Endocrinology Lectures 2021 Flashcards

Question

Hypersecretion

Answer 1

primary or secondary, usually the result of a benign tumour (adenoma), normally treated through inhibition

Answer 2

– lack of receptors or biochemical machinery at the target cell Eg: Hyperinsulinemia *Target cell responsiveness is also altered naturally!

Answer 3

1. UP & DOWN REGULATION – Receptors at the target cell are themselves regulated in response to hormone levels influencing ABUNDANCE and AFFINITY 2. PERMISSIVENESS – One hormone CANNOT fully exert its effect without the other being present 3. SYNERGISM – The COMBINED effect is greater than the sum of the parts 4. ANTAGONISM - The actions of one hormone REDUCES the effectiveness of the second – can be direct or indirect (happens naturally) Measurement of binding kinetics for hormone/receptor complexes relies heavily on the chemical law of mass action: Kd = [H] [R] / [HR]

Answer 4

LOW (easy for molecule to dissociate from receptor)

Answer 5

NON-COOPERATIVE = Law of mass action is upheld POSITIVELY COOPERATIVE = ligand binding increases receptor affinity of vacant receptors NEGATIVELY COOPERATIVE = ligand binding decreases receptor affinity of vacant receptors

Answer 6

glucagon + epinephrine + cortisol combo is greater than parts

Answer 7

1. MEMBRANE BOUND → Ligand gated, enzyme linked, guanylyl cyclase and Gprotein linked receptors → Second messenger systems include: adenylate cyclase guanylate cyclase inositol phosphate and diacyl glycerol 2. NUCLEAR RECEPTORS Most lipophilic hormones act through nuclear receptors and many genes will have responsive elements

Answer 8

1. INFUNDIBULUM - is the stalk that connects the pituitary to the brain 2. POSTERIOR PITUITARY - is an extension of the neural tissue (connected directly to hypothalamus) 3. SPHENOID BONE 4. ANTERIOR PITUITARY (is a true endocrine gland of epithelial origin)

Answer 9

Anterior Pituitary: - Pars distalis - Adenohypophysis Posterior pituitary: - Pars nervosa - Neurohypophysis Trophic hormones will typically stimulate production of hormones from anterior pituitary

Answer 10

1. The hypothalamus and posterior pituitary form a neuroendocrine system with cell bodies based in the hypothalamus 2. Posterior pituitary hormones synthesised in the hypothalamus 3. Axons then extend down the INFUNDIBULUM and terminate in the posterior pituitary

Answer 11

Anterior pituitary: constitutive release --> constant Posterior pituitary: these hormones are released on demand --> regulated (most hormone release is regulated)

Answer 12

Vasopressin --> supraoptic nucleus Oxytocin --> paraventricular nucleus

Answer 13

Two nonapeptides (OT and AVP) *Simple in structure but do diff things Precursor peptides produced in the hypothalamus – neurophysins Closely related but one can work without the other. - pos. pit is the storage & release site for 2 neurohormones: oxytocin & vassopressin - the neurons producing OT & AVP are clustered together in areas of the hypothalamus known as the paraventricular & supraoptic nuclei - these 2 pos. pit. neurohormones are composed of 9 AA's each eg: Brattleboro rats - genetically diabetic (tasted urine) diabetes --> running through (have to go to the bathroom a lot) diabetes insipidus (insipid --> sour) --> vasopressin diabetes mellitus (honey "sweet" - full of glucose) --> insulin

Answer 14

packaged in secretory granules and begin to migrate down the axon to the neurohypophysis where the nerve terminals are located

Answer 15

Reduced ECFV → ↑ plasma osmolality → ↑ osmoreceptor activity → ↑ vasopressin release Reduced ECFV → ↓ left atrial volume → ↓ arterial blood pressure → ↑ vasopressin release

Answer 16

1. Loss of blood through hemorrging 2. Loss of fluid through an INCREASE in plasma osmolarity as fluid moves from the EC space to IC space (ex: working out & sweating --> loose volume & you want to protect cellular fluid space so as a result that INCREASES concentration of salts & solutes in the ECF space we will get INCREASE in plasma osmolarity - that triggers osmoreceptor & that causes vasopressin release from posterior pituitary

Answer 17

↑ H2O reabsorption in renal tubules --> 1 reason why its called ADH (diuresis --> increase in urine flow rate & anti-diuresis --> reduction) Vasoconstriction of vascular smooth muscle NET EFFORT: - CLOSED caridovas space - if you loose volume in that closed space, 1 way to maintain volume & same pressure is to make that space smaller

Answer 18

Birth canal distension → ↑ oxytocin release Infant suckling → ↑ oxytocin release BOTH (+) feedback

Answer 19

↑ uterine muscle (myometrium) contraction during parturition | ↑ milk ejection from mammary gland

