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HOM > Renal > Flashcards

Renal Flashcards

1
Q

At the most basic level, what are the kidneys responsible for

Why is this important

A

Urine production

By regulating urine composition, integrated with the CV system, the kidneys control the composition and volume of the body fluids

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2
Q

What kind of organs are the kidneys

A

Regulatory rather than excretory

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3
Q

Give 4 functions of the kidneys that are not studied in detail in these lectures

A

Excretion of metabolic waste, inactivated hormones, and foreign substances

Regulation of RBC production by producing erythropoietin

Activation of vitamin D3 to 1,25-dihydroxycholecalciferol as part of Ca2+ homeostasis

Gluconeogenesis in prolonged fasting

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4
Q

3 things that the kidneys regulate in bodily fluids

A

Osmolarity
Volume
Composition

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5
Q

How is the composition of body fluids maintained

A

Matching output to intake

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6
Q

Name 4 processes that the kidneys work in conjunction with

A

Regulation of ingestion (hunger etc)

Other excretory routes (CO2 excretion by lungs etc)

Regulation of metabolic processes

Control of absorption (eg Zn absorption is controlled by intestinal epithelium)

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7
Q

What is the extracellular compartment divided into

Give the volume of each

A

Blood plasma (within vasculature) ~3L

Interstitial fluid (around cells) ~13L

Trans cellular fluid (eg CSF) ~1L

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8
Q

How much intracellular fluid is there

A

~25L

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9
Q

Which bodily fluid compartment is the largest

A

ICF

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10
Q

Which compartment of fluid can the kidneys directly affect

A

Plasma

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11
Q

How much of the blood is plasma

What is the percentage make up of blood plasma

A

55%

91% water
7% protein
2% electrolyte, hormones, nutrients

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12
Q

How much osmotic pressure do ions eg K Ca and Cl exert across the capillary wall

A

NONE

their concentrations are similar either side as they freely cross the membrane

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13
Q

What is oncotic pressure

A

Colloid osmotic pressure

The osmotic pressure of proteins in blood
It pulls water into the blood

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14
Q

What resists oncotic pressure

A

Hydrostatic pressure (forces water out of capillaries)

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15
Q

Give the simplified renal version of Starling’s equation for Starling forces

A 
Jv = Kf(Pc - σπc)
Jv = volume flow
Kf = filtration coefficient 
σ = protein reflection coefficient (usually close to 1)
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16
Q

Why can Pif and πif be removed from the starling equation in renal

A

They are v small and vary v little

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17
Q

What is the filtration coefficient

A

The product of surface area and hydraulic conductivity this varying greatly between different capillaries

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18
Q

How does Pc (capillary hydrostatic pressure) vary across a capillary length? Why?

What about πc

A

Decreases linearly along the capillary

Due to resistance

No change

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19
Q

What is the net flux like from a capillary at the arteriolar and venous ends?

A

Net filtration at arteriolar (inward)

Net reabsorption at venous end (outward)

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20
Q

If there is a small net outward flux at the end of a capillary, why do we not swell

A

It is removed my lymphatics

If outward flux exceeds lymphatic removal, oedema ensues

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21
Q

What is autotransfusion

A

When capillary pressures are low (eg after blood loss), starling forces may favour movement from IF into capillary

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22
Q

What clinically happens to Starling forces in capillaries in cardiac failure

A

Hydrostatic pressure increases due to increased atrial pressure

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23
Q

What happens to capillaries in septicaemia

A

Capillaries become leaky to plasma proteins reducing σ (colloid reflection coefficient)

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24
Q

What happens in Kwashiorkor

What other syndrome would have a similar effect

A

Protein intake is low so plasma protein levels drop and πc falls

Nephrotic syndrome

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25
Q

Is oedema always life threatening?

A

No sometimes it is purely aesthetic

However, increased IF volume increases diffusion distance which can produce ulceration in the peripheries and pulmonary oedema is DEADLY

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26
Q

What is extravasation? When would it occur and what can it cause?

A

Movement out of blood vessels

Septicaemia

Circulatory collapse

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27
Q

What is the hydrostatic pressure like between the interstitial and intracellular spaces?

A

THERE IS NONE

Therefore only osmotic water movement is considered

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28
Q

Compare movement of fluid between the interstitial and intracellular spaces vs between plasma and interstitium

A

No hydrostatic pressure between first 2

Small ions cannot freely cross cell membranes do exert some osmotic pressure

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29
Q

True or false?

The osmolarity if the intracellular and interstitial fluid is equal at steady state

Why is this

A

True

If the osmolarity if IF changes water will flow across the cell membrane until equilibrium is reached

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30
Q

What is the major extracellular cation

A

Na+

(Makes up nearly 1/2 of total extracellular osmolarity)

It is membrane impermeable apart from Na/K pump

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31
Q

What are the major extracellular anions

What excludes them from cells

A

Cl- and HCO3-

The membrane potential

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32
Q

What are the 2 ways to change the osmolarity of a solution

How is it primarily done in the body

A

Change amount of solute

Change volume of solvent

Regulating amount of water in the body

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33
Q

Which phase is most important to osmoregularity

A

Water follows salt 🧂

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34
Q

Give an example of what can happen to cells if they swell

A

Ion channels open, disrupting membrane potential and cell signalling

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35
Q

Which organ is most vulnerable to damage by swelling

A

The brain as it is encased in the rigid skull

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36
Q

What is the normal range of osmolarity

A

268-290 mOsm.kg-1

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37
Q

What are the units used for osmolarity

A

mOsm.kg-1

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38
Q

How do each of the following affect cells:

a) hypertonic
b) hypotonic
c) isotonic

A

a) causes cell to shrink
b) causes cell to swell
c) does not affect cell

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39
Q

Is there a link between osmo and volume regulation

A

Yes

A Change in Na content translates to a change in ECF volume

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40
Q

Give an example of water intoxication

A

Girl in 1995 collapsed after drinking too much after taking Ecstasy

Occurs when someone drinks >7 litres in a short time, diluting the blood. Her plasma Na level had dropped to 252 mOsm.kg-1
Water was sucked into her brain under osmotic pressure swelling the brain
The increased pressure on the brain resulted in coma and death

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41
Q

Does all water enter the body through the digestive tract

A

No

Most does but some is produced by cellular metabolism

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42
Q

What is the net daily intake of water

A

2.5L

+700 from food
+1600 from drink
+0.2L from cellular respiration

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43
Q

What is insensible loss of water

A

Loss we are unaware of eg exhalation and sweat

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44
Q

How much water is lost by the kidney daily

A

1400ml

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45
Q

What mechanisms is water balance mostly controlled by

A

Water loss by ADH and water intake by thirst

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46
Q

What is the hypophysis

A

The pituitary gland (beneath hypothalamus)

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47
Q

Where is the pituitary gland found

How big is it

A

Below the hypothalamus in a skull depression called the sella turcica

Size and shape of a chickpea

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48
Q

Give a brief description of the pituitary

A

Divided into anterior and posterior

Hypothalamus is connected to anterior via short axons which innervate hypophyseal portal system

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49
Q

Give an example of neuroendocrinology

A

Hypothalamus releases factors into the hypophyseal portal system which stimulate the anterior pituitary. The anterior pituitary then releases long range endocrine signals

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50
Q

Name 3 endocrine hormones secreted by the anterior pituitary

A

TSH
FSH
ACTH

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51
Q

What is the adenohypophysis

A

Anterior pituitary

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52
Q

What is the other name for the posterior pituitary

What is its connection to the hypothalamus

A

Neurohypophysis

Neural only

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53
Q

What hormones does the posterior pituitary produced

A

Only 2

Oxytocin and ADH (vasopressin)

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54
Q

What is similar about the hormones produced by the posterior pituitary

A

Both constrictors of smooth muscle

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55
Q

How does vasopressin cause vasoconstriction

A

Binds to V1 receptors

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56
Q

Name some differences between vasopressin and ADH

A

there are none! They are the same hormone

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57
Q

Where does ADH act in the nephron

A

On the V2 receptors in All parts of the collecting duct? Including cortical collecting duct

Increases water reabsorption

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58
Q

How else does ADH increase the antidiuretic effect, other than increasing water reabsorption

A

Increasing urea permeability of inner medullary collecting duct

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59
Q

Compare affinity of ADH to V1 vs V2

A

Much higher affinity to V2

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60
Q

Why is ADH synthesised

A

In the neuroendocrine cells in the SON and PVN of the hypothalamus

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61
Q

What does SON and PVN stand for

A

Supraoptic nuclei

Paraventricular nuclei

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62
Q

How is newly synthesised ADH transported

A

ADH is packaged into granules and transported down neuron axon to be stored at terminal in posterior pituitary

Following an AP, ADH is secreted into systemic circulation by exocytosis

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63
Q

What dictates the amount of ADH released

A

Frequency of APs arriving at the SON

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64
Q

2 systems controlling ADH

Major physiological stimulus controlling ADH

A

Osmoregulatory system
Circulatory

ECF osmolarity

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65
Q

What detects ECF osmolarity

A

Hypothalamic osmoreceptors located near the SON and the OVLT

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66
Q

What is the OVLT

A

Organum vasculosum of the lamina terminalis

It is a circumventricular organ (acts outside blood brain barrier)

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67
Q

How does the OVLT detect a need for ADH

A

High [Na+] draws water out of OVLT, causing it to shrink and increase firing rate to SON/ PVN …

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68
Q

How Do changes in osmolarity affect the gut and ADH

How does this effect systemic ADH

What does this do ultimately

A

Reflexes in the gut and liver inhibit ADH release during drinking and water absorption respectively

Water absorption will dilute the plasma and promote a fall in ECF osmolarity which is detected by hypothalamic osmoreceptors. This results in a inhibition of ADH synthesis

Promotes water loss

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69
Q

How does the circulation detect changes in water content

A

An increase in blood volume leads to an increase in ABP which is detected by arterial baroreceptors

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70
Q

Where are the arterial baroreceptors

A

At the bifurcation of the common carotid in the carotid sinus

Aortic group are in the aorta

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71
Q

What happens when arterial baroreceptors sense an increase in BP

A

Signal to brainstem to increase frequency of discharge in afferent pathways. Brainstem interacts with hypothalamus to inhibit ADH synthesis and release

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72
Q

Where else (other than arterial baroreceptors) are blood volume sensors?

