) -45)

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306
Q

What are the features of ABG calcium?

A
  • Measures the ionised fraction only
  • Is under very close homeostatic control
  • Measured with precise ion selective electrode
  • Gives an accurate measurement of calcium homeostasis
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307
Q

What is a disadvantage of only measuring the ionised fraction in ABG calcium?

A
  • Labour intensive process

* Can’t be done in a high throughput manner

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308
Q

When is ABG calcium recommended?

A
  • TPN – total parenteral nutrition
  • Acidosis
  • ICU patients
  • End stage renal failure
  • Some cases of hyperparathyroidism
  • Citrated blood products
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309
Q

What sample is used for measuring PTH?

A

Plasma EDTA sample - increased stability

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310
Q

How is PTH measured?

A
  • Analysed immediately/frozen for storage due to instability of the molecule
  • Immunoassay-photometric detection of free electron post formation of an immune complex
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311
Q

What is the reference range of PTH?

A

1.1-5.5 pmol/L

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312
Q

What sample is used for measuring calcitriol?

A

SST (gel separator tube) or tube without preservative

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313
Q

What method is used to measure PTH?

A
  • Immunoassay-photometric detection of free electron post formation of an immune complex
  • Stable molecule – long ½ life
  • Doesn’t need to be frozen
  • UPLC-MS/MS (low throughput laboratories)
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314
Q

What is the reference range of calcitriol?

A

48-145 nmol/L

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315
Q

What are some features of hypercalcaemia?

A

• High albumin adjusted (>2/6 mmol/L) or ionised calcium (>1.23 mmol/L)
• Occurs when rate of entry of calcium to ECF > capacity of kidney to excrete it
o Increased absorption from GIT
o Increased bone loss
o Decreased renal excretion

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316
Q

What are the most common causes of hypercalcaemia?

A
  • Primary hyperparathyroidism – sporadic, familial, PTH mediated
  • Malignant disease – disrupts calcium homeostasis – PTHrP, skeletal metastasis, haematological malignancy
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317
Q

What are some less common causes of hypercalcaemia?

A
  • Granulomatous disease – sarcoidosis, TB, histoplasmosis, berrylliosis, leprosy
  • Vitamin D toxicity
  • Persistent hyperparathyroidism after renal transplant – PTH mediated
  • Severe thyrotoxicosis
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318
Q

What systems are affected by hypercalcaemia?

A
  • CNS
  • Gastrointestinal tract
  • Cardiovascular
  • Renal
  • Muscles and bones
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319
Q

What symptoms of hypercalcaemia are due to the CNS?

A
  • Lethargy
  • Depression
  • Confusion
  • Coma
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320
Q

What symptoms of hypercalcaemia are due to the GIT?

A
  • Anorexia
  • Nausea
  • Vomiting
  • Abdominal pain
  • Constipation
  • Pancreatitis
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321
Q

What symptoms of hypercalcaemia effect the cardiovascular system?

A
  • Hypertension
  • ECG changes (reduced QT, prolonged PR)
  • Arrhythmias (severe hypercalcaemia)
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322
Q

What symptoms of hypercalcaemia effect the renal system?

A
  • Polyuria
  • Polydipsia
  • Volume depletion
  • Reduced GFR
  • Calculi
  • Nephrocalcinosis
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323
Q

What symptoms of hypercalcaemia effect muscles and bones?

A
  • Bone pain
  • Fractures
  • Hypotonia
  • Hyporeflexia
  • Muscle weakness
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324
Q

What are some rare causes of hypercalcaemia?

A
  • Thiazides
  • Lithium
  • Anti-oestrogens/Tamoxifen
  • Vitamin A toxicity
  • Immobilization
  • Acute renal failure-diuretic phase
  • Islet cell tumours/phaeochromocytoma
  • Addison’s disease
  • Milk-alkali syndrome
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325
Q

What are some features of primary hyperparathyroidism?

A
  • Most common cause of hypercalcaemia
  • More common in women
  • Parathyroid carcinoma very rare (<1%)
  • Often symptom free – increased prevalence of osteoporosis and 15% have renal complication (stones)
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326
Q

What is the laboratory investigation of calcium disorders?

A 
•	Plasma
o	Calcium
o	Albumin
o	Creatinine
o	Phosphate
o	ALP
o	PTH
o	GGT
o	Vitamin D
•	Urine 
o	Calcium
o	Phosphate
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327
Q

Hypercalcaemia usually means hypercalciuria except in which condition?

A
  • Familial benign hypocalciuric hypercalcaemia (FBHH)

* Sometimes known as just FHH

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328
Q

What is the reference range of having FHH?

A

<0.01

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329
Q

If the Ca:Cr ratio is >0.03, what condition does the patient have?

A

Primary hyperthyroidism

330
Q

If the Ca:Cr ratio is <0.01, what condition does the patient have?

A

Familial hypocaliuric hypercalcaemia

331
Q

What treatment is required in a patient with FBHH?

A

No treatment required

332
Q

How is hypercalcaemia treated?

A
  • If severe (>3mmol/L) would have to treat each separately
  • Mild to moderate (up to 2.8-3 mmol/L) needs no treatment if asymptomatic
  • Mild to moderate with symptoms would have a low calcium diet – avoid thiazide diuretics, lithium and volume depletion
333
Q

In acute hypercalcaemia what can be used as treatment?

A
  • Rehydration – normal saline/5% dex will reduce Ca within 24-48 hrs
  • Biphosphates – if it is due to increased bone reabsorption (may take 1 week to respond)
  • Calcitonin for severe refractory hypercalcaemia
  • Dialysis – last resort
334
Q

In chronic hypercalcaemia what can be used as treatment?

A
  • Identify and treat underlying cause

* Cinacalcet – lowers PTH secretion and therefore lowers [Ca]

335
Q

What are some features of hypocalcaemia?

A
  • Less common
  • Important to assess albumin – ionised Ca required in patients with very low albumin
  • Common causes relate to secretion and/or action of PTH and vitamin D
  • Increased excitability of neuromuscular tissue
  • Chronic hypocalcaemia has calcification of basal ganglia
336
Q

What occurs with hypocalcaemia and excited neuromuscular tisse?

A
  • Tetany or carpopedal spasm or paraesthesia (perioral and fingers)
  • Laryngeal stridor and seizures
  • Prolonged QT and ST intervals
  • Arrhythmias, heart block and congestive heart failure
337
Q

What occurs in calcification of basal ganglia in chronic hypocalcaemia?

A
  • Psychiatric (depression, memory loss, anxiety and hallucinations
  • Cataracts may occur
338
Q

What are the main causes of hypocalcaemia?

A 
•	Hypoparathyroidism
o	Post-surgery
o	Hypomagnesaemia
o	Malignancy 
•	Abnormal vitamin D metabolism
o	Deficiency
o	Deficiency 1α-hydroxylation (RIMP)
•	Acute pancreatitis 
•	Hyperphosphataemia – PO4 administration
•	Acute rhabdomyolysis
•	Abrupt inhibition of bone reabsorption – hungry bones
339
Q

What are some other less common causes of hypocalcaemia?

A
  • Parathyroid hormone resistance
  • Sepsis
  • Osteoblast metastasis
  • Vitamin D resistance
  • Pseudohypoparathyroidism
340
Q

What is investigated in hypocalcaemia?

A
  • Serum calcium
  • Albumin
  • PTH
  • Urea and creatinine
  • Magnesium
  • Vitamin D
  • Phosphate
341
Q

How can false results be generated in the laboratory when measuring hypocalcaemia?

A
  • EDTA contamination – decrease/undetectable Ca, increased K+ (decrease Mg, decreased Zn, decreased ALP)
  • Improper blood taking/contamination
342
Q

What is the flow order of diagnosis in suspected hypocalcaemia?

A
  • Suspected hypocalcaemia
  • Determine corrected calcium (<2.2 mmol/L)
  • Assess renal function (if evidence of renal function stop)
  • No renal disease
  • Measure the PTH
  • If low PTH or undetectable can be post-surgery, magnesium deficiency or idiopathic
  • If high PTH then either vitamin D deficiency, pseudohypoparathyroidism or rare cause of hypocalcaemia
343
Q

What must be considered with suspected hypocalcaemia?

A
  • Consider ionised calcium (check albumin)
  • Check creatinine
  • Serum Mg
  • Phosphate – low in vitamin D, raised in cell lysis and pseudohypoparathyroidism
  • Vitamin D
344
Q

What is the treatment of hypocalcaemia?

A
  • Depends on symptoms and cause
  • Give calcium if necessary IV – 10-20ml 10% gluconate over 5 mins – continuous infusion of 9-19 mmol Ca in 2L over 24 hrs
  • Vitamin D deficiency – give vitamin D-25(OH)D not 1(OH)D unless required
345
Q

What type of anion is phosphate?

A

Trivalent anion

346
Q

What percentage of the earth’s crust is phosphate?

A

0.1%

347
Q

How much phosphate is in a 70kg adult?

A

23 mol

348
Q

How much of the body’s phosphate is in skeleton and teeth?

A

85%

349
Q

How much of the body’s phosphate is within cells and soft tissues?

A

14%

350
Q

How much of the body’s phosphate is within the ECF?

A

1%

351
Q

How is phosphate present within the body?

A
  • Organic (phosphoproteins and phospholipids)

* Inorganic (phosphate)

352
Q

How much of phosphate is non-covalently bound to proteins?

A

15-20%

353
Q

What are the roles of phosphate?

A
  • Phospholipids, nucleic acids, enzyme cofactors etc
  • Cellular energy source (ATP, ADP, creatinine phosphate and diphosphoglycerate, electron transport chain)
  • Second messenger systems (cAMP, IP3)
  • 2,3-diphosphoglycerate – oxygen dissociation from OxHb
  • Buffer of H+ and therefore important in acid-base balance
354
Q

What does severe hypophosphataemia do to intracellular (PO4)3-?

A

Deplete

355
Q

What regulates (PO4)3-?

A
  • PTH
  • Calcitriol
  • Fibroblast growth factor (FGF-23)
356
Q

What does PTH do to regulate phosphate?

A

Increases renal excretion

357
Q

What does calcitriol do to regulate phosphate?

A

Increased absorption from GIT

358
Q

What does FGF-23 do to regulate phosphate?

A

Decreases phosphate reabsorption

359
Q

What is the reference range of plasma phosphate?

