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Veterinary medicine year 2 > Endocrinology > Flashcards

Endocrinology Flashcards

1
Q

What are the different types of cell communication?

A

Autocrine
Paracrine
Endocrine

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2
Q

What determines the strength of autocrine signalling?

A

Depends on the amount of cells that are producing the signal and the amount of cells with the receptor for the signal

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3
Q

What are the 2 types of hormones?

A

Lipid soluble
Water soluble

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4
Q

How do lipid soluble hormones enter cells?

A

Transported in the blood by carrier proteins

Diffuse through plasma membrane
Expression of genes at the level of the nucleus

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5
Q

How do lipid soluble hormones enter cells?

A

Dissolved in blood
Bind to receptors on the surface fo teh cells
= Intracellular events

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6
Q

What are the different lipid soluble hormones?

A

Steroid hormones
Thyroid hormones
Retinoids
Vitamin D

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7
Q

What are the different water soluble hormones?

A

Most signalling molecules like GF
Cytokines
EPO

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8
Q

What hormones are produced in the adrenals?

A

Androgens
Cortisol
Corticosterone
Aldosterone

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9
Q

What hormones are produced in the ovaries

A

Oestradiol

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10
Q

What hormones are produced in the testes?

A

Testosterone
Dihydrotestosterone

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11
Q

What is the action of a lipid soluble hormone on a receptor?

A
  1. Binding
  2. Receptor is activated
  3. Active receptor binds to DNA
  4. Regulates transcription of specific genes
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12
Q

What do nuclear receptors work with?

A

nuclear receptors work with coactivator proteins which then regulate activation and repression of nearby genes

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13
Q

What are the two ways that water soluble hormones can interact with membrane bound receptors?

A

Inhibitory
stimulatory

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14
Q

What substances are involved in the intracellular signal transduction pathways?

A

Adenyl cyclase
Guanyle cyclase
Phospholipase C
Tyrosine kinase
Ion channels

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15
Q

What can the binding of a water soluble ligand lead to in a cell?

A

Altered metabolism of a cell
Altered gene expression of a cell
Altered cell shape or movement

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16
Q

Role of adenyl cyclase

A

ACTH, ADH, FSH, LH, TSH

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17
Q

Role of Guanylyl cyclase

A

Rare atrial natriuretic peptide

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18
Q

Role of phospholipas C

A

Hypothalamic hormones
TRH and GnRH

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19
Q

Role of tyrosine kinase

A

Insulin
Prolactin
Growth hormone
IGF

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20
Q

Role of ion channels with water soluble hormones?

A

hormones using multiple pathways

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21
Q

What are the 3 components of the membrane receptor?

A

External domain
Transmembrane domain
Cytoplasmic/ intracellular domain

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22
Q

What is the inter cellular signalling pathway for water soluble hormones?

A

Binds to extracellular hormone binding domain
Will affect the transmembrane domain and cause the cytoplasmic domain to undergo conformational change

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23
Q

Growth factors

A

Polypeptides that promote cell growth or proliferation

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24
Q

Cytokines

A

General term used for factors associated with blood cells (ie derived from immunology)

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25
Q

What processes are controlled by growth factors and cytokines?

A

Cell division and proliferation
Apoptosis

GF and cytokines are implicated in cancer

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26
Q

Why is the removal or termination of a signal important?

A

Signal reduction is required
Response fades once signal is withdrawn
Depends on rate of destruction of molecules that signals effects
Turnover rate depends on the promptness of the signal being turned on

Factors determine the half life of the signalling molecule

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27
Q

Define half life of a signalling moecule

A

Time taken for the concentration of a signalling molecule to fall by half

Determined by rate of synthesis and modifications of proteins

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28
Q

How can the same molecule have different effects?

A

ACh has different effects on the heart, salivary gland and the skeletal muscle
All dependent on the receptor it binds to

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29
Q

What are the main cell surface receptors?