A

In the atria and great veins

These stretch and interact with hypothalamus to inhibit ADH secretion

This is part of the veno-atrial baroreflex

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73
Q

What is diuresis

A

Urine flow rate

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74
Q

Who did experiments on diuresis control

A

Verney

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75
Q

Describe the set up of Verney’s experiments

A

Water was administered to dogs by a stomach tube
Warm water was administered to stomach as high urine flow rate makes anti diuresis easier to measure
Diuresis measured using a catheter
Carotid arteries exteriorised to form carotid loops for introduction of fluid into carotid circulation and delivery to brain

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76
Q

What did Verney find

A

Intracarotid infusions of hypertonic NaCl reduced flow rate
However, isotonic infusions of NaCl and hypertonic infusions in malleolar vein had no effect

Antidiuretic effect also found when pituitary extract was injected into carotid loop

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77
Q

How sensitive are the osmoreceptors

A

Verney’s experiments showed antidiuresis with changes in osmotic pressure of carotid blood of 1.8% (very sensitive)

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78
Q

What did Verney find after performing a hypophysectomy

A

Hypertonic injections into the carotid were without effect but pituitary extract still caused diuresis

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79
Q

Which substances that were injecting hypertonically caused an effect

Which didnt

A

NaCl, fructose, sucrose, and sodium sulphate all caused diuresis

Urea did not cause an effect

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80
Q

Why does an increase in NaCl cause anti diuresis but not urea

A

Increased NaCl forces water out of the cell, making it shrink and triggering a signal

An increase in urea (which can freely enter the cell) is without effect on the volume of water inside the cell. There is no change in cell size and no signal is triggered

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81
Q

What does the graph of [ADH] secreted vs plasma osmolarity look like

Why is this

A

Very steep

So the system can be v sensitive

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82
Q

What the set point of ADH osmolarity and what happens here

A

282-290 mOsm.kg-1 H20

This is the value where ADH secretion begins

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83
Q

How would a fall in blood volume affect [ADH] in the blood

Why

A

Increase

BP would fall and dis-inhibit ADH release from the neurohypophysis via the baroreflex

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84
Q

How sensitive is the baroreceptor system compared to the osmoreceptor system

When can this be seen

What will this fall also do

A

Baroreceptor is much lower

A 5-10% drop in blood volume is required for an increase in plasma ADH

It will sensitise the relationship between plasma osmolarity and plasma ADH

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85
Q

Describe the cellular mechanisms underlying the antidiuretic effect of ADH

A

ADH binds to V2 receptors on the basolateral membrane of the collecting duct cells in the kidney

This results in activation of adenylyl cyclase, forming cAMP, which activates PKA.
PKA phosphorylates certain proteins, triggering the fusion of vesicles and exposing aquaporins on the apical membrane

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86
Q

What does the recruitment of aquaporins (AQPs) do

How much does ADH affect AQP content on the membrane

A

Transfers AQP2 to the membrane increasing its water permeability

Up to 6-fold (Neilson et al)

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87
Q

What is the water permeability like in the basolateral membrane

A

It is always high due to the constitutive presence of AQP3 and AQP4
The rate limiting step is at the apical membrane

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88
Q

How does ADH affect urea permeability

A

ADH stimulates the insertion of VRUT into the apical membrane of the inner medullary collecting duct

There are a number of urea transporters (UTs)
It is thought UTA is the one regulated by ADH

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89
Q

When do you feel thirsty (3)

Which is the most important stimulus

A

Hypertonicity (when body fluid osmolarity increases) this is the most important
Hypotension
Hypovolaemia (when blood volume decreases)

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90
Q

How much must plasma osmolarity change to produce thirst

What kind of thirst is this

A

2-3%

Osmotic thirst

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91
Q

How much must blood volume or pressure change to produce thirst

What kind of thirst is this

A

10-15% decrease

Hypovolaemic thirst

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92
Q

Where are the neural mechanisms controlling water intake located

A

The thirst centre of the hypothalamus near the OVLT

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93
Q

What does OVLT stand for

A

Organum vasculosum of the lamina terminalis

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94
Q

What do thirst centre cells respond to

A

An increase in osmotic pressure as a result of cellular shrinkage

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95
Q

What is thought to inhibit thirst receptors

How would a fall in blood volume affect thirst

A

Circulatory stretch receptors present in arterial baroreceptors, the atria, and the great veins

A fall in volume would dis-inhibit the influence of stretch receptors on the thirst centre, and the individual would perceive thirst

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96
Q

Where are the neural mechanisms controlling water intake located

A

The thirst centre of the hypothalamus near the OVLT

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97
Q

What does OVLT stand for

A

Organum vasculosum of the lamina terminalis

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98
Q

What do thirst centre cells respond to

A

An increase in osmotic pressure as a result of cellular shrinkage

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99
Q

What is thought to inhibit thirst receptors

How would a fall in blood volume affect thirst

A

Circulatory stretch receptors present in arterial baroreceptors, the atria, and the great veins

A fall in volume would dis-inhibit the influence of stretch receptors on the thirst centre, and the individual would perceive thirst

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100
Q

What is a dipsogen and who coined this term

A

A molecule that stimulates thirst

Prof James Fitzsimons in the Downing Site, Cambridge

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101
Q

Name a powerful dipsogen

A

Angiotensin II

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102
Q

How did Fitzsimons show that Angiotensin II is a dipsogen

What is AII mediated by

A

When injected into the OVLT, it causes an immediate increase in water intake

AT1 receptors

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103
Q

What kind of thirst do Angiotensin II injections cause

A

Highly motivated, vigorous drinking

The water drank within 15 minutes of the injection exceeds that which the animal would normally drink in a 24 hour period

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104
Q

What is diabetes insipidus

A

Characterised by the production of large volumes of dilute insipid urine

Can be caused by failed ADH production or secondary to a head trauma, brain tumour or congenital absence or a failure of the kidneys to respond to ADH

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105
Q

What is neurogenic diabetes insipidus

A

Diabetes insipidus caused by congenital absence Leading to reduced/ insufficient production of ADH

Eg inherited mutation of the AVP-NPII gene or Wolfram Syndrome

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106
Q

What is nephrogenic diabetes insipidus

A

DI caused by a failure of the kidneys to respond to ADH

Usually acquired, eg: from kidney disorders (eg poly cystic kidney disease) or lithium toxicity

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107
Q

How Can Diabetes insipidus be treated

A

Administering a synthetic ADH analogue via a nasal spray

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108
Q

Name an ADH analogue

A

Desmopressin acetate

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109
Q

Is DI usually fatal

A

No as thirst mechanisms are usually functional and plenty of water is available

Polydipsia (excessive drinking) gives rise to polyuria (excessive urine production)

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110
Q

Why is ECF volume related to the Frank Starling Law

A

It is related to plasma volume which is related to MSFP and in turn related to venous return. According to the Frank Starling mechanism, increased venous return increases cardiac output.

This therefore means that ECF volume impacts blood pressure

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111
Q

What is the main cation in the ECF

A

Na+

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112
Q

What is the volume of ECF primarily determined by

Why

A

Na+ content as Na+ is excluded from the cells due to the low membrane permeability and Na pump activity

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113
Q

How fast is ECF volume control

What does ECF volume reflect

A

V slow (from hours to days)

Short term changes ranging from -10 to 20%

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114
Q

Is osmoregulation subordinate to ECF volume control

What does this mean

A

No ECF volume is subordinate to osmoregulation

Changes in osmotic pressure will drive changes in ECF volume which will in turn change ABP

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115
Q

What is hypernatraemia and what does it lead to

A

Increased blood [Na+]

It promotes hypertension

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116
Q

How is ECF volume mainly achieved

A

By varying the loss of Na+ lost in urine

There is also a little control via “sodium appetite”

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117
Q

What are the 4 factors affecting sodium balance

A

Physical
Neural
Endocrine
Behavioural

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118
Q

What do the physical factors affect Na balance

A

Net filtration pressure in the glomerulus

Starling forces across the peritubular capillaries

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119
Q

Why can baroreceptors not work in the long term

A

They minimised short term blood pressure changes but sustained changes in blood pressure for over 24 hours causes the baroreceptors to adapt and reset

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120
Q

What does sustained ABP lead to

What is this called

A

Increased GFR leading to increased Na+ loss

The loss of Na due to raised ABP is called pressure natriuresis

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121
Q

What is the response to pressure natriuresis ?