Answer 20

OT: • INcreases maternal behaviour in rats but estrogens need to be present * Plasma OT levels INcrease during sexual arousal in both sexes * Act as neuromodulators in the brain to influence social recognition, memory and affiliative behaviours such as “pair bonding” (rodent research)

Answer 21

AVP: • Stimulates release of ACTH that is synergistic with CRH • Seems to play a greater role in MALES rather than females in regard to social recognition and consolidation of social memory (rodent research) • Aggression, courtship, scent marking, and learning (rodent research)

Answer 22

Portal Capillary bed --> Capillary bed Arteriole --> capillary --> venule

Answer 23

Histological and cytological methods have provided definitive evidence on the cellular source for each hormone released from the adenohypophysis

Answer 24

Hormone: ACTH Staining characteristics: basophil

Answer 25

Hormone: TSH Staining characteristics: basophil

Answer 26

Hormone: FSH, LH Staining characteristics: basophil, basophil

Answer 27

Hormone: PRL Staining characteristics: acidophil

Answer 28

Hormone: Somatotroph Staining characteristics: acidophil

Answer 29

Hormones synthesized and released from the anterior pituitary are under the control of HYPOPHYSIOTROPIC hormones that can be stimulatory or inhibitory ex: Corticotropin releasing hormone (CRH) - pituitary hormone: adrenocorticotropic hormone - "final" hormone: cortisol The hypophysiotropic hormones: - TRH - CRH - GnRH - GHRH

Answer 30

inhibits control stimulates control

Answer 31

GROWTH HORMONE FAMILY: - Growth Hormone - Prolactin Growth hormone is well conserved however there are many different variants of prolactin. GLYCOPROTEIN FAMILY: - Follicle stimulating hormone (FSH), leutinizing hormone (LH), thyroid stimulating hormone (TSH), - So named due to the large percentage of carbohydrate moieties – up to 33% by weight - Each has an α and β subunit. The amino acid sequence of the α subunit is similar between the hormones but the β subunit varies

Answer 32

Many animals have an anatomically separate pars intermedia The predominant endocrine product is αMSH (involved in regulating melanocytes --> melanocyte regulation - skin pigmentation (pleiotropic hormone - means many actions, anorexogenic factor - inhibit food intake) In humans this is also the case during development As adults these cells are not anatomically distinct but still synthesise and secrete αMSH

Answer 33

- happens INTRAcellularly also involved in regulating FOOD INTAKE - within ANTERIOR PITUITARY - diff cell types will express proconvertase enzymes (PC1, 2 & 3) - response for CHOPPING UP POMC in diff places depending on the signal response - no 1 precursor molecule of POMC can synthesize both ACTH & a-MSH & release both of those hormones

Answer 34

1. Protein, fat and cartilage synthesis 2. Cell proliferation - Hyperplasia and hypertrophy 3. Bone lengthening - Increased extracellular matrix

Answer 35

1. Genetic resolve 2. Diet and nutrient transfer 3. Disease and stress 4. Multiple layers of hormonal control

Answer 36

Neonatal growth under the influence of placental hormones Growth rate varies throughout life * GH levels increase during puberty * In males, testicular androgens are v. important and increase dramatically during puberty * Adrenal androgens also increase and may be more important in females (b/c males lack androgen in testes?) * Testosterone and estrogen both ultimately “put the brakes on”

Answer 37

• GH production stimulated by GHRH and inhibited by GHIH (somatostatin) • GH is a 191 amino acid long polypeptide produced in somatotrophs • It is the most ABUNDANT adenohypophysial hormone (4- 10% of the wet weight of the gland ~ 5-10mg) • Spontaneous secretion over a 24 h period usually peaks in the first 90 minutes of sleep • Transported in plasma attached to one or more binding proteins

Answer 38

inhib. factor that inhibits GH release from the anterior pituitary

Answer 39

drives the axis

Answer 40

“Growth hormone does not have a direct effect on growth of any given tissue but rather acts indirectly through somatomedins” There are two main somatomedins – Insulin like growth factors (IGF) I & II (predominantly synthesized & secreted by the liver) They are 70 and 67 amino acids respectively and share many similarities with insulin

Answer 41

indicated to researches that GH was stimulating something else (IGF) into the circulation that facilitated & directed growth in these samples

Answer 42

1. Both SINGLE PASS (1 straight line through the membrane) receptors that are linked to these TKD's on the intracellular side of the cell membrane 2. Both exist as dimers - 2 monomers attached here by sulfate bridges

Answer 43

Circulating levels of IGF I increase massively during pubertal growth spurt but GH increases moderately by comparison (long bone growth excellerates during puberty) Tissue specific regulation of IGF I synthesis GH does not regulate IGF II production to the same extent IGF II is important during fetal development and plays a role in adult growth but not to the same extent as IGF I