A

Ion channel liked receptors
G protein linked receptors
Tyrosine kinase linked receptros
Receptors with intrinsic enzymatic activity

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30
Q

Examples of ion channel linked receptors

A

Postsynaptic membranes

Neuromuscular junction

Nicotinic acetylcholine receptor

GABA receptors

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31
Q

What are the second messenger molecules and how do they work?

A

Small intracellular signalling molecules
generated in large numbers by activation of receptor= amplification of signal
Diffuse away rapidly
Pass on signel by binding to and altering the behaviour of other proteins
Exhibit different ways of passing the signal on

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32
Q

Give some examples of second messenger molecules

A

cAMP
cGMP
Ca2+
Diacylglycerol

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33
Q

What are the functions of intracellular proteins?

A

Scaffolds
Relays
Adaptors
Amplifiers
Modulators

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34
Q

What are the key processes in cell signalling?

A

Protein phosphorylation - protein kinase and phosphoprotein phosphatase
Reversal of protein phosphorylation

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35
Q

What are the types of protein phosphorylation?

A

Phosphorylation of serine/threonine residues
Phosphorylation of tyrosinwe residues

phosphate is added by signal transduction

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36
Q

What is 7 transmembrane?

A

Single polypeptide chain with central hydrophobic region that spans the plasma membrane 7 times

receptor protein interaction = mediated by 3rd protein (G protein)
target is enzyme or ion channel

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37
Q

G protein

A

Guanine nucleotide binding protein
Signal transduction protein

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38
Q

What are the 3 main steps of the G protein mediated signal transduction?

A

No ligand = inactive receptor
Binding of ligand recruits G protein complex
GTP replaces GDP when g alpha and bet proteins dissociate and their subunits regulate second messengers

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39
Q

What are GaS and GaI G proteins?

A

Stimulatory
Inhibitory

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40
Q

How do stimulatory effects mediate the adenylate cyclase system?

A
  1. Subunit of G protein activated to adenylate cyclase
  2. ATP converted to cAMP
  3. cAMP is a catalytic subunit of protein kinase A
  4. pkA is part of the cascade of intracellular phosphorlations
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41
Q

What are the 2 types of enzyme linked receptors?

A

Function directly as enzymes (intrinsic enz activity)
Directly associated with enzymes they activate (associated enz activity)

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42
Q

What is the signal transduction pathway for tyrosine kinase receptors?

A

Ras signal transduction pathway
Phosphoinisitide 3 kinase pathway (PI-3 kinase)
Phospholipase C

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43
Q

What is the Ras pathway?

A

Ligand and receptor bind -> ras pathway is protein kinases are used and formed _> protein kinases pass through nuclear pore= transcription factors activated
Gene activation occurs
Cellular response

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44
Q

What are the 6 classes of enzyme linked receptors?

A
  • receptor tyrosine kinases- Phosphorlyate tyrosines on intracellular signalling molecules
  • Tyrosine kinase-associated receptors- Associate with intracellular proteins with tyrosine kinase activity
  • Receptor-like tyrosine phosphatases- Remove phosphate groups from tyrosine on intracellular proteins
  • receptor serine/threonine kinases- Phosphorylate serines or threonines on regulatory proteins
  • Receptor guanyl cyclases- Catalyse production of cytosolic cGMP
  • Histidine-kinase-associated receptors
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45
Q

How do histidine kinase associated receptors work?

A

Two component system - kinase phosphorylated itself
Passes on phosphate to intracellular signalling protein

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46
Q

What are the 2 intracellular molecular switches?

A

Made of intracellular protein and signal - switch from active to inactive
Signalling must recover
Switch operates by gain or loss of phosphate groups

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47
Q

What are the 2 main classes of molecular switch?

A

Phosphorylation (removal of Pi inactive- kinase adds Pi active)
GTP binding (GDP inactive- GTP active)

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48
Q

In general steroid hormones have a ______ effect on cells

A

Slower by stronger effect

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49
Q

In general water soluble hormones have a _________ effect on cells

A

Faster but less intense effect on cells

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50
Q

What are the 4 organ endrocrine glands?

