Wake Endo/repro

Front 1

What are the differences between endocrine, neurocrine, paracrine, and autocrine factors?

Back 1

* Endocrine: travels through the blood stream to a distal site
* Neurocrine: communicates in the nervous system or from neurons to a vascular bed for transport
* Paracrine: acts on neighboring cells
* Autocrine: acts on the cell from which it was released

Front 2

Name the catecholamines. From what are they synthesized?

Back 2

Dopamine, norepinephrine, and epinephrine are catecholamines and are synthesized from tyrosine

Front 3

From what are catecholamines, serotonin, and acetylcholine synthesized?

Back 3

Catecholamines (dopamine, norepinephrine, and epinephrine) are synthesized from tyrosine. Serotonin is synthesized from tryptophan. Acetylcholine is synthesized from choline and acetyl-CoA

Front 4

Name some peptide hormones. How are they produced?

Back 4

The hormones of the anterior pituitary are peptides. Thyroid-stimulating hormone, growth hormone, adrenocorticotrophic hormone, follicle stimulating hormone, luteinizing hormone, and prolactin are made through normal protein synthesis (DNA transcription, RNA processing, storage in vesicles until release stimulation).

Front 5

Differentiate the carrier mechanisms for IGF-1, growth hormone, and pancreatic C-peptide.

Back 5

* The high-affinity carrier protein of IGF-1 must be degraded to allow the free hormone to interact with its receptor
* GH is synthesized with a membrane receptor that serves as a reservoir and prolongs its half-life. Matrix metalloproteases cleave the carrier portion to free GH.
* Pancreatic C-peptide is bound to insulin within vesicle, but release freely with insulin

Front 6

What mechanistic type of receptor do growth hormone, prolactin, and leptin bind? How does the receptor work

Back 6

Growth hormone, prolactin, and leptin bind JAK-Stat receptors. Depending on what hormone binds to the JAK-Stat tyrosine kinase, Stat will travel into the nucleus and act as a transcription factor, potentiating the hormones physiologic effects

Front 7

Is sex hormone binding globulin a high or low affinity binding protein? Albumin? Where are these transport proteins synthesized?

Back 7

Sex Hormone Binding Globulin is a high affinity carrier protein, while albumin is a low affinity binder. Transport proteins are synthesized in the liver

Front 8

What is the role of hormone binding proteins?

Back 8

Carrier proteins slow the degradation of the hormones, regulate the amount and availability of active hormones, and serve as the storage pool of pro-hormones

Front 9

How do steroid carry out their physiologic activity?

Back 9

Steroids can diffuse freely into the cell. They bind their receptor in the cytosol or the nucleus and change the shape of that receptor so its ZInc fingers find the right portion of DNA. The steroid and its newly configured receptor act as transcription factors

Front 10

What is the distinction between endocrine and exocrine glands?

Back 10

Exocrine glands secrete into ducts line by simple epithelium. Endocrine glands secrete directly into the bloodstream.

Front 11

Describe the gestational development of the pituitary gland. What is the primordial origin of the neurohypophysis? Adenohypophysis?

Back 11

The adenohypophysis (anterior pituitary) comes from oral ectoderm (Rathke's pouch). The neurohypophysis (posterior pituitary) originates from the neuroectoderm (neurohypophyseal bud). The two are connected to the hypothalamus by the infundibulum (or median eminence or pituitary stalk)

Front 12

Does the anterior or posterior pituitary have a portal system with the hypothalamus?

Back 12

The adenohypophysis (with endocrine cells) is in a portal system with hypothalamus, allowing for the travel of necessary releasing hormones. The neurohypophysis (with neurocrine cells) has its own blood supply

Front 13

What are pituicytes?

Back 13

Pituicytes are the specialized glial cells of the neurohypophysis, surrounding the neurosecretory neurons and terminals, insulating them, providing the nutrients, and destroying pathogens

Front 14

What are the different types of cells located in the anterior pituitary?

Back 14

* Chromophobes: 25% of cells, few secretory granules
* Acidophils: 50%; cells secreting GH (somatotrophs) and prolactin (mammotrophs); stains with eosin but not PAS
* Basophils: 25%; cells secreting TSH (thyrotroph), LH and FSH (gonadotrophs), ACTH (corticotroph); stains with hematoxylin and PAS

Front 15

What is the cellular feature of the pars intermedia?

Back 15

The pars intermedia (intermediate pituitary) typically includes several colloid-filled cysts

Front 16

What are the different cell types seen in the thyroid and what are their functions?

Back 16

Follicular cells synthesize thyroglobulin and then secrete it into the colloid of the follicle. Follicle cells are surrounded by basal lamina and a capillary network, interspersed with calcitonin cells (parafollicular cells) that release calcitonin in response to high blood calcium

Front 17

How does the histology of the thyroid change in Grave's disease?

Back 17

Diffuse hyperplasia of the thyroid will show thyroglobulin filled follicles edged with a series of vacuoles. Scalloped perimeters of follicles are indicative of high secretory activity

Front 18

How does the histology of the thyroid change with an adenomatous goiter?

Back 18

Enlarged thyroid follicles of varying size are filled with colloid substance with little or no secretory activity (no scalloped borders)

Front 19

Which form of thyroid hormone is released from the thyroid in higher quantities? Which form is more potent?

Back 19

T4 is released in much higher quantities (20:1) and T3 is more potent

Front 20

Name and describe the 3 types of cells in the parathyroid?

Back 20

* Chief (principle) cells produce parathyroid hormone in the absence of high blood calcium, causing bone demineralization
* Oxyphil cells are large, polygonal, and eosinophilic. Function is unknown
* Adipose cells

Front 21

Differentiate the histology of the three levels of the adrenal cortex

Back 21

* Glomerulosa has circular clusters of cells producing aldosterone in response to the RAAS
* Fasciculata is arranged in columns or cords separated by sinusoids, produces cortisol controlled by hypothalamus and pituitary
* Reticularis cells are smaller, less vacuolated, and produce weak androgen (DHEA)

Front 22

What is the histology and secretion of the adrenal medulla?

Back 22

The adrenal medulla is made of modified neurons called chromaffin cells which secrete catecholamines, norepinephrine, epinephrine in response to direct synaptic stimulation from sympathetic neurons. Norepinephrine is converted to epinephrine in the presence of glucocorticoids from the zona fasciculata

Front 23

Name the 2 major and minor cell types of the endocrine pancreas

Back 23

* beta-cells (insulin) PREDOMINANT CELL
* alpha-cells (glucagon)
* delta-cells (somatostatin)
* F cells (rare, affects secretion of gastric and pancreatic substances)

Front 24

How do the islets of langerhans differ in type I and type II diabetes mellitus?

Back 24

Type I DM is the result of an autoimmune process so there is an infiltration of small darkly staining lymphocytes. Type II DM shows degradation of islet cells, generating scar tissue through hyalinization and amyloid deposits.

Front 25

Name the hormones released from the anterior pituitary

Back 25

Thyroid Stimulating Hormone (or thyrotropin), growth hormone (or somatotropin), ACTH (or corticotropin), FSH, LH, Prolactin

Front 26

What is the prevalence of each type of cell in the anterior pituitary?

Back 26

Somatotrophs (GH), Mammotrophs (Prolactin), Corticotrophs (ACTH), Gonadotrophs (LH/FSH), Thyrotrophs (TSH)

Front 27

What are some functions of luteinizing hormone?

Back 27

* Targets Leydig cells of the testes to produce testosterone.
* Triggers ovulation of ovarian follicle, maintains the corpus luteum.
* Estrogen and progesterone production

Front 28

What are some functions of follicle stimulating hormone?

Back 28

* Targets Sertoli cells in the testes promoting seminiferous tubule growth and spermatogenesis
* Stimulates follicle growth in the ovary

Front 29

What are the design similarities and differences with TSH, LH, and FSH?

Back 29

They all share a common alpha subunit. Their beta subunits are antigenically and functionally unique

Front 30

What regulates TSH release from the anterior pituitary?

Back 30

Thyrotropin-releasing hormone (TRH) stimulates TSH. Somatostatin and T4 levels inhibit TSH

Front 31

What regulates LH and FSH release?

Back 31

Gonadotropin releasing hormone stimulates LH and FSH release

Front 32

What does ACTH stimulate the release of?

Back 32

Adrenocorticotropin hormone stimulates glucocorticoid synthesis and release

Front 33

What are the effects of growth hormone?

Back 33

Stimulates growth, lipolytic, protein anabolism, and triggers somatomedin release

Front 34

What are somatomedin A and B also known as?

Back 34

* Somatomedin A is Insulin-like growth factor 2 (fetal)
* Somatomedin C is Insulin-like growth factor 1 (adult)
They regulate the function of GH

Front 35

What are the effects of prolactin?

Back 35

Mammary gland development in pregnancy, milk protein production after parturition, lactation in response to nursing, parenting behavior

Front 36

What are some stimulators of ACTH release?

Back 36

Corticotropin-releasing hormone, GHRH, Antidiuretic hormone, urocortin, Brain natriuretic peptide

Front 37

What hormones does GHRH regulate? Where is GHRH released from?

Back 37

GHRH, released by the arcuate nucleus of the hypothalamus, stimulates GH, prolactin, ACTH release

Front 38

What hormones do somatostatins regulate? Where is Somatostatin released from?

Back 38

Somatostatin, released by the periventricular nucleus of the hypothalamus, inhibits GH and TSH release

Front 39

What hormones does thyrotropin releasing hormone regulate? Where is GHRH released from?

Back 39

Tryrotropin, released by the paraventricular nucleus hypothalamus, releasing hormone releases prolactin and TSH.

Front 40

What hormone does dopamine regulate? Where is GHRH released from?

Back 40

Dopamine, released by the arcuate nucleus of the hypothalamus, inhibits prolactin release

Front 41

How does dopamine regulate prolactin?

Back 41

A neuroendocrine suckling reflex decreases dopamine release, increasing prolactin release. Prolactin feedback on the hypothalamus increases dopamine synthesis, increasing dopamine's inhibitory tone

Front 42

What are some non-mammary stimuli for prolactin release?