Answer 44

Bone is LIVING TISSUE surrounded by an extracellular organinc matrix with a variety of cell types that have specific roles

Answer 45

Compact bone: is dense & used for support Spongy bone or trabecular bone: forms a calcified lattice LOTS OF CARTILAGE IN BONE

Answer 46

Osteoblasts --> bone BUILDERS Osteoclasts --> bone BREAKERS these bone breakers/builders are critically imp. for the modulation & shaping of bone - also play a very imp. role in Ca2+ balance

Answer 47

EPIPHYSIS: is the end of a long bone EPIPHYSEAL PLATE: is the site of bone growth (imp. in long bone growth) DIAPHYSIS: is the shaft of a long bone (lone part of bone) *The DIAPHYSIS is the mature bone shaft with the EPIPHYSIS at either end. In a growing bone the epiphysis is separated from the diaphysis by the EPIPHYSEAL PLAYE

Answer 48

enzymes (osteoid) collagen and proteins to provide a framework for hydroxyapatite crystals. They deposit new bone on the outer edges of old bone to increase width. This is a dynamic process

Answer 49

osteocytes

Answer 50

is a different process and is regulated by cartilage cells, CHONDROCYTES, located in the epiphyseal plates

Answer 51

divide and multiply, lengthening the epiphysis with the older cartilage cells enlarging at the border of the diaphysis.

Answer 52

Hyperplasia - lots of cell division Hypertrophy - INcrease cell size

Answer 53

Driven by: GH & IGF 1. Development of IGF-I responsiveness 2. Expression of IGF-I gene 1. Local production of IGF-I 2. Stimulation of clonal expansion by autocine/paracrine mechanisms Cytoplasmic maturation

Answer 54

1. Site of lesion in ANTERIOR pituitary - hypopituitary dwarfism - if inhibited - gigantism (infant) or acromegaly (adult) - if stimulated (hyperactivity) Fezik --> Andre the giant - gigantism & acromegaly - hyperactive pituitary gland during infancancy & adulthood Robert Wadlow - 2.7m or 8.9 feet tall - worlds tallest individual suffered from gigantism Maurice Tillet - large forehead - big hands - big jaw - probably had problem in pituitary gland during puberty 2. Laron dwarfism (IGF DEcrease production) - Site of lesion in LIVER - "Little women of Loja" - everyone in that village is short in height (especially women but also men to some extent) - can be lack of GH receptors on liver - lack IGF responsiveness - decrease GH BP (binding protein) - decrease IGF carrying capacity 3. End organ resistance - site of lesion in somatic cells

Answer 55

– involved in energy homeostasis. | Hypothyroidism = reduced growth, TH is largely permissive (neuronal development)

Answer 56

involved in carbohydrate metabolism. Deficiency can | block growth and excess can promote growth, potential cross reactivity with IGF receptors

Answer 57

Arrest “long-bone” length increase by closure of the epiphyseal plate (causes ossification of the epiphyseal plate)

Answer 58

belongs to the GH family and influences mammary gland growth as well as aspects of the immune system (influences lymphocytes)

Answer 59

belongs to the GH family and influences neonatal development, maternal glucose and amino acid supply. Peaks around mid pregnancy until full term - can play a role in gestational diabetes (don't be a diabetic after birth)

Answer 60

nerve growth factors (NGF’s) - used in early treatment of neurodegenerative disorder

Answer 61

red blood cell growth factor - EPO doping (to remote blood cell growth)

Answer 62

vascular injury repair but also involved in the development of artherosclerosis

Answer 63

enhanced proliferation of epidermis, gut lining, pulmonary lining - herbivores grazing (will leave saliva on plant that will use it to grow the plant)

Answer 64

angiogenesis (growth of blood vessels) – Fibroblast growth factors – Transforming growth factors

Answer 65

in bone tissue

Answer 66

locked = bone

Answer 67

Calcium is perhaps the most tightly regulated ion in circulation – 99% of the bodies calcium is in calcified structures – 0.9% is intracellular – 0.1% exists in the ECF, half of this is bound to proteins or negatively charged ions and the rest is in free form Ca2+ (0.05% is in free form) 1. Neuromuscular excitability – reduced calcium leads to tetanic muscle contraction and high levels lead to reduced muscular contraction 2. Stimulus-secretion coupling: many cells will require calcium to enter the cell to stimulate the secretion of a given substance 3. Cell–Cell integrity of tight junctions 4. Cofactor for clotting blood 5. Required for structural form of bone and teeth

Answer 68

balance (input vs output in terms of diet) vs. homeostasis (internal regulation)

Answer 69

Bone is a living tissue that is packed with hydroxyapatite crystals between a collagen matrix 3Ca2+ + 2PO43- --> Ks --> precipitation (can lead to kidney stones - precipate out in wrong place) (happens in bone - crystals precipate out) [Ca2+] X [PO43-] < Ks --> solution So regulation of calcium ALWAYS impacts phosphate concentrations