A

Heart = ANP
Intestine= cholecystokinin
Kidney= 1, 24 dihydroxycholecalciferal and EPO
Placenta= chorionic gonadotropins

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51
Q

What are the function classifications of hormones?

A

Classical hormones
Neurohormones
Local hormones

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52
Q

What are classical hormones?

A

Endocrine cells -> blood -> target tissue

Like cortisol a steroid hormone secreted by the adrenal cortex

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53
Q

What are neurohormones?

A

Neuroendocrine cells-> nerve terminals-> blood

Like cortico releasing hormone - produced by hypothalamus= ACTH from the ant pit-> adrenal = cortisol

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54
Q

What are local hormones?

A

Paracrine and autocrine hormones that diffuse into the interstitial fluid

55
Q

Epinephrine

A

Catecholamine - freely transported

56
Q

How are lipid soluble hormones transported?

A

Bound to transport proteins
Cortisol binding globulin

57
Q

What are the main specific lipid soluble binding hormones?

A

Cortisol binding protein -> cortisol
Vitamin D binding globulin = Vit D
Thyroid binding globin = T 3 and T4

58
Q

What are the non specific lipid soluble binding hormones?

A

Albumin -> steroids
Prealbumin -> T3 and T4

59
Q

Where can thyroid hormones be found in the blood?

A

0.3% fT3
0.03% fT4
70-80% bound to thyroid binding globulin
Rest is bound to albumin and free albumin

Bound hormones have a high concentration
Free hormones have a low concentration

60
Q

What affects total hormone concentrations?

A

Binding protein conc
Hormone level

61
Q

How do transport proteins function?

A

Serves as a hormone reservoir- free diffuse into cell, replace free hormones in the blood
Act as hormone buffer - resp to inc horm conc - short term peaks absorbed, dont necessarily stim tisues
reduce hormone loss from the kidneys- Larger so dont enter ultrafiltrate

62
Q

What are plasma concentrations the net result of?

A

Rate of secretion into bloos
Rate of removal from the blood

63
Q

What are the different elimination mechanisms?

A

Enzymatic degradation
within target cells after binding
Via liver and kidneys

64
Q

How is elimination and function of epinephrine related?

A

Epi= fight or flight hormone
rapid release from adrenal medulla = immediate action on heart and tissues
Fast return to normal
Water soluble hormone binds to receptors and is enzymatically degraded

65
Q

How is elimination and function of T4 (thyroxine) related?

A

Slow action hormones
T4 is predominantly bound
Bound is resistant to degradation
FreeT4 -> T3 to enter cell and alter gene expression or converted to water sol by liver and excreted in urine

66
Q

What factors affect hormone response?

A

Variation by tissue
variation by time
variation by dose
status of target tissue

67
Q

How can the variation of tissue affect the action of thyroxine?

A

T4 increases cellular metabolism measured as O2 consumption
48 hrs after injection most stimulated tissues are heart and gastric mucosa
Least stimulated = skeletal musc
Not stim= brain and spleen

68
Q

How does time affect variation of hormone action?

A

Initial response of hormone may differ from delayed responses

69
Q

How is there variation by dose and duration of hormones?

A

Response associated with hormone is for physiological range
Hormones outside normal range = diff response

Dex steroid short course = no adverse affects
Long course= clinical signs of cortisol excess

70
Q

How will targets tissue status affect hormone function?

A

overstimulation = hypertrophy = more functional= exaggerated response
Under stimulation = atrophy = less functional

71
Q

How does dexamethasone withdrawal cause issues?

A

Immunosuppressive doses for auto immune disease
Dexamethasone suppresses normal syth and secretion of steroid from adrenal gland
Adrenal gland atrophy
Sudden withdrawal = crisis

72
Q

What units are used for measuring hormones?

A

picomol
Nanomol

73
Q

What diagnostic kits can be used to measure hormones?