Back 42

TRH overrides dopamine inhibitory tone. Prolactin levels increase during sleep and times of stress

Front 43

What hormones are released from the posterior pituitary and from where in the hypothalamus are they regulated?

Back 43

Oxytocin (paraventricular nucleus) and antidiuretic hormone (supraoptic nucleus)

Front 44

Are magnocellular or parvicellular neurons associated with the anterior pituitary? Posterior pituitary?

Back 44

Magnocellular neurons are associated with the posterior pituitary. Parvicellular neurons are associated with the anterior pituitary

Front 45

What are the actions of oxytocin?

Back 45

* Contraction of myoepithelial cells for milk let down
* Vaginal and cervical stretch, induction of labor
* Sperm motility

Front 46

What regulates growth hormone release?

Back 46

Growth hormone releasing hormone (from the arcuate nucleus) stimulates GH release, while somatostatin and IGF-1 inhibits GH release

Front 47

What are some modulators of the diurnal, pulsatile release of growth hormone?

Back 47

* Positive Regulation: hypoglycemia, fasting, ghrelin, sleep, decreased free fatty acids, puberty, stress, exercise
* Negative Regulation: IGF-1, glucose, free fatty acids

Front 48

What type of receptor does GH bind at its targets?

Back 48

Class I Tyr kinase-like receptors

Front 49

What are the direct and indirect actions of GH?

Back 49

* Adipose tissue: decreases glucose uptake and increases lipolysis
* Muscle: increases glucose & amino acid uptake and protein synthesis
* Bone: Stimulates osteoblasts, protein synthesis, DNA & RNA synthesis, chondroitin sulfate, collagen, and increased cell size & number

Front 50

What type of receptor does IGF-1 bind to at its targets?

Back 50

Type I IGF tyrosine kinase receptor

Front 51

How is IGF transported and activated in the blood stream?

Back 51

IGF is carried by IGF Binding Protein which is degraded by binding protein proteases and then the liver

Front 52

What hormones are involved in prenatal growth?

Back 52

Placental hormones: placental lactogen (homologous to GH), IGF-2 (under stimulation of hPL and prolactin), human chorionic thyrotropin, t3, t4, estrogen, progesterone, cortisol

Front 53

What hormones are involved in post-natal growth?

Back 53

GH, IGF-1 & IGF-2, T3, T4, estrogen, androgen, glucocorticoids

Front 54

What hormones are involved in pubertal growth?

Back 54

GH, IGF-1 (under stimulation of GH and insulin), androgen, estrogen

Front 55

Are the direct effects of GH more like insulin or more anti-insulin?

Front 56

How does increased protein intake affect GH and insulin action?

Back 56

Increased protein leads to increased arginine which increases both GH (and IGF) and insulin. Both IGF-1 and insulin increases protein synthesis in fat and muscle

Front 57

How does increased carbohydrate intake affect GH and insulin action?

Back 57

Increased carbohydrates will increase insulin and decrease growth hormone (& IGF-1) both of which lead to lipogenesis in fat

Front 58

How does fasting or stress affect GH and insulin release?

Back 58

When in a fasting or stressed state, the body aims to mobilize free fatty acids and decrease protein synthesis. Fasting directly decreases IGF-1, as well as cholesterol which decreases GH and insulin. Decreased insulin, IGF-1, and GH all promote lipolysis and decreased protein synthesis

Front 59

How does GH deficiency manifest in children and adults?

Back 59

In children, GH deficiency caused short stature. In adults, it increases the physiologic affects of aging (decreased immune function, bone mass, and lean body mass)

Front 60

How does excess GH manifest in children and adults?

Back 60

In children, GH excess causes gigantism. In adults, it causes acromegaly (enlargement of jaw, heart, tongue, hands, and feet), carpal tunnel syndrome, and potentially visual problems (proximity to optic chiasm)

Front 61

From where is thyrotropin-releasing hormone released, when is it released, and what does it stimulate?

Back 61

* Thyrotropin releasing hormone is released from the paraventricular and arcuate nuclei of the hypothalamus in response to cold and other metabolic signals.
* It stimulates calcium mediated vesicle release and gene transcription of TSH and prolactin.
* Its release is inhibited by somatostatin

Front 62

What is the function of thyroid hormone?

Back 62

(Bones, Brain, ß-adrenergic, BMR) T3 and T4 are important for normal growth and development, as well as regulating metabolic rates

Front 63

What is responsible for the negative feedback on the TSH release from the pituitary?

Back 63

TSH release from the pituitary is under negative feedback from T4 (from the thyroid and T3 conversion at the liver/kidney) and somatostatin (released from the periventricular nucleus of the hypothalamus)

Front 64

What are the actions of TSH?

Back 64

* TSH increases the intake of iodine via the NIS cotransporter (which is Na/K ATPase coupled). Iodine (via pendrin) and thyroglobulin are transported into the lumen of the follicle.
* TSH also stimulates iodination of thyroglobulin in the follicular lumen (via TPO), endocytosis back into the cell, proteolysis of the iodinated thyroglobulin, and the secretion of T3 and T4 into the blood stream

Front 65

Describe the synthesis of thyroid hormone

Back 65

Thyroglobulin and iodine (via pendrin) are transported into the colloid where Thyroid peroxidase iodizes tyrosine residues on the thyroglobulin forming mono- and diiodotyrosines. These mono- and diiodotyrosines are coupled together, endocytosed back into to follicular cell (via megalin) and proteolysed into either a T3 or a T4 which is released from the cell into the blood stream

Front 66

Does low iodide promote T3 or T4?

Back 66

Low iodide stimulates greater T3 levels

Front 67

Does increased TSH promote T3 or T4?

Back 67

Increased TSH promotes T3 production

Front 68

How does iodine deficiency lead to a goiter?

Back 68

Iodine deficiency (or any inability to make T4) can drive TSH release, which increases thyroid gland size and vascularity

Front 69

Explain the Wolff-Chaikoff Effect

Back 69

100-fold excess iodide will block thyroid activity by inhibiting NADPH oxidase activity and repressing the gene expression of NIS & TPO, effectively blocking the TSH response

Front 70

Name thyroids binding proteins and their respective prevalence and affinity

Back 70

* Thyroxine binding globulin is the least prevalent but has the highest affinity
* Prealbumin has medium prevalence and affinity
* Albumin is by far the most prevalent, but has the lowest affinity

Front 71

Does T3 or T4 have a longer half-life?

Back 71

T4 has a longer half life (6-8 days) than T3 (1 day)

Front 72

What are some states where thyroid binding globulin levels are affected and why is that important?

Back 72

Pregnancy increases TBG levels (resin uptake test to measure real thyroid activity). Many disease states, including liver disease, decreases TBG levels

Front 73

What are some states that promote rT3 production as opposed to T3?

Back 73

Low nutritional states, illness, liver disease promote rT3 production because D1 deiodinase is inhibited by caloric restriction or stress

Front 74

What types of receptors do thyroid hormones bind to?

Back 74

Thyroid hormones bind to nuclear receptors and act as transcription factors.

Front 75

How does thyroid hormone affect bone production?

Back 75

T3 stimulates bone growth and ossification by decreasing PTH and 1,25-vitamin D

Front 76

What are the clinical symptoms of hyperthyroidism?

Back 76

Increased BMR, decreased body weight, nervousness, hyperactive reflexes, heat intolerance, palpitations, muscle weakness, diarrhea, increased appetite, fatigue

Front 77

What are the clinical symptoms of hypothyroidism?

Back 77

Decreased BMR, cold intolerance, prolonged reflex time, weight gain, amenorrhea, goiter, constipation, myxedema, weakness, fatigue, decreased sweating, thick tongue, hoarseness, psychosis, thin brittle hair, slow speech, apathetic appearance, puffy eyes

Front 78

What is cretinism?

Back 78

Cretinism is the irreversible growth and mental retardation caused by deficient thyroid hormones during CNS development

Front 79

What are the embryological origins of the adrenal glands?

Back 79

* Cortex: mesoderm near the mesonephros and urogenital ridge. It splits off the primordial gonadal matrix, wraps around the developing medullary tissue, and hypertrophys during late pregnancy
* Medulla: chromaffin cells from neural crest cells (ectoderm) which becomes encapsulated by the developing cortex still connected to the sympathetic chain

Front 80

Describe the blood flow within the adrenal gland

Back 80

Blood flows from the outside in (glomerulosa, fasciculata, reticularis, medulla), where it is drained by the medullary veins

Front 81

What type of receptors do glucocorticoids bind to?

Back 81

Glucocorticoids bind type II GR intracellular receptors, G-protein coupled receptors

Front 82

What are the 3 functions of glucocorticoids?

Back 82

* Stimulate gluconeogenesis in the liver: increase glucose and hepatic glycogen, lipid metabolism
* Suppress the immune system: impairs cell-mediated immunity and decreases eosinophil and lymphocyte count
* Suppress tissue inflammatory response: support vascular integrity, alter cytokine mix towards anti-inflammatory types

Front 83

What is ACTH's action at the adrenal cortex?

Back 83

ACTH stimulates production of Steroid Acute Regulatory Protein (StAR), which is a cholesterol transporter involved in importing cholesterol into the mitochondria for steroidogenesis

Front 84

What two transporters are responsible for bringing cholesterol into the mitochondria for steroidogenesis?

Back 84

Steroid acute regulatory protein (StAR) transfers cholesterol passed the outer membrane and desmolase (P450) transports across the inner membrane

Front 85

How is cortisol transfered through the blood?

Back 85

Almost all cortisol is bound to the carrier protein transcortin for travel through the bloodstream. Transcortin levels are stimulated by estrogen and decreased by liver cirrhosis

Front 86

What is the clinical picture of cortisol excess?

Back 86

Hyperglycemia, insulin insensitivity, protein wasting, hypertension, increased capillary permeability, decreased immune function and inflammatory response, decreased ACTH

Front 87

What is the clinical picture of cortisol deficiency?

Back 87

Hypoglycemia, insulin oversensitivity, weight loss, anemia, increased ACTH

Front 88

What endocrine hormone is involved in stimulating surfactant development in the newborn fetus?

Back 88

Cortisol

Front 89

What type of receptors do mineralocorticoids use?