A
  • 0.8-1.4 mmol/L

* Higher in infancy and childhood

360
Q

How is phosphate regulated in acid-base balance?

A
  • Acidaemia increases [PTH] – PTH stimulate kidneys to excrete more phosphate from the urine and increases absorption of phosphate from the GIT
  • Acidaemia reduces [Calcitriol] – proximal tubule cells reduce 1α-hydroxylase
361
Q

What are the main causes of hyperphosphataemia?

A
  • Pseudohyperphosphataemia
  • Increased phosphate input
  • Reduced renal excretion
  • Cellular shifts
362
Q

What are the consequences of hyperphosphataemia?

A
  • No specific symptoms but can cause hypocalcaemia (tetany)
  • Complexes with calcium and calcification in soft tissue (blood vessels, skin, heart, lungs, kidneys, conjunctivae and joints) – renal failure
363
Q

What is renal failure as a consequence of hyperphosphataemia treated with?

A

Parathyroidectomy

364
Q

What is the flow order of diagnosis in suspected hyperphosphataemia?

A
  • Laboratory artefact – if yes repeat analysis, if no carry on
  • Increased phosphate intake – if yes phosphate elimination, if no carry on
  • Renal failure – if yes treat renal disease, if no carry on
  • Phosphate moving from ICF to ECF – if yes treat cause, if no carry on
  • Hypoparathyroidism or acromegaly – if yes treat cause, if no rare causes of hyperphosphataemia
365
Q

What investigations need to be conducted when diagnosing hyperphosphataemia?

A
  • PTH
  • Calcium
  • Vitamin D
  • Creatinine
  • CK
  • Urinary phosphate and TmP/GFR
366
Q

What is the therapeutic approach in hyperphosphataemia?

A
  • Medication rarely required if cause is due to altered renal handling
  • Important in RIMP – avoid calcification and hyperparathyroidism
  • Phosphate binding salts, reduce absorption
  • Prevention – saline diuresis prior to chemo (TLS)
367
Q

What are some binding salts with phosphate in hyperphosphataemia?

A
  • Ca
  • Mg
  • Aluminium (issues -toxic)
  • Lanthanum carbonate
  • Sevelamer alternatives
368
Q

What are the causes of hypophosphataemia?

A
  • Decreased absorption
  • Increased renal loss
  • Cellular shifts
  • Alcoholism
  • Liver failure
369
Q

What causes of hypophosphataemia is due to decreased absorption?

A
  • Starvation
  • Parenteral
  • Vitamin D deficiency
  • Phosphate binders
370
Q

What causes of hypophosphataemia is due to increased renal loss?

A
  • Diuretics
  • Hyperparathyroidism (primary and secondary)
  • Renal tubular defects (e.g. Fanconi)
371
Q

What causes of hypophosphataemia is due to cellular shifts?

A
  • Rx of DKA
  • Alkalosis
  • Long distance running
  • Small amount of PO4 in ECF therefore small shift = large change in serum (PO4)3-
372
Q

What is an example of cellular shifts of (PO4)3-?

A
  • Re-feeding

* Respiratory alkalosis

373
Q

What is re-feeding a response to?

A

Starvation

374
Q

What are the risks of re-feeding?

A
  • DKA

* Parenteral nutrition

375
Q

What are the potential consequences of re-feeding?

A
  • Organ failure
  • Cardiac arrest
  • Respiratory arrest
376
Q

How is respiratory alkalosis involved in cellular shifts of (PO4)3-?

A
  • Stimulus to hyperventilate
  • Decrease in blood [CO2]
  • Decreased intracellular [H+]
  • Increased phosphofructokinase (drives glycolysis) activity = increased phosphorylation of glucose
377
Q

What might respiratory alkalosis occur, with cellular shifts of (PO4)3-?

A
  • Liver failure
  • Burns
  • Salicylate poisoning
  • Alcoholic ketoacidosis
  • Alcohol withdrawal
  • Sepsis
378
Q

What are the consequences of decreased (PO4)3-?

A

• Mild 0.35-0.8 mmol/L
o Not harmful in short term
o Chronic = osteomalacia/rickets
• Severe <0.35 mmol/L
o Acute phosphate deficiency – citically ill, decreased metal function, tremor and irritability
o Attempt to predict (PO4)3- deficiency and be alert

379
Q

What is acute phosphate deficiency with tremor and irritability often confused with?

A

Alcoholism

380
Q

What is acute phosphate deficiency with decreased mental function often confused with?

A

Liver disease

381
Q

What systems are affected by acute phosphate deficiency syndrome?

A
  • Haematopoeitic
  • Straited muscle
  • Nervous system
  • GIT
382
Q

How is the haematopoetic system affected by acute phosphate deficiency syndrome?

A
  • Tissue hypoxia
  • Haemolysis
  • Decreased resistance to infection
  • Decreased platelet survival and abnormal clotting
383
Q

How is the striated muscle system affected by acute phosphate deficiency syndrome?

A
  • Respiratory failure
  • Decreased stroke work (Heart Failure)
  • Stiffness
  • Weakness
  • Debility
  • Muscle pain, weakness
384
Q

How is the nervous system affected by acute phosphate deficiency syndrome?

A
  • Lethargy
  • Confusion
  • Irritability
  • Tremor
  • Seizure
  • Coma
  • Parasthesia – peripheral nerves (decreased conduction velocity)
385
Q

How is the GIT affected by acute phosphate deficiency syndrome?

A

Gastric stasis - smooth muscle

386
Q

What is the flow order of diagnosis for suspected hypophosphataemia?

A
  • Medication causing hypophosphataemia – if yes change medication, if no continue
  • Phosphate moving from ECF to ICF – if yes treat cause, if no continue
  • Investigate urinary phosphate excretion – if high excessive renal loss, if low or normal inadequate phosphate intake
387
Q

What is the laboratory investigation of suspected hypophosphataemia?

A
  • Clinical Hx more important
  • Assessment of blood gas/respiration
  • Chronic hypophosphataemia – determination of renal phosphate handling/wasting – FGF-23
388
Q

What is the treatment for hyperphosphataemia?

A

• Mild to moderate – usually transient and no treatment is required
• Replace
o Orally - Na or K-hydrogen phosphate
o IV – K-phosphate, 50-100mmol/L kg in ½ N saline over 12 hrs – repeat as required while monitoring K, Ca and (PO4)3- - stop when PO4 >0.35 mmol/L and replace orally

389
Q

What type of cation is magnesium?

A

Divalent cation

390
Q

What percentage of the earth’s crust id magnesium?

A

2.4%

391
Q

What are the features of magnesium metabolism?

A
  • Majority within the bone
  • 2nd most abundant intracellular cation
  • Important co-factor for enzymes, control of ion channels, protein and nucleic acid synthesis and oxidative phosphorylation
  • Is essential in all enzyme reactions using ATP
392
Q

How much magnesium is present within the plasma?

A

0.5-1%

393
Q

What are the features of magnesium distribution?

A
  • Magnesium in food: green vegetables (principle ion in chlorophyll)
  • Absorbed by both active and passive mechanisms, large bowel can absorb magnesium
  • Magnesium deficiency increases absorption by the GIT
  • Intake=output (bowel and kidney)
394
Q

What is the dietary intake of magnesium per day?

A

15 mmol/day

395
Q

How much magnesium is in ECF?

A

15 mmol

396
Q

How much magnesium is in bone?

A

750 mmol

397
Q

How much is excreted?

A
  • 10 mmol/day in faeces

* 5-10 mmol/day in renal loss

398
Q

How much plasma magnesium is filtered by the kidneys?

A

75%

399
Q

Where in the kidneys is plasma magnesium filtered?

A
  • Approximately 20% in proximal tubules (paracellular)
  • Approximately 65% in cortical thick ascending limb of the loop of Henle (passive)
  • Approximately 5-10% in the distal convoluted tubule (active)
  • No significant reabsorption in the collecting duct
400
Q

What are the features of regulation of magnesium?

A
  • Filtered by the kidneys
  • Magnesium reabsorption is saturable
  • Reabsorption requires sodium to drive it (Na/K-ATPase pumps)
  • In magnesium deprivation – 24hr UMg can be <1 mmol
  • Increased renal Mg loss – osmotic diuretics, thiazides and loop diuretics
401
Q

What is the relation between PTH and magnesium?

A
  • Magnesium has calcium-like effects on PTH secretion (1/3 potency)
  • Increased Mg inhibits PTH
  • Deceased Mg stimulates PTH (PTH increases rate of reabsorption of Mg)
  • However profound decreased [Mg] inhibits PTH secretion and action
402
Q

What are the causes of hypermagnesaemia?

A
  • Increased intake (rare unless CRF)
  • Cellular release
  • Decreased excretion
403
Q

What are causes of increased intake of magnesium?

A
  • Oral
  • Parenteral
  • Antacids
  • Laxatives
  • Bladder irrigation
  • Dialysis
404
Q

What are causes of cellular release of magnesium?

A
  • Cell necrosis
  • DKA
  • Hypoxia
405
Q

What are causes of decreased excretion?

A
  • Renal failure
  • Mineralocorticoid deficiency
  • Hypothyroidism
  • FHH
406
Q

What is the treatment for mild hypermagnesaemia?

A
  • 1.5-2.5 mmol/L

* Asymptomatic but can decrease blood pressure

407
Q

What is the treatment for moderate hypermagnesaemia?

A
  • 2.5-5.0 mmol/L
  • Absent reflexes
  • ECG changes (prolonged PR, QRS and peaked T waves
408
Q

What is the treatment for severe hypermagnesaemia?

A
  • > 5 mmol/L
  • Respiratory paralysis and cardiac arrest
  • Mg >8 mmol/L = almost always fatal – inhibition of acetylcholine release
409
Q

What is the flow order of diagnosis for suspected hypermagnesaemia?

A
  • Medication causing hypermagnesaemia – if yes change medication, if no continue
  • Renal failure – if yes treat renal disease, if no continue
  • Hypothyroidism – if yes treat hypothyroidism, if no continue
  • Addison’s disease – if yes treat Addison’s disease, if no possibly hypocaloric hypercalcaemia
410
Q

What are the causes of hypomagnesaemia?

A
  • Inadequate intake/absorption
  • Malabsorption
  • Renal tubular dysfunction
  • Intracellular shift
411
Q

What are the causes of inadequate intake/absorption in hypomagnesaemia?