Answer 70

Remodelling requires deposition and resorbtion. – Osteocytes = mature bone cells – Osteoblasts = bone builders responsible for depositing the collagen matrix (derived by stromal cells - connective tissue) – Osteoclasts = bone breakers (desolve hydroxyapatite crystals within the bone matrix) (derived by haematopoeitic cells, macrophages & blood cells ex platelets)

Answer 71

1. Rough jaggedy edge to the membrane of the cell in its interface for this bone solid space - INcreases the SA; allowing greater int. of any chemicals released from the osteoclasts

Answer 72

- release hydrogen ions (decrease pH - more acidic) - release cathepsin (enzyme that will degrade collagen) (breaks down structure to free up hydroxyapatite crystals by creating an acidic pH (lower solubility coefficient, makes crystals go into solution faster)

Answer 73

start shape

Answer 74

- solid - explains why its slow - hydroxyapatite crystals in here - where Ca2+ phosphate has exceeded the solubility coefficient & have participated out (it is solid)

Answer 75

slow: taking it from the bone matrix fast: taking Ca2+ & phosphate from the bone fluid space

Answer 76

imp. in context of the role of osteocysts & osteoblasts play: - movement of ions that are liberated from the boney matrix or within this bone fluid space into the blood (requires specific Ca2+ transporters) & in particular Ca2+ ATPase (will allow cell to draw Ca2+ in or pump it out & then influence solubility coefficient in this bone fluid space & allow for movement of Ca2+ from bone fluid space into glut

Answer 77

1. PARATHYROID HORMONE (PTH) – negative relationship between plasma [PTH] concentration and plasma [Ca2+] that is EXTREMELY sensitive - as plasma Ca2+ concen. falls, PTH concen. INcreases, such that PTH is a hypercalcemic hormone (INcreases Ca2+ concen. in the circulation) - parathyroid glands synthesize & release thyroid hormone 2. VITAMIN D3 (cholecalciferol) – needs to be converted to 1,25 – (OH2) – vitamin D3 (calcitriol) 3. CALCITONIN – the ONLY hypocalcaemic hormone (works to reduce the circulating levels of Ca2+ in your blood stream)

Answer 78

Bone (stimulate osteoclast activity to promote the dissolution of hydroxyapatite crystals within that mineralized bone area) 1. Fast homeostatic regulation of Ca2+ from bone fluid space (plasma) 2. Slower balancing of total body calcium from resorptive processes *body might call on that Ca2+ reserve to maintain Ca2+ homeostasis in the ECF space

Answer 79

PTH increases calcium and decreases phosphate reabsorption INCREASE PO43- loss DECREASE Blood PO43- INCREASE Solubilisation of bone INCREASE Ca2+ release

Answer 80

Actions are INdirect through stimulation of vitamin D3 production

Answer 81

• Considered by many as a hormone as it can be produced in the skin from 7-dehydrocholesterol - lipid soluble • Two important enzymatic steps that involve the sequential addition of hydroxyl groups - VD AKA seco-steroid (similar structure as normally steroids that have 4 aromatic ring structures but 1 of the aromatic rings is broken) • Activation of 1α hydroxylase is the most important step and this enzyme is regulated by PTH

Answer 82

Typically, influences gene expression (genomic effect tends to take a little while)

Answer 83

• The gut is probably the best documented area of vitamin D3 action. Where both fast and slow components are initiated. - bind to receptors on cell mem. & cause a rapid response rickets - brittle bones would be result Rapid component --> mainly facilitated by VD binding to cell membrane receptors (Na+ Ca2+ exchanger - NCX) Longer lasting component --> mainly facilitated by VD binding to nuclear receptors (PM - plasma membrane Ca2+ ATPase (pump req's energy)

Answer 84

act as hypercalcaemic hormones - job is to increase Ca2+ concen. in response to hypercalcaemic events slide 79

Answer 85

Not involved in day to day regulation but may be involved during the absorptive state (post meal) and also during pregnancy (newborn req's lots of Ca2+ during new growth) Calcitonin has both hypocalcaemic and hypophosphatemic effects slide 81 satiety hormone - that's enough (baby sucking milk)

Answer 86

For the most part bone resorption and bone deposition balance each other out but there are times when this is not the case Osteoblasts are derived from STROMAL CELLS in the bone marrow and osteoclasts are derived from MACROPHAGES in the bone marrow – Osteoblasts and its precursor cells produce two main messengers RANKL (receptor activator of NFκB ligand) and OSTEOPROTEGERIN – Estradiol stimulates the production of osteoprotegerin

