Endocrine System Flashcards
(215 cards)
1
Q
The endocrine system uses ____ to communicate?
A
Hormones
2
Q
What is a Hormone?
A
A hormone is a chemical messenger that travels in the bloodstream to other tissues or organs to stimulate physiological responses in cells of another tissue or organ
3
Q
What are the 4 principal mechanisms of communication between cells in the body?
GNPH
A
Gap junctions
Neurotransmitters
Paracrines
Hormones
4
Q
What are gap junctions and where are the commonly found?
A
The are pores in cells that allow signaling molecules, nutrients, and electrolytes to move from cell to cell.
Used by smooth and cardiac muscle
5
Q
What are paracrines?
A
The are short acting hormones released by cells to affect a local area
6
Q
The endocrine system is composed of what?
A
Hormone producing glands, tissues, and cells
7
Q
What are exocrine glands?
A
Glands with ducts that secrete substances to an epithelial surface “external secretions”
8
Q
What are endocrine glands?
A
Glands with ducts that secrete hormones into the body “internal secretions”
Composed of dense fenestrated capillary networks which allow easy uptake of hormones by the blood
9
Q
What are three neurotransmitters that also act as hormones?
AND
A
Antidiuretic hormone (ADH)
Nor-epinephrine
Dopamine
10
Q
Where is the pituitary gland located?
A
inferior to the hypothalamus suspended by the infundibulum and housed in the stella turcica of the sphenoid bone
11
Q
What two structures make up the pituitary gland?
A
The anterior and posterior pituitary gland
Adenohypophysis and the Neurohypophysis
12
Q
How is the anterior lobe of the pituitary gland connected to the hypothalamus?
A
Via the hypophyseal portal system
13
Q
What is the hypophyseal portal system?
A
A network of capillaries that begins in the Hypothalamus and travel into the anterior lobe via portal venules
14
Q
how Is the posterior lobe of the pituitary gland different?
A
It is actually an extension of the nervous system it communicates via neurons that originate in the hypothalamus
15
Q
How many hormones are produced in the hypothalamus?
A
8
16
Q
How many hypothalamus hormones regulate the anterior pituitary lobe?
A
6
4 releasing and two inhibiting
17
Q
What are the four releasing hormones that stimulate the anterior pituitary
TCGG
A
TRH-Thyroid Releasing Hormone
CRH- Corticotropin Releasing Hormone
GnRH- Gonadotropin Releasing Hormone
GHRH- Growth Hormone Releasing Hormone
18
Q
What are the two inhibiting hormones that inhibit the anterior pituitary lobe?
PS
A
PIH - Prolactin Inhibiting Hormone
Somatostatin - Inhibits GH and TSH secretion
19
Q
What two Hormones are released by the posterior pituitary lobe?
OA
A
OT- Oxytocin
ADH- Antidiuretic Hormone
20
Q
What does “Tropic” mean?
A
It controls other glands
21
Q
How many hormones does the posterior lobe of the pituitary lobe synthesize?
A
None but it stores two from the hypothalamus
22
Q
How many hormones doe the anterior lobe of the pituitary lobe synthesize?
What are they?
FLTAPG
A
6 FSH- follicle-stimulating hormone LH- luteinizing Hormone TSH- Thyroid Stimulating Hormone ACTH- Adrenocoritcotropic hormone PRL- Prolactin GH- growth hormone
23
Q
The Paraventricular nuclei of the hypothalamus produce what hormone?
A
Oxytocin
OT
24
Q
The Supraoptic nuclei of the hypothalamus produce what hormone?
A
Antidiuretic hormone
ADH
25
What two Hormones are released when GNRH is produced?
| FL
```
Follicle-Stimulating hormone (FSH)
Luteinizing Hormone (LH)
```
26
What hormone is FSH and what is its general function?
Follicle-Stimulating hormone
| Stimulates secretion of ovarian sex hormones, development of ovarian follicles, and stimulates sperm production in males
27
What hormone is LH and what is its general function?
Luteinizing Hormone
Stimulates ovulation, stimulates the corpus luteum to produce progesterone, and stimulates the testies to produce testosterone
28
What hormone is released in the presence of TRH?
Thyroid-stimulating hormone (TSH)
29
What hormone is TSH and what is its general function?
Thyroid stimulating hormone
| Stimulates secretion of thyroid hormone
30
What hormone is released in the presence of CRH?
