module 8: endocrine system disorders

Question 1

What 3 general causes lie behind endocrine disorders?

Answer 1

1. the target tissue receives too much or too little hormone
2. hormone arrives at the target tissue but finds abnormal cell receptor function
3. altered intracellular response to the hormone-receptor complex

Question 2

Describe the 6 ways by which the target tissue can receive the wrong amount of hormone

Answer 2

• over/under production of hormone from the gland
• feedback system isn’t working correctly = release of hormone isn’t correct
• inadequate blood supply to tissues = delivery of hormone is inadequate
• inadequate levels of serum carrier protein
  
  • ex: lipid-based proteins does not have a carrier to bring it over
• hormone being inactivated too quickly/slowly
• abnormal production of hormone by uncontrolled ectopic sources
  
  • tumor that affects hormones

Question 3

Describe the 3 ways in which the receptor function can be abnormal

Answer 3

• decrease in number of receptors
• impaired receptor function
  
  • does not recognize hormone
• presence of antibodies that act as competitive inhibitors or mimic hormone action
  
  • block the hormone from binding to the receptor

**only target tissue has. receptor… if there is a problem, it does not have to do with the hormone itself

Question 4

explain the altered intracellular response to the hormone-receptor complex

Answer 4

• the series of reactions inside the cell that allows the hormone to have an effect on the metabolic pathways do not work correctly
• while the hormone activates the receptor, the internal reactions are disrupted

Question 5

Explain the hypothalamic-pituitary-target gland axis

Answer 5

hormone cascade from hypothalamus → pituitary → target gland

Question 6

Explain primary (with examples), secondary, and tertiary disorders involving the hypothalamus-pituitary-target gland axis of control.

Answer 6

• primary: there is a problem with the final target gland responsible for producing a hormone
  
  • the problem at the end of the cascade
• secondary: problem with the pituitary gland
  
  • problem in the middle of the cascade
  • normally should activate hormone, but doesn’t
• tertiary: problem with hormone production from the hypothalamus
  
  • problem at the beginning of the cascade

Question 7

Describe the most common cause of hypothalamic dysfunction. What would be the outcome of this condition?

Answer 7

• interruption of the pituitary stalk = the physical connection between the hypothalamus and the anterior pituitary
• cause:
  
  • destructive lesions
  • rupture after head injury
  • tumor
• outcome = lose function of releasing hormones from the hypothalamus = no corresponding pituitary hormones

Question 8

Describe hypopituitarism (including panhypopituitarism)

Answer 8

• under-producing hormones from the pituitary
• the result from either an inadequate supply of hypothalamic-releasing hormones or inability of the pituitary gland to produce its hormones
• also brought on through head trauma, infections, etc
• panhypopituitarism = depleting all hormone production from anterior pituitary

Question 9

what is panhypopituitarism

Answer 9

depleting all hormone production from anterior pituitary

Question 10

describe hyperpituitarism

Answer 10

when excess pituitary hormone is produced

• usually caused by a tumor causing excessive production
  
  • excess hormone produced, leading to tumor
  • leads to under secretion of other hormones from tissues surrounding the tumor

Question 11

what is optic chiasm?

Answer 11

disturbance in vision due to a tumor

Question 12

Describe two possible causes for diabetes insipidus. What are two clinical manifestations?

Answer 12

disruption in ADH = not reabsorbing enough water = excessive loss in urination

1. insufficient production/transport/release of ADH
2. inadequate response of the renal tubules to ADH

clinical manifestations:

• thirst from dehydration
• polyuria from the failure to reabsorb water

Question 13

What does SIADH stand for and what hormone is involved? Are levels of this hormone too high or low?

Answer 13

• SIADH= syndrome of inappropriate antidiuretic hormone secretion
• hormone = high levels of ADH

Question 14

What is the most common cause of SIADH?

Answer 14

medications

Question 15

How does hyponatremia occur in SIADH? Which system is noticeably affected by extreme drops in sodium levels?