Answer 87

Reduced bone mineral density Prevalent in pre and postmenopausal women Onset of osteoporosis and ~1% of bone mass is lost every year ``` Therapy includes: – Exercise – Ca2+ supplements – HRT – Calcitonin – SERMS (selective estrogen receptor modulator) and ANGELS (activators of non-genomic estrogen like signalling) ``` * men don't have increase's in estrogens & don't have same levels so as a conseq. there is disconnect - males produce testosterone --> aromatase --> estrogens

Answer 88

- vascularized | - next to imp. blood vessels (cardiac artery - red)

Answer 89

Tetraiodothyronine (T4) and triiodothyronine (T3) are both derived from THYROGLOGULIN and synthesized in the follicular cells and the colloid of the thyroid gland - insufficient way to syn. & release

Answer 90

are collectively referred to as the thyroid hormones (TH) and are involved in the regulation of metabolic rate and are key during development

Answer 91

Tyrosine can be made in the body whereas iodine is an | essential component of our diet

Answer 92

- Thyroxine T4 (most relevent) - Triiodothyronine T3 (primarily biological active comp. of this active pathway) - Reverse T3 (T2 & T1 - loss of I on INNER RING) * functionally, is conferred by a loss of 1 I molecule on OUTER phenol ring

Answer 93

slide 90 TRH --> TSH --> T3/T4 HPT Thyroglobulin - has 2 identical subunits, both 330 kDa - maybe ~4-6 typosine residues (inefficient) - get limited # of synthesized monoiodotyrosine diiodotyrosine --> go to make T3 or T4 - still attached to TG 1. A Na+-I- symporter brings I- into the cell. The pendrin transporter moves I- into the colloid. 2. Follicular cell synthesizes enzymes & thyroglobulin for colloid. 3. Thyroid peroxidase adds iodine to tyrosine to make T3 & T4. 4. Thyroglobulin is taken back into the cell in vesicles. 5. Intracellular enzymes separate T3 & T4 from the protein. 6. Free T3 & T4 enter the circulation.

Answer 94

• Deiodinases can have a strong preference for specific TH’s * Type I has a strong preference for reverse T3 * Type II deiodinates ONLY the outer ring (highly expressed in the liver) * Type III deiodinates ONLY the inner ring • These enzymes can be tissue specific

Answer 95

CALORIGENIC – TH is the most important regulator of basal metabolic rate (brown adipose tissue will generate heat through futile cycles (imp. for generating heat) SYMPATHOMIMETIC EFFECT – action is similar to the sympathetic nervous system (increases target response to catecholamines - in the heart, NE & E INcrease heart rate - chronotropic effect - time rate, & INcrease stroke volume - ionotropic - INcrease contraction force) CARDIOVASCULAR – largely as a result of the increase in catecholamine receptors and calorigenic effects GROWTH – synergistic actions with both GH and IGF’s. TH is essential for normal growth and neural development

Answer 96

* This is one of the more common endocrine disorders and is very prevalent in young adult women * Includes both hypothyroidism and hyperthyroidism either of which are characterised by GOITER

Answer 97

is an over stimulation of the thyroid gland and not necessarily related to the capacity of the gland to synthesize and release TH

Answer 98

Exophthalmos is a common feature of Graves disease | which is an autoimmune disease

Answer 99

↓T3 & T4, ↑TSH Goiter

Answer 100

↓T3 & T4, ↓TRH and/or ↓TSH NO

Answer 101

↓T3 & T4, ↑TSH GOITER

Answer 102

↑T3 & T4, ↓TSH GOITER

Answer 103

↑T3 & T4, ↑TRH and/or ↑TSH GOITER

Answer 104

↑T3 & T4, ↓TSH NO

Answer 105

``` Low BMR Decreased perspiration Slow pulse Lowered body temperature Cold intolerance Lethargy, tiredness Weight gain Loss of hair Edema of face and eyelids Menstrual irregularities Goiter (may or may not be present) ```

Answer 106

``` Elevated BMR Increased perspiration Rapid pulse Increased body temp Heat intolerance Nervousness and anxiety Weight loss Muscle wasting Increase appetite Exophthalmos (sometimes) Goiter (primary or secondary in origin) ```

Answer 107

is the primary hormone released from the pineal gland and is | synthesized from the amino acid tryptophan

Answer 108

Synthesised and released in a rhythmical fashion that is closely related to circadian rhythms – SCOTOPHASE (dark) and PHOTOPHASE (light) Darkness is a universal stimulus for the synthesis and release of melatonin from the pineal gland suggesting a strong link between the pineal and the optic tract The link comes in the form of the SUPRACHIASMATIC NUCLEUS (SCN) which is our major biological clock where the interaction between PER genes and CLOCK proteins cycle at a remarkably constant rate that shifts depending on light cues

Answer 109

the pineal gland - individuals maintain a daily rhythm of melatonin & synthesis release if they live where it is dark all day