Back 89

Mineralocorticoids use type I (MR) intracellular receptors

Front 90

What are the actions of mineralocorticoids?

Back 90

Sodium retention at the expense of potassium.
* Activates transcription of Na/K ATPase
* Affects collecting ducts, sweat glands, and distal intestinal tract

Front 91

What characteristic makes DHEA from the zona reticularis so weak?

Back 91

DHEA can undergo sulfate esterification, making it water soluble and rapidly excreted

Front 92

What hormone is responsible for most of the hair growth in women?

Back 92

DHEA, the weak androgen, generated by the adrenal gland is responsible for most of the hair growth in women. It also possibly contributes to women's libido.

Front 93

Explain the action of metyrapone and how it is used

Back 93

Metyrapone blocks the action of 11ß-hydroxylase, effectively blocking the production of glucocorticoids. Cortisol plays a role in generating sensations of stressful memories, so metyrapone is now being used to decrease symptoms of PTSD

Front 94

What are the main therapeutic uses of adrenal steroids?

Back 94

The 4 A's. Arthritis, allergies, asthma, autoimmune syndromes. Also used for topical inflammation and to replace deficiency (either primary or secondary)

Front 95

What are the adverse effects of adrenal steroid use? How are those side effects combated?

Back 95

* Related to the "gluco" actions, creating a catabolic state. Muscle and fibrous tissue is broken down to produce glucose, hyperglycemia, poor wound healing, edema, ulcers, osteoporosis.
* Intermittent therapy with higher doses in the morning, continually reducing/tapering the dose

Front 96

Does epinephrine have a higher affinity for alpha or beta adrenergic receptors?

Back 96

Epinephrine has a higher affinity for ß-receptors

Front 97

What is the amino acid precursor for catecholamines?

Back 97

Tyrosine is used to make DOPA, dopamine, norepinephrine, and epinephrine

Front 98

What are the general actions of adrenal medullary secretions?

Back 98

Blood delivery, arousal, and metabolic stimulation. Pupil dilation, vasoconstriction, piloerection, tachycardia, bronchial dilation, increase blood glucose

Front 99

What are the alpha and beta receptor actions of catecholamines?

Back 99

* Alpha: arteriolar vasoconstriction, stimulates GH secretion, increases metabolic rate, and reduces peristalsis
* Beta: hepatic and muscle vasodilation and glycogenolysis, lipolysis, insulin and glucagon release, venous vasodilation (TPR decreases), bronchodilation, increased heart rate and force

Front 100

What name is given to adrenal medullary excess and what are its symptoms?

Back 100

Pheochromocytoma. HTN, tachycardia, sweating, palpitations, hyperglycemia, weight loss

Front 101

What are the general actions of the adrenal hormones?

Back 101

* Glucocorticoids: raise blood glucose, anti-inflammation, anti-immunity
* Mineralocorticoids: Na+ retention
* Estrogen: female phenotype
* Progestin: transform certain estrogenic actions
* Androgen: male phenotype

Front 102

What hormones stimulate the desmolase reaction and what process does that promote?

Back 102

ACTH (in the adrenals) and FSH/LH (in the ovaries/testes) are responsible for upregulating desmolase, which transports cholesterol passed the inner membrane of the mitochondria to initiate steroidogenesis

Front 103

What hormones stimulate the steroid acute regulatory protein and what process does that promote?

Back 103

ACTH (in the adrenals) and LH (in the ovaries/testes) are responsible for upregulating StAR, which transports cholesterol passed the outer membrane of the mitochondria to initiate steroidogenesis

Front 104

What enzymes are responsible for bringing cholesterol in to the mitochondria for steroidogenesis?

Back 104

Steroid acute regulatroy protein (StAR) and desmolase bring cholesterol passed the outer and inner mitochondrial membranes, respectively

Front 105

What enzymes are responsible for congenital androgenital syndromes?

Back 105

* Congenital adrenal hyperplasia
* Congenital absences of 21ß-hydroxylase blocks progesterone transformation into glucocorticoids and mineralocorticoids leading to a salt-losing state.
* Congenital absences of 11ß-hydroxylase blocks progesterone transformation into glucocorticoids, but allows for lots of mineralocorticoids leading to a salt-retaining state.
* Both syndromes are virilizing from the increase in androgen production

Front 106

How is aldosterone generated in individuals with 11ß-hydroxylase deficiency?

Back 106

21-hydroxylase produces 11-deoxycorticosterone. This 11-DOC cannot be acted upon by 17a-hydroxylase or 11ß-hydroxylase. 11-DOC is a weak mineralocorticoid, which is why 11ß-hydroxylase deficiency is a salt-retaining syndrome.

Front 107

What enzyme is responsible for transforming androgen to estrogen?

Back 107

Aromatase

Front 108

How is most of the estriol produced necessary to maintain pregnancy?

Back 108

The mother cannot produce enough estrogen to maintain preganacy and a male fetus doesn't want excess estrogen around. Within the fetal adrenals, cholesterol is transformed into DHEA which is sulfated in the liver and then crosses to the placenta. DHEA-SO4 is de-esterified and placental aromatase transformes it to estriol.

Front 109

Are most thyroid nodules benign or malignant?

Back 109

Most thyroid nodules are benign

Front 110

What type of prognosis does thyroid malignancy carry?

Back 110

Most thyroid malignancy are well-differentiated and have a very good prognosis

Front 111

What is the first test that should be done to workup a thyroid nodule? What are the potential outcomes and what should be the next step in each case?

Back 111

Fine needle aspiration should be performed and can end up with a benign, malignant, or indeterminant diagnosis. If benign, observation. If malignant, surgery. If indeterminant, perform a nuclear medicine thyroid scan to differentiate follicular neoplasm (adenoma or carcinoma). If the nodule is hot, it is benign, if it is cold, it should be excised.

Front 112

What is the meaning of organification?

Back 112

Organification is referring to iodide being transformed into iodine by thyroperoxidase (TPO). Iodine then binds to 1 of 4 tyrosine residues on the thyroglobulin molecule forming MIT or DIT.

Front 113

What are some primary and secondary etiologies of multinodular goiters?

Back 113

* Primary: familial (TG, MNG-1, TSHR, NIS) or gender (women)
* Secondary: low iodine intake, smoking, natural goitrogens, certain drugs, stress, infections

Front 114

What are some common etiologies of hyperthyroidism?

Back 114

Graves' disease, hyperfunctioning adenoma, multinodular goiter, thyroiditis, iatrogenic, hCG-related (pregnancy/cancer), TSH related (rare)

Front 115

What is the pathogenesis of Graves' disease?

Back 115

Agonistic antibodies are present for the TSH receptor, up-regulating thyroid hormone production.

Front 116

How can pregnancy or cancer cause hyperthyroidism?

Back 116

hCG, sometimes present in higher levels in pregnancy and certain cancers. hCG is similar enough to agonistically bind the TSH receptor.

Front 117

What will serum T4 levels be when tested using a resin uptake test in the following situations: estrogen-treated, pregnancy, hypothyroid, hyperthyroid? How about free thyroxine levels?

Back 117

* Estrogen-treated and pregnancy: low-normal. normal
* Hypothyroid: low. low
* Hyperthyroid: high. high

Front 118

How do you calculate the free thyroxine index and why is it used?

Back 118

The free thyroxine index is used to normalize thyroxine levels in the presence of altered thyroid binding globulin. FTI = T4 * (T3RU/Normal T3RU)

Front 119

What is the treatment of hyperthyroidism and what are their advantages?

Back 119

* Hyperthyroidism is mostly treated using radioactive iodine. It is outpatient ready, simple, safe, and effective
* If radioactive iodine is contraindicated (pregnancy or young children: Propylthiouracil (PTU) is used in pregnancy because it doesn't cross the placenta. Methimazole is used in everyone else

Front 120

What is the mechanism of action of hyperthyroid treatments?

Back 120

* Radioactive iodine is taken up and can destroy thyroid glandular cells
* Propylthiouracil and methimazole block TPO from iodinating thyroglobulin
* Propylthiouracil additionally blocks thyroxine (T4) conversion to triiodothyronine (T3) in peripheral tissues

Front 121

What form of thyroid hormone is administered as a hypothyroid treatment and why?

Back 121

T4 is administered in hypothyroidism because the ability of peripheral tissue to decide between the production of T3 and rT3 is an important regulatory point

Front 122

What is the most likely cause of a diffuse goiter?

Back 122

Autoimmune etiologies , graves' or hashimoto's, most often cause diffuse goiters

Front 123

What is the concern for malignancy in a patient with diffuse goiter?

Back 123

Thyroid lymphoma. Otherwise there is a very low possibility of malignancy

Front 124

What is the order of the layers of the adrenal cortex from outside to inside?

Back 124

GFR - salty, sweet, sex. Zona glomerulosa, mineralocorticoids. Zona fasciculata, glucocorticoids. Zona reticularis, androgens

Front 125

What are some states that affect the release of ACTH by the pituitary?

Back 125

* Vasopressin (hypotension) and pro-inflammatory cytokines stimulate ACTH release by the pituitary
* Stressors such as hypoglycemia, hypotension, fever, surgery, or illness stimulate CRH release from the hypothalamus, increasing ACTH release
* Cortisol levels negatively feedback at both the hypothalamus and pituitary, decreasing ACTH release

Front 126

What is the name and clinical features of primary adrenal excess?

Back 126

Cushing's Disease.
* Glucocorticoid: central obesity, buffalo hump, moon facies, catabolism (thin skin, striae, myopathy, osteoporosis, insulin resistance, irritability, depression, psychosis, immune impairment
* Mineralocorticoid: sodium retention (hypertension, edema), hypokalemia
* Androgen: hirsuitism, amenorrhea

Front 127

How do cortisol levels and release patterns differ in a normal patient and a patient with cushing's disease?

Back 127

Cushing's syndrome patients have high levels of cortisol and their release loses their diurnal release pattern

Front 128

What is the dexamethasone suppression test used for and how does it work?