A
  • Alcoholism
  • Protein calorie malnutrition
  • Prolonged infusion or ingestion of low Mg solution or diet
412
Q

What are the causes of malabsorption in hypomagnesaemia?

A
  • IBD (diarrhoea)
  • Proton pump inhibitor (omeprazole)
  • Gluten enteropathy (diarrhoea)
  • Intestinal bypass/fistula
  • Radiation enteritis
  • Laxative abuse
413
Q

What are the causes of renal tubular dysfunction in hypomagnesaemia?

A
  • Alcoholism
  • Hyperaldosteronism
  • Hyperparathyroidism
  • Hypoparathyroidism
  • Nephrotic drugs (cisplatin, ciclosporin, gentamicin, FK506)
  • Diuretics
  • Osmotic diuresis
  • Rare familial disorders
414
Q

What are the causes of intracellular shift in hypomagnesaemia?

A
  • Post MI
  • Post parathyroidectomy
  • Recovery from DKA
  • Refeeding
  • Acute pancreatitis
415
Q

What systems are affected as a consequence of hypomagnesaemia?

A
  • Neuromuscular
  • GIT
  • Neurological
  • Biochemical
  • Cardiovascular
416
Q

What are the neuromuscular consequences of hypomagnesaemia?

A
  • Tremor
  • Muscle weakness
  • Twitching
  • Cramps
  • Arrythmia
417
Q

What are the gastrointestinal consequences of hypomagnesaemia?

A
  • Anorexia
  • Nausea
  • Vomiting
418
Q

What are the neurological consequences of hypomagnesaemia?

A
  • Apathy
  • Depression
  • Agitation
  • Confusion
  • Delirium
  • Convulsions
  • Coma
419
Q

What are the biochemical consequences of hypomagnesaemia?

A
  • Hypokalaemia

* Hypocalcaemia

420
Q

What are the cardiovascular consequences of hypomagnesaemia?

A

Arrythymia (secondary to hypokalaemia)

421
Q

What is the serum magnesium reference range for hypomagnesaemia?

A

<0.5 mmol/L

422
Q

Most patients with hypomagnesaemia will also have what other low molecule?

A

Albumin - only 25% have low ionised magnesium

423
Q

What is the reference range of normal urinary magnesium (uMg)?

A

2-7 mmol/24hrs

424
Q

What is the calculation of uMg fractional excretion of Mg?

A

FEMg (%) = (uMg x plasma creatinine)/((0.75x plamsa magnesium)x urea creatinine)X 100

425
Q

What does FEMg >2% mean?

A

Renal magnesium wasting

426
Q

How would magnesium deficit be determined?

A
  • Combine urinary Mg fractional excretion with Mg infusion test
  • UMg <0.7mmol/24hrs = inadequate intake or malabsorption
427
Q

What is the flow of diagnosis for suspected hypomagnesaemia?

A
  • Medication causing hypomagnesaemia – if yes change medication, if no continue
  • Magnesium moving from ECF to ICF – if yes treat cause, if no continue
  • Urinary magnesium excretion – if normal consider GIT losses, if high consider renal losses
428
Q

When should hypomagnesaemia be treated?

A
  • Ventricular tachycardia
  • Hypokalaemia unresponsive to K supplements
  • Neurological symptoms
  • Diuretic therapy (stop/change)
  • Hypocalcaemia unresponsive to Ca supplementation
  • Asymptomatic hypomagnesaemia
429
Q

What should hypomagnesaemia be treated with?

A
  • IV MgSO4 in saline or dextrose for symptomatic deficiency
  • Requires repeat treatment over several days
  • Oral supplements where suitable
430
Q

When calcium levels are too high or too low, which body systems is primarily affected?

A

Nervous system

431
Q

What is likely to be released when blood calcium levels are elevated?

A

Calcitonin

432
Q

An individual with very low levels of vitamin D presents themselves to you complaining of seemingly fragile bones. explain how these might be connected

A

Vitamin D is required for calcium absorption by the gut. Low vitamin D could lead to insufficient levels of calcium in the blood so the calcium is being released from the bones. The reduction of calcium from the bones can make them weak and subject to fracture

433
Q

Describe the effects caused when the parathyroid gland fails to respond to calcium bound to its receptors

A

Under “normal” conditions, receptors in the parathyroid glands bind blood calcium. When the receptors are full, the parathyroid gland stops secreting PTH. In the condition described, the parathyroid glands are not responding to the signal that there is sufficient calcium in the blood and they keep releasing PTH, which causes the bone to release more calcium into the blood. Ultimately, the bones become fragile and hypercalcaemia can result

434
Q

When blood calcium levels are low, what does PTH stimulate?

A

The activity of osteoclasts

435
Q

What can result from hyperparathyroidism?

A

Fractures

436
Q

Describe the role of negative feedback in the function of the parathyroid gland

A

The production and secretion of PTH is regulated by a negative feedback loop. Low blood calcium levels initiate the production and secretion of PTH. PTH increases bone reabsorption, calcium absorption from the intestines and calcium reabsorption by the kidneys. As a result, blood calcium levels begin to rise. This, in turn, inhibits the further production and secretion of PTH

437
Q

Explain why someone with a parathyroid gland tumour might develop kidney stones

A

A parathyroid gland tumour can prompt hypersecretion of PTH. This can raise blood calcium levels so excessively that calcium deposits begin to accumulate throughout the body, including the kidney tubules, where they are referred to as kidney stones

438
Q

What happens to the total serum calcium values when blood is drawn from a patient who is supine?

A

Lowered compared to a patient in an upright position

439
Q

What does the renal system include?

A
  • Kidneys
  • Ureter
  • Bladder
  • Urethra
440
Q

What are the roles of the renal system?

A
  • Critical homeostasis of electrolytes and acid-base status
  • Excretion of waste
  • Endocrine role
  • Degradation/synthesis of hormones such as insulin and aldosterone
441
Q

What is the primary role of the renal system?

A

Homeostasis to maintain composition of the blood and interstitial and intracellular fluids

442
Q

What does the excretory function of the kidney get rid of?

A
  • Non-protein nitrogenous compounds

* Excess inorganic substances ingested in the diet

443
Q

What non-protein nitrogenous compounds are excreted by the kidneys?

A
  • Urea
  • Creatinine
  • Uric acid
444
Q

What excess inorganic substances that are ingested in the diet are excreted by the kidneys?

A
  • Sodium
  • Potassium
  • Chloride
  • Calcium
  • Phosphate
  • Magnesium
445
Q

What is the functional unit of the kidney?

A

Nephron

446
Q

What is the anatomy of the nephron?

A
  • Bowman’s Capsule containing Glomerus
  • Proximal convoluted tubule
  • Proximal straight tubule
  • Loop of Henle descending
  • Loop of Henle ascending
  • Ascending thick limb
  • Macula densa
  • Distal convoluted tubule
  • Connecting tubule
  • Cortical connecting duct
  • Outer medullary collecting duct
  • Inner medullary collecting duct
447
Q

What are the 4 stages of urine formation?

A
  • Filtration
  • Reabsorption
  • Secretion
  • Excretion
448
Q

What occurs in filtration stage of urine formation?

A

Distal tubule collects a filtrate from the blood containing water and low Mr solutes

449
Q

What occurs in reabsorption stage of urine formation?

A

Reclaims valuable substances from the filtrate returning them to the body fluids

450
Q

?What occurs in secretion stage of urine formation

A

Toxins and excess ions, for example, are secreted into the distal tubule

451
Q

What occurs in excretion stage of urine formation?

A

Urine leaves the system and the body

452
Q

What are the features of urine formation?

A
  • Useful metabolites are reabsorbed
  • Waste products excreted in urine
  • Continuous process – 99% of filtrate is reabsorbed, approximately 200L per day filtered but only produces 1L of urine
  • Requires good blood flow and perfusion in kidneys
  • Renal vascular tone is modulated by multiple mechanisms
  • Renal hypoperfusion results in renin release
  • At rest 25% of all cardiac output is to the kidneys
453
Q

What does renal hypoperfusion that results in renin release, trigger?

A
  • Triggers RAA system

* Vasoconstriction, increased blood pressure and increased blood flow to kidneys

454
Q

What are the features of the glomerulus?

A
  • Afferent arteriole brings blood into the glomerulus and efferent arteriole flows blood away
  • Ultrafiltrate – water and small molecules
  • Filtrate from blood drain into the bowman’s capsule space
  • Hypovolaemia detected by kidneys in the juxtaglomerular apparatus
  • Renin is secreted from this region
455
Q

What is the physiology of the glomerulus?

A
  • Juxtalomerular apparatus
  • Bowman’s capsule
  • Proximal tubule
456
Q

What cells are found within the glomerulus?

A
  • Podocytes
  • Endothelium
  • Glomerular basement membrane
  • Mesangium
457
Q

What is the filtrate contents in the proximal convoluted tubule?

A
  • Approximately 70% of Na+ is reclaimed here
  • Nearly all of K+ is claimed here
  • HCO3- is reabsorbed here
  • H+ >90% into urine
  • Glucose and uric acid are in a Na+ dependant manner
  • Creatinine is excreted at a constant rate
458
Q

What are the features of the proximal convoluted tubule?

A
  • Most metabolically active region
  • Contains ion transport channels and pumps
  • These tubes are “convoluted” to increase length and therefore filtration area
459
Q

What is the renal physiology of the Loop of Henle?

A
  • The concentration of the filtrate is greatly increased as it passes through the Loop of Henle
  • Water leaves the tubule by osmosis and the filtrate increases in concentration
  • The ascending loop is permeable to salts but impermeable to water
  • Water, sodium and urea diffuse out of the collecting ducts into the interstitial fluid
  • Loss of water = osmotic loop
460
Q

How is the permeability of the ascending Loop of Henle?

A

Permeable to salts but impermeable to water

461
Q

What are the features of the distal convoluted tubule?

A
  • They are the fine-tuning apparatus
  • Of 200L plasma filtered/24hrs only 1-2 L of urine is formed
  • Aldosterone mediates reabsorption of Na+ at distal convoluted tubule via sodium pumps
  • Leads H+/K+ balance and excreted - critical function in acid-base homeostasis
  • Urine then passes into collecting ducted
462
Q

How is the permeability of the collecting ducts?

A

Impermeable to water but can permit reabsorption of solute-free water via ADH regulation

463
Q

What is the endocrine function of the kidneys?