A

Radioimmunoassay
ELISA

74
Q

Clearance rate

A

Use of radioactively labelled hormone or halt secretion

75
Q

Secretion rate

A

If concentration rate remains stable then it is assumed secretion = clearance

76
Q

How do feedback loops play a role in hormone secretion?

A

Negative feedback
hormone exceeding necessary levels
High level is sensed by hypo or pit gland
= decrease in hormone synth
free hormone levels monitored and adapts to changes in the binding protein

77
Q

Main water soluble hormones

A

Glycoproteins
Catecholamines
Peptide hormones
Calcitonin
Epinephrine
Thymosin
Melatonin

78
Q

Which hormones exclusively uses adenyl cyclase pathway?

A

Insulin
ADH
glucagon

79
Q

What is the adenyly cyclase pathway?

A

Pathway regulated by GaS and GaI
Any reaction where ATP is converted to cAMP uses this pathway

80
Q

Which hormone exclusively uses the phospholipase C pathway?

A

PTH
TSH

81
Q

Which hormones exclusively uses the tyrosine kinase pathway?

A

peptide hormones like insulin, and growth hormones
such as IGF-1
Growth hormone

82
Q

ANP

A

Atrial natiuretic peptide - increases renal excretion of salt and water, vasodilation, inc vasc permeability
uses guanylate cyclase transduction system (cGMP)

83
Q

What can somatotropes become?

A

GH
Somatotropin
Somatotrophic hormoen

84
Q

How is growth hormone regulated?

A

GH in liver produces IGF-1 or somatomedin C
these stim GHRIH or somatostatin in order to inhibit release of GHRH from hypothalamus
IGF 1 directly inhibits GH release from Ant pit
Grehlin stims GH release from pit

Negative feedback loop

85
Q

What is the long term and short term actions of GH?

A

Long = promoted growth- protein synthesis
Short= starvation response = lipolysis and insulin resistance

86
Q

What receptors does growth hormone require?

A

STAT1 and STAT2 receptor mechanisms
Needs a surface receptor and a second messenger hormone

87
Q

What growth response is produced by GH?

A

inc nuclear transcription
inc translation
inc aa transport through cell membrane
dec catabolism of proteins and aa

88
Q

What are the different stimuli for the starvation response by growth hormone?

A

dec blood glucose
dec free FA
dec protein
Trauma stress excitement
Exercise

89
Q

What are the properties and actions of IGF1?

A

lnsulin mimicer
Stim by GH
produced mainly in liver
Inc chondrogenesis and growth
Inc chondrocytes and osteogenic cell replication and protein for more bone growth
Chondrocytes-> osteoblasts = new bone

90
Q

Affect of IGF1 on bone growth?

A

Open growth plates or epiphyseal cartilage
GH inc cartilage deposition
GH stim osteoblasts
Cartilage minerlises inc bone length

Closed growth places
Epiphyseal cartilage fused to bone shaft

91
Q

Pituitary dwarfism

A

autosomal recessive condition causes proportionate growth retardation, soft wooly hair
2-3 months of age
mutation in LHX3 that regulates pit stem cell differentiation
Defect after corticotrope differentiation so ACTH not affected
Decreases GH,TSH prolactin and gonadotropins
+/- pitui cyst

92
Q

How does pituitary dwarfism affect the repro tract?

A

Males = unilateral or bilateral crytochidism
Females= persistent oestrus , failure to ovulate

93
Q

How is a diagnosis of pituitary dwarfism made?

A

decreased GH - species specific radio immunoassay
dec IGF-1 - longer half life, less species spec aa sequence - human assay

94
Q

What occurs with GH excess?

A

Giantism= develops in young patients before closure of epiphyses
Acromegaly= develops in adult patients after closure of epiphyses, inc soft tissues over eyes, macroglossia, inc interdental space, organomegaly

95
Q

Feline acromegaly

A

Middle age- old = 90% female
Pituitary tumour secreting excess GH
Diabetic at presentation (caused by insulin resistance)

96
Q

Canine acromegaly

A

Middle- old
ALWAYS female
excess exogenous progesterons and endogenous progesterone
Induction of GH gene in mammary glands
mammary GH = normal GH

97
Q

Acromegaly diagnosis?

