Endo IV Flashcards
1
Q
What is Addison’s disease? What is its cause?
A
- Characterized by failure of adrenal cortex to produce adrenocortical hormones (hypofunction)
- May involve total destruction of the gland
- Mostly due to atrophy of the adrenal glands due to tuberculosis and involves medulla as well as cortex
2
Q
How does Addison’s disease affect glucocorticoid production? Explain the consequences on the body.
A
Glucocorticoid deficiency leads to:
- Decreased blood sugar (particularly between meals)
- Decreased lipolysis
- Decreased gluconeogenesis
- Lack of energy, muscular weakness, inability to take stress
3
Q
How does Addison’s disease affect mineralocorticoid production? Explain the consequences on the body.
A
- Plasma: decreased Na+, Cl-, and H2O - all lost in urine
- Leads to decreased extracellular fluid, plasma volume, and cardiac output
- Increased K+ (hyperkalemia), H+ (acidosis) - reabsorbed from urine
- Patient dies in shock 7 days after complete absence of mineralocorticoids
4
Q
What is Cushing’s disease? What is its cause?
A
- Characterized by the hyperplasia of the adrenal cortex due to increased circulating levels of ACTH (hyperfunction), often via pituitary tumour.
- Excessive production of glucocorticoids as well as mineralocorticoids.
5
Q
Describe the problems caused by Cushing’s disease related to glucocorticoid production.
A
- Increased blood glucose (adrenal diabetes)
- Increased insulin secretion (if prolonged, beta cells burn out)
- Decreased protein synthesis
- Increased protein breakdown
- Osteoporosis: loss of protein and Ca2+ from bone
- Can cause masculinization in women due to increase in sex steroids
6
Q
Describe the problems caused by Cushing’s disease related to mineralicorticoid production.
A
- Plasma: increased Na+, Cl-, H2O - reabsorbed from urine
- Leads to increased extracellular fluid, plasma volume, hypertension
- Decreased K+ (hypokalemia), H+ (alkalosis) - lost in urine
- Also causes masculinization in women due to increase in sex steroids
7
Q
What are the diagnostic features of Cushing’s disease?
A
- Puffiness of face
- Masculinizing effect
- Hypertension
- Increased blood glucose
- Increased steroid metabolites in urine
8
Q
What is the treatment for Cushing’s disease?
A
Surgery: subtotal removal of adrenal cortex
9
Q
What is the treatment for Addison’s disease?
A
- Cortisol administration to improve carbohydrate metabolism
- Aldosterone administration to control electrolyte blood levels.
10
Q
Where is the pancreas located?
A
Behind the stomach
11
Q
What is the main function of the pancreas?
A
99% of the pancreas is exocrine and secretes digestive enzymes. However, it also has small endocrine structures called the islets of Langerhans. They have beta cells that produce insulin and alpha cells that produce glucagon.
12
Q
Describe the cellular composition of the islets of Langerhans and what they produce.
A
- 60% of cells are beta cells, which synthesize insulin
- 25% of cells are alpha cells, which synthesize glucagon
13
Q
What is the type and function of insulin and glucagon?
A
Small protein hormones and both control of glucose concentration in blood
14
Q
Compare the importance of insulin and glucagon and explain why.
A
Insulin is more important than glucagon and insulin deficiency or absence compromises the wellbeing of the individual, possibly leading to death.
Glucagon function is somewhat redundant with that of glucocorticoids.
15
Q
What is the main function of insulin?
A
It is the only hormone that acts primarily to decrease blood glucose by transporting it into the cell, where there is very little free glucose.
16
Q
What is the fate of glucose once it is transported into the cell by insulin?
A
a) in the liver and muscle cells it is converted to glycogen
b) in the adipose tissue it is converted to fat and stored for later use
c) in many cells of the body it is oxidized to produce energy
17
Q
What is the role of insulin receptors?
A
Stimulates the insertion of glucose transport proteins stored in the cytoplasm into the plasma membrane, increasing glucose uptake.
18
Q
What is the cause of insulin deficiency?
A
Results when beta cells are destroyed, leading to diabetes mellitus. Make tissues cannot take up glucose and glucose accumulates in the circulation.
This will occur even without glucose in the diet because of increased gluconeogenesis.
19
Q
When insulin deficiency occurs, what is the principal source of energy for cells? How does this affect the composition and pH of the circulation?