A
  • Erythropoietin into bone marrow
  • 1,25 Dihydroxycholecalciferol into the gut
  • Renin to convert angiotensinogen to angiotensin I and angiotensin converting enzyme to convert angiotensin I to angiotensin II
  • Angiotensin II stimulates aldosterone from the adrenal cortex
  • Parathyroids release PTH into the kidneys
  • Post-pituitary releases arginine vasopressin (ADH) into the kidneys
464
Q

How is the renal system involved in controlling acid-base balance?

A
  • Recycling of HCO3

* Generation of HCO3- and phosphate/ammonia removal of H+

465
Q

How is HCO3- recycled in renal control of acid-base balance?

A

From the blood into the glomerulus to the renal tubular cell and out into the interstitial fluid – going through molecular changes

466
Q

How is HCO3- generated and phosphate/ammonia removal of H+ in renal control of acid-base balance?

A

Phosphate from blood into glomerulus filtered with ammonia. H+ from renal tubular cell to glomerulus in exchange for Na+ pulls the bicarbonate buffer equation to the right as H+ is being produced from carbonic anhydrase. Generated HCO3- goes out into the interstitial fluid

467
Q

What type of simple urinalysis is there?

A
  • Physical exam
  • Chemical exam
  • Microscopic exam
468
Q

What is the physical exam of simple urinalysis?

A

Colour and clarity of sample

469
Q

What is the chemical exam of simple urinalysis?

A

Dipstick

470
Q

What is the microscopic exam of simple urinalysis?

A
  • Cells, bacteria, yeast

* Casts and crystals

471
Q

What does a dipstick test analyse?

A
  • Glucose
  • Ketones
  • Bilirubin/urobilinogen
  • Proteinuria
  • Haemoglobin
  • Ph
  • Nitrites
  • Leukocyte esterase (pyuria)
  • Specific gravity
472
Q

What is glucose analysed for in a dipstick test?

A

Diabetes

473
Q

What are ketones analysed for in a dipstick test?

A

Ketoacidosis

474
Q

What is bilirubin/urobilinogen analysed for in a dipstick test?

A

Liver damage

475
Q

What is proteinuria analysed for in a dipstick test?

A

Kidney function

476
Q

What is haemoglobin analysed for in a dipstick test?

A

Blood levels in urine

477
Q

What is pH analysed for in a dipstick test?

A

Renal tubular acidosis

478
Q

What are nitrites analysed for in a dipstick test?

A

Absent in urine unless bacteria present

479
Q

What is leukocyte esterase (polyuria) analysed for in a dipstick test?

A

UTI

480
Q

What is specific gravity analysed for in a dipstick test?

A

Osmolality

481
Q

What measurement on the dipstick test is mandatory in kidney disease classification?

A
  • Protein measurement

* >450 mg/L per 24hrs is usually pathological

482
Q

What are the different types of proteinuria?

A
  • Glomerular
  • Tubular
  • Overflow
483
Q

What are the causes of glomerular proteinuria?

A
  • Glomerular
  • Tubular
  • Overflow
484
Q

What are the causes of tubular proteinuria?

A
  • Decreased tubular capacity, heavy metals, anoxia – due to low molecular weight protein such as B2M, alkaline phosphatase
  • Decreased nephron number due to kidney disease – due to low molecular weight protein such as B2M and alkaline phosphatase
  • Distal tubular damage (secreted proteinuria) – due to Tamm Horsfall glycoprotein
485
Q

What are the causes of overflow proteinuria?

A

Increased plasma concentration: multiple myeloma, rhabdomylosis – due to Bence Jones protein

486
Q

What is renal proteinuria caused by?

A
  • Damage to nephrons – e.g. inflammation of glomerulonephritis or nephrosis
  • Need to eliminate urinary tract disease and infections – high protein in urine with infections
487
Q

What can kidney function be affected by in the glomerulus?

A
  • Net pressure across glomerular membrane
  • Physical nature of the glomerular membrane
  • Number of functioning glomerular
488
Q

What is the amount of blood getting to the kidneys measured by?

A

Renal plasma flow (RPF)

489
Q

What is the number of functioning glomerular estimated by?

A

Glomerular filtration rate (GFR)

490
Q

What can indicate the degree of renal impairment by disease?

A

RPF and GFR

491
Q

What molecule is used to be able to calculate the renal plasma flow?

A

Para-aminohippuric acid (PAH)

492
Q

What are the features of PAH in renal plasma flow?

A
  • Injected IV, not produced endogenously
  • PAH doesn’t affect renal flow in any way
  • PAH entering the nephron is totally cleared by filtration (20-30%) and secretion (70-80%)
  • However, PAH clearance is about 90% of total RPF
493
Q

What is the gold standard to produce accurate GFR?

A
  • Inulin (plant carbohydrate)

* Administered by IV – can be “tracked”. Inulin is NOT reabsorbed but the kidneys

494
Q

What is the silver standard to produce accurate GFR?

A
  • 51Cr-EDTA

* GFR can be accurately calculated by clearance of Chromium 51 injected into the blood

495
Q

What is the main issue of accurate GFR?

A
  • Very specialist
  • Time consuming
  • Labour intensive
  • Expensive
  • Requires urine collection at late time point
496
Q

What is the bronze standard to produce accurate GFR?

A
  • Creatinine
  • Muscle mass will not rapidly change and creatinine secretion constant
  • Creatinine is not significantly reabsorbed by the kidneys
  • Creatinine is ultimately excreted in urine and measured
497
Q

How is creatinine measured?

A
  • Creatinine clearance

* Widely accepted as the standard in measurement of kidney function

498
Q

What is the calculation of GFR?

A

GFR= (UxV (ml/min))/P

499
Q

How is creatinine clearance done?

A
  • Determine [substrate] in blood vs urine – clearance by kidneys
  • GFR= (U x V)/P
  • U is [substance in urine]
  • V is volume excreted per time unit (ml/min)
  • P is [substance in plasma]
  • Corrected against body surface area of 1.73 m2
  • Requires timed urine collection
500
Q

How is GFR corrected?

A

GFR corrected = GFR measured x 1.73/BSA m2

501
Q

What is the reference range of serum creatinine in adults?

A

60-120 µmol/L

502
Q

What does a progressive rise on serial creatinine measurement, even within the reference range, indicate?

A
  • Declining renal function

* Can be part of the definition of acute kidney injury

503
Q

Does estimated GFR (eGFR) require timed urine collection?

A

No, only serum creatinine

504
Q

What Cockcroft and Gualt creatinine clearance equation?

A

• GFRcockcroft = ((140-age) x mass(kg) [x 1.23 if male] [x1.04 if female])/serum creatinine (µmol/l)

505
Q

What is the clinical reference range for males with GFRcockcroft?

A

90-125

506
Q

What is the clinical reference range for females with GFRcockcroft?

A

85-120

507
Q

What can cause a decrease in plasma creatinine in the creatinine clearance equation?

A
  • Pregnancy

* Reduced muscle bulk through starvation or steroid therapy

508
Q

What can cause an increase in plasma creatinine in the creatinine clearance equation?

A
  • High meat intake, strenuous exercise
  • Drug effects (salicylates)
  • Analytical interference (due to cephalosporin antibiotics)
  • Renal causes (acute or chronic)
509
Q

Where is urea formed?

A

Liver from ammonia

510
Q

How is urea released by the liver?

A

Released by deamination of amino acids

511
Q

What excretes urea?

A

Kidneys

512
Q

What are plasma urea measurements accepted as?

A

Giving a measure of renal function

513
Q

How relevant to clinical tests is urea?

A
  • Inferior to plasma creatinine as it is passively reabsorbed through tubules
  • But when coupled to creatinine, increasing plasma urea remains an indicator of renal impairment
514
Q

What are the causes of low plasma urea?

A
  • Malabsorption/starvation
  • Liver disease – less production
  • Water retention associated with SIADH
515
Q

What are the pre-renal causes of high plasma urea?

A
  • Hypovolaemia
  • Impaired renal perfusion
  • Congestive heart failure
  • Haemorrhage
  • High protein diet
  • Increased protein catabolism
516
Q

What are the intra-renal causes of high plasma urea?

A
  • Renal failure

* Reduced GFR

517
Q

What are the post-renal causes of high plasma urea?

A
  • Obstruction of urine flow
  • Benign prostate disease
  • Bladder blockage
518
Q

What does next generation testing of GFR include?

A

Cystatin C

519
Q

What is cystatin C?

A

GFR marker

520
Q

What are some features of cystatin C?

A
  • Produced by all cells
  • Not reabsorbed
  • Secreted by kidneys
521
Q

When would cystatin C be a more appropriate choice as an alternative to creatinine measurement?

A
  • Liver cirrhosis
  • Morbidly obese
  • Malnourished
  • Reduced muscle mass
522
Q

What is conducted in a renal test?

A
  • Urinalysis
  • Proteinuria
  • Electrolyte panel
  • Acid-base panel
  • BUN
  • Creatinine
  • Glucose
  • Cystatin C
523
Q

Why is a urinalysis conducted in a renal test?

A
  • General inspection
  • UTI
  • Crystals
524
Q

Why are proteinuria tests conducted in a renal test?

A

High levels of protein due to kidney damage

525
Q

Why is an electrolyte panel done in a renal test?

A

Check for kidney function in relation to Na+, K+, Cl- and HCO3-

526
Q

Why is an acid-base panel done in a renal test?

A
  • Renal acid-base regulation
  • pH
  • acidosis/alkalosis
527
Q

Why is BUN tested in a renal test?

A

Blood urea

528
Q

Why is creatinine tested in a renal test?

A

Kidney function - clearance of creatinine from serum to urine

529
Q

Why is glucose tested in a renal test?

A

Diabetes associated kidney disease

530
Q

Why is cystatin C tested in a renal test?

A

If available - kidney marker

531
Q

What does BUN stand for?

A

Blood urea nitrogen

532
Q

What calculations are performed in a renal test?

A
  • eGFR

* Anion gap

533
Q

Where is erythropoietin produced?

A

Kidneys

534
Q

What does erythropoietin stimulate?

A

Red blood cell production

535
Q

How does kidney disease affect erythropoietin?

A
  • Causes reduced production of erythropoietin
  • Fewer RBCs leads to anaemia
  • Reduced iron following kidney dialysis can impair haemoglobin production causing anaemia
536
Q

What excretes potassium?