Back 128

Dexamethasone suppression tests are used to determine the etiology of a high serum cortisol level. Dexamethasone binds the glucocorticoid receptor at the pituitary, providing negative feedback and lowering ACTH release. High doses of dexamethasone are given in the evening and if cortisol levels are still high in the morning, the patient has cushing's syndrome. If cortisol levels are low, there is another reason for the corticoid excess.

Front 129

What is the name of primary adrenal insufficiency and what is its clinical picture?

Back 129

Addison's disease.
* Glucocorticoid: nausea, vomiting, anorexia, weight loss, asthenia, weakness, hyperpigmentation, hypoglycemia
* Mineralocorticoid: sodium wasting (hyponatremia, hypovolemia, orthostatic hypotension, azotemia), hyperkalemia, metabolic acidosis

Front 130

Where is the skin hyperpigmentation most likely to be found in a case of Addison's disease?

Back 130

Hyperpigmentation occurs most often at skin folds (knuckles, finger creases)

Front 131

What is known about a patient with vitiligo and hyperpigmentation?

Back 131

The patient with both vitiligo and hyperpigmentation has Addison's disease (adrenal insufficiency) of an autoimmune origin

Front 132

What is the cortrosyn stimulation test used for and how does it work?

Back 132

Cortrosyn is an ACTH analog and is given in low doses to determine whether adrenal insufficiency is primary or secondary. If cortisol levels do not increase, the etiology is primary (Addison's disease). If cortisol levels do increase, there is a secondary problem causing the adrenal insufficiency

Front 133

What are the common etiologies of primary adrenal insufficiency?

Back 133

Autoimmune (70%), tuberculosis (20%), other (10%)

Front 134

What are common manifestations of secondary adrenal insufficiency?

Back 134

NO HYPERPIGMENTATION or mineralocorticoid deficiency. Nausea, vomiting, anorexia, weight loss, asthenia, weakness, hypoglycemia, hyponatremia (from free water retention)

Front 135

What is the insulin tolerance test used and how does it work?

Back 135

Insulin tolerance test used to be used to access the integrity of the hypothalamus - pituitary - adrenal axis. It is very dangerous and glucagon must be on hand. Insulin is injected to induce hypoglycemia. CRH release from the hypothalamus, ACTH release from the pituitary, and cortisol release from the adrenals.

Front 136

What are the most common etiologies of secondary adrenal insufficiency?

Back 136

Suppression from chronic glucocorticoid therapy, or cushing's syndrome therapy. Pituitary or hypothalamic lesions (adenoma, meningioma, radiation, sheehan's syndrome)

Front 137

What are the clinical manifestations of primary hyperaldosteronism?

Back 137

Hypertension and unexplained hypokalemia

Front 138

What enzymes can be responsible for congenital adrenal hyperplasias? What will the presentation be in each?

Back 138

* 21-hydroxylase: salt-wasting. precocious puberty. females can have male appearing genitalia
* 11ß–hydroxylase: salt-retaining. precocious puberty. females can have male appearing genitalia
* 17a-hydroxylase: undervirilization in boys. no puberty in girls

Front 139

What is the difference in t-score and z-score for bone mineral density tests?

Back 139

T-score compares the individual to the a 20yo female. Z-score compares the individual to other women of the same age

Front 140

What factors are involved in the regulation of osteoclast activity?

Back 140

* Resorptive: PTH and 1,25 Vitamin D3, RANKL
* Deposition: osteoprotegerin, corticosteroids, prostaglandin E2, IFN-Y, TGF-ß

Front 141

What is RANKL, where is it found, and what does it do?

Back 141

RANKL is found on the membrane of osteoblast and bind RANK, found on osteoclasts. The binding of RANK and RANKL signals osteoclast precursors (monocytes) to stimulate their fusion, differentiation, and activation

Front 142

How does osteoprotegerin affect bone resorption?

Back 142

Osteoprotegerin blocks bone resorption

Front 143

What is M-CSF and how is it involved in bone density?

Back 143

Monocyte-colony stimulating factor promotes pre-osteoclast production, increasing bone resorption

Front 144

How do glucocorticoids affect bone density?

Back 144

Glucocorticoids inhibit osteoprotegerin promoting bone resorption

Front 145

How does estrogen affect bone density?

Back 145

Estrogen blocks RANKL and up-regulates osteoprotegerin, promoting bone deposition

Front 146

How do PTH and vitamin D affect bone density?

Back 146

PTH and vitamin D up-regulate RANKL. PTH also inhibits osteoprotegerin. Together they promote bone resorption.

Front 147

What osteoporosis treatments work by decreasing resorption of bone?

Back 147

Estrogen, selective estrogen receptor modulators (SERMs) like tamoxifen or raloxifene, bisphosphonates like alendronate or risedronate, and calcitonin

Front 148

What is the mechanism of action of bisphosphonates and what are they used to treat?

Back 148

Bisphophonates such as alendronate or risedronate are used to treat osteoporosis. They have a tropism for the calcium in bone, are ingested by osteoclasts, promoting their apoptosis. This fixes the balance of bone resorption and formation

Front 149

What are the osteoporosis treatments that decrease resorption and what common worries surround them?

Back 149

* Estrogen: cancer, vascular events
* Selective estrogen receptor modulators: clots
* Bisphosphonate: frozen bones, jaw osteonecrosis, subtrochanteric or femoral fractures
* Calcitonin: efficacy

Front 150

What osteoporosis treatment works by increasing bone formation?

Back 150

Teriparatide is a PTH analog and increases bone formation

Front 151

What are some lifestyle and nutritional preventions of osteoporosis?

Back 151

Smoking cessation, ethanol limitation, increased exercise, adequate calcium and vitamin D intake,

Front 152

What are some major risk factors for osteoporotic fractures?

Back 152

70+, postmenopausal, caucasian or asian, positive family history, short stature, leanness, low calcium intake, hypogonadism, malabsorption, long term glucocorticoids, hyperparathyroidism, hyperthyroidism, smoking, heavy alcohol use

Front 153

What is the most common cause of anterior pituitary hyperfunction?

Back 153

The most common cause of hyperfunction of the anterior pituitary is an adenoma, with a prolactinoma being the most common adenoma (30%)

Front 154

What are the symptoms of prolactinomas?

Back 154

In men, impotence and decreased libido. In women, galactorrhea, amenorrhea, infertility, and decreased libido

Front 155

What are the symptoms of growth hormone adenomas?

Back 155

If it is before the fusion of the epiphyses, gigantism. If it is after fusion of the epiphyses, acromegaly (enlargement of long bones, macroglossia, visceromegaly, diastolic HTN, DM)

Front 156

What is the origin of craniopharyngiomas? What is seen histologically and what is the clinical presentation?

Back 156

Craniopharyngiomas are derived from Rathke's pouch and are composed of cystic and solid components. Cysts are lined with squamous epithelium. They present with pituitary compression, visual field defects, and hydrocephalus

Front 157

What are some common etiologies of hypopituitarism?

Back 157

Pituitary adenoma, apoplexy (acute hemorrhage into adenoma), or necrosis (Sheehan's), empty-sella syndrome, craniopharyngioma, trauma, surgery, radiation, inflammation, or infiltration

Front 158

What is a major characteristic of decreased posterior pituitary function?

Back 158

Central diabetes insipidus. Excessive urination owning to an inability of the kidney to reabsorb water. (nephrogenic DI is decreased sensitivity to ADH, primary polydipsia is excessive water intake decreasing ADH release)

Front 159

What are the 3 main syndrome that can result from hyperfunction of the adrenal cortex?

Back 159

Hyperaldosteronism, hypercortisolism (Cushing's), androgenital syndromes (CAH)

Front 160

What are some etiologies of cushing's syndrome?

Back 160

Exogenous steroids leading to adrenal cortical atrophy, adrenal adenoma, hyperplasia of the adrenal glands from elevated ACTH (pituitary adenoma - cushing's disease or ectopic) or autoantibodies to ACTH receptors

Front 161

What is Conn's syndrome?

Back 161

Primary hyperaldosteronism, most often from an aldosterone-producing adrenal adenoma. This adenoma is usually single, unilateral, small, and bright yellow

Front 162

What are some causes of hypofunction of the adrenal glands?

Back 162

Autoimmune (addison's disease), abrupt withdrawl of corticosteroids, infections (TB, histo, CMV, Waterhouse-Friderichsen syndrome is hemorrhage into adrenal from Neisseria meningitidis), DIC with bilateral adrenal hemorrage, metastasis

Front 163

What is the clinical picture of a patient with adrenal cortical carcinoma?

Back 163

Children from southern brazil under the age of 5. Associated with congenital syndrome of Li-Fraumeni (p53 mutations) and Beckwith-Wiedemann syndromes. Treat with mitotane

Front 164

What are the major associations with a pheochromocytoma?

Back 164

Neurofibromatosis, MEN IIa & MEN IIb, von Hippel-Lindau

Front 165

What is proptosis and what disease is it associated with?

Back 165

Proptosis is the forward displacement of the eye seen in Graves' disease

Front 166

What is the histology seen in Grave's disease?

Back 166

Follicles lined by tall cells with prominent scalloping formed by vacuoles in the colloid

Front 167

What is the most common cause of hypothyroidism in iodine sufficient areas?

Back 167

Chronic autoimmune thyroiditis

Front 168

What accounts for the facial edema seen in hypothyroidism?

Back 168

Accumulation of myxomatous tissue in the skin. Causes edema, broadening and coarsening of facial features, enlargement of the tongue, deepening of the voice

Front 169

What is the most common thyroiditis and are its effects chronic or acute?

Back 169

Hashimoto's is a chronic autoimmune disease leading to gradual thyroid failure

Front 170

What is the epidemiology of hashimoto's thyroiditis?

Back 170

Women, aged 45-65. Clustered in families and is associated with HLA-D5R

Front 171

What are the microscopic features of Hashimoto's Thyroiditis?

Back 171

Lymphocytes, oxophilic (Hurthle) cell changes, lymphoid follicles, plasma cells

Front 172

What are Hurthle cells and what disease are they associated with?

Back 172

Hurthle cells are big, blue oxophilic cells with granular cytoplasm and are seen in Hashimoto's Thyroiditis

Front 173

What is DeQuervain's thyroiditis?