ACTH (Adrenocorticotropic hormone)
31
What hormone is ACTH and what is its general function?
Adrenocorticotropic hormone
| Stimulates the adrenal cortex to secrete glucocorticoids (cortisol)
32
What hormone stimulates the release of Prolactin?
TRH
33
What hormone is PRL and what is its general function?
Prolactin
| Stimulates mammary glands to produce milk
34
What hormone is released in the presence of GHRH?
GH
| Growth Hormone
35
What Hormone is GH and what is its general function?
Growth hormone
| Stimulates mitosis and cellular differentiation
36
What hormone is ADH and what is its general function?
Antidiuretic Hormone
Increases water retention, reduces urine volume to prevent dehydration
also know as vasopressin because it is a vasoconstricter
increases BP
37
What are the functions of OT
Oxytocin
promotes sexual satisfaction
stimulates labor contractions via positive feedback
stimulates the flow of milk
promotes bonding between child and mother
38
Are the rates of hormone release constant?
no
39
What are the four main targets of GH?
Cartilage, bone, muscle, fat
40
When GH reaches the liver what does it induce?
it causes the liver to produce growth stimulants
IGF-1
IGF-2(somatomedins)
41
What do IFG-1 and IGF-2 do?
```
Stimulate target cells
prolong the action of GH
increase protein synthesis
increase lipid metabolism (protein sparing effect)
Stimulates glucose release from liver
Reduce dependence of other cells on glucose
(glucose sparing effect)
Balance electrolytes
```
42
Hormone Half life is defined as-
The amount of time it takes for 50% of the hormone to be cleared from the blood
43
What is the half life of GH?
6-20 minutes
44
What is the half life of IGF-1?
20 hours
45
How does GH affect bone growth?
it cause thicker bones and induces remodeling
46
What causes the release of ghrein and how does it effect GH?
and empty stomach
| activates GH
47
Where is the pineal glad located?
the roof of the third ventricle of the brain
48
When does the pineal gland begin to shrink?
around age 7
49
What is the assumed function of the pineal gland?
Synchronization of circadian rhythms
Synthesizes melatonin from serotonin
influences the time of puberty
50
What three body systems does the thymus play a role in?
Endocrine
Lymphatic
Immune
51
Where is the thymus located?
Superior to the heart
52
What important cell matures in the thymus?
T cells
53
What is function of the thymus?
secretes hormones that stimulate the development of lymphatic organs and the activity of T lympocytes
54
Where is the thyroid gland located?
Inferior to the larynx
55
Most of the thyroid is made up of thyroid ____ which are?
Thyroid follicles
| sacs lined with simle cuboidal epi cells that contain colloid
56
What hormones does the thyroid glad produce and secrete? their funtion?
Thyroxine (T4)
Triidothyronine (T3)
Responsible for metabolism in virtually all cells
57
Between the follicles of the thyroid are ____ cells also called C cells. What is their function?
Parafollicular cells
| the secrete calcitonin
58
What is the function of calcitonin?
stimulates osteoblast activity and bone formation
59
Where are the parathyroid glands located?
embedded in the posterior surface of the thyroid gland
60
What hormone is secreted by the parathyroid glands and what is its function?
PTH (parathyroid hormone)
- Increases blood Ca++ levels
- Promotes synthesis of calcitriol*active Vit D*
- increases absorption of Ca++
- Decreases urinary excretion
- increases bone reabsorbtion
61
The adrenal medulla consists of _ to _ % of the adrenal gland
12-20%
62
The adrenal medulla is primarily a part of the ___ system?
sympathetic nervous system
63
The adrenal medulla consists of postganglionic neurons called____cells
chromaffin cells
64
When the adrenal medulla is stimulated it releases ____ directly into the blood stream
Catecholamines
65
What are the two Catecholamines released by the adrenal medulla?
Epinephrine and nor-epinephrine
66
What are the three main effects that catecholamines have on the body?
ABD
- Alerts the body and prepares it for physical activity
- Increases Vitals, Airflow, and metabolic rate
- Decreases Digestion and Urine
67
How do catecholamines prepare the body for activity?