A

The response is two fold:

Increase filtration and decrease reabsorption

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122
Q

Discuss the filtration response to pressure natriuresis

A

Increased ABP will increase glomerular capillary hydrostatic pressure (Pc).
This increases net filtration pressure and increases GFR

This all results in a promotion of Na+ excretion in the collecting duct

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123
Q

Describe the decreases reabsorption side of the response to pressure natriuresis

A

Increased ABP leads to increased peritubular capillary hydrostatic pressure
This reduces movement of fluid into these capillaries, raising renal interstitial hydrostatic pressure (RIHP), thus reducing fluid reabsorption in proximal tubule
This will increase tubular hydrostatic pressure, reinforcing natriuresis

Back leakage in tubule increases due to leaky proximal tubule

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124
Q

Why do we think other factors affect the response to pressure natriuresis

A

The effect of pressure changes in vivo is greater than in perfused kidneys (in vitro)

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125
Q

How does ECF affect colloid osmotic pressure (COP)

A

An increase in ECF volume leads to a decrease in COP due to [plasma proteins] being lower as volume has increased

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126
Q

What is the dual mechanism that alter Na excretion when there is a change in COP

A

A decrease in glomerulus capillary COP will favour Na excretion

Decreased peritubular capillary COP will reduce movement of fluid into these capillaries, raising RIHP, which reduces fluid reabsorption from the tubule
This increases tubular hydrostatic pressure and reinforces natriuresis

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127
Q

What are the main nerve fibres comprising the renal nerves

A

Sympathetic post ganglionic fibres from the coeliac plexus and the inferior splanchnic nerves

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128
Q

Where do the renal nerves enter the kidney

What is their course

A

At the hilum

Follows the tributaries of the renal arteries to reach individual nephrons

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129
Q

What modulates renal sympathetic nerve activity

A

Altered inputs to the CNS from cardiopulmonary receptors (atria and great veins) and arterial baroreceptors

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130
Q

How does a fall in ABP affect renal sympathetic nerves

A

increased ABP elicits a dose dependant increase in the frequency of renal sympathetic nerve activity

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131
Q

Where can the measure of the baroreflex sensitivity be seen

A

The linear part of a MAP vs RSNA graph

The baroreflex set point is the midpoint of this graph

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132
Q

What are the 3 main effects of RSNA

A

Directly stimulates Na+ reabsorption (mainly via the proximal tubule) via α1 adrenoreceptors. It promotes Na+/H+ exchange

Constriction of both afferent and efferent glomerular arterioles

Promotion of the secretion of renin, resulting in increased production of Na+ retaining hormones and therefore interacting with endocrine factors affecting Na+ balance

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133
Q

Does RSNA constricting glomerular arterioles affect GFR?

A

No tubulo- glomerular feedback maintains GFR

Only under intense RSNA (eg in haemorrhage) does renal blood flow fall low enough to significantly decrease GFR, minimising Na+ excretion

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134
Q

Are both efferent and afferent arterioles affected by RSNA equally

A

No there is evidence of a greater density of α1 receptors in the afferent for greater constriction of afferent arteriole

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135
Q

What are the 3 main hormones influencing Na+ excretion

Give their abbreviations

A 
Angiotensin II (AII)
Aldosterone (Aldo)
Atrial Natriuretic Peptide (ANP)
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136
Q

Where is renin secreted

A

By modified smooth muscle in the wall of the afferent arteriole of the nephron - (part of the juxta glomerular apparatus)

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137
Q

What is the juxta glomerular apparatus

A

The relationship between the juxtaglomerular cells of the afferent arteriole and the macula Densa in the ascending loop of Henle

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138
Q

What does the macula densa do, simply?

A

Detects changes in tubular fluid composition

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139
Q

What does renin do to angiotensin

A

Renin catalysed the production of Angiotensin I from the precursor plasma globulin, angiotensin

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140
Q

What is the structure of angiotensin I

A

A decapeptide

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141
Q

How is angiotensin I converted to AII

A

It is cleaved into a octapeptide (AII) by angiotensin converting enzyme (ACE)

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142
Q

Where is ACE found

A

In lung capillaries

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143
Q

What is the normal circulating Level of AII

How may this change in severe Na+ depletion

A

500-600 pMolar

Ten fold

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144
Q

What are the 3 main factors for renin release

A

1) afferent arteriole acts as intrarenal baroreceptor. A fall in P here promotes renin secretion
2) renal sympathetic nerves release noradrenaline that can stimulate renin secretion via β2 adrenoreceptors
3) change in composition/ flow rate of fluid at the macula densa

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145
Q

What regulates sympathetic nerve stimulation of renal β1 receptors

A

Atrial/ great vein volume receptors and arterial baroreceptors

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146
Q

How will GFR affect renin release

What does this result in

A

A fall in GFR will Lowe the Na load at the macula densa, stimulating renin

Increased renin will promote Na reabsorption at proximal tubule, further decreasing Na load at macula densa
This creates a positive feedback loop

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147
Q

Once AII is synthesised it has 3 distinct effects. What are these

A

Vasopressor effects

Sodium retention effects

Stimulation of aldosterone secretion

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148
Q

Discuss the vasopressor effects of AII

A

It can directly and powerfully cause vasoconstriction via its Action on AT1 receptors
This raises TPR as arterioles constrict and thereby ABP

after volume depletion, AII contributes to the general increase in vascular tone

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149
Q

Discuss the Na retention effects of AII

A

Mimics effects of sympathetic stimulation on the kidney:
Na reabsorption at proximal tubule
Increases Na+/H+ exchange

Increased Na+ reabsorption increases water reabsorption, increasing blood volume

Constricts renal arterioles (but efferent more than afferent unlike RSNA)

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150
Q

What does AII induced efferent arteriole constriction do

What is the short term and long term effect of this

A

Promotes an increase in the filtration fraction

Short term: favours Na+ excretion
Long term: the opposite- assists An+ reabsorption

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151
Q

How does AII induced efferent arteriole constriction promote Na reabsorption

A

Increased GFR drags water with it, increasing COP downstream of peritubular capillaries

This increases fluid reabsorption from renal interstitial space into blood vessel
A more concentrated interstitial will drag more fluid out of the proximal tubule, reducing renal hydrostatic pressure.

This reduced pressure will reduce speed of urinary Na loss and increase time for Na reabsorption in the collecting duct

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152
Q

Discuss the aldosterone secreting property of AII

A

AII stimulates aldosterone synthesis and secretion by the adrenal glands via AII action on AT2 receptors

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153
Q

How big are the suprarenal glands and what shape are they

A

Drawn as a triangle

Size of a walnut

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154
Q

Discuss the structure of the suprarenal glands

A

2 zones: inner adrenal medulla and outer adrenal cortex

Cortex is divided into 3 layers: zona glomerulosa; zona fasciculata; and zona reticulartis (from out inward)

Remember with acronym (GFR)

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155
Q

Where is adrenaline secreted

A

Adrenal medulla

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156
Q

What are the 2 families of hormones

What distinguishes each

A

Peptides and steroids

Peptides are water soluble
Steroids are fat soluble

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157
Q

What does the different solubility of peptides vs steroids mean for their action

A

Peptides have to act on membrane receptors

Steroids can diffuse through the cell’s lipid membrane and act directly inside the cell

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158
Q

What are the 3 kinds of steroid hormones

A

Mineralcorticoids
Glucocorticoids
Sex hormones

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159
Q

What are the 3 types of sex hormone

A

Oestrogens
Progesterones
Androgens

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160
Q

Where are mineralcorticoids secreted and give an example of one

A

The zona glomerulosa

Aldosterone

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161
Q

What does the zona fasciculata synthesise

Give an example

A

Glucocorticoids

Cortisol

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162
Q

Where are androgens made

Give an example of an androgen

A

Zona reticularis

DHEAS

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163
Q

Where does aldosterone act

A

On the distal parts of the renal tubule, mainly the cortical collecting duct

May also act on thick ascending loop of Henle

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164
Q

What does aldosterone do

What is its main regulatory role

A

Promotes:
Na+ reabsorption
K+ secretion
H+ secretion

K+ excretion

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165
Q

Where does aldosterone act primarily

A

The distal nephron in principal cells

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166
Q

What does aldosterone do on a cellular level?

A

Acts on DNA to increase mRNA in principal cell for 3 different proteins:
ENaC
SK
Na/K pump

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167
Q

What is ENaC

A

Epithelial Na+ channel found in the epithelial of the distal nephron

It increases in density and activity when aldosterone levels increase

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168
Q

What are SK channels

A

Small conductance K+ channels believed to be responsible for K+ secretion increase

They increase in density when Aldosterone levels rise

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169
Q

What do the extra channels formed by aldosterone action result in

A

Additional ENaC increase Na+ entry across apical membrane
The resulting increase in cytosolic [Na+] stimulates removal by Na/K pump across basolateral membrane - Na pumping capacity is increased

Increased SK channels favour K+ diffusion into the tubule lumen. This increases trans-epithelial potential

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170
Q

What is the effect of aldosterone on type A intercalated cells

A

Increase H+ secretion from these acid secreting cells

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171
Q

How does AII affect thirst

A

AII is a dipsogen and increases thirst, helping to maintain blood volume

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172
Q

What behaviour does AII stimulate

A

Thirst and sodium appetite

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173
Q

Discuss the effect of AII on sodium appetite

Give experimental evidence

A

Increases Na appetite
Increased Na increases the blood’s osmotic pressure. This leads to an increase in blood volume and thus ABP

Repeated injections of AII into rat brains stimulate drinking of NaCl solutions in preference to fresh water

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174
Q

Where is ANP made

Discuss the structure of ANP

Where is it present

A

Atrial myocytes contain granules of the precursor of ANP

It is a hormone made of 28αα
It is present in the plasma and it’s concentration increases when atrial stretch is increased

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175
Q

What is the overall aim of ANP

A

To promote natriuresis

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176
Q

When do ANP levels decrease

A 
ANP’s overall aim is natriuresis and a loss of Na leads to a loss of water, 
reducing ECF volume
MSFP falls
VR falls
Atrial stretch falls
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177
Q

Give the 5 actions of ANP

A
  1. Vasomotion of the glomerular arterioles
  2. Inhibition of renin secretion
  3. Inhibition of Na reabsorption in medullary collecting duct
  4. Inhibition of Na reabsorption in proximal tubule
  5. Inhibition of ADH secretion
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178
Q

Why does ANP inhibit ADH

A

To increase water loss, decreasing blood volume and pressure

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179
Q

How does ANP inhibit Na reabsorption in medullary and cortical collecting duct

A

Direct action by increasing intracellular cGMP

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180
Q

How does ANP Inhibit Na reabsorption in proximal tubule

A

Indirect action

ANP stimulates proximal tubule cells to secrete dopamine which inhibits Na reabsorption

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181
Q

What is the effect of ANP decreasing renin secretion

A

AII and aldosterone levels fall this reducing Na reabsorption

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182
Q

What is the effect of ANP on glomerular arterioles

A

Efferent remains the same or is constricted and afferent diameter increases

This raises GFR and thus the amount of Na filtered

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183
Q

What is Addison’s disease

A

Adrenal insufficiency

Both aldosterone and glucocorticoids are deficient
Loss of aldosterone leads to natriuresis and reduced ECF volume and eventually circulatory collapse
Extracellular [K+] control also fails

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184
Q

What does excess aldosterone result in

A

Increased ECF volume, hypertension, K depletion and metabolic alkalosis

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185
Q

Is the movement of fluid between the interstitial and intracellular spaces influenced by the same variables as between the plasma and interstitium?