A

Kidneys

537
Q

How does kidney disease affect potassium?

A
  • Reduces potassium excretion leading to hyperkalaemia

* Can lead to cardiac arrythmias

538
Q

How does kidney disease affect vitamin D?

A

Lowers vitamin D activation

539
Q

What is the knock-on effect of lowered vitamin D activation by kidney disease?

A
  • Lower calcium absorption
  • Hypocalcaemia which causes PTH release
  • PTH stimulates bone demineralisation to replace calcium in the blood making bones brittle (renal osteodystrophy)
540
Q

In impaired renal function, what type of causes are there?

A
  • Pre-renal
  • Renal
  • Post-renal
541
Q

What are the pre-renal causes of impaired renal function?

A
  • Reduced renal blood flow due to drop in blood pressure
  • Overstimulation of ADH/RAA system
  • Renal blood flow (congestive heart failure)
542
Q

What are the renal causes of impaired renal function?

A
  • Acute kidney injury or chronic kidney disease

* Reduced GFR

543
Q

What are the post-renal causes of impaired renal function?

A
  • Outflow obstructions anywhere in the renal system
  • Stones, prostate causes, various genitourinary cancers
  • Blockage may progress to actual kidney damage
544
Q

Where can the outflow obstructions in the renal system occur in post-renal causes of impaired renal function?

A
  • Ureter
  • Bladder
  • Urethra
545
Q

What is acute kidney injury (AKI) also known as?

A

Acute tubular necrosis

546
Q

What is the mortality of AKI if uncomplicated?

A

5-10%

547
Q

What is the mortality of AKI if complicated?

A

50-70%

548
Q

What are the pre-renal causes of AKI?

A
  • Dehydration
  • Haemorrhage
  • Diarrhoea
  • Sepsis
  • Cardiac failure
549
Q

What are the intra-renal causes of AKI?

A
  • Drugs
  • Nephropathy
  • Many kidney related diseases
  • Embolism/thrombosis
  • Injury/accident (myoglobin)
550
Q

What are the post-renal causes of AKI?

A
  • Bladder obstruction
  • Fibrosis
  • Benign/malignant bladder or prostate cancer
551
Q

What is the treatment for AKI?

A
  • Surgical if blockage
  • Electrolyte management to correct biochemical abnormalities
  • Renal replacement therapy
552
Q

What are the stages of AKI?

A
  • Oliguric phase (initial stage)
  • Diuretic phase (clinical improvement)
  • Recovery stage (not always)
553
Q

What occurs in the oliguric phase of AKI?

A
  • Urine has high osmolality (mainly Na+)
  • Hyponatraemia – water retention due to low GFR
  • Metabolic acidosis which can lead to hyperkalaemia (can be life threatening)
  • High plasma creatinine and urea
  • Daily measurements of plasma creatinine, Urea and K+ required
554
Q

What occurs in the diuretic phase of AKI?

A
  • Urine volume increases but plasma [creatinine] and [Urea] do not
  • Plasma [K+] falls
  • Urine [Na+] and [K+] may increase and electrolyte replacement is required
555
Q

How much urine is in the oliguric phase of AKI?

A

<400 ml due to reduced GFR

556
Q

How is AKI managed?

A
  • Ensure that there is no renal blockage
  • IV fluids (balancing electrolytes)
  • Close eye on acid-base levels
  • Diuretics – furosemide a loop diuretic
557
Q

What is the management of persistent AKI?

A
  • Control sodium in diet
  • Examine fluids and nutrition
  • Renal replacement therapy
558
Q

Is AKI reversible?

A

Yes

559
Q

Is chronic kidney disease (CKD) reversible?

A

No

560
Q

What does CKD indicate?

A

Decrease in functioning nephrons which leads to impaired filtration

561
Q

What are the causes of CKD

A
  • Hypertension
  • Diabetes
  • Glomerular disease
  • Polycystic kidney disease
  • Kidney stones
  • Toxic neuropathy (drugs)
562
Q

How is hypertension and the kidney linked?

A

• Fluid and salt retention lead to increased blood pressure which is activated by the RAA system

563
Q

What is usually an additional worry with hypertension and CKD?

A

Renal artery stenosis

564
Q

What is the impact of CKD as it progresses?

A
  • Inability to regenerate HCO3- (leads to metabolic acidosis)
  • Loss of the ability to excrete H+ (leads to metabolic acidosis)
565
Q

What does advanced CKD lead to?

A
  • Hyperkalaemia

* End-stage renal disease – eventual loss of reserve function with a need for dialysis or kidney transplant

566
Q

What is overworking caused by in CKD?

A

In the early stages of CKD, the remaining functioning nephrons workload is increased to compensate for the loss of nephrons

567
Q

What is the GFR clinical reference range for CKD?

A

<60 ml/min for >3 months

568
Q

How many stages are there of CKD?

A

5

569
Q

What are the 5 stages of CKD?

A

1) Kidney damage with normal or increased GFR
2) Kidney damage with mild decrease in GFR
3) Moderate decreased GFR
4) Severe decreased GFR
5) Kidney failure

570
Q

What are the practical complications of reduced GFR?

A
  • Anaemia – iron deficiency
  • Blood pressure increases
  • Calcium absorption decreases
  • Dyslipidaemia/heart failure/volume overload
  • Hyperkalaemia
  • Hyperparathyroidism
  • Left ventricular hypertrophy
  • Metabolic acidosis
  • Malnutrition
571
Q

What is nephrotic syndrome?

A

Destruction of the filtration membrane of nephrons

572
Q

What is the primary cause of nephrotic syndrome?

A
  • Inflamed
  • Damaged glomerulus – glomerular nephritis
  • Renal transplant rejection
573
Q

What does chronic glomerular nephritis do to the filtration membrane?

A

Causes it to thicken

574
Q

When does acute glomerular nephritis often occur?

A

1-3 weeks after a severe bacterial infection

575
Q

What are the secondary causes of nephrotic syndrome?

A
  • Diabetes mellitus
  • Drugs
  • Heavy metals
  • Hypothyroidism
  • Hypertension
576
Q

What is nephrotic syndrome characterized by?

A
  • Large proteinuria >0.5 g/24hrs (x5 normal)
  • Hypoalbuminemia
  • Oedema (water retention)
577
Q

What is diabetic nephropathy?

A
  • Progressive kidney disease caused by damage to the capillaries in the kidney glomeruli
  • Later stage disease leads to increased proteinuria
  • Chronic hyperglycaemia has been implicated with nephropathy
578
Q

What percentage of diabetics may develop diabetic nephropathy?

A

30-40%

579
Q

When is kidney damage more likely in diabetic nephropathy?

A 
When one or more of the following is present:
•	Poor control of blood glucose
•	High blood pressure
•	Type 1 diabetes mellitus
•	A family history of kidney disease
580
Q

What can help with diabetic nephropathy?

A

ACE inhibitors

581
Q

How is renal tubular disease acquired?

A

Can be inherited or acquired

582
Q

What do renal tubular diseases affect?

A

Proximal or distal tubules

583
Q

What is renal tubular acidosis (RTA)?

A

Syndrome due to either a defect in proximal tubule bicarbonate reabsorption, or a defect in distal hydrogen ion secretion, or both

584
Q

How many types of renal tubular diseases are there?

A

4

585
Q

What is type I renal tubular disease?

A

Defective hydrogen ion secretion in distal tubule

586
Q

What is type II renal tubular disease?

A

Absorption of HCO3 in the proximal tubule is reduced

587
Q

What is type IV renal tubular disease?

A

HCO3 reabsorption in the renal tubule impaired as a consequence of aldosterone deficiency

588
Q

What is hepato-renal syndrome?

A
  • The development of renal failure in patients with advanced chronic liver disease
  • Kidneys are histologically normal and functioning (no tubular necrosis)
  • Severe vasoconstriction of the blood vessels of the kidneys
589
Q

What is the main theory of hepato-renal syndrome?

A
  • The liver controls intestinal blood flow, drop in pressure leads to decreased blood flow to the kidneys – activation of RAA system
  • But cannot outcompete liver effects
590
Q

What is the biochemistry of hepato-renal syndrome in patients with cirrhosis?

A
  • Low urine flow
  • Increasing creatinine
  • Urea is common
591
Q

What happens to the condition when the patient has a liver transplant?

A

It is reversed

592
Q

How high is the risk of death with hepato-renal syndrome?

A

Very high

593
Q

What might environmental chemicals and poisons do to the kidneys?

A

Injure kidney by increasing large blood flow and filtration

594
Q

What do heavy metals do to the kidney?

A

Such as mercury and cadmium, target the kidney after glutathione/cysteine conjugation

595
Q

How do paraquat or diquat (weed killers) damage the kidney?

A

Damage the kidney via production of reactive oxygen species (ROS)

596
Q

What does low solubility of poisons such as ethylene glycol metabolites do to kidneys?

A

Causes crystal formation within tubular lumen and nephrotoxicity

597
Q

How are electrolytes managed in CKD?

A
  • Prevent sodium overload (restriction/diuretics)

* Control hyperkalaemia

598
Q

How is diet managed in CKD?

A
  • Restrict protein intake
  • Limit lipids and restrict non-complex CHO
  • Restrict potassium
599
Q

How are drugs managed in CKD?

A
  • Administer vitamin D, calcium and iron supplements

* Erythropoietin

600
Q

When is dialysis used for patients with CKD?

A

If ESKD

601
Q

What are some inherited kidney disorders?

A
  • Polycystic kidney disease
  • Alport syndrome
  • Inherited Tubulopathology
602
Q

What are the features of polycystic kidney disease?

A
  • Enlargement of kidneys and cyst formation
  • Autosomal dominant polycystic kidney disease most common
  • It effects 1:400 – 1:1000 births
  • PKD1 and PKD2 gene mutations
603
Q

What are the features of Alport syndrome?

A
  • Genetic mutation in collagen genes found in glomerular (COL4A5)
  • It effects 1 in 5,00-10,000 people
604
Q

What are some inherited Tubulopathology disorders

A
  • Dents disease - defects in proximal tubule
  • Bartters syndrome - Loop of Henle defects
  • Gitelmans syndrome - distal tubule
605
Q

What is ESKD?

A
  • When kidneys can no longer support life

* Kidneys require assistance

606
Q

What stage of CKD will enter ESKD?