- Mobilizes high energy fuels, lactate, fatty acids, glucose
- boosts glucose levels but initiating Glycogenolysis and Glucogenesis in the liver
- Epi inhibits insulin to spare glucose for the brain
*basically, it causes your body to produce more glucose and spare it for use by the brain while making high energy fuels available for the rest of the body
68
the Adrenal cortex is the ___ portion of the adrenal gland and is part of the ___ system
Outer
| Endocrine
69
The main function of the adrenal cortex is to secrete ____ hormones
Corticosteriods
70
How may layers does the adrenal cortex have? What are they? super to deep
GFR
Zona glomerulosa
Zona fasciculata
Zona reticularis
71
Describe the zona glomerulosa and list its function
Thin outer layer of the cortex
cells arranged in round clusters
secretes mineralocorticoids that regulate the body's electrolyte balance
72
Describe the zona fasciculata and list its function
Thick middle layer
Cells arranged in fascicles separated by capillaries
Secretes glucocorticoids *cortisol* as well as a small amount of androgens
73
Describe the zona reticularis and list its function
Narrow inner layer
cells in branching network *reticulated*
secretes glucocorticoids and sex steroids *androgens*
74
Glucocorticoids are secreted by the ____ and ___ of the adrenal ___
Zona Fasciculata and reticulata
| cortex
75
Glucocorticoids function to____
regulate metabolism of glucose and other fuels
76
Glucocorticoids are released in responce to the hormone _____ which is released by ___ from the ___ gland
ACTH
CRH
anterior pituitary
77
The Glucocorticoids cortisol and corticosterone stimulate what 3 things?
FGF
Fat/protein catabolism
gluconeogenesis
release of fatty acids and glucose
78
What effect do Glucocorticoids have on the body that can suppress the immune system with long term exposure?
the anti-inflammatory effects can suppress the immune system
79
What are the two main sex steroids released by the adrenal cortex?
Androgens and Estradiol
80
What is the general function of Androgens?
they set libido
| play a large role in prenatal male development
81
are the cortex and medulla of the adrenal gland functionally independent?
no
82
What happens to the medulla of the adrenal gland in the absence of cortisol?
it atrophies
83
How do the cortex and the medulla work together?
some of the chromaffin cells of the medulla extend into the cortex and stimulate it to release corticosteroids when stress activates the sympathetic nervous system
84
What are the three main endocrine cells located within the pancreatic islets?
Alpha
Beta
Delta
85
What hormone is secreted by the alpha cells of the pancreatic islets?
Glucagon
86
What is the function of glucagon? when is it released
- It is released between meals when blood glucose is falling and when amino acid levels are rising in the blood
- in the liver it stimulates glycogenolysis, gluconeogenesis, and the release of glucose into the blood stream
- in adipose tissue it stimulates fat catabolism to release fatty acids
- in the blood when amino acid levels rise to promote absorption
87
What hormone is secreted by the beta cells of the pancreatic islets?
Insulin
88
What is the function of insulin? when is it released?
- It is released during and after meals when glucose and amino acid levels are rising
- It stimulates cells to absorb, store, and metabolize glucose
- promotes synthesis of fat, protein, and glycogen
89
What parts of the body do not need insulin to absorb glycogen?
Brain, liver, Kidneys, and RBC's
90
The insufficiency of insulin is called?
type one diabetes mellitus
91
The inaction of insulin is called
type two diabetes mellitus
92
What hormone is secreted by the delta cells of the pancreatic islets?
Somatostatin
93
What is the function of somatostatin?
- it partially suppresses secretion of glucagon and insulin
| - it inhibits nutrient digestion and absorption effectively prolonging the absorption of nutrients
94
What are the 5 main hyperglycemic hormones?
| GGENC
```
Glucagon
Growth hormone
Epi
Nor-epi
Cortisol
```
95
What are the endocrine products of the gonads?
gonadal hormones
96
What are the exocrine products of the gonads?
eggs and sperm
97
What are the three main Ovarian hormones?
Estradiol, progesterone, and inhibin
98
What are the four main testicular hormones?
Testosterone, weaker androgen's, estrogen, and inhibin
99
What cells within the ovary will synesize androstenedione (estradiol and progestrone precursor)
The Theca cells
100
What cells convert androstenedione into estradiol and progestrone?
granulosa cells
101
What becomes of the ovarian follicle after ovulation?
It becomes the corus luteum
102
What is the function of the corpus luteum?
it produces progestrone for 12 days to help support possible pregnancy
103
The follicle and the Corpus luteum also produce what hormone to assist in the entire process?