A

No they are entirely different

There is no hydrostatic pressure
Small ions cannot move across membranes freely so exert osmotic effect

186
Q

The osmolarity if the intracellular and interstitial fluid is equal. What happens if one changes

A

Water will flow across the membrane until equilibrium is attained

187
Q

How can hyper hydration be treated

A

With mannitol
It is an unreactive sugar that can cross capillary membrane but not cell membranes, thereby drawing water out of cells by osmosis

188
Q

Osmolarity =

A

Amount of solute
————————-
Amount of solution

189
Q

How do kidneys regulate osmolarity

A

Changing water (the solvent)

190
Q

What are the 5 things necessary for a material used to test ECF

A 
Restricted to one compartment 
Evenly distributed 
Not change volume itself
Not change over time (via excretion etc)
Non toxic
Easily measurable
191
Q

How is total body water measured

Why

A

D2O

Volume distribution is very large cf it’s rate of excretion

192
Q

How does the single injection method work

A

If there is a single injection, substance is not immediately equally distributed so you must wait until it is, but then some will be lost!

Therefore you extrapolate back to time of injection

193
Q

What is used in single injection method to measure blood volume

Why

A

Albumin with Evan’s blue

Confined to plasma and lost slowly

194
Q

When is constant infusion method used

What is it used to measure

What substance is used

A

If excretion is fast but lost by a single measurable route

Used to measure total ECF

Inulin- Something that can cross capillary membrane but not that of the cell

195
Q

How does constant infusion method work

A

Infuse substance at a constant rate until measured plasma concentration is constant
Stop infusion and then measure amount of substance excreted from that time

196
Q

How is ICF measured

A

Total body water-ECF

197
Q

How much of the blood at resting CO do the kidneys receive

How much do they weigh

A

25%

2% of human body weight

198
Q

What are the interlobular and arcuate arteries

A

Interlobular: in renal columns to renal cortex and Medulla

Arcuate: run along corticomedullary border and branch into interlobular arteries

199
Q

Where is most of the filtrate reabsorbed

A

Peritubular capillaries which follow the efferent arteriole

200
Q

What are the vasa recta

What do they do

A

Capillary loops that descend into the medulla before returning to the cortex

Maintenance of hyperosmotic environment within the medulla

201
Q

How much of the plasma is filtered from the glomerular capillaries

A

20%

202
Q

Give the basic function of the proximal tubule

A

Reabsorption of 70% of filtrate and all glucose and αα

Reabsorption is varied so proximal tubule is useful in volume regulation

Isotonic fluid reabsorption

203
Q

Mention the histology of the proximal tubule cells

A

Large surface area and many mitochondria

204
Q

Give the basic function of the loop of Henle

A

Separate reabsorption of solutes and water

Makes fluid leaving the loop hypo-osmotic to plasma and the inner medullary hyperosmotic

Therefore is central to concentration of urine

205
Q

Give the basic function of the distal tubule

A

Control of K+ and pH

Water reabsorption occurs here in concentrating kidney
In the diluting kidney it is water impermeable

206
Q

Give the basic function of the collecting duct

A

Allows water reabsorption into first the iso-osmotic cortex and then the hyper osmotic medulla

207
Q

What are the 2 populations of nephrons

A

Cortical and juxta medullary (only these have loops of Henle that descend into the inner medulla)

208
Q

Why can all nephrons use the hyperosmotic inner medulla to concentrate urine

A

All nephrons join collecting ducts that run in the inner medulla

209
Q

What is filtration

A

Movement of water and dissolved solutes through a filter due to a pressure gradient

210
Q

How does water pass from the glomerular capillaries into the Bowman’s capsule

Give detail

A

Through a 3 layer filter

3 layers: fenestrated capillary membrane, basal lamina, filtration skits between podocytes that line the capsule

211
Q

What is the most restrictive part of the 3 layered filtration in Bowman’s capsule

A

The diaphragms bridging the floors of the podocytes

212
Q

What is the role of the fenestrated capillary membrane

A

Large pores (~70nm) prevent passage of cells (~7μm) but allow passage of large proteins

213
Q

What is the role of the basement membrane in the glomerular capillary

A

Negatively charged to repel large negative proteins eg albumin but is too large to interact with small ions

restricts passage of large solutes

214
Q

What do the renal podocytes do

A

Most restrictive layer and carries a negative charge

215
Q

How is GFR primarily regulated

A

Changing capillary hydrostatic pressure by varying resistance in arterioles

216
Q

How does changing resistance in the glomerular arterioles change GFR

A

Increasing afferent resistance protects capillaries from high blood pressure and reduces Pc

Constructing efferent increases Pc

217
Q

Why have 2 arterioles

A

Flow=ΔP/ R

Allows control of Pc and plasma flow separately

Dilating afferent increases Pc AND renal plasma flow

Dilating efferent decreases Pc and increases renal plasma flow

218
Q

Equation for RBF (renal blood flow)

A

ΔP
———-
R(aff)+R(eff)

ΔP= arterial pressure - renal venous pressure

219
Q

How does the GFR change with ABP

A

Changing ABP has little effect on GFR within the normal range

220
Q

What are the mechanisms in place to keep GFR constant when ABP increases

A

Myogenic

Tubulo-glomerular feedback

221
Q

Describe the myogenic mechanism to control GFR

A

Afferent arteriole constricts when stretched and relaxes when released from stretched

222
Q

Describe tubulo glomerular feedback

A

Macula densa senses NaCl uptake
Increased NaCl suggests extra NaCl is being filtered / flow rate is too high for NaCl to be reabsorbed
Macula densa releases ATP, which releases a paracrine hormone to constrict adjacent hormone

223
Q

What are the most important mechanisms controlled GFR

A

Renin - Angiotensin system

RSNA

224
Q

How does the filtration coefficient effect GFR

A

Kf is the product of glomerular capillary permeability and capillary area for filtration

Kf can drop if pores are blocked or mesangial cells contract

225
Q

Why may a kidney stone impede filtration

A

Increases hydrostatic pressure in Bowman’s capsule

226
Q

What can affect the reflection constant in the kidneys

A

An increase in glomerular protein permeability reduces its value
This is nephrotic syndrome

Protein loss here can cause oedema due to reduced COP

227
Q

How does COP change in the glomerular capillaries

A

Increases along the capillary as fluid is filtered out

RBF therefore affects GFR because a high RBF reduces the rise in COP along the capillary so more filtration takes place at the end of the glomerular capillary

228
Q

What is reabsorption in the proximal tubule primarily responsible for

What about the distal parts of the nephron

A

Conservation

Regulation

229
Q

Clearance =

A

Rate of excretion
—————————
Plasma concentration

230
Q

What are the units for clearance

A

ml/ min

ml of plasma per minute

231
Q

If a substance in filtered freely, what is the equation for rate of filtration

A

Rate= GFR x plasma concentration

232
Q

If the substance is neither reabsorbed nor secreted, what is the rate of excretion equal to

A

Rate of filtration

233
Q

When does clearance= GFR

A

If a substance is freely filtered, not reabsorbed and not secreted

234
Q

What requirements is there for a substance needed to measure GFR

Give an example of such a substance

A 
Freely filtered
Not reabsorbed
Not secreted
Not metabolised/ synthesised
Not toxic 
No influence of GFR

Inulin

235
Q

What method is used to measure GFR using inulin

A

Constant perfusion

236
Q

What else can GFR be calculated using

How is its clearance calculated

A

Creatine

Using rate of excretion and plasma concentration

237
Q

What does estimation using creatine require

Why

A

Adjusting for weight height etc

It is produced by muscle and so proportional to muscle mass

238
Q

Clearance ratio of X =

A

Clearance of X
————————-
Clearance of inulin

239
Q

What does a clearance ratio greater than 1 suggest

What about less than 1

A

CR>1 implies secretion

CR<1 implies reabsorption/ incomplete filtration

240
Q

What can be used to estimate renal plasma flow

Why

By how much does this underestimate

A

Para-aminohippurate (PAH)

Freely filtered and secreted by kidney so almost completely cleared by the kidney

Almost all PAH entering the kidney ends up in the urine

By ~10%

241
Q

Why does using PAH to measure renal plasma flow underestimate by 10%

A

PAH is only secreted from cortical peritubular capillaries and 10% of blood travels through the medullary capillaries

242
Q

What is a more accurate way to use PAH to estimate renal plasma flow

A

Fick Principle

Flow x (Δ[PAH])