Answer 15

• anorexia fatigue that can progress to confusion, lethargy, convulsions with extreme drops in sodium levels due to ADH problems = urinate more sodium

Question 16

Describe thyrotoxicosis, including common signs and symptoms of disease

Answer 16

hyperthyroidism

• thyrotoxicosis = the clinical syndrome that results from increased levels of thyroid hormones
• signs & symptoms:
  
  • excessive sympathetic nervous system activity
  • weight loss
  • heat sensitivity
  • increased metabolic rate
  • goiter
  • exophthalmos (bulging of the eyes)

Question 17

describe an example of a primary disorder that would result in thyrotoxicosis

Answer 17

thyroid is functioning abnormally

• ex: Grave’s disease

Question 18

describe an example of a secondary disorder that would result in thyrotoxicosis

Answer 18

the pituitary is the problem,

ex: thyroid stimulating hormone (TSH) secreting pituitary adenoma

Question 19

Name and explain the mechanism of the cause of Graves disease.

Answer 19

because the thyroid is an end target tissue in the “hypothalamus-pituitary-target axis”, there can be a primary disorder when the thyroid is functioning abnormally

• caused by type 2 hypersensitivity reaction
• onset is 20-40 years old
• 10x more frequent in females

Question 20

Name and describe the most common cause for primary hypothyroidism

Answer 20

the thyroid itself

• can result from an autoimmune reaction (ex: Hashimoto disease), drugs, radiation therapy, etc.

Question 21

Describe a cause for a secondary hypothyroid disorder.

Answer 21

the pituitary is the problem

• may result from a pituitary tumor compressing surrounding pituitary cells reducing hormone secretion

Question 22

Name 4 signs/symptoms for hypothyroidism.

Answer 22

1. low metabolic rate
2. cold intolerance
3. lethargy
4. myxedema

Question 23

Describe the basis of Cushing’s syndrome

Answer 23

adrenal glands secrete excess glucocorticoids

Question 24

describe the 3 forms that contribute to Cushing’s syndrome

Answer 24

• primary = disease of the adrenal cortex
• secondary = hyperfunction of the anterior pituitary
• tertiary = hypothalamic dysfunction or injury

Question 25

which are the most common causes of Cushing's syndrome?

Answer 25

* an overproduction of adrenocorticotropic (corticotropin) hormone * either through hypersecretion at the anterior pituitary or as a paraneoplastic effect * in 70% of patients

Question 26

Describe the manifestations and complications associated with Cushing’s syndrome.

Answer 26

manifestations: * weight gain * buffalo hump * thinning extremities with muscle wasting * muscle weakness * thin, fragile skin and scalp hair * bruising * impaired wound healing complications: * excess cortisol * could include osteoporosis and pathologic fractures * peptic ulcers * lipidosis * impaired glucose tolerance

Question 27

Describe the basis of Addison’s disease

Answer 27

* adrenal hypofunction or adrenal insufficiency

Question 28

describe the primary form that contributes to the development of Addison's disease

Answer 28

primary disorders: * most common * originate with the adrenal gland where more than 90% of tissue is destroyed * usually due to an autoimmune reaction * can also be caused by hemorrhaging into the adrenal glands, infection, or neoplasms

Question 29

describe the secondary form that contributes to the development of Addison's disease

Answer 29

there is hypopituitarism (decreased adrenocorticotropic hormone) * may result from pituitary damage or a tumor compressing surrounding pituitary cells = less hormone secretion * disorders in hypothalamic-pituitary function may also cause reduced ACTH production

Question 30

What is adrenal crisis and who is at risk for this complication?

Answer 30

adrenal crisis = serious complications of Addison's disease those at risk: * unresponsive to hormone replacement therapy * undergo trauma * undergo extreme stress without glucocorticoid replacement * develop gland thrombosis after a severe infection

Question 31

Which two hormones contribute to adrenal crisis?

Answer 31

* absent/low cortisol * absent/low aldosterone

Question 32

How can a decrease or absence of the two hormones lead to shock with the possibly of coma or death in Addison's?