Back 173

Subacute (granulomatous) thyroiditis. Rare thyroiditis in 30-50yo women believed to be associated with viral infections (coxsackie, mumps, measles, adenovirus). Associated with HLA-B35.

Front 174

What is the clinical presentation of Subacute (granulomatous) thyroiditis? What microscopic changes are seen?

Back 174

* DeQuervain's thyroiditis. Gradual or sudden onset, transient hypothyroidism.
* Multinucleated giant cells, lymphocytes, plasma cells

Front 175

Are thyroid nodules more common in men or women?

Back 175

Thyroid nodules are more common in women

Front 176

What are the morphologic changes seen in goiters?

Back 176

Stages of hyperplasia and involution. Hyperplasia shows increased follicular cells and colloid. Degeneration shows colloid, histiocytes, and few follicular cells

Front 177

What is the relative prevalence of the different forms of thyroid neoplasm?

Back 177

Papillary (75-85%), follicular (10-20%), medullary (5%), anaplastic (rare)

Front 178

What cells are proliferating in thyroid adenomas?

Back 178

Thyroid adenomas a discrete solitary masses derived from clonal proliferation of follicular cells

Front 179

Do thyroid adenomas progress to carcinomas?

Back 179

No

Front 180

Describe the morphology of thyroid adenomas

Back 180

Thyroid adenomas are solitary, spherical masses separated by a well defined, fibrous capsule composed of uniform follicular cells

Front 181

Which types of thyroid carcinomas are the most common?

Back 181

Papillary, followed by follicular. Follicular is the most aggressive because it tends to metastasize to the bone and lungs instead of only the cervical lymph nodes

Front 182

How is follicular carcinoma differentiated from follicular adenoma?

Back 182

Follicular carcinoma cannot be distinguished from an adenoma using FNA. Follicular carcinomas will invade the vasculature and will lack an outer capsule

Front 183

What is the epidemiology of papillary carcinoma?

Back 183

Papillary carcinoma is the most common thyroid cancer. 20-40yo, exposure to radiation (Chernobyl). Associated with a rearrangement of the RET/PTC proto-oncogene and BRAF gene mutations

Front 184

What are the morphologic findings in papillary carcinoma?

Back 184

Papillae, ground-glass (Little orphan annie) nuclei and nuclear grooves, intranuclear pseudo-inclusions, concentric calcifications (psammoma bodies)

Front 185

Does papillary carcinoma of the thyroid have a good or poor prognosis? What are some prognostic factors?

Back 185

Papillary carcinoma of the thyroid has a good prognosis 98% @ 10yrs. Prognostic factors include age, size, extra-thyroid extension, completeness of surgery, and metastases

Front 186

What is the epidemiology of follicular carcinoma? How do they present?

Back 186

Older (40-60yo) women. They present as slow growing, painless, intrathyroid masses and are cold on nuclear scan. They often invade vasculature and metastasize to lung and bone

Front 187

Is cytopathology of histology used more often to diagnose follicular carcinoma of the thyroid?

Back 187

Follicular carcinoma of the thyroid can only be diagnosed from histological preparation. Malignancy depends on the demonstration of capsule or vascular invasion. On cytology there will be hypercellular aspirate with dispersed microfollicules and scant colloid

Front 188

What are the genetic associations with follicular carcinoma of the thyroid?

Back 188

Genetic rearrangement of the PPAR, PAX8, and RAS genes are implicated

Front 189

What is the prognosis of follicular carcinoma?

Back 189

Prognosis depends on age, size, level of invasion, and grade. Minimally invasive mortality is 3-5%. Widely invasive mortality is 50% long-term

Front 190

From what type of thyroid cells are medullary carcinomas derived?

Back 190

Medullary carcinomas are neuroendocrine neoplasms derived from parafollicular C cells.

Front 191

Why are medullary carcinomas considered neuroendocrine neoplasms?

Back 191

Medullary carcinomas are derived from the parafollicular C-cells and secrete calcitonin or other peptide such as somatostatin, and VIP

Front 192

What are the genetic or familial associations of medullary carcinoma?

Back 192

Medullary carcinoma of the thyroid are often sporadic (80%). MTC can be associated with MEN2a or MEN2b. The RET proto-oncogene plays an important role in development

Front 193

What are the morphological changes seen in medullary carcinoma?

Back 193

Polygonal or spindle shaped cells in nest or sheets with acellular amyloid deposits derived from calcitonin present in the stroma

Front 194

Describe the epidemiology, gross findings, and histology of anaplastic carcinoma of the thyroid

Back 194

* Rapidly expanding neck mass in older patients (65yo) with a history of goiter, previous or concurrent carcinoma. BRAF mutation
* Large, fleshy tumors with white and tan areas of necrosis and hemorrhage
* Widely invasive tumors composed of spindle cells, pleomorphic giant cells, and epithelioid cells

Front 195

What are the general dysfunctions in the three main types of Diabetes Mellitus?

Back 195

* Type I: ß-cell destruction, lack of insulin
* Type II: ß-cell dysfunction, insulin resistance
* Gestational: ß-cell dysfunction and insulin resistance during pregnancy

Front 196

How is diabetes diagnosed?

Back 196

Any abnormal test requires repeat test for confirmation
* Symptoms of diabetes plus random plasma glucose ≥ 200mg/dL
* Fasting plasma glucose ≥ 126 mg/dL
* 2h plasma glucose during a 75g OGTT ≥ 200 mg/dL
* Hemoglobin A1c ≥ 6.5%

Front 197

What percentage of ß-cell are usually left when Type I DM clinically presents?

Back 197

Typically, clinical onset of Type I DM present when there are 10% ß-cells left

Front 198

How does prolonged increased food intake lead to type II DM?

Back 198

Increased food intake increases blood glucose, stimulating insulin release. When insulin binds its receptor, both the hormone and the receptor are endocytosed and broken down, leading to a decreased number of insulin receptors. The decrease in prevalence of insulin receptors decreases insulin sensitivity, which further perpetuates increasing blood glucose levels. MORE FOOD, DECREASES INSULIN RECEPTOR LEVELS

Front 199

Why do type II diabetics sometimes eventually need to use insulin as treatment?

Back 199

In uncontrolled DMII, chronically high insulin levels tire out and destroy ß-cells, decreasing its ability to release insulin

Front 200

What are the 3 main modified insulin types? What are their modifications and how does it modify their action?

Back 200

* Lispro inverts a lysine and proline decreasing its ability to form a hexamer and shortening its action time
* Aspart substitutes asparagine, decreasing its ability to form a hexamer and shortening its action time
* Glargine substitutes a glycine and adds arginines. This increases their ability to hexamerize, lengthening is time of action

Front 201

What are the pharmacokinetic profiles of insulin and its analogs, from shortest to longest?

Back 201

Aspart and lispro< regular< NPH< detemir< glargine

Front 202

What is the mechanism of action of sulfonylureas?

Back 202

Sulfonylureas (glipizide, glyburide) bind K+ channels on ß-cells, inhibiting depolarization, and stimulating insulin secretion

Front 203

What is the mechanism of action of meglitinides?

Back 203

Meglitinides (repalinide) have the same MOA as sulfonylureas. They bind K+channels on ß-cells, inhibiting depolarization, and stimulating insulin secretion

Front 204

What is the mechanism of action of a-glucosidase inhibitors?

Back 204

A-glucosidase inhibitors (acarbose, meglitol) slow the absorption of carbohydrates. They have no effect on fasting blood sugar, but lower post-prandial glucose peak. They have GI side effects

Front 205

What is the mechanism of action of biguanides?

Back 205

Biguanides (metformin) is an insulin sensitizer by inhibiting hepatic glucose output and enhancing insulin effects on muscle and fat

Front 206

What is the mechanism of action of thiazolidinediones?

Back 206

Thiazolidinediones (TZD, glitazones, pioglitazone) improves insulin sensitivity in muscle and fat by binding to PPARY, working synergistically with insulin. Might inhibit hepatic glucose output

Front 207

What is the mechanism of action of incretins?

Back 207

Incretins (GLP-1, liraglutide, exenatide) enhance insulin secretion, reduce glucagon levels, and delay gastric emptying

Front 208

What is the mechanism of action of DPP-4 inhibitors?

Back 208

DPP-4 inhibitors (sitagliptin, saxagliptin) inhibit the enzyme responsible for breaking down incretins like GLP-1. This enhances insulin secretion, reduces glucagon levels, and delays gastric emptying. DPP-4 inhibitors also promote satiety

Front 209

What is the mechanism of action of pramlintide?

Back 209

Pramlintide is an amylin analog, which modulates gastric emptying, prevents postprandial increase in glucagon, increases satiety decreasing food intake

Front 210

What is the general mechanism of sulfonylureas, meglitinides, GLP-1, and DPP-4 inhibitors?

Back 210

Sulfonylureas, meglitinides, GLP-1, and DPP-4 inhibitors increase insulin production

Front 211

What is the general mechanism of metformin and thiazolidinediones?

Back 211

Metformin and thiazolidinediones increase sensitivity to insulin

Front 212

Name some acute and chronic complications of diabetes

Back 212

* Acute: hypoglycemia, ketoacidosis, hyperosmolar states
* Chronic: nephropathy, retinopathy, neuropathy, vascular disease

Front 213

Why is sorbitol important in diabetic complications?

Back 213

Glucose can be reduced to sorbitol (by NADPH and aldose reductase). Sorbitol has oxidative and osmotic effects and can get trapped in retinal and Schwann cells. This sorbitol back up causes retinopathy and peripheral neuropathy

Front 214

What are the two ways to prevent retinopathy in DM?

Back 214

Diabetes control and annual dilated eye exams

Front 215

How do you prevent vascular complications from diabetes?

Back 215

Smoking cessation, blood pressure control, diabetes control, cholesterol control

Front 216

What are the three types of neuropathy seen in diabetes?

Back 216

* Peripheral: symmetric and distal
* Mononeuropathy: bell's palsy
* Autonomic: gastroparesis, neurogenic bladder, impotence, orthostatic hypotension

Front 217

What are three things that predispose diabetic patients to amputation?