243
Q

3 forms of passive reabsorption mechanisms

A

Simple diffusion
Facilitated diffusion
Solvent drag

244
Q

What is facilitated diffusion

A

Movement of a substance across a membrane via a channel or transporter

245
Q

What is solvent drag

A

Para cellular flow of water carries dissolved substances with it

246
Q

3 forms of active transport

A

Primary
Secondary
Endocytosis

247
Q

What is primary active transport

A

Transmembrane transport directly coupled to ATP by a transport protein

248
Q

What is secondary active transport

A

Transmembrane transport of a substance coupled to the electrochemically favourable movement of another substance

249
Q

2 types of secondary active transport

A

Symport- substances travel in same direction

Antiport- travel in opposite directions

250
Q

Difference between channels and transporters

A

Channels are simply pores whereas transporters require an active change

Carrier proteins therefore have a transport maxima

251
Q

Where can transport maxima be seen in the kidneys

A

Diabetic patient

Glucose is freely filtered but actively reabsorbed so reaches a maximum rate and cannot keep up with filtration

252
Q

Why does Na concentration remain constant in the proximal tubule despite being reabsorbed

A

Reabsorption is isotonic and water follows the solute

253
Q

Give the concentration of glucose and αα after the proximal tubule

A

0

254
Q

What are the 2 glucose transporters in the nephron

Where are they and why are they different

A 
SGLT-2 = early proximal tubule
SGLT-1 = late

SGLT-1 transports 2 Na for each glucose as glucose is in lower concentrations later

255
Q

Give experimental evidence of isotonic reabsorption in the PCT

A

Simple micropuncture:
Samples from early and late reveal same osmotic pressure

Injected inulin increases in concentration is found and as it is not secreted or reabsorbed it must be caused by fluid reabsorption

256
Q

Describe stopped flow perfusion / split oil drop method to show isotonic reabsorption in the PCT

A

Inject mineral ion into Bowman’s so some enters PCT

Isotonic NaCl is injected to split oil drip such that solution between droplets is known
Droplets move towards each other, indicating reabsorption of fluid

257
Q

Name 4 organic anions secreted into the PCT

A

Prostaglandins
cAMP and cGMP
Bile salts
Drugs eg penicillin

258
Q

Name 4 organic cations that are secreted in the PCT

A

Creatine
Adrenaline and NA
dopamine
Drugs eg morphine

259
Q

2 things worth considering about reabsorption

What does this mean for drug administration

A

Transport maxima for these transporters is low

Different anions or cations May compete for the same transporter

Co-administering 2 drugs that are excreted by the same transporter can raise concentrations of both

260
Q

What is the ratio of K+ in the ECF compared to in the cells

A

98% inside to 2% in ECF

261
Q

What is the physiological role of K+

A

Membrane potential

It is thus important for cell functions including volume and pH regulations as well as excitability

262
Q

What is normal extra and intracellular [K+]

A

Extracellular: ~4mmol
Intracellular: 125mmol

263
Q

Why do changes in amount of K+ in extracellular space have a bigger effect on membrane potential than changes inside the cell

A

Extracellular space is smaller than intracellular and [K+]i»[K+]e

264
Q

How much K+ might you take in during 1 meal

How much would [K+] increase if all this entered the extracellular space (16L) at once

Why is this relevant? ( the numbers are massively important to remember, just understand the gist)

A

33mmol

33mmol/16L =2mmol-1

This would increase membrane potential of K by +10mV whereas if K+ was quickly taken into cells, intracellular [K+] would only change by 1.4mmol-1 so Ek would differ by -0.3mV
Hence, by moving K+ into cells the change in membrane potential is decreased 30 fold

265
Q

True or false:

Intracellular K+ is more tightly controlled than extracellular K+

A

False
Normal functioning of cells requires tight control over extracellular K+ whereas intracellular can vary considerably without affecting membrane potential too much

266
Q

How is extracellular [K+] regulated in

a) short term
b) long term

A

a) moving K+ between intracellular and extracellular compartments
b) controlling amount of K+ in the body

267
Q

How much K+ is ingested each day

A

100mmoles

268
Q

What are the insensible losses of K+

A

10mmol lost in faeces and sweat

269
Q

What are the controlled losses of K+

A

Kidneys can excrete between 1% and 80% of filtered K+

270
Q

Name 4 physiological or pathological factors causing intracellular to extracellular K+ shift

A

Action potentials
Dehydration
Cell lysis
Acidosis

271
Q

How do action potentials change the distribution of K+

Where is this significant

A

Repolarisation shifts K+ out of the cell

In skeletal muscle

272
Q

In what type of tissue is most of the body’s K+ stored

What proportion

A

Skeletal

70%

273
Q

Why does dehydration change K+ distribution

A

An increase in plasma osmolarity causes cell shrinkage, increasing intracellular [K+]. Therefore the cell may lose K+

274
Q

How does cell lysis change K+ distribution

When does this become a problem

A

Cell death releases K+ into extracellular space

When lots of cells die rapidly eg severe burns, trauma, when the blood supply is restored rapidly to an ischaemic limb or in tumour lysis syndrome

275
Q

What is tumour lysis syndrome

A

Excessively rapid chemotherapy induced death of tumour cells

276
Q

How does acidosis change K+ distribution

A

Movement of H+ into cells displaces K+

As cells are well buffered they can take up lots of H+

277
Q

What factors can cause an extracellular to intracellular K+ shift

Why

A

Hyper hydration (cell swelling from decreased plasma osmolarity can cause cells to take up more K+)

Insulin (activates Na/K pump and increases Na+ entry via Na+/ glucose transport)

Adrenaline (activates Na/K pump

278
Q

What does high and low [K+]e cause

A

High: hyperpolarisation
Low: depolarisation, can also reduce Na/K pump activity

279
Q

Low [K+]e and digoxin is a bad combination. Why?

A

Low [K+]e reduces Na/K pump activity and digoxin is a Na/K pump blocker so there is a potentiation effect

280
Q

How do the effects of slight hyperkalaemia and extreme hyperkalaemia differ

What is the ultimate effect of both

A

Hyperkalaemia causes depolarisation, bringing excitable cells closer to the threshold but eventually causes inactivation of VG Na+ channels

Therefore small degrees of depolarisation causes increased excitability but greater depolarisation causes inexcitability

Both increase risk of cardiac arrest

281
Q

What are the effects of hypokalaemia

A

Hyperpolarisation, reducing excitability thus causing muscle weakness or in extreme cases paralysis (including diaphragm paralysis) and cardiac arrhythmia

282
Q

When is regulation of internal K+ balance particularly important in 2 physiological stresses

A

Eating (rapid intake into extracellular space)

Exercise (prolonged muscular activity causes a shift of K+ from within skeletal muscle into the extracellular space

283
Q

What are the fees forward responses to eating and exercising to prevent severe hyperkalaemia

A

Eating: rise in blood glucose stimulates insulin release

Exercise: adrenaline release

Both insulin and adrenaline stimulate Na/K pumps driving K+ into cells in exchange for Na+

284
Q

If the Na/K pump requires intracellular Na+, how can insulin effectively increase the pump’s activity?

A

It also stimulates the Na+_glucose transporter thereby bringing both Na+ and glucose into the cell from the blood after/ during a meal

285
Q

Which hormone is important in feedback control of K+

How

A

Aldosterone

A rise in plasma [K+] is detected by aldosterone secreting cells in the adrenal cortex. Aldosterone controls K* excretion in kidneys and stimulates Na/K pump, driving K+ into cells

286
Q

What are beta blockers

Temporary exercise induced what can occur in patients taking these

A

β2 adrenergic blockers taken for hypertension

Transient hyperkalaemia

287
Q

What are the 5 stages K+ takes through the kidney

A

1) K+ is freely filtered
2) unregulated absorption of K+ in proximal tubule
3) unregulated reabsorption of K+ occurs in TAL of loop of Henle
4) some unregulated reabsorption in Type A Intercalated of distal tubules and collecting duct
5) regulated secretion from principal cells of distal tubule and collecting duct

288
Q

How much of the filtered K+ is reabsorbed in the proximal tubules

A

67%

289
Q

How much of the filtered K+ is reabsorbed in the thick ascending loop of Henle

A

20%

290
Q

How much of the filtered K+ enters the distal tubule and collecting duct

A

~13%

291
Q

How much of the filtered K+ is reabsorbed in the Type A cells of the distal tubule and in the collecting duct

A

Type A: (3%)

Collecting duct:9%

292
Q

Where is regulated secretion of K+

A

In the principal cells of the distal tubule and in collecting duct

293
Q

Where does all regulation of K+ excretion occur

A

Principal cells of the DCT and collecting duct

294
Q

Usually does secretion or reabsorption of K+ dominate in the DCT and CCT

A

Secretion as K+ intake»insensible losses

295
Q

3 ways to increase K+ secretion

A

High plasma [K+]
Aldosterone
High tubular flow rate

296
Q

How does high plasma [K+] increase control of K+ secretion

A

It increases interstitial [K+] thus enhancing K+ transport into principal cells, increasing K+ gradient across luminal membrane

297
Q

How does aldosterone increase control of K+ secretion

Where is it released from and when

How long does it take to work? Why?

A

Increases activity of SK, ENaC and Na/K pump

Released from adrenal cortex in response to raised plasma [K+]

At least an hour Cos it stimulates protein synthesis

298
Q

Does aldo increase the channels themselves?

A

Possible but it might instead increase the number of activatory proteins

However the Na/K pump density does increase in the long term

299
Q

How does high tubular flow rate increase control of K+ secretion

A

K+ secretion across luminal membrane is passive so will slow if K+ builds up in tubule. This is prevented by a high flow rate.