A

IGF-1 conc
GH conc - species spec assay
supportive clinical signs and lab work w normal thyroid adrenal testing

98
Q

Chromophobes stain ________ while chromophils stain _________

A

chromophobes stain poorly while chromophils stain well

99
Q

What are the two types of chromophils?

A

Acidophils - acid dyes somatotropes and lactotropes, mammotropes, luteotropes
Basophils - Basic dies
Cortictropes, thyrotropes, gonadotropes

100
Q

What are the most and least dense cells of the pars distalis?

A

Most = somatotropes = GH 50%
Least = thyrotropes = TSH 5%

All the others make up 15-20%

101
Q

what is grehlin

A

a hormone from the stomach that releases growth hormones in response to food

102
Q

Which 3 hormones regulate growth hormone secretion

A

Grehlin
GHSH
Somatostatin

103
Q

What is the role of the growth hormone?

A
  • Stimulates IGF-1 secretion from the liver
  • Growth
  • Stimulates protein synthesis (anabolic effects)
  • Stimulates lipolysis (mobilizes fatty acids and glycerol)
  • Inhibits glucose utilisation (inhibits insulin)
104
Q

What are the 2 forms of lactotropes and when is each relevant?

A

Lactotropes may be chromophils when storing PRL in the cytoplasm

However, lactotropes are chromophobes when PRL has been released

105
Q

How are lactotropes regulated?

A
    1. Tonic inhibition by dopamine via the D2 receptors
    2. Lactotropes can be stimulated by TRH
    3. There is hypertrophy of lactotropes during pregnancy for lactation
106
Q

What is produced by the corticotropes?

A

POMC (proopiomelanocortin)
Proteolytic hormones cleave POMC into
- Adrenocoticotropine hormone
- Melanocyte-stimulating hormone
- beta-lipotrophic hormone
- beta-endorphin
- enkephalin
- corticotropin-like intermediate lobe peptide (CLIP)

107
Q

What is enkephalin?

A

A type of endorphin

108
Q

What controls the local production of POMC derived hormones?

A

Discrete localisation of processing enzymes within the anterior pituitary

Prohormone convertase I
Prohormone convertase II

109
Q

How are corticotropes regulated>

A
    1. By corticotropin-releasing hormone
    2. Tonic stimulation
    3. By a negative feedback loop

More corticotropin-releasing hormone increases the ACTH secretion

Less corticotropin-releasing hormone decreases ACTH secretion

110
Q

How are gonadotropes regulated?

A
  1. By GnRH from the hypothalamus
  2. In a negative feedback loop
111
Q

Describe the structure of the pars intermedia?

A
  • The pars intermedia is a series of small cystic cavities
  • It has follicles filled with colloid
  • The pars intermedia originated from the residual lumen of Rathke’s pouch
  • Contains Basophils and chromophobes
  • The pars intermedia extends into the pars nervosa
112
Q

What is the role of the pars intermedia in horses>

A

Referred to as melanotropes in horses

Where prohormone POMC is converted into MSH

Not under negative feedback control

113
Q

Closed feedback loops

A

Target cells secreted hormones that affect their own secretion

There is feedback regulation that is usually negative

114
Q

Describe open feedback loops

A

There is no direct feedback

Instead, they are stopped by the removal of the stimulus or depletion of biochemicals

Stimulation of milk let down

115
Q

What are the 4 independent systems?

A
  1. Glucose regulation
  2. Calcium regulation
  3. Sodium and potassium regulation
  4. Gastrointestinal enzyme secretion
116
Q

How do hormone deficiencies occur?

A
  1. There is less functional tissue to produce to hormone
  2. Interference with hormone synthesis
  3. Less stimulation from higher in the pathway
117
Q

How can loss of negative feedback occur?