Answer 32

* absent/low cortisol → * LIVER: lower glucose output = hypoglycemia * STOMACH: lower digestive enzymes, vomiting, and diarrhea = hypotension * absent or low aldosterone → * KIDNEY: Na+/K+ imbalance → water loss = hypotension * HEART ARRHYTHMIAS: lower cardiac output = hypotension ## Footnote **ALL OPTIONS CAN LEAD TO SHOCK, COMA, DEATH**

Question 33

Describe how Cushing’s syndrome and Addison’s disease are treated

Answer 33

cushing's: * radiation * drug therapy * surgery depending on the cause Addison's: * hormone replacement therapy

Question 34

Explain how the endocrine response to stress can affect the immune system

Answer 34

* **catecholamines** (epinephrine and noepinephrine) * increases blood sugar and breaks down protein and fat * increases HR, vasoconstriction, and bronchodilation * **corticotropin-releasing hormone (CRH)** from the hypothalamus * stimulates **adrenocorticotrpoic (ACTH)** from the anterior pituitary * leads to **glucocorticoids (cortisol)** from the adrenal glands * inhibits reproductive system, digestive system, inflammation, and immune system * **mineralcortocoids (aldosterone), and ADH** * aldosterone increases sdium reabsorption (blood volume) * ADH increases water reabsorption (blood volume), and vasoconstriction (increased BP to get O2 and nutrients to muscles)

Question 35

Describe how the relationship between endocrine and stress response relates to the manifestations seen with chronic stress

Answer 35

* can depress the immune system * some of the messenger molecules and cell receptors are the same in the endocrine and the immune system * ex: receptors for glucocorticoids, insulin, etc. have been found on lymphocytes and IL1, 6, and TNF could activate the hypothalamus-pituitary-adrenal gland axis * chronic stress has been linked to diseases of the cardiovascular, gastrointestinal, immune, and neurologic systems * cortisol, and the catecholamines can increase the production of pro-inflammatory compounds = contributors to these diseases

Question 36

Define prediabetes and outline how insulin imbalances may arise that produce this condition.

Answer 36

* prediabetes = impaired fasting plasma glucise and impaired glucose tolerance * insulin imbalances arise from: * an absolute insulin deficiency * impaired release of insulin by the pancreatic beta cells * inadequate or defective insulin receptors * production of inactive insulin or insulin that is destroyed before it can carry out its action

Question 37

Define the three key clinical manifestations of diabetes mellitus – the “three Ps”.

Answer 37

* polyuria = excessive urination * polydipsia = excessive thirst, from dehydration * polyphagia = excessive hunger * cells in a starvation state, so person feels hungry despite eating huge amounts of food

Question 38

Describe type 1 diabetes

Answer 38

* previously called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes * developed when the body's immune system destroys pancreatic beta cells * the only cells in the body that make the hormone insulin that regulates blood glucose * usually strikes children and young adults, although disease onset can occur at any age * may account for 5-10% of all diagnosed cases of diabetes * risk factors: * autoimmune * genetic * environmental factors

Question 39

describe the pathogenesis of type 1 diabetes

Answer 39

* slow, progressive **autoimmune T cell-mediated disease** that destroys **beta cells** of the pancreas * **autoantigens** develop on the surface of pancreatic beta cells and then circulate in blood and lymph * autoantigens stimulate **cellular and humoral immune responses** that result in beta cell destruction leading to **hypoinsulinemia** (too little insulin) * **hyperglycemia** (high blood sugar) develops

Question 40

Describe the clinical manifestations of type 1 diabetes

Answer 40

* glucose accumulates in the blood → **hyperglycemia** (high blood sugar levels) * glucose appears in the urine as it exceeds “renal threshold” for glucose = **glycosuria** * **the 3 P's**- cardinal features of diabetes mellitus * wide fluctuations in blood glucose occur * protein and fat breakdown = **weight loss** * diabetic **ketoacidosis** (DKA) due to starvation state

Question 41

define type 2 diabetes

Answer 41

a condition characterized by hyperglycaemia resulting from the impaired utilization of insulin * insulin is being produced, but cells are not stimulated * could be because the cell receptors are not responding to insulin * may account for 90-95% of all diagnosed diabetes * usually begins as insulin resistance = a disorder where the cells do not use insulin properly * as insulin rises, the pancreas initially increases insulin production * as it becomes overworked, it gradually produces its ability to produce insulin

Question 42

what are the risk factors of type 2 diabetes?