300
Q

How can you show the the importance of [K+] plasma and aldosterone

A

Compare effects of variation in dietary K+ intake in normal animals vs without adrenal glands given constant aldosterone infusion

301
Q

In hypovolaemia, how is K+ secretion decreased

A

Increased Na+ reabsorption in earlier segments reduces tubular flow rate reaching the distal tubule , so less K+ is secreted

302
Q

Why is increased Na+ retention in hypovolaemia not associated with increased K+ loss, if aldosterone is released

A

Other Na+ retention mechanisms are also activated leading to a decreased flow rate in distal tubule

303
Q

Does ADH have a big impact on K+ excretion

A

No

It actively avoids altering K+ excretion

304
Q

Why does ADH have to enhance K+ secretion

A

ADH promotes water absorption, reducing flow in DCT and CCT. Therefore ADH must balance this (as decreased flow decreases K+ secretion) by stimulating luminal K+ conductance in principal cells

305
Q

3 causes of hypokalaemia

A

Diuretic treatment
Diarrhoea, vomiting
Nil by mouth

306
Q

3 causes of hyperkalaemia

A

Renal failure (glomerular filtration below 20% of normal prevents adequate K+ excretion despite normal diet)

Iatrogenic: IV cannot have too much K+

Acidosis: H+ enters from cells, displacing K+ so K+ shifts from ICF to ECF
H+ also increases K+ reabsorption in DCT and CCT so less lost in urine

307
Q

Treatment for hypokalaemia

A

K+ supplement (must be gradual to avoid sudden changes in membrane potential)

308
Q

Treatment for hyperkalaemia

A

Glucose and insulin administered

Ca2+ can stabilise membrane potential in short term to reduce chance of arrhythmia

K+ chelating agents can reduce K+ absorption from diet in patients with renal failure

309
Q

Why is pH regulation important

A

Protein charges are pH dependent meaning enzyme and ion channel function are pH sensitive

310
Q

Give the normal pH range in the average human cell

What about in plasma in extremes

A
  1. 35-7.45

6. 8-7.8 in plasma

311
Q

What is the [H+] range in humans

A

Normal: 45 to 35nmol-1
Abnormal: 160 to 16 nmol-1 (a ten fold difference!!!)

312
Q

How much metabolic CO2 is produced each day by a human

A

15-20 moles (NOT nmol)

313
Q

Why does a normal diet make the blood acidic

A

Food contains both acids and bases but bases are usually lost in faeces

314
Q

Name 3 static buffer systems for blood plasma pH

A

Inorganic phosphate
Plasma proteins
Haemoglobin

315
Q

Give the buffer equation for inorganic Phosphate

A

H2PO4- ↔️ H+ + HPO4 2-

316
Q

Give the equation for plasma proteins as a buffer

A

Protein - + H+↔️protein-H

317
Q

True or false

The bicarbonate system is a powerful static buffer system

A

False

The bicarbonate buffer system is dynamically controlled by the respiratory and renal systems

318
Q

How is non volatile acid buffered

A

By HCO3- and it is excreted as CO2

319
Q

Give the buffer equation involving non volatile acids

A

Metabolic acids + NaHCO3 —> CO2 + H2O + Na*salt of the acid

320
Q

According to which equation does the state of the bicarbonate system determine plasma pH

A

The Henderson Hasselbalch equation:

6.1 + log([HCO3-]/0.03PCO2)

321
Q

How is the concentration of CO2 given in the Henderson Hasselbalch equation

A

As 0.03PCO2

This is the solubility of CO2 multiplied by its partial pressure (Henry’s Law)

322
Q

What is important to consider when calculating the influence on pH of addition of a non volatile acid

A

The acid reduces [HCO3-] by an equimolar amount and does not influence PCO2

323
Q

Do the kidneys usually net produce or excrete HCO3-

A

Produce

But can do both

324
Q

4 steps required for production of HCO3- by the kidneys

A

1) reabsorption of filtered HCO3-
2) production of HCO3- and H+ in proximal tubule …
3) … allowing secretion of H+ and the return of HCO3- to the plasma
4) buffering of tubule H+ to allow further secretion

325
Q

How is HCO3- produced in proximal tubule

How does it enter the tubule

A

From glutamine

It is freely filtered and can be secreted by Type B intercalated cells in collecting duct

326
Q

How is H+ buffered in the urine

A

As H2PO4- and NH4+

327
Q

How is HCO3- reabsorbed in all parts of the tubule

A

Secretion of H+, acidifying the tubule

This pushes HCO3- + H+↔️CO2+H2O to the right

Neutral CO2 diffuses into the cell

The cell is more alkaline due to secretion of H+ so equation is pushed to the left producing HCO3- and H+

HCO3- is transported across the basolateral membrane and H+ is secreted

This is catalysed by carbonic anhydrase

328
Q

Does HCO3- reabsorption replace the HCO3- lost to buffer metabolic H+

A

No some must be produced

329
Q

What is the problem with the kidneys’ production of HCO3-

How do we fix this

A

The associated H+ must be excreted BUT

the minimum urine pH 4.5
At pH 4.5, [H+]= 30μm but daily intake is 50-100mmol so we would either have to produce 3300L of urine a day at pH 4.5 or produce pH 1 wee

Buffering pH in urine

330
Q

Why can’t we use HCO3- to buffer urine

A

We can not afford to lose it

331
Q

Why can’t we use inorganic phosphate to buffer urine

What is employed instead

A

There is not enough to buffer all H+ to be excreted

Ammoniagenesis

332
Q

What is the net effect of ammoniagenesis

What is the buffer

What else is produced

A

H+ is excreted as NH4+

NH3

2 HCO3-

333
Q

How is glutamine found for ammoniagenesis

What is this an alternative to

A

Produced from waste amino acids in the liver by trans animation

Deamination into urea

334
Q

Where is NH4+ excreted

A

The proximal tubule

335
Q

What happens to NH4+ from glutamine one proximal tubule cells

A

It dissociates into NH3 and H+
NH3 freely diffuses across the membrane into the tubule
The lumen is acidic due to Na/H exchange and H+ ATPase so NH4+ is formed and is trapped in the tubule

336
Q

What is the path of NH4+ throigh the nephron

A

After entering as NH4+ in the proximal tubule, it is reabsorbed in the TAL, substituting for K+ in the Na/K/2Cl- co-transporter

NH4+ builds up in the medullary interstitium and the NH3 formed diffuses through collecting duct cells to be protonated in the tubule. Here it is finally trapped in the tubule as NH4+ to be excreted

337
Q

What is the key control point in the journey of NH4+ through the kidney

A

The ammonium trapping stage

338
Q

Ammonium is trapped in the tubule if pH is low. What happens if pH is high

A

Much of the NH4+ is instead converted to urea in the liver

339
Q

How much of NH4- and HCO3- is produced from the catabolism of glutamine each day

A

1 mole of ESV

340
Q

What is the equation in the urea cycle to remove NH4+ and HCO3- and form urea

What pathway is instead Up regulated in metabolic acidosis

A

2 ammonium + 2 bicarbonate —> H2N-CO-NH2 + 3H2O + CO2

2 ammonium + α-ketoglutarate —> glutamine

341
Q

Describe the intrinsic control of HCO3- absorption and acid secretion in the kidneys

A

H+ is required for HCO3- reabsorption and H+ secretion is enhanced by low pH and reduced by high pH

Increased PCO2 enters tubules, lowering pH thus enhancing H+ secretion and HCO3- absorption

Expression and activity of transporters increases in low pH (possibly due to autocrine and paracrine effects of endothelin

342
Q

Name 4 hormones that respond to pH change

A

Cortisol
PTH
AII
Aldosterone

343
Q

How does cortisol react to low pH

A

Cortisol levels increase and it increases transcription of NHE and NBC in proximal tubule

344
Q

How does PTH react to low pH

A

In prolonged acidosis, PTH promotes acid secretion in the TAL and DCT

PTH also reduces inorganic phosphate reabsorption in PCT, increasing buffering in tubule

345
Q

How does AII react to low pH

A

Stimulates Na/H exchanger in proximal tubule

346
Q

What does aldo do in low pH

A

Stimulates K/H ATPase in Type A cells, increasing H+ secretion and K+ reabsorption

347
Q

Why may respiratory acidosis occur

A

Chronic obstructive pulmonary disease

348
Q

Why may respiratory alkalosis occur

A

Hyperventilating at altitude

349
Q

Why may metabolic acidosis occur

A

Diabetic ketoacidosis

Sever diarrhoea

350
Q

Why may metabolic alkalosis occur

A

Prolonged vomiting

351
Q

Why are non compensated metabolic acid base disorders rarely seen

A

Respiratory compensation is usually v quick

352
Q

What is the Davenport diagram used for

A

Diagnosis of acid base disorders

353
Q

True or false:

Urine osmolarity is regulated by controlling the amount of water in the urine

A

True

NOT by controlling its solute content

354
Q

What mainly controls the amount of water in the urine

A

ADH, released from the posterior pituitary in response to changes in osmolarity

355
Q

What are the 3 priorities for the body

A

Avoid hypotension

Maintain ECF volume

Maintain ECF osmolarity

356
Q

Why does osmoregulation take precedent over volume regulation normally

A

ECF volume should not drop by >10-20% to threaten blood pressure

357
Q

What is the major determinant of ECF osmolarity

A

NaCl

358
Q

Why does changing NaCl in the body not change plasma osmolarity (2)

A

1) Most NaCl reabsorption is isotonic

2) ADH and thirst adjust water excretion to maintain osmolarity

359
Q

Where are water movements not isotonic in the nephron

A

LoH
DCT
CCT

360
Q

What is the range of osmolarity of urine

How does this compare to plasma

A

30 to 1200 mOsm/kg

Between 1/10 and 4x osmolarity of plasma

361
Q

What are the 2 problems with the range of the osmolarity of urine

Give a solution to each

A

1) problem: no such thing as an active water pump so water must flow according to a gradient (osmotic or pressure)