Answer 110

sunlight DEcreases NE release

Answer 111

Melatonin release peaks in humans usually in the MIDDLE of the night Enzymes involved in melatonin synthesis also follow a RYTHYM Reproduction follows cycles so there is a link between melatonin - sex hormones and reproduction (antigonadotrophic actions of melatonin = long day breechers) Melatonin supplements go in and out of favour. It is evident that the actions of melatonin are far reaching (like TH). (pleiotrophic)

Answer 112

aldosterone

Answer 113

Zona glomerulosa – Mineralocorticoids (aldosterone) - balance minerals Zona fasiculata – Glucocorticoids (cortisol) - glucose/energy Zona reticularis – Adrenal androgens (DHEA) - adrenal sex steroids

Answer 114

– Mineralocorticoids: Aldosterone – Glucocorticoids: Cortisol – Sex hormones: Dehydroepiandrosterone androstenedione (androgens) & estrogens

Answer 115

– Epinephrine ~ 80% – Norepinephrine ~ 20% often considered an extension of the sympathetic NS

Answer 116

imp. in our diet | - and a precursor

Answer 117

P450 side chain cleavage enzyme (P450 SCC) - 1st step in pathway - cleaves side chain off to provide the backbone - takes off the side chain here for cholesterol to provide precursors for steroid synthesis - we can lump these precursors based on the # of C atoms they have

Answer 118

C21 - Pregnane --> pregnenolone or progesterone C19 - Androstane --> androgens C18 - Estrane --> estrogens

Answer 119

Glucocorticoids Mineralocorticoids

Answer 120

Androgens Estrogens

Answer 121

- very imp. enzyme in conversion of androgens --> estrogens - creates an aromatic ring structure 1st in ring A that confers estrogen activity - therefore, location of that enzyme is imp. in terms of optimal function within the tissue

Answer 122

very imp. enzyme in conversion of androgens to estrogens & action of aromatase

Answer 123

b/c they don't have as much of a decline in androgen as women

Answer 124

Aldosterone acts on the distal and collecting tubules of the nephron in the kidney (Goal: promote Na+ reabsorption) Regulates body fluid volume which has implications on the renal and cardiovascular systems The steroid is essential for life. It promotes Na+ retention and K+ excretion in the kidney Secretion is regulated by the renin angiotensin system (angiotension II) and also directly by circulating K+ concentrations (as K+ increases, aldosterone syn & release is promoted). *Aldosterone regulation is largely independent of the pituitary gland (if there is a primary dysfunction with aldosterone synthesis, if there is not enough made the organism will die) Hyperaldosteronism can be either primary dysfunction (site of syn of the hormone itself) (Conn’s syndrome - in adrenal gland, increasing aldosterone syn & release from the adrenal gland)) or secondary. Symptoms present as hypernatremia, hypokalemia and usually hypertension

Answer 125

too much aldosterone & is responsible for Na+ retension

Answer 126

too little K+

Answer 127

INcrease Na+ in ECF, normally water follows INcrease Volume --> INcrease pressure

Answer 128

b/c we have a fixed cardiovascular space (fluid volume) - we pull in Na+ into that space, water will follow - INcrease volume in that fixed space - water gonna have pressure & so we get hypertension

Answer 129

b/c estrogens are predominantly produced in female gonads & androgens predominant in male gonad tissue The adrenal gland produces small amounts of both as DHEA is an adrenal androgen In males Testosterone overpowers the actions of DHEA. However as females otherwise lack androgens DHEA plays a role in the pubertal growth spurt, hair growth and the female sex drive Adrenogenital syndrome – symptoms are dependent on sex and age of hyperactivity onset – Adult females – masculinisation, facial hair, deepening of voice etc – Newborn females – psuedohermaphrodism – Adult males – no effect – Pubertal males – precocious pseudopuberty

Answer 130

unique to humans & old world monkeys

Answer 131

↑ Blood glucose (by stimulating gluconeogenesis and inhibiting glucose uptake) ↑ Blood amino acids (by stimulating protein degradation) ↑ Blood fatty acids (by stimulating lipolysis)

Answer 132

– Stimulates gluconeogenesis – generation of glucose from non-carbohydrate substrates (amino acids, pyruvates, glycerol) – Inhibits glucose uptake by many peripheral tissues – Stimulates protein degradation in muscle – Stimulates lipolysis, mobilising fatty acids as an alternative energy source

Answer 133

– vascular collapse during acute stressful events in the absence of glucocorticoids

Answer 134

– The anti-inflammatory effects are seen following administration of supra physiologic or pharmacologic levels – Prevention of leucocyte infiltration into the wound site – Atrophy of lymphatic system (chronic stress)