Answer 42

* older age * obesity * family history of diabetes * history of gestational diabetes * impaired glucose metabolism * physical inactivity * race/ethnicity

Question 43

Define insulin resistance

Answer 43

below optimal response of insulin-sensitive tissues (liver, muscle, and adipose tissue) to insulin * cells fail to response to the normal acions of the hormone insulin

Question 44

explain the mechanisms that insulin resistance is related to obesity that underlie its development

Answer 44

1. adipose tissue produces **hormones** (adipokines) that are associated with decreased insulin sensitivity 2. **intracellular deposits** of cholesterol and triglycerides found in obese individuals interfere with intracellular insulin signalling 3. adipose tissue releases **inflammatory cytokine**s which are toxic to beta cells and induce insulin resistance

Question 45

Describe the development of Type 2 diabetes

Answer 45

* i**nsulin resistance** occurs * **compensatory hyperinsulinemia** results and prevents the clinical appearance of diabetes (hyperglycemia and its effects), possibly for many years * eventually, **beta-cell dysfunction** develops and leads to both a decrease in the **number** of beta-cells and a reduction of **normal beta-cell function** * remaining cells undergo “exhaustion” from increased demand for insulin biosynthesis * loss of insulin = **hyperglycemia** * after meals and due to increased glucose production by the liver

Question 46

Describe the clinical manifestations of type 2 diabetes

Answer 46

* individual often overweight, but may have recent unexplained weight loss * hyperglycemia (high blood glucose) and glycosuria (high urine glucose) * often has diagnostic features of **metabolic syndrome** * class symptoms: * polyuria * polydipsia * nonspecific symptoms: * fatigue * pruritus (itching) * recurrent infections * visual changes

Question 47

Describe metabolic syndrome

Answer 47

a collection of disorders that confer a high risk of developing type 2 diabetes * central obesity * dyslipidemia * prehypertension * elevated fasting blood glucose level

Question 48

What is gestational diabetes mellitus?

Answer 48

any degree of glucose intolerance with onset or first recognition during pregnancy * higher risk for complications * women who have gestational diabetes mellitus have a 60-70% chance of developing diabetes mellitus within 5-15 years

Question 49

Describe the following acute complication of diabetes mellitus, including underlying causation, clinical manifestations and treatment (if appropriate): hypoglycemia

Answer 49

* “insulin shock/reaction” due to mismatching insulin need with supply * pallor, tremor, tachycardia, palpitations, dizziness, confusion, seizures, coma * more so in type 1 than type 2 since T2DM still have mechanisms to increase blood glucose levels * requires immediate replacement of glucose * eating or drinking something with sugar

Question 50

Describe the following acute complication of diabetes mellitus, including underlying causation, clinical manifestations and treatment (if appropriate): diabetoc ketoacidosis (DKA)

Answer 50

* with insulin deficiency (more with type 1), lipolysis (breakdown of triglycerides) is enhanced = more fatty acids delivered to liver * gluconeogenesis is also occurring = production of more ketones that can be used in the body * buildup = metabolic acidosis * hyperventilation * dizziness * nausea * CNS depression

Question 51

Describe the following acute complication of diabetes mellitus, including underlying causation, clinical manifestations and treatment (if appropriate): somogyi effect

Answer 51

characterized by alternating episodes of hypoglycemia and hyperglycemia * insulin induced hypoglycemia occurs = release of epinephrine, growth hormone, and corticosteroids (cortisol) * hormones stimulate glucogenesis = hyperglycemia = “rebound hyperglycemia” * worse effect if combined with dawn phenomenon

Question 52

Describe the following acute complication of diabetes mellitus, including underlying causation, clinical manifestations and treatment (if appropriate): dawn phenomenon