A

Most stage 5 patients

607
Q

What is the typical GFR for ESKD?

A

<15 ml/min

608
Q

What therapy is used in patients with ESKD?

A

Renal replacement therapy

609
Q

What are some diuretics used to treat ESK?

A
  • Carbonic anhydrase inhibitors
  • Loop or high-ceiling diuretics
  • Thiazide and thiazide-like diuretics
  • Potassium-sparing diuretics
  • Osmotics
610
Q

What is the site of action of carbonic anhydrase inhibitors?

A

Proximal convoluted tubules

611
Q

What is the site of action of Loop or high-ceiling diuretics?

A

Thick ascending limb (Loop of Henle)

612
Q

What is the site of action of thiazide and thiazide-like diuretics?

A
  • Thick ascending limb (Loop of Henle)

* Distal tubules

613
Q

What is the site of action of potassium-sparing diuretics?

A
  • Distal tubule

* Collecting duct

614
Q

What is the site of action of osmotics?

A
  • Proximal tubule
  • Loop of Henle
  • Collecting tubule
615
Q

What is the mechanism of action of carbonic anhydrase inhibitor?

A
  • Inhibition of renal carbonic anhydrase

* Decreases HCO3- reabsorption

616
Q

What is the mechanism of action of Loop or high-ceiling diuretics?

A

Inhibition of the luminal Na+/K+/2Cl- reabsorption

617
Q

What is the mechanism of action of thiazide and thaizide-like diuretics?

A

Inhibition of sodium reabsorption

618
Q

What is the mechanism of action of potassium-sparing diuretics?

A
  • Inhibition of Na and H20 reabsorption (competes with aldosterone)
  • Blockade of Na+ uptake at the luminal membrane
619
Q

What is the mechanism of action of osmotics?

A
  • Decrease Na and H2O reabsorption
  • Decease medullary hypertonicity
  • Elevated urinary flow rate
620
Q

When should renal replacement therapy be done?

A
  • Pulmonary oedema – fluid overload
  • Severe/persistent hyperkalaemia
  • Severe acidosis
  • Renal system can no longer fully support patients’ needs
  • Other major complications such as pericarditis or neuropathy
621
Q

What is renal replacement therapy?

A
  • Haemodialysis through peritoneal dialysis and hemofiltration
  • Renal transplantation
622
Q

What are the types of dialysis?

A
  • Haemodialysis

* Peritoneal dialysis

623
Q

What are the features of haemodialysis?

A
  • Artificial membrane (dialysis tubing)
  • Blood and dialysis solutions
  • Small molecules diffuse from blood into rinsing fluid
  • “cleansed” blood returned to patient
624
Q

What are the features of peritoneal dialysis?

A
  • Permanent catheter
  • Membrane is now the peritoneal membrane
  • Place rinsing fluid into peritoneal cavity
  • Discard fluid every 6 hours
625
Q

What does the type of dialysis depend on?

A

Patient condition and choice

626
Q

What are the features of a renal transplant?

A
  • Ideal solution, providing donor can be found
  • Restores renal function
  • Requires lifelong immunosuppression
  • Immunosuppressants can be nephrotoxic
  • Must monitor and routinely check creatinine levels
627
Q

What is used as immunosuppressants for renal transplants?

A

Cyclosporin or tacrolimus

628
Q

What is autocrine?

A

Cells releases hormone that acts on the same cell

629
Q

What is an example of an autocrine hormone?

A

Numerous growth hormones

630
Q

What is paracrine?

A

Cell releases hormone that acts on the adjacent/local cell

631
Q

What is an example of a paracrine hormone?

A

Nuerotransmitter

632
Q

What is endocrine?

A

Cell releases hormone into circulation with a systemic effect on cell types at a distant site

633
Q

What are some examples of endocrine hormones?

A
  • Insulin

* Cortisol

634
Q

What are types of stimulus in hormone function?

A
  • Humoral
  • Hormonal
  • Neuronal
635
Q

What is an example of humoral?

A
  • Ions

* Nutrition

636
Q

What does hormonal do?

A

Hormone that acts on another hormone

637
Q

What is an example of neuronal?

A

Nervous system - adrenaline

638
Q

What is the action of hormones?

A
  • Affect growth and development
  • Homeostatic control of metabolic pathways
  • Regulate production, use and storage of energy
639
Q

What are hormones?

A
  • Signalling molecules produced by glands
  • Regulate many processes
  • Tightly regulated by positive and negative feedback
640
Q

What is the endocrine system defined as?

A

The collection of glans that produce hormones that can regulate metabolism, growth of tissues, reproduction, mood, sleep, and most physiological responses

641
Q

What type of hormones are there?

A
  • Water soluble

* Lipid soluble

642
Q

What are the three general classes of water-soluble hormones?

A
  • Amines
  • Peptide/protein hormones
  • Eicosanoids
643
Q

What are amine hormones derived from?

A

Amino acids

644
Q

What are peptide/protein hormones derived from?

A

Amino acids

645
Q

What are eicosanoids derived from?

A

Arachidonic acid

646
Q

What are some examples of amine hormones?

A
  • Epinephrine (adrenaline)

* Dopamine

647
Q

What are some examples of peptide/protein hormones?

A
  • Antidiuretic hormone (ADH)
  • Insulin
  • Growth Hormone (GH)
  • Adrenocorticotrophic hormone (ACTH)
  • Follicle stimulating hormone (FSH)
  • Luteinizing hormone (LH)
  • Thyroid stimulating hormone (TSH)
  • Renin
648
Q

What is an example of eicosanoids?

A

Prostaglandins

649
Q

How are water soluble hormones present within the body?

A

Freely available

650
Q

Where are water soluble hormones situated?

A

ECF

651
Q

What is the action of water-soluble hormones?

A
  • Does not enter cell
  • Binds to cell surface receptor – G protein-coupled receptor (GPCR)
  • Triggers a signal cascade
652
Q

What is a lipid soluble hormone?

A
  • Broad class of compounds with the same basic structure
  • Hydrophobic
  • Either natural or synthetic
  • Need a carrier molecule to move
653
Q

What is the same basic structure that all lipid soluble hormones have?

A

Common 4 aromatic ring structure

654
Q

What are the types of steroid lipid soluble hormones?

A
  • Glucocorticoids
  • Mineralocorticoids
  • Oestrogens
  • Androgens
  • Progestogens
655
Q

What are some examples of glucocorticoids?

A
  • Cortisol

* Dexamethasone – synthetic used to treat some inflammatory conditions

656
Q

What is an example of a mineralocorticoid?

A

Aldosterone

657
Q

What is an example of oestrogens?

A

Oestrogen

658
Q

What is an example of androgens?

A

Testosterone

659
Q

What is an example of progestogens?

A

Progesterone

660
Q

How is water and lipid soluble hormones transported in the blood?

A
  • Water soluble hormones circulate freely

* Lipid soluble hormone are bound to a transport protein

661
Q

What type of receptor does water soluble hormones interact with?

A

Cell surface receptor

662
Q

What type of receptor does lipid soluble hormones interact with?

A

Internal receptor

663
Q

What is the exception to the rule with water and lipid soluble hormones?

A
  • Some water-soluble hormones can interact with internal receptors
  • Some lipid soluble hormones can interact with cell surface receptors
664
Q

What are the features of nuclear hormone receptors?

A
  • Non-membrane bound receptors form a complex with hormones in the cytoplasm
  • This complex is transported into the nucleus where it directly binds DNA
  • Hormone/receptor complexes activate gene transcription
665
Q

What is the main precursor hormone?

A

Cholesterol

666
Q

What are the main enzymes in converting hormones?

A
  • 17α-hydrolase
  • 21-hydrolase
  • 11β-hydrolase
  • 5α-reductase
  • Aromatase
667
Q

Which converting enzyme of hormones occurs in the mitochondria?

A
  • Cholesterol side-chain cleavage enzyme
  • 11β-hydrolase
  • Aldosterone synthase
668
Q

Where does the converting of the hormones mainly take place?

A

Smooth endoplasmic reticulum

669
Q

What happens if the converting enzymes for hormone production are deficient?

A

Hormones won’t be produced

670
Q

What is the HPA axis?

A

Hypothalamus, anterior pituitary gland, and the adrenal cortex

671
Q

What does the HPA axis do?

A

Controls and coordinates the endocrine system through secretion of inhibitory, releasing, and trophic hormones

672
Q

What is the generic mechanism for controlling/inhibiting production of too many hormones?

A

Negative feedback

673
Q

How might the secretion of anterior pituitary and hypothalamic hormones be inhibited?

A

By the circulating hormones, whose release they stimulate

674
Q

What are trophic hormones?

A

Hormones which target other endocrine glands

675
Q

What are the higher centres of the brain responsible for?

A
  • Speech
  • Emotion
  • Consciousness
  • Awareness
  • Feelings
  • etc
676
Q

What can impact on hormone production?

A

Heightened states such as stress, anxiety, euphoria, and fear

677
Q

Where is the hypothalamus located?

A

At the base of the brain, just below the thalamus

678
Q

How is the hypothalamus linked to the pituitary gland?

A
  • Infundibulum also known as the pituitary stalk

* It is a hypothalamic channel

679
Q

What is the main function of the hypothalamus?

A
  • To respond to homeostatic changes
  • Maintain homeostasis
  • Stimulate the pituitary gland
680
Q

What hormones does the hypothalamus produce?

A
  • Thyrotropin Releasing Hormone (TRH)
  • Gonadotrophin-Releasing Hormone (GnRH)
  • Growth Hormone Releasing Hormone (GHRH)
  • Growth Hormone Inhibiting Hormone (GHIH)
  • Corticotrophin-Releasing Hormone (CRH)
  • Dopamine
681
Q

What does Thyrotropin Releasing Hormone (TRH) stimulate in the anterior pituitary gland to release?

A
  • Thyroid Stimulating Hormone (TSH)

* Prolactin (PRL)

682
Q

What does Gonadotropin Releasing Hormone (GnRH) stimulate the anterior pituitary gland to release?

A
  • Luteinising Hormone (LH)

* Follicle Stimulating Hormone (FSH)

683
Q

What does Growth Hormone Releasing Hormone (GHRH) stimulate the anterior pituitary gland to do?

A

Release Growth Hormone (GH)

684
Q

What does Growth Hormone Inhibiting Hormone (GHIH) stimulate the anterior pituitary gland to do?