A
Under these conditions, free fatty acids become the principle source of energy -> increased lipolysis.
However, they are inefficiently used, leading to incomplete oxidation of fatty acids and increased circulating acetoacetic acid and beta-hydroxybutyric acid (metabolic acidosis) and acetone. -> smell of acetone in breathe of untreated diabetics.
Leads to decreased blood pH, diabetic coma, and death unless treatment is provided.
20
Q
Insulin deficiency due to the destruction of beta cells leads to the condition […]
A
diabetes mellitus
21
Q
Aside from direct impacts on the circulation, name 3 other symptoms of diabetes mellitus.
A
- At >180 mg% glucose spills over into the urine, causing glucosurea
- Leads to loss of water in urine, causing polyurea - dehydration and increased thirst (polydipsia). As mentioned above, untreated diabetes leads to ketosis, and metabolic acidosis.
22
Q
What is the treatment for diabetes mellitus?
A
- Administration of insulin is needed to restore individual back to normal.
- In diabetic comas, acidosis and associated electrolyte imbalance must be corrected in addition to insulin administration.
23
Q
What are the two types of diabetes mellitus? Explain the difference between them.
A
In adults, diabetes mellitus might be due to a deficiency of insulin (type 1) or hyporesponsiveness to insulin (type 2)
24
Q
How much glucose is typically present in the bloodstream?
A
Present at around 80 mg/100 ml. However, there is very little free in the tissues.
25
What is the effect of administering too much insulin in response to type 1 diabetes? Include key metrics.
Too much insulin could lead to severe decrease in blood glucose content. When blood glucose reaches 20-30 mg/100 ml, the availability of glucose for the brain is not sufficient and the individual can fall into insulin shock/hypoglycemic coma. This can kill the individual if they are not administered glucose immediately.
26
In type 2 diabetes, insulin levels are [...]
normal or abnormally high
27
What is the cause of type 2 diabetes?
The problem is hyporesponsiveness to of target cells to insulin via a decreased number (downregulation) of insulin receptors on target cells. This often associated with obesity due to overeating.
28
What is the treatment for type 2 diabetes?
Proper diet and exercise. Decreased caloric intake, decreased insulin, upregulation of receptors. Insulin receptors increase in response to frequent endurance exercise, independent to changes in body weight.
29
What is the cause of juvenile diabetes mellitus? What is the treatment?
Juvenile diabetes appears in childhood and is insulin dependent. The beta cells of the pancreas do not produce insulin. Treatment requires administration of insulin.
30
How is a glucose tolerance test administered?
After an overnight fast, patient given 0.75 to 1.5 g of glucose/kg body weight. Blood is taken before administration and at 30-60 min intervals for 3-4 hours, and glucose is measured.
31
How does glucose tolerance differ between normal and diabetic individuals?
Blood glucose in a normal individual increases in 1 hr from 80g/100 ml to 130 mg/100 ml and returns to normal after 2-3 hours.
In a diabetic, increase in blood glucose is greater and returns to normal more slowly.
32
Name the primary and secondary controls of insulin secretion and how they work.
Most important: beta cells respond to levels of blood glucose, secreting little or no insulin when blood glucose is low, secreting much more when the blood glucose is high.
Also, release of gastrin and vagal impulses to the beta cells induce insulin release, as a result insulin starts to leave the pancreas even before the blood glucose begins to rise during meals.
33
What is the function of glucagon?
Raises blood sugar by promoting glycogenolysis (breakdown of glycogen) and gluconeogenesis (synthesis of glucose) in the liver.
In adipose tissue, glucagon increases rate of lipolysis leading to increased concentration of free fatty acids in circulation.
34
How is glucagon release controlled?
Glucagon released controlled by concentration of glucose in circulation. Low blood glucose stimulates pancreatic alpha cells to increases synthesis and release of glucagon, while high blood glucose content decreases release and synthesis.
35
What type of hormone is growth hormone? Where is it produced?
Single chain polypeptide produced by anterior lobe of the pituitary.
36
What is the main function of growth hormone?
It is responsible for growth.
37
Explain how growth hormone works to fulfill its purpose.
- Increases protein synthesis in many tissues such as bone, muscle, kidney, and liver by enhancing amino acid uptake by cells and by accelerating the transcription and translation of mRNA.