Answer 52

* early morning rise in blood glucose levels * related to an increased release of growth hormone, epinephrine, and cortisol in early morning = increased blood sugar * idea is to increase glucose levels for energy production o prepare the body for daily activity

Question 53

Describe the following acute complication of diabetes mellitus, including underlying causation, clinical manifestations and treatment (if appropriate): HHS (hyperosmolar hyperglycemic syndrome)

Answer 53

* complication of type 2- can be fatal * high glucose levels and plasma osmolarity and dehydration = no ketoacidosis) * if blood glucose is high, the kidneys excrete more fluid * if fluid is not replaced, dehydration occurs * excessive dehydration pulls water out of cells, including brain cells * weakness, dehydration, polyuria, neurological signs and symptoms * more common in elderly people * onset can be very gradual - may be mistaken for a stroke

Question 54

Name and describe the molecular pathological effects of chronic hyperglycemia

Answer 54

* **advanced glycation end products (AGEs)** * long term excess of glucose can result in glucose permanently binding to proteins inside/outside cells (AKA **glycation**) = interference with cell metabolism, produces endothelial changes, or microvascular damage * **polyol pathway**: * tissues that do not require insulin to import glucose (kideys, RBCs, blood vessels, eye lens, and nerves) cannot down-regulate the uptake * excess glucose is converted into **sorbitol**, which is osmotically active * buildup of sorbitol may damage schwann cells producing neuropathies, and damage the eye lens from swelling due to osmotic pressure * **altered hemoglobin-o2 binding affinity**: * due to glycation of the hemoglobin molecule * causes impaired oxygen release to tissues * **inappropriate protein kinase C (PKC) activation**: * KC = an intracellular messenger controlling various cell functions including permeability and dilation of blood vessels * inappropriate activation is linked to vascular damage in the retina, nerves, and kidneys

Question 55

Describe the following chronic complications of diabetes mellitus, including the underlying pathological effects of chronic hyperglycemia and its clinical manifestations: diabetic retinopathy (vision problems)

Answer 55

* a leading cause of blindness in diabetes mellitus * results from increased capillary permeability and ischemia of the retinal blood supply * leaking macular capillaries can lead to **macular edema** = severe loss of central vision

Question 56

Describe the following chronic complications of diabetes mellitus, including the underlying pathological effects of chronic hyperglycemia and its clinical manifestations: diabetic nephropathy (kidney problems)

Answer 56

* the **glomeruli** are progressively injured by glycation and high renal blood flow in response to hyperglycemia * characterised by **nephrotic syndrome**, proteinuria, edema, and high blood cholesterol * most common cause of **end stage renal disease** (complete loss of kidney function)

Question 57

Describe the following chronic complications of diabetes mellitus, including the underlying pathological effects of chronic hyperglycemia and its clinical manifestations: diabetic neuropathy (nervous system problems)

Answer 57

* due to metabolic factors (including build up of sorbitol in neurons) and vascular effects (ischemia) * **sensory deficits are more common** than motor and often involved extremities * loss of sensation in toes/fingers means minor injuries go unnotices, may become infected and gangrenous

Question 58

Describe the following chronic complications of diabetes mellitus, including the underlying pathological effects of chronic hyperglycemia and its clinical manifestations: infection

Answer 58

* those with diabetes mellitus are at an increased risk of infection due to: * impaired senses * impairment of the immune system * increase in pathogen growth due to higher level of glucose in body fluids

Question 59

To what are macrovascular disorders due?

Answer 59

advanced glycation end products (AGEs) and poor tissue oxygenation

Question 60

Name and be able to describe 4 macrovascular disorders that can be caused by long-term diabetes mellitus.

Answer 60

* accelerated atherosclerotic disease * coronary artery disease * most common cause of morbidity and mortality in people with diabetes mellitus * stroke * twice as common in those with diabetes mellitus * peripheral vascular disease * narrowing or obstruction of peripheral arteries, usually below the knee as a result of atherosclerosis and inflammation * occulsions of small arteries can lead to neuropathy, diabetic foot ulcers and dry and sometimes wet gangrene