Back 217

Vascular disease affects perfusion, neuropathy increases deformity and decreases awareness of injury, hyperglycemia impairs WBC function and decreases wound healing

Front 218

How is diabetic nephropathy prevented?

Back 218

Diabetic control, blood pressure control, annual urine microalbumin, ACEi when microalbumin >30 mg/dL

Front 219

Differentiate anabolic and catabolic states.

Back 219

Anabolic (fed) states are when nutrients are available for immediate use and storage. Catabolic (fasting) states are when there is limited nutrient intake, requiring mobilization and use of stored energy supplies

Front 220

What are the consequences of hypoglycemia?

Back 220

Acutely impaired CNS function: vision, cognition, muscle coordination, lethargy, weakness. These lead to coma, death

Front 221

What are the consequences of chronic hyperglycemia?

Back 221

Increased oxidative stress, osmotic burden, cellular lipotoxicity. These lead to diseased vasculature, nerves, kidney, and other organs

Front 222

How are glucose, ketone bodies, and amino acids utilized to supply ATP?

Back 222

* Glucose is the primary supplier of ATP.
* Ketone bodies can cross the blood brain barrier & are used in fasting
* Amino acids are utilized to make neurotransmitters, not energy

Front 223

How does the hypothalamus and limbic forebrain work together to modulate nutrient uptake?

Back 223

The hypothalamus controls hunger and satiety. The limbic forebrain provides motivation for palatable food

Front 224

What are the important glucose transporters, where are they located, and how do they work?

Back 224

* GLUT-2 is a low affinity receptor in the ß-cells of the pancreas and the liver. It is responsible for the post-prandial release of insulin. Glucose enters a ß-cell, is undergoes glycolysis and the ATP released closes a K+ channel, depolarizing the cell and allowing the influx of Calcium extracellularly and from the ER. This stimulates insulin release from storage vesicles.
* GLUT-4 present on the cell surface of muscle, cardiac, and adipose tissue. It is inserted in the presence of insulin and brings glucose into the cell
* GLUT-5 is a fructose transported located in the small intestine and sperm

Front 225

What is the consequence of hexokinases?

Back 225

Hexokinase acts on intracellular glucose, turning it into glucose-6-phosphate, which is difficult to get out of the cell

Front 226

How does most hexokinases differ from glucokinase?

Back 226

Glucokinase is located in the ß-cells of the pancreas and in the liver and have a much lower affinity for glucose. This allows for much tighter responses to changes in glucose control

Front 227

What products of carbohydrates, free fatty acids, and proteins are used to generate energy?

Back 227

* Pyruvate becomes acetyl-CoA which enters the TCA cycle
* Free fatty acids are brought into the mitochondria via the carnitine shuttle, ß-oxidized to acetyl-CoA which enter the TCA cycle
* Amino acids are transaminated into pyruvate, acetyl-CoA, a-ketoglutarate, succinyl-CoA, fumarate, and oxaloacetate and produce ketone bodies

Front 228

Where are ketone bodies generated and utilized?

Back 228

Ketone bodies (acetoacetate and ß-hydroxybutyrate) are byproducts of fatty acid breakdown (acetyl-CoA) in the liver. Peripheral tissues, specifically brain and heart, convert ketone bodies back to acetyl-CoA

Front 229

How do insulin, glucagon, and epinephrine affect glycogen stores?

Back 229

* Insulin promotes the uptake and storage of glucose as glycogen chains. Glycogen stores increase.
* Glucagon and epinephrine promote glycogenolysis. In the liver, glucose is transported out by GLUT2. In the muscle, lactate diffuses out. Glycogen stores decrease

Front 230

How does high-caloric intake promote FFA storage in adipose tissue?

Back 230

After high-caloric intake, there is glucose present for the pentose phosphate pathway to produce the NADPH needed for FA synthesis, glucose metabolism is turned off and energy storage as FFAs is up-regulated. Glucose is transformed int MGs, DGs, and TGs. The TGs are packaged into VLDLs, coated with ApoB100 and secreted into the blood stream where capillary lipoprotein lipase in adipose tissue removes and store the TG for future need

Front 231

What lipoprotein is needed to activate lipoprotein lipase and from where is it acquired?

Back 231

ApoC2, acquired from HDLs, is responsible for activating lipoprotein lipase

Front 232

Where does lipoprotein lipase come from and what is its mechanism of action?

Back 232

Lipoprotein lipase is released from the adipose tissue, binds to the capillary endothelium via heparin-sulfate proteoglycans, and digests lipoprotein, releasing FFA and glycerol. Those released FFA and glucose are transported into the adipocyte where it is esterified into TGs

Front 233

How does blood flow within the islets of langerhans?

Back 233

Blood flows from the ß-cells and passes across the alpha and delta cells

Front 234

What are the hormone, general fuel source, and processes involved in a catabolic versus an anabolic state?

Back 234

* In an anabolic state, there is increased insulin and decreased glucagon, the primary fuel source comes from the diet, and glycogen, triglyceride, and protein synthesis are occurring.
* In catabolic states, there is decreased insulin so an increase in glucagon. The primary fuel source is from storage pools and glycolysis, glycogenolysis, lipolysis, proteolysis, and ketogenesis are all taking place

Front 235

What is C-peptide used for?

Back 235

C-peptide is released with insulin and is used as a diagnostic measure of endogenous insulin release

Front 236

How does the cellular organization of the endocrine pancreas support its regulatory functions?

Back 236

Within the islet, ß-cells are located centrally, where blood flow initiates. As insulin is released and flows from the middle of the islet to the periphery, it flows over alpha and delta cells, inhibiting glucagon and somatostatin release

Front 237

What are glucagons regulatory functions on insulin and somatostatin?

Back 237

Glucagon stimulates release of insulin by increasing blood glucose. Glucagon also stimulates somatostatin release

Front 238

What type of receptor does insulin interact with?

Back 238

The insulin receptor is a receptor tyrosine kinase. Downstream it triggers the transport of glucose transporters to cell membranes and changes enzymes to increase fuel storage

Front 239

What are the actions of glucose at the liver?

Back 239

When insulin increases the uptake of glucose in the hepatocyte glycogen synthesis is up-regulated, as is lipogenesis, glycolysis, and protein metabolism

Front 240

How is glucagon transported in the blood

Back 240

Glucagon circulates unbound in serum

Front 241

What hormone does GLP-1 mimic?

Back 241

Glucagon-like peptide mimics insulin in its actions. GLP-1 increases glucose-stimulated insulin release, increases ß-cell hypertrophy and growth

Front 242

How do glucagon and epinephrine act at the muscle and liver?

Back 242

Glucagon and epinephrine are glycogenolytic. At the liver they promote freshly-freed glucose being transported out by GLUT2. In muscle cells, they lead to lactate being diffused out following glycolysis

Front 243

What are some states that decrease insulin sensitivity?

Back 243

Stress hormones (cortisol, growth hormone, catecholamines), FFA levels, and disease state cytokines like TNFa all decrease insulin sensitivity

Front 244

How do the actions of ghrelin and leptin differ?

Back 244

Ghrelin is an appetite stimulator. Leptin is more or a metabolic thermostat, regulating long-term hunger and metabolic activity

Front 245

How does increased adipose tissue affect leptin levels, food intake, and metabolic activity?

Back 245

Increases in total adipose tissue increases plasma leptin, which decreases food intake and increases metabolic activity (temperature, reproduction, growth)

Front 246

How many mature spermatozoa are produced each month?

Back 246

12 billion. 50-500 million per ejaculation. 200 reach fertilization site

Front 247

Describe the layers covering the testes

Back 247

2 layers of the extension of the peritoneum, the tunica vaginalis. The tunica albuginea is a collagenous connective tissue layer, which invaginates to form septula testis. Each lobule has 1-4 seminiferous tubules surrounded by interstitum

Front 248

What cells make up the interstitial tissue of the testes?

Back 248

The interstitial tissue of the testes is loose connective tissue with Leydig cells, macrophages, blood vessels, fibroblasts, and blood vessels

Front 249

What variety of cells are present in the epithelium of seminiferous tubules?

Back 249

The epithelium of seminiferous tubules is made up of Sertoli cells and spermatogenic cells (spermatogonia, 1˚ and 2˚ spermatocytes, and spermatids

Front 250

What cells concentrate testosterone and how do they do it?

Back 250

Sertoli cells in the seminiferous tubule epithelium surround spermatogenic cells until they are released. Sertoli cells use androgen-binding protein to concentrate testosterone over the developing spermatozoa

Front 251

What are the integral cells for the blood-testis barrier?

Back 251

Sertoli cells for junctional complexes excluding plasma proteins and antibodies from the lumen and protecting developing sperm cells from chemical toxins

Front 252

What steps are necessary for spermatids to become mature spermatozoa?

Back 252

Spermatids undergo
* Golgi phase: golgi present, beginning of acrosomal vesicle
* Cap phase: axonemal complex develops, acrosomal cap
* Acrosome phase: long axonemal complex, microtubules
* Mature phase: mitochondria into middle piece, residual body

Front 253

What is the acrosomal cap?

Back 253

The acrosomal cap is adjacent to the nucleus of the spermatid. It contains enzymes required for fertilization

Front 254

When are spermatids officially individual cells?

Back 254

Spermatids undergo spermatogenesis and spermiogenesis as daughter cells connected by cytoplasmic bridges. At the end of spermiogenesis, spermatozoa are separated from their residual bodies and released as individual cells

Front 255

How long does it take from spermatogonia to complete development?

Back 255

74 days

Front 256

What is the epithelium of the tubuli recti made up of?

Back 256

Tubuli recti has an epithelium of only Sertoli cells

Front 257

What type of cells line the rete testis?

Back 257

The epithelium of the rete testis is simple cuboidal/low columnar

Front 258

What tubule make up the intratesticular ducts and which make up the excurrent ducts?

Back 258

The tubuli recti and rete testis are intratesticular ducts. The efferent ductules, the epididymis, and the vas deferens are excurrent ducts

Front 259

What is the structure of the efferent duct epithelium in the testis?

Back 259

The efferent duct has a pseudostratified columnar epithelium made up of taller ciliated cells and shorter absorptive cells

Front 260

What is the structure and function of the epididymal epithelium?