Inhibin
104
What are the three main functions of progestrone and estradiol?
- Development of female reproductive system
- regulation of menstrual cycle, and to sustain pregnancy
- prepare mammary glands for lactation
105
what hormone does inhibit inhibit?
FSH
106
Which portion of the testes produce sperm?
the semiferous tubules
107
Where are the nurse cells of the testes located?
the tubule walls
108
What cells lie in clusters between the tubules of the testes?
interstital cells ( leydig cells)
109
Where is testosterone produced in the testes?
from the interstital cells
110
What is the function of testosterone?
stimulates the development of male reproductive system
| sustains sperm production
111
Where is inhibin produced in males?
nurse cells of the testes
112
What is the endocrine function of the skin?
UV light causes keratinocytes to produce cholecalciferol which is a cholesterol-like steroid precursor to Vit D
113
What happens to cholecalciferol after it is produced in the skin?
it is converted to calcidiol by the liver
114
what happens to calcidiol after it is converted from cholcaliferol in the liver?
it is converted to calcitriol by the kidneys
115
What are the functions of mineralocorticoids from the adrenal cortex?
Regulates electrolyte balance
| Aldosterone stimulates Na+ retention and K+ excretion which causes water retention to maintain BP and blood volume
116
The ___ secretes 15% of erythropoietin
liver
117
What is the function of erythropoietin?
stimulates bone marrow growth and hemopoiesis
118
What is the sorce of IGF-I
the liver
119
What is the function of hepcidin?
promotes intestinal absorption of iron
120
The kidneys are responsible for the production of what three hormones?
Calcitriol
Renin
85% of erythropoietin
121
What is the function of Renin?
It converts angiotensinogen to angeotensin I
122
What happens to Angeotensin I
it is converted into angeotensin II by the ACE enzyme in the lungs
123
What is the function of Angeotensis II?
it is a vasoconstrictor that raises BP
124
What endocrine functions does the heart have?
it produces two natriuretic peptides in response to high BP
125
What is the function of the natriuretic peptides produced by the heart in response to high BP?
They decrease BP and blood volume by increasing Na+ and H2O output by the kidneys
*opposing action to angiotensin II*
126
How many hormones are produced by the digestive system?
10
127
What is the main function of digestive hormones?
To coordinate digestive motillity and glandular secretion
128
What hormone is secreted by adipose tissue? its function?
Leptin
| slows appetite
129
What hormone is produced and secreted by osseous tissue? its function?
Osteocalcin secreted by osteoblasts
- increases the number of pancriatic beta cells, output of insulin, and insulin sensitivity
- inhibits weightgain
130
What hormones are produced by the placenta? their general function?
Estrogen, progestrone, and others
| Regulate pregnancy, stimulate development of fetus and mammary glands
131
What are the three chemical classes of hormones?
Steroids
monoamines
peptides/glycoproteins
132
What are steroids?
| Examples?
hormones derived from cholesterol
they can pass through plasma membranes because they are lipid based
*testostrone estrodiol, cortisol
133
What are monoamines?
| examples?
Hormones made from amino acids
| Dopamine, epi, nor-epi,melatonin, thyroid hormone*
134
What are peptides/glycoproteins?
| examples?
created from chains of amino acids
hormones from the pituitary and hypothalamus
*insulin*
135
How are steroids synthesized?
from cholesterol
136
How are peptides synthesized?
the same way any protein is
137
How and where is a peptide hormone modified after it is translated?
in the ER and the Golgi
138
How are monoamines synthesized?
-Melatonin is made from the amino acid tryptophan
| others come from the amino acid tyrosine
139
Why is thyroid hormone lipid soluble?
because it is composed of two tyrosines
140
In the thyroid, once follicular cells absorb iodide ions from the blood what do they do?
oxidize them to a more reactive form
141
In the thyroid, what protein do the follicular cells produce and where do they store it?
thyroglobulin (Tg) to be stored in the follicle lumen
142
In the thyroid, how are the forerunners of T3 and T4 made?
Iodine atoms are added to tyrosines withinn Tg and link together
143
In the thyroid, how are T3 and T4 produced?
whe TSH reaches the follicle cell, it absorbes Tg (with attached iodine atoms) and splits them with lysosomal enzymes releasing T3 and T4 from the basal side of the follicle cell
144
What are the 3 types of stimuli that influence the release of hormones?