A

Inhibit Growth Hormone (GH)

685
Q

What does Corticotrophin-Releasing Hormone (CRH) stimulate the anterior pituitary gland to release?

A

Adrenocorticotrophic hormone

686
Q

What does dopamine stimulate in the anterior pituitary gland to do?

A

Inhibit prolactin releasing factor (PRL)

687
Q

What are the hormones that the anterior pituitary gland releases?

A
  • Adrenocorticotrophic Hormone (ACTH)
  • Follicle stimulating Hormone (FSH)
  • Luteinising Hormone (LH)
  • Growth Hormone (GH)
  • Thyroid Stimulating Hormone (TSH)
688
Q

What hormones are released from the posterior pituitary gland?

A
  • Antidiuretic Hormone (ADH)

* Oxytocin

689
Q

How is ADH and oxytocin activated for synthesis?

A

Activated by osmoreceptors

690
Q

Where is antidiuretic hormone (ADH) synthesised?

A

Supraoptic nucleus

691
Q

Where is oxytocin synthesised?

A

Paraventricular nucleus

692
Q

How is the posterior pituitary gland stimulated?

A

Neurological signals are passed down the nerve axons of the supraoptic and paraventricular nucleus into the posterior pituitary

693
Q

What is the role of oxytocin in the body?

A

Reproduction

694
Q

What is oxytocin medically used for?

A

To induce uterine contraction -> labour

695
Q

Why is oxytocin known as the happy hormone?

A

Pregnancy amnesia - forget the stress associated with giving birth

696
Q

What is the target organ of adrenocorticotrophic hormone?

A

Adrenal cortex

697
Q

What is the action stimulated on the adrenal cortex by adrenoocorticotrophic hormone?

A
  • Glucocorticoid synthesis

* Pigmentation

698
Q

What is the target organ of follicle stimulating hormone?

A
  • Ovary

* Testis

699
Q

What is the action stimulated by the ovaries by the follicle stimulating hormone?

A
  • Oestrogen synthesis

* Oogenesis

700
Q

What is the action stimulated by the testis by the follicle stimulating hormone?

A

Spermatogenesis

701
Q

What is the target organ of growth hormone?

A
  • Liver

* Other

702
Q

What is the action stimulated on the target organ by the growth hormone?

A

IGF-1 synthesis - liver only

703
Q

What is the target organ of luteinising hormone?

A
  • Ovary

* Testis

704
Q

What is the action stimulated on the ovaries by luteinising hormone?

A
  • Ovulation

* Progesterone synthesis

705
Q

What is the action stimulated on the testis by luteinising hormone?

A

Testosterone

706
Q

What is the target organ of prolactin?

A

Breast

707
Q

What is the action stimulated on the breast by prolactin?

A

Lactation

708
Q

What is the target organ of thyroid stimulating hormone?

A

Thyroid

709
Q

What is the action stimulated on the thyroid by thyroid stimulating hormone?

A

Synthesis of thyroid hormone - T3 and T4

710
Q

What is the target organ of antidiuretic hormone?

A

Kidneys

711
Q

What is the action stimulated on the kidneys by antidiuretic hormone?

A

Osmolality regulation

712
Q

What is the target organ of of oxytoxcin?

A
  • Uterus

* Breast

713
Q

What is the action stimulated on the uterus by oxytocin?

A

Uterine contractility

714
Q

What is the action stimulated on the breasts by oxytocin?

A

Lactation

715
Q

When is growth hormone produced?

A

In pulses during the night/while sleeping

716
Q

What is the role of GH?

A
  • Produce IGF-1

* Glycogenesis – breakdown of glycogen

717
Q

How does GH and insulin interact?

A

Antagonistic function with insulin as it inhibits it, preventing insulin induced absorption of glucose to try to regain normal serum [glucose]

718
Q

What does IGF-1 do?

A
  • Stimulates cell growth
  • Increase protein synthesis
  • Enhance lipolysis of adipose tissue
  • Decrease glucose uptake
719
Q

What negatively regulates GH?

A

IGF-1, which inhibits both the hypothalamus and pituitary

720
Q

What stops the hypothalamus and anterior pituitary gland from producing more hormones when activated by GHRH?

A
  • IGF-1

* GH – before reaching the liver

721
Q

What glucocorticoids are released under the control of adrenocorticotrophic hormone (ACTH)?

A

Cortisol from adrenal cortex

722
Q

When is cortisol secreted?

A
  • Secreted in a circadian rhythm

* High at 8am, low at 12pm

723
Q

How is adrenocorticotrophic hormone important in pigmentation?

A

Stimulates melanocytes to produce melanin

724
Q

What are the functions of glucocorticoids?

A
  • Increase protein concentration
  • Increase hepatic glycogenolysis
  • Increase hepatic gluconeogenesis
  • Permissive effect on water excretion
725
Q

What triggers adrenocorticotrophic hormone?

A
  • Stress
  • Fear
  • Illness
726
Q

What stops the hypothalamus and the anterior pituitary gland from producing more hormone when activated by corticotrophin releasing hormone?

A

Cortisol

727
Q

What stops the hypothalamus and the pituitary gland from producing more hormones when activated by thyrotropin releasing hormone?

A
  • Free thyroid hormones – T3 and T4

* Main exertion is towards TSH secretion

728
Q

What are gonadotrophins?

A
  • Follicle stimulating hormone (FSH)

* Luteinising hormone (LH)

729
Q

What stops the hypothalamus and the anterior pituitary from producing more hormones when activated by gonadotropin releasing hormone in females?

A
  • Oestradiol

* Progesterone

730
Q

What stops the hypothalamus and the anterior pituitary from producing more hormones when activated by gonadotropin releasing hormone in males?

A
  • Testosterone

* Inhibin

731
Q

What is the process of ovarian follicular development?

A
  • FSH and LH rise and fall in the follicle maturation
  • They fall in response to rising oestradiol
  • Once near ovulation LH and FSH rise and oestradiol falls
  • Once ovulation occurs LH and FSH drop and oestradiol and progesterone rise
732
Q

What produces oestradiol in ovarian follicular development?

A
  • Follicle cell

* Corpus luteum

733
Q

What produces progesterone in ovarian follicular development?

A

Corpus luteum

734
Q

What produces follicle stimulating hormone in ovarian follicular development?

A

Follicle cell

735
Q

What produces luteinising hormone in ovarian follicular development?

A

Follicle cell

736
Q

What can occur if [prolactin] is high?

A

Can inhibit GnRH in the hypothalamus and LH/FSH in the pituitary - inhibits ovulation

737
Q

What is a feature of prolactin releasing factor?

A
  • It is hypothetical
  • All other hormones have known positive regulators, none has yet been determined for prolactin
  • Dopamine is thought to negatively regulate prolactin
738
Q

What are some pituitary disorders?

A
  • Hypopituitarism
  • Growth hormone deficiency
  • Acromegaly/Gigantism
  • Pituitary tumours
  • Anorexia Nervosa
739
Q

What is hypopituitarism?

A
  • Reduced (or no production) of 1 or more of the pituitary hormones
  • Can be pronounced in children, less so in adults
740
Q

What are the most common causes of hypopituitarism?

A

• Pituitary tumours – destructive is hypopituitarism, functional is hyperpituitarism

741
Q

What are the causes of hypopituitarism?

A
  • Hypothalamus disorder
  • Genetic/congenital
  • Trauma/haemorrhage
  • Infection
  • Surgery
  • Cerebral tumours
  • Pituitary tumours
742
Q

What are the symptoms of hypopituitarism?

A
  • Fatigue
  • Weight loss
  • Decreased sex drive
  • Decreased appetite
  • Facial puffiness
  • Anaemia
  • Infertility
  • Irregular or no periods
  • Loss of pubic hair
  • Inability to produce milk for breast-feeding in women
  • Decreased facial or body hair in mean
  • Short stature in children
  • Diabetes insipidus (posterior)
743
Q

What is the relation of GH deficiency with morbidity and mortality?

A

In adults - significant

744
Q

What are the symptoms of growth hormone deficiency?

A
  • Non-specific – may be asymptomatic
  • Reduced bone mineral density
  • Increased risk of bone fractures
  • Impaired cardiac function
  • Accelerated cardiovascular disease
  • Central obesity
  • Increased insulin sensitivity
  • Reduced exercise capacity
  • Emotional disturbances
  • Decreased quality of life
  • Reduced life expectancy
745
Q

What are the causes of growth hormone deficiency?

A
  • Pituitary tumours
  • Surgical/radiation treatment for pituitary tumours
  • Head injury
  • Hemochromatosis
  • Lymphocytic hypophysitis
  • Sarcoidosis
746
Q

What is anorexia nervosa when the BMI falls below 20 kg/m2?

A
  • The secretion of GnRH often impaired

* Causing low levels of LH, FSH and oestradiol

747
Q

What are the thyroid levels in anorexia nervosa?

A
  • T4 often falls below normal values

* T3 nearly always subnormal

748
Q

What are the cortisol and growth hormone levels in anorexia nervosa?

A

Often increased because of starvation

749
Q

Can anorexia nervosa be reversed?

A

Yes, once normal eating patterns and normal weight has been restored

750
Q

What re the features of baseline investigations of growth hormone disorder?

A
  • GH levels are usually undetectable during the day

* IGF-1 is stable so is used as a marker of GH function

751
Q

What is the IGF-1 level that is consistent with GH deficiency?

A

Low serum [IGF-1]

752
Q

What are the features of glucose administration to measure GH disorder?

A
  • Administering glucose will lead to suppression of GH
  • Patient fasts for 12hrs and given glucose
  • GH levels monitored over time to detect excess
753
Q

What does an insulin stress test, test?

A

HPA axis

754
Q

What are the features of the insulin stress test?

A
  • Induced hypoglycaemia leads to an increase in GH, ACTH, and cortisol
  • If the hypothalamus or pituitary are affected this will not happen
  • Emergency glucose must be available in case of hypoglycaemia
755
Q

What is a treatment of hypopituitarism?

A

Replacement hormone therapy - stimulation of affected pathway

756
Q

If deficient in ACTH what would be the replacemnet hormone?

A

Hydrocortisone

757
Q

If deficient in TSH what would be the replacement hormone?

A

Thyroxine

758
Q

If deficient in LH/FSH in males what would be the replacement hormone?