Back 260

The epididymis has an pseudostratified columnar epithelium made up of basal cells and principal cells.
* Basal cells serve as stem cells.
* Principal cells have long luminal immotile microvilli which reabsorb most of the remaining luminal fluid produced in the seminiferous tubules. They also phagocytose faulty spermatozoa and residual bodies and produce glycerophosphocholine which inihibits capacitation

Front 261

Describe the epithelium and muscular layers of the vas deferens

Back 261

The vas deferens has a pseudostratified columnar epithelium similar to the epididymis. The muscular coat is 3 layers (longitudinal, circular, longitudinal)

Front 262

What is the ejaculatory duct?

Back 262

The ejactulatory duct is formed by the merging of the duct from the seminal vesicle and the distal vas deferens. The right and left ejaculatory ducts run through the central zone of the prostate gland and open into the prostatic urethra

Front 263

What are the products of the 3 male accessory genital glands?

Back 263

* Seminal vesicles produce a fructose-rich fluid that accounts for 60-80% of seminal volume. Lipochrome makes it pale yellow
* Prostate glands add acidic serous fluid (lipids, proteolytic enzymes, acid phosphate, fibrinolysin, citric acid)
* Bulbourethral glands produce thick, slippery mucus that lubricates the urethra

Front 264

Where are mucosal, peripheral, and sub-mucosal glands found in the prostate?

Back 264

Mucosal glands are in the transitional zone and empty into the urethra. Sub-mucosal glands are in the central zone and empty into the urethra through the ejaculatory ducts. Peripheral glands in the peripheral zone empty into long ducts along the urethral crest, which then empty into the urethra

Front 265

What are corpora amylacea?

Back 265

Corpora amylacea a glycoprotein deposits within the prostate that progressively calcify to form prostatic concretions

Front 266

What hormone controls the functional status of the bulbourethral glands?

Back 266

Testosterone

Front 267

How does the ovum get to the uterus?

Back 267

The ovum is released from the ovary, is captured by the fimbriae of the oviduct, and travels through the infundibulum, ampulla, isthmus, and intramural segment before it reaches the uterus

Front 268

Where is the normal site of fertilization?

Back 268

The ampulla of the oviduct is the normal site of fertilization

Front 269

When does the final meiotic division of the ovum occur?

Back 269

The final meiotic division of the ovum occurs at the time of fertilization

Front 270

What is the function of the zona pellucida?

Back 270

The zona pellucida prevents polyspermy and remains intact around the fertilized egg through several cell divisions

Front 271

Describe the layers of the oviduct

Back 271

* Mucosa of folded, simple columnar epithelium with lamina propria
* Muscularis with 2 layer (inner circular, outer longitudinal)
* Serosa with thin underlying layer of connective tissue

Front 272

Describe changes in the oviduct moving proximally

Back 272

The distal portion of the oviduct has a large diameter with a thinner wall and more complexly folded mucosa. More proximally the oviduct narrows with a more muscularis wall, smaller lumen, and less convoluted mucosa. Distally, the ovum is propelled by the ciliated mucosa. Proximally, the ovum is propelled by smooth muscle

Front 273

Describe the epithelium of the oviduct

Back 273

The oviduct epithelium is made up of short ciliated cells and columnar peg cells that secrete oviductal fluid to nourish the ovum. The closer to the uterus, the fewer the ciliated cells

Front 274

Grossly describe the organization of the uterus

Back 274

Endometrium (stratum functionale and stratum basale), myometrium, and perimetrium (broad ligament). Fundus is the roof, cervix is the floor

Front 275

What types of arteries are found in the stratum basale and stratum functionale?

Back 275

The stratum basale is supplied by straight arteries that lack steroid receptors. The stratum functionale is supported by spiral arteries, the integrity of which are regulated by changing levels of hormones which interact with steroid receptors on their surface

Front 276

What are the changes with uterine glands seen during the ovarian cycle?

Back 276

In the proliferative phase, glands are straight, but not secretory. In the initial secretory phase, glands begin to coil and cells accumulate glycogen in the basal region. Late in the secretory phase, the glands are highly coiled and show extensive secretory activity

Front 277

How long after ovulation will estrogen and progesterone levels begin to fall if no fertilization has ocurred? What effects do that drop have?

Back 277

Estrogen and progesterone levels will begin to drop 10-12 days after ovulation. These hormonal declines cause contraction and necrosis of the spiral arteries, ischemia of the stratum functionale, bleeding from ruptured vessels, and sloughing of the detached stratum functionale layer

Front 278

What are the epithelial boundaries of the cervix?

Back 278

The internal os is the junction of the uterus and cervix. The external os is the junction of the cervix (columnar) and vagina (squamous).

Front 279

Describe cervical softening

Back 279

Cervical ripening is when the cervix become distensible in preparation for labor and delivery. Hyaluronic acid content increases, trapping more water within collagen fibers. This reduces cross-bridges among collagen fibers, decreasing alignment and strength. Prostaglandin E2 helps increase collagen degradation and hyaluronic acid. Nitric oxide plays a role.

Front 280

Describe the wall of the vagina

Back 280

* Mucosa is stratified squamous with lamina propria with elastic fibers and thin-walled vessels
* Fibromuscular layer with ill-defined inner circular and outer longitudinal smooth muscle
* Adventitia with collagenous and elastic fibers, blood vessels, and nerves

Front 281

When does mitosis of the oogonia cease?

Back 281

In the second trimester

Front 282

In what phase do oocytes pause?

Back 282

Oocytes start meiosis I, but stop in prophase. They remain as 1˚ oocytes for years

Front 283

Approximately how many oocytes are present at birth, at puberty, and how many are released?

Back 283

1 million left at birth, 250K by puberty, 400 are typically released during reproductive life

Front 284

Describe the progression of 1˚ oocytes

Back 284

Primordial follicle to 1˚ follicle to multilaminar 1˚ follicle (with zona pellucida and theca folliculi) to 2˚ follicle (theca folliculi, zona pellucida, and granulosa cells). The 1˚ oocyte then becomes a 2˚ oocyte or a graafian follicle with an antrum

Front 285

Describe when during oogenesis the phases of mitosis and meiosis occur

Back 285

Mitosis occurs before birth and produces 1˚ oocytes. The 1˚ oocytes complete meiosis I after puberty, produce a polar body, and become 2˚ oocytes. 2˚ oocytes begin meiosis and are ovulated in metaphase of meiosis II. If fertilization of the 2˚ oocyte occurs, meiosis II is completed

Front 286

What is the corona radiata?

Back 286

The corona radiata covers the ovum as it is transported into the oviduct. Sperm must penetrate it, permitting the last steps of capacitation

Front 287

Where are hormone produced after ovulation and fertilization?

Back 287

The follicular wall will form the corpus luteum and granulosa and thecal cells secrete large quantities of hormones required to maintain fertilization and pregnancy

Front 288

Which type of diabetes is more prone to ketoacidosis and why?

Back 288

Type I DM is more prone to ketoacidosis, a state that occurs in states of hypoinsulinemia. When type I diabetic have too little insulin, they cannot utilize glucose for energy and begin producing ketone bodies. This can occur in a state of hyperglycemia

Front 289

What structure is insulin found in in solution?

Back 289

In solution, insulin forms hexamers

Front 290

How do bio-engineered insulin preparations change their function?

Back 290

* Aspart, lispro, and glulisine have changed their structures so they do not form hexamers. Very short-acting
*Glargine, detemir form very stable hexamers, prolonging their action

Front 291

Which oral anti-diabetic drugs enhance insulin release?

Back 291

Sulfonylureas, meglitinides, incretins, DPP-4 inhibitors

Front 292

Which oral anti-diabetic drugs enhance insulin sensitivity?

Back 292

Biguanides and thiazolidinediones

Front 293

Which oral anti-diabetic drugs reduce glucose absorption?

Back 293

Incretins, DPP-4 inhibitors, a-glucosidase inhibitors

Front 294

Which oral anti-diabetic drugs suppress hepatic glucose production?

Back 294

Biguanides

Front 295

Which oral anti-diabetic drugs suppress appetite?

Back 295

Incretins and DPP-4 inhibitors

Front 296

Can sulfonylureas cause hypoglycemia? Biguanides? Thiazolidinediones?

Back 296

Sulfonylureas can cause hypoglycemia, biguanides and thiazolidinediones do not

Front 297

What is the mechanism of action of pramlintide and what is it used for?

Back 297

Pramlintide is an islet amyloid polypeptide that slows the gastric emptying rate, diminishing carbohydrate yield from a meal

Front 298

What is the mechanism of action of canagliflozin?

Back 298

Canagliflozin is an anti-diabetic drug that blocks NaGLUT2 in the kidneys, blocking reabsorption of glucose

Front 299

What is the mechanism of action of berberine?

Back 299

Berberine is a plant alkaloid that inhibits DPP-4 and up-regulates insulin receptor expression

Front 300

Describe the electrophoretic mobility of the major lipoproteins

Back 300

HDL are alpha and travel the farthest, VLDL are pre-ß, LDL are ß, and chylomicrons do not travel

Front 301

Where are the key apolipoproteins found and what are their functions?

Back 301

* ApoA-I is needed for HDL synthesis and is a cofactor for LCAT
* ApoB is needed for chylomicron & VLDL synthesis and is a ligand for LDL receptor-mediated uptake
* ApoC2 is a cofactor for lipoprotein lipase
* ApoE is a ligand for hepatic chylomicron remnant uptake

Front 302

What is the general itinerary for chylomicrons?

Back 302

Chylomicrons take exogenous lipids from the gut to the liver

Front 303

What is the general itinerary for VLDL and LDL?

Back 303

VLDL and LDL transport lipids from the liver to the periphery

Front 304

What is the general itinerary of HDL?

Back 304

HDL is responsible for reverse transport of lipids from the periphery to the liver for disposal

Front 305

What is the function and metabolism of chylomicrons?

Back 305

Chylomicrons carry dietary TGs from the small intestines to peripheral adipocytes (via LPL + ApoC2) and then onto the liver (via ApoE + LDLR).

Front 306

What is the function and metabolism of VLDL?