Neural
Hormonal
Humoral
145
What is Humoral stimuli?
blood borne stimuli
| rise and fall of different subsences in the blood trigger hormone release
146
Why cant steroid hormones be produced and stored?
because they are lipid soluble and can diffuse through plasma membranes
147
Most monoamines and peptides mix with blood plasma easily because they are _____
hydrophilic
148
How are steroids and thyroid hormone transported in the body?
Via transport proteins
149
Why do bound hormones have a longer half life?
because they are protected from liver enzymes and kidney filtration
150
Where are transport proteins synthesized?
the liver
151
What are some transport proteins?
albuin, thyretin, thyroxine-binding globulin (TGB)
152
What is the transport protein for cortisol?
transcortin
153
What are hormone receptors composed of?
Proteins or glycoproteins
154
Which hormones have receptors inside the cells?
steroids
155
How does Thyroid hormone enter cells?
ATP-dependent transport proteins
156
What happens to T4 after entering the cell?
it is converted into T3
157
What is the function of T3?
it binds to nuclear receptors and activates genes for the sodium potassium pump
158
How do peptides and catecholamines activate cells?
via second messenger systems
159
Explain hormone signal amplification
One hormone molecule can activate many enzyme molecules and produce a large effect
160
How is target-cell hormone sensitivity adjusted?
by changing the number of receptors
161
If the number of hormone receptors is up-regulated than___
hormone sensitivity is increased
162
What is a cause of Down-regulation of hormone receptors?
Long term exposure to high hormone concentrations
163
What is a hormonal synergistic effect?
| Example?
When multiple hormones act together for a greater effect.
| FSH + Testosterone create large sperm production
164
What is a permissive hormonal effect?
| example?
when one hormone increases a target hormones response to a later hormone
Estrogen prepares the uterus for the action of progesterone
165
What is a hormonal antagonistic effect?
| example?
One hormone opposes the action of another
| insulin lowers blood glucose and glycogen raises it
166
How are hormones cleared from the body?
By the liver and kidneys
167
What is the MCR of hormones?
the metabolic clearance rate
| rate of removal from the blood
168
What is stress?
a situation that upsets homeostasis and threatens ones physical or emotional well-being
169
What is GAS in terms of stress
GAS stands for General adaptation syndrome
| it is the consistant way that the body reacts to stress that occurs in three stages
170
What are the three stages of General adaptation syndrome?
Alarm reaction (30 seconds)
Stage of resistance (30 minutes)
Stage of exhaustion(30 days)
171
What is the Alarm reaction?
your body's initial response to stress as it prepares for fight or flight
172
What hormones mediate the alarm reaction and where do they come from?
norepinephrine from the sympathetic NS
| Epinephrine from the adrenal medulla
173
What occurs in the body during the alarm reaction
Stored glycogen is consumed
BP is raised by angiotensin
Aldosterone causes water and Na+ retention also raising BP
Basiclly BP and BG are increased
174
What stage comes after the alarm reaction?
the stage of resistance
175
What occurs in the body during the stage of resistance? (General)
- Glycogen stores are depleted so the body provides pathways to create more
- Cortisol is the main player here as it spares glucose for the brain and promotes the catabolism of fat and protein to create more glucose
176
The stage of exhaustion is reached when stress contines for _____ and ___ reserves are gone
several months
| fat reserves
177
What occurs during the stage of exhaustion?
Death and decline
- Fat stores are depleted
- muscles have been broken down for glucose
- Adrenal cortex stops functioning which causes a loss of glucose homeostasis
- Large amounts of K+ lost leads to hypokalemia from aldosterone productions
178
What are paracrines?
Chemical messengers that diffuse short distances and stimulate nearby cells
179
What are the three types of paracrines?
Histamine
Nitric oxide
Catecholamines
180
what are the main histamine producing bodies?
Mast cells in connective tissue
181
Where does nitric oxide come from?
the endothelium of blood vessels
182
What is the action of histamines?
relaxation of blood vessels
183
What is the action of nitric oxide?
vasodilation
184
Where do catecholamines come from?
They diffuse from the adrenal medulla to its cortex
185
What is an autocrine?
a chemical messenger that stimulates the same call that secretes it.