- Also increases the rate of lipolysis and utilization of free fatty acids as a source of energy. This is a direct effect of GH not mediated by the somatomedins.
38
What are somatomedins? What is their function?
- Produced by the liver under stimulation of GH
- Are structurally similar to insulin and are named insulin-like growth factors 1 and 2. They can bind to insulin receptors and insulin at high concentrations may bind to somatomedin receptors.
- Increases protein synthesis and stimulates growth.
39
The release of GH is controlled by which two hormones? Where are they secreted?
Complex feedback mechanism mediated by two hypothalamic neurohormones:
a. Growth hormone releasing hormone somatoliberin, which stimulates growth hormone release
b. Somatostatin, which inhibits growth hormone release.
40
Draw and explain the feedback loop associated with GH release.
- Hypothalamus produces GRH.
- Anterior pituitary produces GH
- GH goes into liver
- Liver produces somatomedins in plasma
- Somatomedins have negative feedback on hypothalamus and anterior pituitary.
- Exercise, sleep, stress, and low blood sugar all cause hypothalamus to release stomatostains, which inhibit GH release in anterior pituitary.
41
What are the four triggers for the release of somatostatins?
Exercise, sleep, stress, and low blood sugar
42
What is the effect of GH deficiency on a young individual?
In the young, absence of growth hormone leads to decreased physical growth - dwarfism.
43
What is the effect of excess GH in young people?
Leads to gigantism
44
What is the effect of excess GH in adults?
Acromegaly, in which many bones (particularly cartilaginous regions) get longer and heavier.
45
The primary reproductive organs are referred to as [...]. What are they?
gonads.
Testes in the male, ovaries in the female.
46
What are the two functions of the gonads?
Serve 2 functions:
1. Gametogenesis: the production of reproductive cells known as gametes; the spermatozoa in the male and ova in the female.
2. Secretion of sex hormones; testerone (androgen) in the male, and estrogen and progesterone in the female.
47
What reproductive hormone do male or females have that the other does not? Explain.
There are none. The differences in reproductive endocrinology in males and females is quantitative and not qualitative.
48
What is the main function of estrogen in males?
It maintains bone density.
49
How is estrogen produced in males?
Estrogen in males produced locally in tissues by the conversion by aromatase of testosterone to estrogen estradiol.
49
What are the two effects of estrogen deficiency in males?
1. Increased body fat
2. Contributes to sexual desire and erectile function
50
Describe the HP-end organ axis for reproductive function, including what gets produced and the feedback loop.
1. Hypothalamus releases GnRH
2. GnRH causes anterior pituitary to release gonadotropins: FSH and LH
3. FSH and LH stimulate the gonads to develop spermatozoa/ova and sex steroids
4. Sex steroids exert effects in the gonads, in other parts of the reproductive tract, and in other parts of the body.
5. Local action of hormones produces steroid hormones, estrogens, and androgens.
5. Gonads also produce inhibin, which feeds back on the anterior pituitary.
51
What are gonadotropins? Which sex produces them?
They are the pituitary hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH). They are produced and function in both sexes.
52
Give 2 examples of sex steroids.
Estrogen and testosterone
53
What is the main function of the testes?
The principal function of testes in the production mature germs cells (spermatogenesis) and steroid hormones (steroidogenesis)
54
How does the supply of germ cells differ between males and females
The male continually renews his pool of precursor germ cells so that a relatively constant supply is available throughout his life.
Females have their entire life's supply of ova at birth.
55
The process of spermatogenesis takes place in the [...]
seminiferous tubules
56
The process of maturation of spermatogonia into [...] takes approximately [...]
Spermatozoon, 60 days
57
The two cells types critical for the maturation of the spermatozoa are [...]. Where are they located?
Leydig cells and Sertoli cells.
Leydig cells are outside of the seminiferous tubules and Sertoli cells are within the seminiferous tubules.
58
What is the function of the Leydig and Sertoli cells? How are they activated?
Leydig cells produce androgens in response to LH.
Sertoli cells produce androgen binding protein (ABP) and inhibin in response to FSH. They also envelop germ cells throughout their development.
59
What is the role of androgen in spermatogenesis? How much must be present?
Spermatogenesis is critically dependent on androgen concentrations within seminiferous tubules, which must be approximately 10 times higher than androgen circulation. Otherwise, spermatogenesis ceases.