Back 306

VLDL transports TG and CE synthesized in the liver to the peripheral tissues (LPL + ApoC2) and is intravascularly converted to IDL and the LDL, which is mostly full of CE.

Front 307

What is the function and metabolism of LDL?

Back 307

LDL carries CE to peripheral cells and brings HDL-derived CE back to the liver. It can be taken up by either hepatic or peripheral LDL receptors (+ ApoB)

Front 308

What is the function and metabolism of HDL?

Back 308

HDL is responsible for reverse CE (& plasma lipids) transport, carrying it from the periphery to the liver. It is synthesized in the liver at ABCA1. HDL can pass CE to LDL for export in the bile system

Front 309

What co-hormones are needed for lipoprotein lipase action?

Back 309

LPL, made and released by adipocytes, requires insulin and thyroxine to function

Front 310

What are the relative half-lives of the major lipoproteins?

Back 310

* Chylomicrons: <15 min
* VLDL: 1-3 hrs
* LDL: 2-3 days
* HDL: 5-6 days

Front 311

Elevated and depressed levels of chylomicrons are responsible for what conditions?

Back 311

* Elevated chylomicrons levels cause hypertriglyceridemias and pancreatitis
* Depressed chylomicron levels causes fat malabsorption

Front 312

Elevated and depressed levels of VLDL are responsible for what conditions?

Back 312

* Elevated VLDL levels cause hyperlipidemia, pancreatitis, and an increased risk of ASCVD
* Depressed VLDL levels increase HDL levels

Front 313

Elevated and depressed levels of LDL are responsible for what conditions?

Back 313

* Elevated LDL levels leads to hypercholesterolemia and an increased risk of ASCVD
* Depressed LDL levels decreases the risk of ASCVD

Front 314

Elevated and depressed levels of HDL are responsible for what conditions?

Back 314

* Elevated HDL levels cause hypercholesterolemia, a decreased risk of ASCVD, and an increased longevity
* Depressed HDL levels increase the risk of ASCVD

Front 315

What are some common 2˚ causes of dyslipoproteinemias?

Back 315

* Dietary: sensitivity to cholesterol, alcohol use
* Metabolic: hypothyroidism, diabetes, obesity
* Drugs: thiazides, steroids, ß-blockers, isotretinoin
* Diseases: renal, liver, autoimmune, infectious

Front 316

What is the genetic defect, lipoprotein phenotype, important clinical findings, clinical course, and treatment of familial chylomicronemia?

Back 316

* Very rare, autosomal recessive mutation of LPL or ApoC2
* Plasma TG and chylomicrons greatly increased
* Lipemia retinalis, eruptive xanthomas
* Severe HTG, hepatosplenomegaly, acute pancreatitis
* Low fat diet, MCTg

Front 317

What is the genetic defect, lipoprotein phenotype, important clinical findings, clinical course, and treatment of lipoprotein lipase deficiency?

Back 317

* Very rare, autosomal recessive mutation of LPL
* Plasma TG and chylomicrons greatly increased
* Lipemia retinalis, eruptive xanthomas
* Severe HTG, hepatosplenomegaly, acute pancreatitis
* Low fat diet, MCTg

Front 318

What is the genetic defect, lipoprotein phenotype, important clinical findings, clinical course, and treatment of ApoC2 deficiency?

Back 318

* Very rare, autosomal recessive mutation of ApoC2
* Plasma TG and chylomicrons greatly increased
* Lipemia retinalis, eruptive xanthomas
* Severe HTG, hepatosplenomegaly, acute pancreatitis
* Low fat diet, MCTg

Front 319

What is the genetic defect, lipoprotein phenotype, important clinical findings, clinical course, and treatment of familial hypercholesterolemia?

Back 319

* Common, autosomal co-dominant mutation of LDL receptor
* Increased total and LDL cholesterol. (hetero ~350, homo ~700)
* Tendon xanthomas, xanthalasma, corneal arcus
* Hetero - MI at 35-45; homo - MI in childhood
* Hetero - low fat/cholesterol diet, statins, bile binders, zetia; homo - liver transplant, LDL-pheresis

Front 320

What is the genetic defect, lipoprotein phenotype, clinical course, and treatment of polygenic hypercholesterolemia?

Back 320

* Common, polygenic defect
* Increased total and LDL cholesterol (~200-300)
* Increased risk of ASCVD, 10% of relatives will have increased LDL
* Low fat/cholesterol diet, weight loss, exercise, statins, bile acid binders, zetia

Front 321

What is the genetic defect, lipoprotein phenotype, important clinical findings, clinical course, and treatment of familial combined hyperlipidemia?

Back 321

* A common, autosomal dominant defect causing increased VLDLs
* Elevated combinations of TC, TG (~400), LDL (~300), VLDL, and ApoB
* Confusing hetrogeneous FH; increased risk of ASCVD, doesn't usually apear until middle age
* Low fat/cholesterol, statins, bile acid binders, zetia

Front 322

What is the genetic defect, lipoprotein phenotype, important clinical findings, clinical course, and treatment of familial hypertriglyceridemia?

Back 322

* Common, autosomal dominant polygenic defect leading to increased TG packing into VLDL
* Increased TG (>200) and VLDL, with decreased HDL
* Lipemic plasma (tomato blood), lipemia retinalis, eruptive xanthomas (if TG>1000)
* Slight risk of ASCVD, pancreatitis (TG>1000)
* Weight loss, exercise, fibrates, niacin, fish oil

Front 323

What is the genetic defect, lipoprotein phenotype, important clinical findings, clinical course, and treatment of metabolic syndrome?

Back 323

* Extremely common, polygenic condition with increased TG packed into VLDL. Associated with DMII
* Increased TG (>150) and VLDL, decreased HDL
* Insulin resistance, HTN, increased ASCVD risk
* Weight loss, exercise, control HTN and DM, fibrates, niacin, fish oil

Front 324

What is the genetic defect, lipoprotein phenotype, important clinical findings, clinical course, and treatment of ß-sitosterolemia?

Back 324

* An extremely rare, autosomal recessive mutation of ABDG5/G8, restricting dietary sterols from being released from the enterocyte, except for into chylomicrons.
* Increased plasma phytosterol (>20) and LDL
* Tendon xanthomas, increased risk of ASCVD, hemolysis
* Low cholesterol/plant sterol diet, zetia, bile acid binders

Front 325

What is the genetic defect, lipoprotein phenotype, important clinical findings, clinical course, and treatment of familial dysbetalipoproteinemia?

Back 325

* Uncommon, autosomal co-dominant ApoE2 defect restricting chylomicrons from returning to the liver
* "Broad beta disease". Elevated TC, TG (~500), chylomicrons, and VLDL
* Palmer and tuboeruptive xanthomas
* Premature ASCVD and PVD
* Low fat/cholesterol diet, fibrates, niacin, statins

Front 326

What is the genetic defect, lipoprotein phenotype, important clinical findings, clinical course, and treatment of Tangier disease?

Back 326

* Extremely rare autosomal recessive mutation of ABCA1 gene responsible for producing HDL
* Low total cholesterol (<50) and no HDL (<5), mild TG elevation
* Large orange tonsils (cholesterol accumulation in macrophages), hepatospenomegally, sensory neuropathy, premature ASCVD

Front 327

Why does hypothyroidism produce a dyslipidemia? What lipoprotein is affected?

Back 327

Thyroxine is needed to for lipoprotein lipase function. Hypothyroidism will lead to a cholesterol dyslipidemia

Front 328

What is the mechanism of action for statins?

Back 328

Statins a competitive inhibitors of HMG-CoA reductase blocks the conversion of HMG-CoA to mevalonate, thereby blocking cholesterol and LDL production

Front 329

What are the adverse effects of statins?

Back 329

Myalgias, potential hepatic damage, metabolized by p450 (CYP3A4)

Front 330

What dyslipidemias are niacin used for? What are its side effects?

Back 330

* Niacin effectively lowers both cholesterol and TG, as well as raises HDL.
* Flushing, pruritus, fatigue, blurred vision (all relived with ASA)

Front 331

What is the mechanism of action of bile acid binding resins? What is a major concern? What are its common side effects?

Back 331

* Bile acid binding resins slow bile salt reabsorption so plasma LDL has to be dissolve to free more cholesterol for bile salts.
* Will up-reguate hepatic TG and VLDL, aggravating hyperTGemias
* GI discomfort, expensive, slows absorption of imports lipid-soluble substances

Front 332

What are fibrates used for? What is their mechanism of action?

Back 332

* Fibrates lower TGs by acting on lipoprotein lipase in the adipose vasculature, causing VLDL to release FFAs.
* They potentiate PPARa transcription and promote fatty acid oxidation. They also increase expression of ApoA1, promoting HDL

Front 333

What is the mechanism of ezetimibe?

Back 333

Zetia (ezetimibe) blocks uptake of dietary cholesterol into enterocytes from the GI tract

Front 334

Name some markers of neuroendocrine cells

Back 334

Silver stain, secretory granules under electron microscopy, immunohistochemical stains (synaptophysin, chromogranin, neuron specific enolase, neural cell adhesion molecule)

Front 335

What are the specific names of the neuroendocrine cells in the skin and lungs?

Back 335

Neuroendocrine cells in the skin are Merkel cells, in the lungs they are called Kulchitsky cells

Front 336

Which type of diabetes will contain amyloid deposits?

Back 336

Type II DM has amyloid deposits

Front 337

When do you see Kimmelstiel-Wilson nodules?

Back 337

Diabetic nephropathy

Front 338

What is the most common cause of death among diabetics?

Back 338

Myocardial infarction

Front 339

What are the clinical symptoms of an insulinoma?

Back 339

Hypoglycemic syndrome: confusion, behavioral changes, fatigue, seizures, coma. Surgically resect. Mostly benign, but can be malignant in older adults

Front 340

What are the clinical symptoms of a gastrinoma?

Back 340

Zollinger-Ellison syndrome: peptic ulcer disease, GERD, diarrhea. MEN1. 80% malignant. 50% 10yr survival

Front 341

What are the clinical symptoms of a glucagonoma?

Back 341

The 4 D's. Diabetes, dermatitis, DVT, depression