186
What acid are Eicosanoids *paracrine family* derived from?
A fatty acid called arachidonic acid
187
Where does arachidonic acid come from?
it is made from the phosolipid by-layer of cells plasma membranes.
188
What paracrine is produced when lipoxygenase converts arachidonic acid?
Leukotrienes
189
What is the function of Leukotrienes?
The mediate allergic and inflammatory reactions
190
What 3 eicosanoid paracrines are produced when Cyclooxygenase (COX) converts arachidonic acid?
PTP
Prostacyclin
Thromboxanes
Prostaglandins
191
What is the action of Prostacyclin?
Inhibits blood clotting and vasoconstriction
192
What is the action of Thromboxanes?
- Produce platelets after injury
- overrides prostacyclin***
- stimulates vasoconstriction and clotting
193
What are the two Prostaglandins? and their actions?
PGE- Relaxes smooth muscle in bladder, intestines, bronchioles, uterus, stimulates contraction of blood vessels
PGF- Opposite effect of PGE
194
How does cortisol act against inflammation?
It is a (SAID)
It and other corticosterones inhibit inflammation by blocking the release of arachidonic acid and inhibits the synthesis of eicosanoids
195
What are the disadvantages of using SAIDs
They produce symptoms of cushings disease
196
Howdo NSAID's act against inflammation?
- inhibits COX
| - does not block leukotriene production
197
Why are NASID's good at treating thrombosis?
Because the block COX and as a result inhibit the production of Prostaglandin and Thromboxane *blood clotting*
198
What is endocrine Hyposecretion? what are some causes?
inadequate hormone release
- tumor or trauma destroy or injure hormone producing bodies
- Autoimmune disorders
199
What is endocrine Hypersecretion? what are some causes?
Excessive hormone release
| Tumors or autoimmune disorders
200
What is a toxic goiter (graves disease)?
Autoimmune disorder where antibodies mimic the effect of TSH on the thyroid causing hypersecretion of TH
201
What is acromegaly?
thickening of bones and soft tissue in adults due to hypersecretion of GH
202
What is Myxedema?
Adult hypothyroidism
203
What is a goiter?
enlarged thyroid glad due to the body not producing TH caused by iodine deficiency
204
What is a fatal symptom of Hypoparathyroidism?
Fatal tetany (Spasms in larynx) due to loss of calcium levels in the blood
205
What are some symptoms of Hyperparathyoidism
Soft bones due to excess leeching
blood Ca2+ and phosphate levels increase
Excess blood Ca++ promotes renal calculi formation
206
What is cushing syndrome?
Excess cortisol secretion
- Causes hyperglycemia, weakness, edema
- rapid bone and muscle loss due to cortisol promoting catabolism of bone and protein*glucose sparing effect*
- Abnormal fat deposition*moon face buffalo hump*
207
What is Adrenogenital syndome(AGS)?
* accompanies cushings disease*
- Adrenal androgen hypersecretion
- Enlargement of external sex organs in children and causes early onset puberty
- Has masculizing effects of women
208
What is Diabetes Mellitus? *general*
DIsruption of metabolism due to hyposecretion or inaction of insulin
209
What are symptoms of Diabetes Mellitus?
-Polyuria (excessive urination)
Polydipsia (intense thirst)
Polyphagia (Hunger)
All caused by the excess of glucose in the blood
210
What is the difference between type 1 and type 2 diabetes?
Type one is due to the the bodies immune system attacking beta cells in the pancreatic islets causing the under production of insulin
Type 2 is dues to resistance to insulin that the body produces -caused by many factors including inactivity, poor diet, also could be genetic and it can be sured
211
What occurs when cells are unable to absorb glucose?
then they must rely on fat and protein for energy resulting in weight loss and weakness
212
What causes the production of ketones in the blood. how?
The catabolism of fat releases ketones and fatty acids from stored fats
213
What are the negative effects of the production of excessive ketones?
Ketonuria_loss of Na+ and K+ leads to irregular heartbeat and neurological issues.
Ketoacidosis- ketones are acidic and will decrease the pH of the blood
214
What is a main observable symptom of ketoacidosis?
Deep gasping breaths as the body tries to increase the pH of the blood
215
What are the results of chronic hyperglycemia?
Neuropathy
arterial damage to kidneys and retinas
atherosclerosis