Solution: pumping ions across water impermeable cells builds an osmotic gradient that can later be used to transport water

2) problem: max transcellular osmotic gradient= 200mOsm/kg

Solution: employing countercurrent multiplication

362
Q

Why is the the max transcellular osmotic gradient 200 mOsm/kg

A

Ion transport becomes less energetically favourable and back leakage increases

363
Q

How does the kidney produce anisosmotic urine

A

by first separating ion transport and water in LoH (where ions enter the interstitium and water is retained, making the fluid dilute)

As the fluid leaving the LoH is hypo-osmotic it is v easy to make hypo-osmotic urine; in the absence of ADH the nephron is impedance to water and other solutes are reabsorbed, making the fluid increasingly hypo-osmotic

364
Q

How do we produce hyperosmotic urine

A

Separate ions from fluid in LoH while retaining water

ADH makes the rest of the nephron water permeable so water is drawn out of the distal tubule and CCD into the isosmotic cortex. Therefore, the fluid entering the medullary collecting duct is hyperosmotic to plasma due to the action in the LoH, thus water is reabsorbed from the medullary collecting duct and hyperosmotic urine is produced

365
Q

4 steps of water movements in the diluting kidney

A

1) Ions pumped out of LoH but water doesn’t follow
2) This Medulla becomes hyperosmotic
3) and makes the tubular fluid leaving the LoH hypo osmotic
4) absence of ADH makes water permeability low in the nephron and further ion reabsorption gives hypo osmotic urine

366
Q

5 steps of water movements in the concentrating kidney

A

1) Ions pumped out of LoH but water doesn’t follow
2) This Medulla becomes hyperosmotic
3) and makes the tubular fluid leaving the LoH hypo osmotic
4) high ADH allows water to move from hypo osmotic fluid into isosmotic cortex in DCT and CCT
5) from the now isosmotic tubular fluid, water is drawn into the hyperosmotic medulla

367
Q

How do we know the medullary interstitial space is significantly hypertonic to plasma

A

Microcryoscopy (rapid freezing and sectioning of the kidney allows estimation of solute concentrations bf measuring the melting point of different regions, as solute depresses the melting point

368
Q

Give the 4 stages of the process to Make the medulla interstitium hypertonic

Which are only significant in the concentrating kidney

A

1) active active NaCl reabsorption
2) countercurrent multiplication
3) urea cycling
4) passive NaCl reabsorption

3 and 4 are only relevant in the concentrating kidney

369
Q

Where are ions removed from water to make the medulla hypertonic

A

TAL of the LoH

370
Q

How effective is the ion transport in the TAL

A

Very

One cycle of the Na/K pump could allow transport of 12 ions across the luminal membrane

371
Q

Why is K+ allowed to leak across the luminal membrane in the TAL

A

To keep the tubule fluid positive with respect to the interstitial fluid

372
Q

Ion transporters are energy favourable. True or false?

A

False

They’re more like energy efficient

373
Q

How does countercurrent multiplication work

A

1) TAL makes medulla hypertonic
2) water is drawn out of descending limb
3) fluid entering ascending limb is hypertonic
4) therefore the TAL can make the medulla more hypertonic and back to step 2

374
Q

Why is K+ allowed to leak across the luminal membrane in the TAL

A

To keep the tubule fluid positive with respect to the interstitial fluid

375
Q

Ion transporters are energy favourable. True or false?

A

False

They’re more like energy efficient

376
Q

How does countercurrent multiplication work

A

1) TAL makes medulla hypertonic
2) water is drawn out of descending limb
3) fluid entering ascending limb is hypertonic
4) therefore the TAL can make the medulla more hypertonic and back to step 2

377
Q

How many DCTs feed into the collecting tubule

A

Many

378
Q

How much of the medullary tonicity is countercurrent multiplication directly responsible for?

A

600 mOsm/kg: Half the maximum possible medullary tonicity

379
Q

What is the concentration of urea in the renal medulla thanks to urea cycling

How much does this contribute to the osmolarity

A

600 mmol/kg

600mOsm/kg

380
Q

What is the range of concentrations of urea in the filtrate

A

2.5-7.5mmol/kg

381
Q

What happens to urea in the PCT

A

Freely filtered in the glomerulus and 50% is passively reabsorbed in the PCT

382
Q

How is urea reabsorbed in the PCT

A

A gradient for passive reabsorption is created by the reabsorption of water

383
Q

Where is the distal nephron permeable to urea

How is permeability increased

A

In the inner medullary collecting duct ONLY

Increased by ADH

384
Q

How much of the urea reaching the IMCD is reabsorbed

A

> 50%

385
Q

How is urea reabsorbed from the IMDC

A

Water is reabsorbed in the DCT, CCD and outer medullary collecting duct in the presence of ADH but these are impermeable to urea so tubular [urea] increases
This creates an outward gradient for urea reabsorption in the IMCD so [urea] is high in the medullary interstitium

386
Q

What is the urea cycle in the nephron

A

1) water reabsorbed in the DCT and CCT
2) this makes a steep gradient for urea reabsorption in the IMCD
3) as medullary [urea] is high, and the deepest thin limbs of the LoH are urea permeable, urea is secreted into the deep LoH, increasing overall tubular [urea]

387
Q

Does the thick ascending limb actively extrude NaCl

A

No NaCl is reabsorbed passively due to gradients that result from urea cycling

388
Q

In the maximally concentrating kidney what is the composition of medullary tonicity

What about in the tubular fluid?

A

Half due to NaCl and half due to urea
(600mOsm/kg each )

Fluid has more NaCl (300mmol/kg of NaCl) and much less urea

389
Q

How is NaCl reabsorbed in the thin ascending limb

A

It is permeable to NaCl and the fluid ascending through the thin limb has a much higher [NaCl] than the medullary interstitium, increasing the NaCl concentration in the deepest parts of the medulla

390
Q

Why must active transport be limited in the deep renal medulla

How is this overcome for NaCl reabsorption

A

It has a poor blood supply so active transport must be minimal

Transport in the TAL in the outer medulla powers NaCl reabsorption in the thin limb in the inner medulla

391
Q

How does urea concentration in the medulla vary between the diluting and concentrating kidneys

A

[urea] in the medulla of the diluting kidney is far lower because without ADH no water is reabsorbed in the DCT, CCT and MCD so urea does not become concentrated in these segments

392
Q

How long does it take [urea] to build up in the medulla after release of ADH

A

Several hours ago

393
Q

Fluid in the descending limb of the LoH is always hypertonic and it is always hypotonic as it leaves the ascending limb. How is it pattern affected by ADH?

Why?

A

The degree of hyper tonicity increases as ADH levels increase

ADH does not act on the LoH so this effect is due to the effect of ADH on urea cycling

394
Q

Why can there not be a simple capillary network in the renal medulla

A

Water would move into the vessels via osmosis and solutes would diffuse in, dissipating the medullary concentration gradient

395
Q

Where do the vasa recta come from

A

From the efferent arterioles of nephrons closest to the medulla (juxtamedullary nephrons)

396
Q

What is the course of vasa recta after they leave the efferent arterioles of juxtamedullary nephrons?

A

They descend straight down into the deepest medulla, form a hair pin loop, then ascend up to the cortex, forming veins.

397
Q

Describe the countercurrent exchange of the vasa recta

A

As blood descends, the surrounding interstitium becomes increasingly hypertonic, so water moves out and urea and NaCl move in. However, as it ascends, the blood is hypertonic to the interstitium so water moves in and urea and NaCl moves out

398
Q

Is the vasa recta’s countercurrent system perfect?

A

No some solute is retained from the descent so some water is accumulated in the ascent

399
Q

Is it good that vasa recta does remove some solute and water?

A

Yes because the action of the LoH and MCD makes NaCl, urea and water build up in the medulla and the vasa recta is the only route for these to leave

400
Q

What can cause plasma hypo-osmolarity

A

Extremely excessive and rapid water intake

Excessive Na+ loss (eg in severe diarrhoea and only water, not electrolytes, is replaced)

Inappropriate ADH secretion (eg head injuries, severe infections and some cancers cause abnormally high ADH secretion)

401
Q

What can cause hyper osmolarity

A

Dehydration

Very high blood glucose

402
Q

Is hyper osmolarity seen in badly treated type 1 diabetes

A

No

They become ill due to ketosis before glucose levels can become high enough to significantly influence plasma osmolarity

403
Q

Why can we tolerate slow changes to plasma osmolarity (over days or weeks rather than hours)

Why is it important to remember this

A

Many cells types (including brain Cells) can regulate volume by eliminating or synthesising intracellular osmoles, minimising the effect of extracellular osmolarity

Rapid correction of long standing abnormality in extracellular osmolarity is very dangerous

404
Q

How long does it take for the diuretic response to begin once you start drinking

A

Within minutes because drinking causes inhibition of ADH from the posterior pituitary by a nervous reflex from the throat and gut

405
Q

How is the liver involved in the reflex when drinking

A

Osmo receptors in the liver contribute to the diuretic response because the osmolarity of the hepatic Portal blood falls due to water arriving in the guts

406
Q

How would the response drinking isotonic saline differ from drinking freshwater

A

A small initial diuresis via nervous inhibition of ADH occurs however there is no change in osmolarity so the response is short lived

407
Q

What is the maximum concentration of eerier in the interstitium of the kidney?