Answer 135

* Increased amounts of CRH or ACTH (caused by anemias in hypothalamus or pituitary, get excess production of these signals that will promote cortisol synthesis) * Adrenal tumours (primary dysfunction where we get excess cortisol being syn or released at the adrenal gland) * Ectopic ACTH release (being made of released from a site not typical)

Answer 136

* Excess glucose (coining the term adrenal diabetes) * Fat deposition in the face and abdomen, thin legs and arms * Facial hair excess

Answer 137

* General name for bilateral damage to the adrenals | * Can also be primary or secondary in nature

Answer 138

* Increased integument pigmentation | * Weakness, weight loss, hypotension, salt craving and hypoglycemia

Answer 139

Developed from Canon’s ideas on “ Fight or flight” and Hans Seyle’s “General adaptation syndrome” 1. Primary alarm response: • catecholamine surge into the system • ↑ in BMR • ↑ in blood flow to required organs (brain in particular) (blood flow tends to go away from intestine & towards skeletal muscle to power) • hepatic glycogenolysis (breakdown of glycogen into glucose to provide that energy) 2. Secondary resistance response • described actions of cortisol on metabolism • continued mobilisation of glucose for central organs • continued breakdown of alternative energy stores (lipids and proteins) 3. Tertiary exhaustion response • muscle wasting, hyperglycemia (diabetes mellitus) • atrophy of the immune system, gastric ulcers • vascular derangements

Answer 140

The adrenal medulla essentially acts as an extension of the sympathetic nervous system Catecholamine release from the adrenal medulla is largely under the control of the SNS Both catecholamines are stored in chromaffin granule vast maj. of catecholamine released from adrenal medulla during acute stressful event is: 80% epinephrine and 20% nor-epinephrine Both are the active ligands in the adrenergic system and they will bind to adrenergic receptors: α1, α2, β1, β2, β3 (also lots of isoforms)

Answer 141

Rapid mobilisation of the bodies energy reserves Increase cardiac output and total peripheral resistance Increase coronary and skeletal muscle arteriolar dilation Reduce gut motility Increases glycogenolysis in liver and muscle Increased CNS alertness Dilates pupils and flattens the lens Increases sweating ex: almost stepping in front of bus

Answer 142

slide 119 β1 Heart & kidney NE = E ↑ cAMP Inotropic and chronotropic actions if someone is on B blockers they will target this & red impact of NE & E on cardiac function - are 7-transmembrane receptors which mediate the central & peripheral actions of the n.t., NE & E

Answer 143

Numerous agonists/antagonists for adrenoreceptors Phenylephrine is an antagonist specific for α adrenoceptors can constrict or dilate --> multiple diff receptors will confer multiple diff physiological responses, to the extent where they could actually reverse that response

Answer 144

acinar cells secrete pancreatic enzymes into pancreatic duct

Answer 145

islets of Langerhan cells secrete hormones into blood vessels

Answer 146

Released from B or β cells 10:1 hypoglycaemic hormone

Answer 147

Released from α cells hyperglycaemic hormone

Answer 148

Released from D or δ cells inhibiting GH

Answer 149

Released from PP or F cells

Answer 150

All these hormones are involved in regulating fuel metabolism and all act at multiple levels

Answer 151

– Released with insulin following a meal *– Slows down the appearance of glucose in the blood * while insulin does a very good job in moving that glucose to where it needs to be - it cannot handle a huge influx at 1 time so amylin (go to 2nd point)

Answer 152

– Released in response to increased glucose and amino acid levels – D cells are always found in close association with α and β cells – Inhibits digestive and absorptive processes (inhibits the mobilization of energy reserves, plays an integral role in regulating locally insulin & amylin release from the a & b cells)

Answer 153

– Dramatic postprandial increase in plasma PP – PP levels suppress SST levels and vice versa (antagonist role b/t pancreatic polypeptide & SST within the pancreas) – D and F cells may be regulating each other (as well as α and β cells) - results in an overall balance of glucose within the circulation

Answer 154

glucose enters B cell, increase ATP/ADP, inhibits KATPchannel, ALLOWING L-type Ca2+ channel, and insulin secretion into the blood

Answer 155

Fuel – Carbohydrates, Fats and Proteins Metabolism – A generalist term for the chemical reactions that occur in the body Anabolism – this requires energy input (ATP) and is the synthesis of larger macromolecules either for function or energy storage Catabolism – breakdown of macromolecules eg: – hydrolysis: glycogen → glucose – oxidation: glucose → ATP The balance between anabolism and catabolism is not always straightforward – Growth periods – Short and long term “gaps” in food intake – Absorptive (fed) and post-absorptive (fasted) states

Answer 156

- glucose absorption from digestive tract - *Hepatic glucose production a. glycongenolysis - breakdown of glycogen into glucose b. gluconeogenesis - conversion of fats or proteins into carbs & ultimately glucose lead to increase in blood glucose concentration