60
What is the role of ABP in spermatogenesis?
Presence of ABP synthesized by Sertoli cells ensures that androgen concentration within seminiferous tubules.
61
Draw and describe the feedback loop that controls testicular androgen synthesis.
Testicular androgen synthesis regulated by two negative feedback loops:
a. Hypothalamic-pituitary-Leydig cell axis: GnRH stimulates release of LH and FSH - stimulate Leydig cells and Sertoli cells. Leydig cells produce androgen, which inhibits the release of GnRH, LH, and FSH
b. Hypothalamic-pituitary-seminiferous-tubules axis: non steroidal inhibin secreted by the sertoli cells inhibits FSH release only.
62
What is the purpose of inhibin in males? Where is it secreted?
Inhibin gets secreted from the sertoli cells in response to FSH. It inhibits FSH release from the anterior pituitary in a negative feedback looop to help control testicular androgen synthesis.
63
What are the main functions of the ovary?
Production of mature eggs and steroid hormones, which regulate the reproductive tract and influence sexual behaviour.
64
In the ovary, the germ cells are called [...]. There are [...] at birth and [...] left at puberty.
Oocytes, 2 million, 400,000
65
Describe the structure of primordial follicle
They are surrounded by a single layer of granulosa cells and a basement membrane making up the structures called primordial follicles - the fundamental reproductive units of the ovary.
66
Name the 5 stages of ovarian follicular growth.
Primordial -> primary -> preantral -> early antral -> mature
67
What prompts the growth of primordial follicles into primary follicles?
It begins by an unknown initiating event that is independent of the pituitary.
68
Once initiated, the growth of ovarian follicles is controlled by [...]
gonadotropins and steroid hormones
69
Describe the process involved in the development of a primary follicle from the oocyte.
1. Initially, enlargement and differentiation of the oocyte, which grows and elaborates zona pellucida (an acellular layer rich in glycoproteins surrounding the oocyte)
2. Granulosa cells divide and increase to 2 or more layers - primary follicles. Influenced by FSH and estrogen. Estrogens important for expression of LH receptors on granulosa cells.
70
Describe the process involved in the development of a primary follicle into a secondary follicle.
Under influence of FSH and LH, primary follicle develops into a secondary follicle which expresses receptors for FSH, estrogens, and LH. Also, appearance of the follicular antrum which contains secretions from the granulosa cells.
71
Describe the process involved in the development of a secondary follicle into a pre-ovulatory follicle.
Under combined influence of FSH and LH, the granulosa cells elaborate follicular fluid, which takes up the larger portion of the preovulatory follicle.
72
What are theca cells? When do they form?
As follicle matures from primary to secondary follicle, cells from ovarian stroma surrounding follicle differentiate and become steroid producing cells known as theca cells. Theca and granulosa cells collaborate for synthesis of higher amounts of estrogen.
73
What are the possible outcomes of follicular development?
1. Follicular atresia - most fail and die off
2. Ovulation - one follicle ovulates per cycle. The follicle gets transformed into the corpus luteum.
74
What is leuteinization? When does it occur?
Luteinization occurs after ovulation. It is when a ruptured follicle gets transformed into the Corpus Luteum.
75
The Corpus Luteum secretes [...]
progesterone and estrogen
76
What is the Corpus Luteum composed of? What is its function?
Both theca and granulosa cells contribute to formation of the corpus luteum, a temporary endocrine structure within the ovary that synthesizes progesterone and estrogens,
77
Describe the pattern of hormone production by the corpus luteum and state what determines it.
Progesterone and estrogens are produced in large amounts by corpus luteum for a few days following ovulation but then drop off unless implantation of the fertilized ovum occurs.
78
What happens to the corpus luteum if implantation occurs? What function does it serve?
Upon implantation, corpus luteum transformed into corpus luteum of pregnancy, responsible for synthesis of progesterone and estrogens, and creation of proper endocrine environment for maintenance of pregnancy until progesterone and estrogen synthesis established.
79
What happens to the corpus luteum if implantation does not occur?
Luteolysis - in absence of implantation, luteal regression may be induced by prostaglandins, which decrease LH binding and thus steroidogenesis.
This decrease of plasma progesterone and estrogen may be the trigger for the initiation of the next reproductive cycle.