What is the maximum area of concentration in urine

A

600 mOsm

600 mOsm
Because the inner medullary collecting duct is freely permeable to area under the conditions of the concentrating kidney

408
Q

What is the net gain of water if you drink 1 L of seawater

A

There is a net loss of of 0.67 L (you in take 1L but have to loose 1.67)

409
Q

What is the effect of salt water on the gut

A

The salt concentration of seawater is 3 to 4 times higher than that of plasma

Once in the gut it would draw water into it and promote diarrhoea thus enhancing dehydration

410
Q

As seawater draws water into the gut, how is ECF affected

What will this lead to

A

Osmotic pressure will increase

Hypothalamic osmoreceptor is will be stimulated: this has 3 effects: stimulate ADH release, stimulate hyperosmotic thirst and promote antidiuresis

ECF volume decreases, reducing blood volume and eventually arterial blood pressure which is detected by baroreceptors which will decrease the firing, disinhibiting the thirst centre of the hypothalamus

411
Q

Why might you want to drink more seawater after drinking some already

A

Water absorption into the gut, increases ECF osmotic pressure, stimulating hypothalamic osmo receptors which in turn stimulate hyperosmotic thirst

412
Q

True or false

Hypovolaemic thirst occurs if you drink sea water

A

True

ECF volume decreases, reducing blood volume and eventually arterial blood pressure which is detected by baroreceptors which will decrease the firing, disinhibiting the thirst centre of the hypothalamus

413
Q

What effect will a fall in arterial blood pressure to the kidney in haemorrhage have (2)

Why is each done

A

It will reduce Sodium excretion:

1) the glomerular capillary pressure will decrease - GFR and filtration of sodium will decrease
2) peritubular capillary pressure will decrease - This favours reabsorption of fluid from interstitial space into peritubular capillary. This will reduce the renal interstitial hydrostatic pressure which will favour reabsorption of fluid from the PCT into the interstitial space, slowing moving of tubular fluid

414
Q

How does colloid osmotic pressure change in haemorrhage

A

Usually it does not change as both ECF and plasma proteins are lost

However during severe haemorrhage which result in a fall in a BP, COP will fall – this is because the decreased ultrafiltration would reduce blood COP

415
Q

Give an overview of the result of a fall in ABP after a haemorrhage

A

An increase in sympathetic discharge which will affect both cardiovascular and renal systems to restore blood pressure

416
Q

What is the cardiovascular response to a fall in ABP after haemorrhage?(4)

A

Baroreceptors will decrease frequency of discharge to the medulla oblongata

This will stimulate vasoconstriction to increase TPR and venoconstriction to increase VR - Starling’s Law

Sympathetic nerves also innovate pacemaker cells of the heart increasing both heart rate and contraction

This is all reinforced by sympathetic signals to the adrenal medulla via splanchnics to release adrenaline

417
Q

Describe the endocrine factors affecting the kidney after a haemorrhage

A

Angiotensin II concentration increases:

This causes vasoconstriction via AT1 receptors thus increasing TPR

Also increases sodium retention by mimicking RSNA and stimulating aldosterone secretion via AT2 from the zona glomerulosa

418
Q

2 behavioural effects of angiotensin II after haemorrhage

A

Sodium appetite

Thirst

419
Q

What does hypocalcaemia result in

A

Reduced action potential threshold, causing spontaneous activity

As muscles are particularly susceptible, tetanus occurs. Death by asphyxiation can result due to tetanic contraction of larynx muscles

420
Q

What is the effect of hypercalcaemia

A

Raises threshold for action potentials, resulting in sluggish CNS function, muscle weakness and arrhythmia

Calcium phosphate may precipitate leading to kidney stones

(Moans, groans, bones, stones)

421
Q

How is calcium found in the body

A

99% is found in bones

422
Q

What is the most common form of calcium in bone

A

Hydroxyapatite (1Kg of Ca2+ is stored this way)

423
Q

What is the extracellular fluid calcium content in weight

What is plasma calcium concentration? How is this found?

What is the weight of calcium present in cells? How is this mostly found?

A

1g

2.5 mM: either free (1.075mM) or bound to proteins/ anions (1.2mM)

10g

Sequestered in organelles but free [Ca2+]i =50-100nM

424
Q

What is bone resorption

A

Breakdown of bone

425
Q

What are the three Endocrine control factors of calcium

A

Parathyroid hormone

Calcitonin

Calcitriol

426
Q

What secretes PTH

A

Chief cells in the parathyroid glands

427
Q

What is the effect of parathyroid hormone basically

A

Raises ECS calcium concentration and lowers ECF phosphate concentration

428
Q

How is PTH regulated

A

Arise in plasma concentration reduces PTH secretion

This works through a GPCR which has a low calcium affinity

429
Q

How does PTH work

A

Axed directly on bone and kidney and indirectly via calcitriol on the gut

430
Q

What to osteoblasts do

How are they affected by PTH

A

Laid out new bone
They synthesise collagen and secrete calcium and phosphate to calcify surrounding matrix

Inhibited

431
Q

What happened to osteoblasts once they are surrounded by calcified bone matrix

A

They become osteocytes

432
Q

Why do bone lining cells have PTH receptors

What do these cells do

A

They are of osteoclastic lineage

Separate normal interstitial fluid from that filling bone canals

433
Q

How does PDH affect osteocytes

A

Stimulates taking up of calcium from bone fluid and transferring it to bone lining cells which secrete calcium into the ECF

434
Q

How are osteoclasts activated

A

They are stimulated by cytokines such as interleukin-6 but not by PTH as they lack PTH receptors

435
Q

What happens when PTH binds to PTH receptors on bone lining cells

A

PTH stimulates them to decrease in size and attract, exposing bone surface to the osteoclast action

436
Q

How does calcitonin affect osteoclasts

A

Calcitonin directly inhibits osteoclast differentiation from progenitors

437
Q

How much calcium is usually reabsorbed in the kidney

A

99% (mostly paracellularly)

70% in PCT and 20% in thick ascending limb - This is fixed

Regulation is over the last 10% in the DCT and collecting duct

438
Q

Which channel is used for calcium reabsorption

What happens when it is in the cell

A

TPRV5 and 6

Binds to calbindin D and is then transported out by the Ca2+ ATPase or by NCX

439
Q

What is TRPCV5 also called

TRPV6

A

ECaC1

CaT1 (Calcium transport protein 1)

440
Q

What is the calcium reabsorption in the distal convoluted tubule like

What does PTH do

A

Transcellular

(Paracellular is impossible due to negative transepithelial potentials here )

Stimulates NCX in DCT and CD

441
Q

How is Vit D3 formed

A

The action of ultraviolet light on a cholesterol derivative in skin

A similar vitamin can be ingested from plants

442
Q

How are Vit D3 and its derivatives metabolised

What is the end product

A

Addition of hydroxyl groups in the liver and then in the kidney

1,25-(OH)2D3 : AKA calcitriol

443
Q

What are the three functions of calcitriol

A

AIDS calcium mobilisation from bone

Facilitates calcium renal reabsorption

Increases calcium uptake from gut

444
Q

How does PTH influence calcitriol

Name another hormone that is involved

A

Increases calcitriol when Ca2+ levels drop

Prolactin also stimulates calcitriol synthesis

445
Q

What secreted calcitonin (CT)

What is its main action

What is its aim

A

Parafollicular cells (C cells) in the thyroid

Inhibit osteoclast activity and favour osteoblasts activity

To prevent hypercalcaemia (rather than cause hypocalcaemia)

446
Q

What is calcitonin important in

A

Protecting maternal bone against excessive demineralisation during pregnancy when there is a high flux of calcium to the fetus and during lactation when there is secretion of calcium in milk for the neonate

CT ensures Ca2+ demand is met by the gut rather than resorption of bone

447
Q

What is EGTA

A

A calcium chelator

448
Q

What stimulates calcium secretion

A

A rise in ECF [Ca2+] directly

Gastrin also directly stimulates CT release as a feedforward mechanism to direct new Ca2+ to the bone

449
Q

What does hypoparathyroidism lead to?

What are the consequent effects

A

PTH deficiency

Low ECF calcium concentration result in reduced threshold for action potentials and moderate cases may involve Trousseau’s sign and Chvostek’s sign

Severe cases can result in Long QT syndrome and even death from larynx muscle contraction and asphyxiation

450
Q

What is Trousseau’s sign

A

Sustained wrist spams

451
Q

What is Chvostek’s sign

A

Contraction of facial muscles

452
Q

What kind of animal is known to be hypocalcaemic

A

High yielding dairy cattle at the onset of lactation (milk fever)

Although this appears to result from in sensitivity to PTH rather than PTH deficiency

453
Q

Will hypocalcaemia always be PTH deficiency

A

May also be calcitriol insufficiency

The primary symptoms of calcitriol insufficiency is abnormal bone demineralisation and presents as a Ricketts or osteomalacia

454
Q

What is the most common cause of hypercalcaemia?

A

Hyperparathyroidism

This may be due to malignant disease of bones causing erosion and calcium release

455
Q

What does hypercalcaemia lead to

A

Raised threshold for action potentials as well as bone erosion and pain and renal stones, abdominal pain and psychiatric troubles

(Bones, Moans, groans, stones)

456
Q

What is a common problem related to secondary hyperparathyroidism

A

Chronic kidney disease

Deficient renal response to pH leading to concentrations of calcium in the blood insufficient to promote negative feedback at the parathyroid glands. As a result there are sustained PTH levels which affect bones primarily

Osteitis fibrosis cystic may occur (similar to osteoporosis)

457
Q

Name some symptoms of chronic kidney disease (5)

A

Diabetes

Hypertension

Autoimmune glomerulonephritis

Polycystic kidney disease

Myeloma

458
Q

When does the secondary hyperparathyroidism occur

A

When the response of the target organs to decreased calcium or increased phosphate is deficient

459
Q

Name an anti insulin protein hormone

A

GH

460
Q

How is vitamin D3 metabolised

3 functions of it

A

By addition of hydroxyl groups, first in the liver then in the kidney

AIDS calcium mobilisation
Facilitates calcium renal reabsorption
Increases calcium uptake from the gut

AKA calcitriol

HOM (11 decks)

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