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- * Transport of glucose into the cells a. Energy production b. Energy storage - Urinary excretion of glucose

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it's osmotically active - if you have a INcrease conc. of glucose on 1 side of a semi-permeable membrane & a low conc. on the other, then the glucose will balance but water may follow to balance the osmotic pressure on the side of that semi-permeable membrane - a key symptom of a diabetic - a INcrease urine flow rate that is a very INcrease conc. of glucose

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syn. as a pro molecule - cleaved to become mature peptide - cysteine residues create disulfide bonds

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– Glucose cannot simply diffuse into cells it is transported by a family of proteins known as GLUT or by Na+ glucose cotransport SGLT’s – GLUT-4 transports most of the circulating glucose during the absorptive state into skeletal muscle and adipose tissue – GLUT-4 are housed in intracellular vesicles and are recruited onto the cell membrane in response to insulin – In the post absorptive state glucose is transported out of the hepatocyte by GLUT 2 transporters – In the absorptive state insulin facilitates conversion of glucose into glucose 6-phosphate to keep intracellular concentrations low – Glucose uptake in the brain is by GLUT-1 & 3 and is largely independent of insulin

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Fasted state: a) in the absence of insulin, there are no GLUT4 transporters in the membrane - rather sitting waiting in these secreted vesicles, ready to be inserted when the appropriate signal comes along Fed state: b) insulin signals the cell to insert GLUT4 transporters into the membrane, allowing glucose to enter cell

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- more in older ppl - exercise can help - b/c imp. remedy to aleviate symptoms - 2 pathways: 1. insulin indep. 2. insulin dep. - exercise may increase GLUT4 insertion into cell membrane - exercise may increase insulin receptors * 1 of the main issues with type II diabetes is insulin insensitivity & so cells don't respond to insulin the way they should in a type II diabetic - with exercise you're promoting insulin receptors - resulting in an INcrease in insulin sensitivity at the target site - therefore as a consequence, that glucose challenge when there is an increase in blood glucose conc. not as much insulin is req. to initiate this response that we see, so less work is done by the pancreas to syn that insulin

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fasted state: c) the hepatocyte makes glucose & transports it out into the blood, using GLUT2 transporters fed state: d) the glucose concen. gradient reverses, & glucose enters the hepatocyte (just at a meal)

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– Favoring carbohydrate storage

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– Reduces circulating amino acids

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– Inhibits lipolysis – Stimulates fatty acid uptake in adipose tissue – Stimulates glucose uptake and conversion to triglycerides

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– Promotes amino acid uptake – Stimulates protein synthesis – Inhibits protein degradation all about energy storage in terms of the action insulin might play

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There is a positive relationship between blood glucose and amino acid concentrations and insulin concentration Feed forward regulation by glucagon-like peptide-1 and gastric inhibitory peptide (Balis & Stalling were looking for these peptides when they were doing their original experiments)

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- all the transporters for glucose to be reabsorbed by the kidney are occupied (no more room for glucose to be transported so it stays in the primary urine) - you will get increase come of glucose in that primary urine, that pulls water into that primary urine as well as you get a lot of urine with increase conc. of glucose in it - b/c glucose is osmotically active

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is likely the most common endocrine disorder in the | western world, literally means “honey running through”

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lack of insulin secretion | – Normally seen in children and represents a small proportion of diabetics

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lack of insulin sensitivity | – The most common form and invariably seen alongside obesity (80-90%)

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typically related to T1 diabetics that are early on with dealing with their meds & what levels & understanding the level of their meds & etc. - may administer too much med so too much insulin - so cells have to use alternate energy source (ketosis) - emergency response that is short lived

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Hyperglycemic hormone There is a negative relationship between blood glucose levels and glucagon • Carbohydrates: – Stimulates hepatic glycogenolysis and gluconeogenesis • Fats: – Promotes fat breakdown (lipolysis) increases release of TG, DG and MG lipase’s from fats – Inhibits hepatic ketogenesis reducing FFA conversion to ketone bodies. • Proteins: – Promotes hepatic protein catabolism

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Pancreatic α and β cells respond in the opposite direction to sugars and fats in the blood but in the same direction in response to amino acids

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secondarily

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an increase in growth of the zona glomerulosa much like TSH on the thyroid gland

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Conn's syndrome

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b/c estrogens are predominantly produced in female gonads & androgens predominant in male gonad tissue

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Predominantly ovarian gonads but the phenotype presents itself with male genitalia - extreme cases are not uncommon - it is often accompanied by a lack of cortisol production - not -ve feedback on ACTH production that targets the adrenal cortex - stimulating steroid synthesis - however, the metabolics that accumulate due to enzymatic failure to convert them to cortisol are shunted over to other steroidogenic pathways & the net result is an increase in adrenal androgens

Endocrinology Lectures 2021 Flashcards

(206 cards)