A

Testosterone

759
Q

If deficient in LH/FSH in females what would be the replacement hormone?

A

Oestrogen

760
Q

If deficient in GH what would be the replacement hormone?

A

GH

761
Q

If deficient in ADH what would be the replacement hormone?

A

DDAVP - desmopressin

762
Q

If deficient in prolactin what would be the replacement hormone?

A

None

763
Q

Who is the most famous with gigantism?

A
  • Robert Wadlow
  • Nearly 9 feet tall – 10’9” coffin
  • Died aged 22 – septic blister on ankle
764
Q

What are the symptoms of acromegaly?

A
  • Pronounced/coarse facial features
  • Protruding brow and jaw
  • Enlarged hands and feet
  • Abnormal height (tall)
765
Q

What percentage of acromegaly cases are due to adenomas of the anterior pituitary gland?

A

99%

766
Q

What is the biochemistry of acromegaly?

A
  • Increased GH

* Increased IGF-1

767
Q

What is the test used to diagnose acromegaly?

A

Oral glucose tolerance test (OGTT)

768
Q

What are the features of OGTT?

A
  • Response of plasma [GH] to an oral glucose tolerance test

* Blood samples are taken measuring [GH] and [glucose]

769
Q

In patients with acromegaly what does the OGTT look like?

A

Plasma [GH] does not fall in response to stimulus of hyperglycaemia - may even increase

770
Q

What does OGTT used to diagnose?

A
  • Diabetes mellitus
  • Renal failure
  • Anorexia
  • Liver disease
771
Q

What is the treatment of acromegaly?

A
  • Surgery to remove adenoma

* Medication

772
Q

What medication is used to treat acromegaly?

A
  • Dopamine agonists
  • Somatostatin analogues such as octreotide
  • Pegvisomant
773
Q

What does dopamine agonists do to treat acromegaly?

A

Can supress GH production (not always effective)

774
Q

What does somatostatin do to treat acromegaly?

A
  • Injection into muscle once a month

* Controls GH release and lead to tumour shrinkage in some people

775
Q

What does pegvisomant do to treat acromegaly?

A
  • Daily injection

* Lowers IGF-1 but not GH

776
Q

What are the three zones of the adrenal cortex?

A
  • Zona glomerulosa
  • Zona fasciculata
  • Zona reticularis
777
Q

Where in the adrenal cortex is aldosterone produced?

A

Zona glomerulosa

778
Q

Where in the adrenal cortex are glucocorticoids produced?

A

Zona fasciculata and zona reticularis

779
Q

Where in the adrenal cortex are androgens produced?

A

Zona reticularis and to some extent zona fasciculata

780
Q

Where does adrenaline bind?

A

Adrenergic receptors – α1, α2 or β

781
Q

Where do beta blockers target?

A

Adrenergic receptors to tamper down adrenaline

782
Q

What does binding of adrenaline do?

A
  • Activates adrenergic receptors
  • GPCR receptors
  • Increases blood pressure, heart rate, constrict blood vessels and pupil dilation
  • Increased oxygen and glucose to muscles
  • Fight or flight
783
Q

What enzymes is adrenaline metabolised by?

A
  • Catechol-o-methyl transferase (COMT)

* Mono amine oxidase (MAO)

784
Q

What is the flow of adrenaline metabolism?

A
  • Epinephrine is metabolised by catechol-o-methyl transferase into metanephrine
  • Metanephrine is metabolised by mono amine oxidase to vanillylmandelic acid
785
Q

In what condition is large amounts of vanillylmandelic acid found?

A

Neuroblastoma - abdominal swelling

786
Q

What does the mechanism of adrenaline (catecholamine) metabolism prevent?

A

Prevents negative effects of adrenaline - fear, trembling

787
Q

How is cortisol activated?

A
  • Protein bound to cortisol binding globulin
  • Binds to glucocorticoid receptor (GR) in the nucleus
  • Gene transcription
  • Activating many pathways
788
Q

What percentage of glucocorticoid activity is cortisol?

A

95%

789
Q

What does glucocorticoid secretion effect?

A
  • Carbohydrate metabolism
  • Fat metabolism
  • Protein metabolism
790
Q

What does cortisol do in the liver?

A
  • Stimulates gluconeogenesis
  • Amino acid uptake
  • Degradation
791
Q

What are the effects of glucocorticoid secretion?

A
  • Lipolysis is increased in adipose tissue
  • Proteolysis and amino acid release promoted in muscle
  • Glucocorticoids are mainly protein bound (90%)
792
Q

What are glucocorticoids chiefly bound to?

A

Cortisol-binding globulin or transcortin (CBG)

793
Q

What are the three factors that regulate adrenocorticotrophic acid and therefore cortisol secretion?

A
  • Negative feedback control
  • Stress
  • Diurnal rhythm of plasma [cortisol]
794
Q

How does negative feedback regulate adrenocorticotrophic acid?

A
  • ACTH release from anterior pituitary is stimulated by hypothalamic secretion of CRH
  • Increased plasma [cortisol] or synthetic glucocorticoids supress secretion of CRH and ATCH
795
Q

How does stress regulate adrenocorticotrophic acid?

A
  • Sudden large increase in CRH (and ACTH) secretion

* Due to major surgery or emotional stress

796
Q

How does diurnal rhythm of plasma [cortisol] regulate adrenocorticotrophic acid?

A

Relates to the individuals sleeping/waking cycle

797
Q

What does aldosterone regulate?

A
  • Water
  • Electrolyte balance
  • Blood pressure
798
Q

What converting enzyme converts androstenedione to testosterone?

A

Aromatase

799
Q

What do patients presenting with acute adrenal failure require?

A

Immediate treatment

800
Q

What samples should be taken with adrenal hypofunction?

A
  • Blood – electrolytes and glucose measurement

* Later plasma [cortisol]

801
Q

What is Addison’s disease caused by?

A
  • Destruction of adrenal cortex
  • Tuberculosis
  • Idiopathic atrophy
  • Trauma
  • Drugs
  • Infection
  • Medication (iatrogenic)
802
Q

What is autoimmune Addison’s disease caused by?

A

Adrenal enzyme antibodies block 21-hydroxylase

803
Q

What are most clinical features due to in Addison’s disease?

A
  • Lack of glucocorticoids and mineralocorticoids

* Due to cortisol deficiency

804
Q

What are the symptoms of Addison’s disease?

A
  • Bronze pigmentation of skin
  • Changes in distribution of body hair
  • GI disturbances
  • Weakness
  • Weight loss
  • Postural hypotension
  • Hypoglycaemia
805
Q

What is the adrenal crisis of Addison’s disease?

A
  • Profound fatigue
  • Dehydration
  • Vascular collapse (decreased blood pressure)
  • Renal shut down
  • Decreased serum [Na]
  • Increased serum [K]
806
Q

What is hyperpigmentation due to?

A
  • High [ACTH]
  • No cortisol so pituitary continue to signal ACTH
  • Caused by melanocyte hormone production
807
Q

How is hyperpigmentation tested?

A
  • Synacthen test (synthetic ACTH)
  • Inject synthetic ACTH – measure cortisol
  • If no change this indicates adrenal failure
808
Q

What are the symptoms of Cushing’s syndrome?

A
  • Central obesity
  • Urinary free glucose and cortisol increased
  • Suppressed immunity
  • Hypercortisolism, hypertension and hyperglycaemia
  • Increased corticosteroids
  • Neoplasms
  • Glucose intolerance, growth retardation
809
Q

What can hyperfunction of the adrenal cortex lead to overproduction of?

A
  • Cortisol

* Aldosterone

810
Q

What is Cushing’s syndrome an overproduction of?

A

Cortisol

811
Q

What is Conn’s syndrome an overproduction of?

A

Aldosterone

812
Q

What are the clinical features of Cushing’s syndrome?

A
  • Women 3x more likely to develop
  • Prolonged cortisol production and exposure
  • Obesity
  • Thinning of skin
  • Purple striae
  • Excessive bruising
  • Hirsutism
  • Skin pigmentation
  • Glucose intolerance
  • Hypertension
  • Muscle weakness and wasting
  • Menstrual irregularities
  • Back pain
  • Psychiatric disturbances
813
Q

What are the causes of Cushing’s syndrome?

A
  • ACTH treatment
  • Pituitary hypersecretion of ACTH
  • Adrenal adenoma
  • Adrenal carcinoma
  • Ectopic ACTH secretion by tumours
814
Q

What is the main cause of Cushing’s syndrome?

A

Pituitary tumour - approximately 70% of cases

815
Q

What is the difference between Cushing’s syndrome and disease?

A
  • Syndrome – excessive medication or tumour leads to excess cortisol by adrenal glands
  • Disease – cause is pituitary tumour effecting ACTH
816
Q

What is the treatment of Cushing’s?

A
  • If drug related withdraw medication slowly
  • Tumours are surgically removed
  • Glucocorticoid antagonists/agonists depending on level
  • In severe cases of tumours removal of entire adrenal glands
817
Q

What is used to diagnose Cushing’s?

A

Dexamethasone - synthetic cortisol

818
Q

How is dexamethasone used to diagnose Cushing’s?

A
  • Dexamethasone supresses the secretion of CRH, ACTH, and cortisol
  • Therefore, cortisol levels fall below 50 nmol/L
  • Cortisol is metabolised before excretion into urine, high cortisol in urine indicate Cushing’s
819
Q

What is the biochemistry of Cushing’s in a diagnostic positive test?

A
  • Serum [cortisol] is increased at 10pm
  • Urinary [cortisol] is increased
  • Diurnal rhythm is lost
  • Plasma [ACTH] is normal or increased
  • Dexamethasone, high dose is suppressed
  • CRH increased response
820
Q

What is the biochemistry of adrenal tumour in a diagnostic positive test?

A
  • Serum [cortisol] is increased at 10pm
  • Urinary [cortisol] is increased
  • Diurnal rhythm is lost
  • Plasma [ACTH] is not detectable
  • Dexamethasone, high dose is not suppressed
  • CRH no response
821
Q

What is the biochemistry of ectopic ACTH-secreting tumour in a diagnostic positive test?

A
  • Increased serum [cortisol] at 10pm
  • Increased urinary [cortisol]
  • Diurnal rhythm is lost
  • Plasma [ACTH] is often much increased
  • Dexamethasone, high dose is not supressed
  • CRH test no response

Clinical Biochemistry (2 decks)

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