A

Hormone from tissue that was never under negative feedback control

Tissue continues secreting hormones regardless of stimulating hormone

118
Q

What are the pituitary neoplasms

A

Adenomas of the pars distalis or intermedia
GH secreting pars distalis tumour

119
Q

What is the affect of a GH secreting pars distalis tumour?

A
  • Affects the acidophils within the pars distalis
  • very rare
  • There is an excess of growth hormone (and IGF-1 from the liver)
  • This alters the growth and affects energy metabolism
  • Differential diagnosis for diabetes mellitus
120
Q

Where is the thirst centre located>

A

Hypothalamus
Input from osmo and stretch receptors
Info -> ADH producing neurones to PP -> capillary bed

121
Q

How does ADH increase AQP density on the tubule surface?

A

Aquaporin-2 is under ADH control

  1. ADH binds to receptors
  2. Activation of adenyl cyclase occurs
  3. This produced cAMP
  4. Vesicles containing aquaporins move to the cell surface
  5. Inserted via exocytosis
  6. Proportional to plasma ADH concentration
  7. They are then removed by endocytosis
122
Q

What is DI>

A

Diabetes increased urine output
Insipidus is caused by ADH dysregulation

123
Q

What are the 2 types of DI?

A

Neurogenic= inadequate ADH from pit
Nephrogenic = inadequate nephron response

124
Q

How is DI diagnosed>

A

Injection of exogenous ADH

if the urine is concentrated then it is neurogenic DI

If the urine is dilute then it is nephrogenic DI

125
Q

What causes congenital diabetes insipidus?

A

AQP-2 deficiency
Nephrogenic

126
Q

What is the neuronal transmission from the mammary glands?

A

-sensory nerve fibres in the teats detct the suckling
- Impulses transmitter via the superficial sensory pathways and inguinal nerve
- Afferent sensory neurones enter the lumbar segments of the spinal cord
- Ascend the spinal cord sensory tracts
- To the thalamus, influence cell bodies of neuroendocrine cells
- Secretion of oxytocin from nerve endings in PP

127
Q

What is the role of oxytocin once released in the mammary gland>

A
  1. Increases pressure within the alveoli
  2. Reduced resistance in excretory ducts
  3. Reduced resistance in the teat canal
  4. The result is increased milk outflow
128
Q

Describe the physiology of oxytocin in the mammary gland

A
    1. Binds to receptors on myoepithelial cells
    2. Myoepithelial cells surround alveoli and walls of small secretory ducts
    3. Oriented along the long axis of the secretory duct
    4. The duct becomes shorter and wider
    5. Opposite effect on circular sphincter muscle of teat - causes relaxation
    6. Both actions increase the milk flow
129
Q

What are the stages of parturition?

A
  • Stage 1Myometrial contractions and dilation of the cervix
  • Stage 2Expulsion of the fetus through the birth canal
  • Stage 3Expulsion of placenta
130
Q

What is the neuroendocrine reflex during birth?

A
  • Stimulate sensory nerve endings in the cervix
  • Afferetn nerve impulses to the hypothalamus
  • Neuroendocrine cells of the paraventricular and supraoptic nuclei depolarize
  • Secrete oxytocin from pars nervosa
  • Enters blood circulation
  • Act on oxytocin receptors of myometrium
  • Strong uterine contractions
131
Q

Outline the biological clock mechanism

A
  1. Light is sensed by the retina
  2. transmitted via nerve pathways
  3. Arrive at hypothalamus
    1. Specifically the suprachiasmatic nucleus
  4. Stimulates the pineal gland and other pathways
132
Q

Define sensitivity

A

The true positive rate

Measures the proportion of actual positives which are correctly identified as such

the percentage of healthy horses who are correctly identified having PPID

133
Q

Define specificity

A

The true negative rate

Measures the proportion of actual negatives which are correctly identified as such

  • The % of healthy horses who are correctly identified as not having PPID
134
Q

How can we differentiate between PPID and EMS?

A

signalment and other clinical signs
ACTH does not increase with EMS

Difficult when animal is stressed

Veterinary medicine year 2 (23 decks)

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