Endocrine Flashcards
1
Q
What is the EC and IC amount of phosphate in the body?
A
EC is 500mg, IC is 50,000mg.
2
Q
What is cortisone?
A
An inactive metabolite of cortisol, made by 11-HSD. Glycyrrhenic acid in licorice inhibits.
3
Q
What is desmolase stimulated by and what is it?
A
It converts cholesterol to progestins. Stimulated by ACTH.
4
Q
How does IGF1 affect the chondrocytes?
A
Stimulates AA uptake/protein synthesis, DNA/RNA sythesis, chondroitin sulfate, collagen production, hyperplasia, hypertrophy.
5
Q
How is Vit D production affected as we age?
A
Production reduced as renal 1alphahydroxylase function decreases.
6
Q
What is metformin?
A
A biguanide - activates AMP-activated protein kinase. Decreases gluconeogenesis and glycogenolysis, has insulin like effects.
7
Q
Which NSAIDs are specific for COX2?
A
Celebrex, arcoxia.
8
Q
Describe the thyroid follicle.
A
Simple cuboidal epithelium surrounding a lumen filled with ‘colloid’ glycoprotein thyroglobulin. Often stripey. Has thyroid follicular cells and also C/parafollicular cells (pale staining).
9
Q
What’s the difference between T3 and T4?
A
T4 has a longer half life (7 vs 1 day), T3 more potent.
10
Q
How is fructose metabolized?
A
Made to F1P by fructokinase. Converted to DHAP and glyceraldehyde by aldolase B.
11
Q
What is the distribution of glucokinase vs hexokinase?
A
Hexokinase is in muscle, glucokinase is most everywhere else.
12
Q
What is Liothyronine and how is it given?
A
T3 - orally (IV in myxedema coma)
13
Q
What is Dinoprostone and how is it administered?
A
It is PGE2. Administered by locally-applied gel or control-release vaginal insert. To induce labour, IV or intravaginal.
14
Q
What are the effects of X-linked TBG deficiency?
A
20-30% of T3 and T4, no signs of hypo thyroidism generally.
15
Q
What are COX1 and COX2?
A
Cycloxygenases, COX1 constitutive, COX2 inducible. Induced in response to injury and infection by immune cells. Can also make 15-HPETE which can be made to leukotrienes.
16
Q
What carries IGF1 through the blood?
A
IGFBP-3.
17
Q
What is von Gierke disease?
A
Deficiency in G6 phosphatase (found in the ER). Needed in gluconeogenesis and glycogenolysis. Disease results in severe fasting hypoglycemia.
18
Q
What % of endogenous Cushing’s is ACTH dependent?
A
80% - 70% pituitary adenoma, 10% other tumor making ACTH or CRH.
19
Q
What hormones inhibit glycogen synthase?
A
Glucagon (PKA cascade inactivates). Also epinephrine in the liver and muscle.
20
Q
What is Misoprostol used for and what are the adverse effects?
A
Protective agents in NSAID therapy, used with mifepristone as a terminator of early pregnancy. Adverse effects are cramping or diarrhea.
21
Q
What is pegvisomant?
A
A GH antagonist - binds receptors but doesn’t activate the JAK/STAT pathway.
22
Q
What kind of molecule are D vitamins and their metabolites?
A
Secosteroids - Lipophilic, orally absorbed.
23
Q
What does eicosatrienoic acid become through COX action?
A
PGE1, PGFalpha1, PGI1, TxA1
24
Q
Describe the ‘insulin cascade’.
A
Insulin binds, IRS-1 recruited, PI3K activated. PIP2 is made to PIP3, which binds PKB and PDK1, ending up in PKB phosphorylation and activation. PKB phosphorylates TBC1D4, allowing vesicle fusion with the PM.
25
How does Teriparatide work?
Himan PTH1-34 Used to promote bone formation. Short half life - small spikes enhances the bone formation of the pathway.
26
What are the primary functions of calcium in the body?
Skeletal structure, second messenger, cofactor for lipases and AChE, stabilizes RNA and RNA, blood coagulation, nutrient absorption, cellular mechanisms for endocrine secretion, platelet mechanism for thromboplastin release.
27
What is the starting lipid for prostamide?
Anandamide (ethanolamine or arachidonic acid).
28
What is the dorsomedial nucleus of the hypothalamus responsible for?
Controls food intake and does body weight regulation - stimulation results in hyperphagia (obesity) and rage.
29
Describe growth hormone. What's its release rhythm and how's it stimulated?
Large, water-soluble. Peaks at puberty. Has circadian cycle - pulsatile through day. Stimulated by hypoglycemia, protein deficiency, exercise, trauma, peaks during sleep.
30
What % of endogenous Cushing's is ACTH independent?
20% - 10% adrenal adenoma, 5% adrenocortical carcinoma, 5% primary cortical hyperplasia.
31
What is calcitonin? What stimulates its production?
A peptide hormone. Inhibits osteoclast action, promotes renal Ca++ excretion. Stimulated by gastrin or elevated plasma Ca++.
32
What are the adverse effects of aprostadil?
Penile pain, urethral burning.
33
What kind of hormones are androgens, prostaglandins, leukotrienes?
Steroid and lipid derived.
34
Describe the major routes for calcium absorption and secretion.
~1000mg taken in through diet, intestine absorbs 350, secretes 250, net expels 900. Kidney reabsorbs 9880mg, filters ~9980, gives off net 100. Bone takes in and gives off about the same amount ~250mg
35
What are some symptoms of CAH?
Ambiguous genitalia in females, male precocious puberty. Salt cravings in 21-hydroxylase deficiency. Deoxycortisone can act like mineralocorticoids so you actually get hypokalemia, hypernatremia, hypertension, edema.
36
What is cretinism?
Congenital hypothyroidism. Growth and mental retardation, developmental issue.
37
What is ketoacidosis?
Complication of DM type 1. Hyperglycemia \>250, metabolic pH \<7.3
38
How does a more acidic environment affect calcium absorption?
Increases.
39
What is Laron syndrome?
GH receptors don't dimerize properly.
40
What are the contraindications of Dinoprostone?
Acute PID, active cardiac, pulmonary, renal, or hepatic disease. Also specified obstructive conditions making induction dangerous.
41
Pathologically, how do you tell apart exogenous and endogenous Cushing's?
Exogenous will have cortical atrophy from lack of ACTH stimulation, endogenous will have the opposite - diffuse hyperplasia.
42
How does GH respond to high protein, high carb, and fasting states?
Elevated in high protein and fasting, lowered in high carb.
43
What type of receptor is the IGF1 receptor?
Tyrosine kinase.
44
What is hyperglycemic hyperosmolar nonketotic state?
Complication of DM type 2. plasma glucose can be \>600, serum osmolality \>320mOsm/kg
45
What typically has the longer half life, the prohormone or the active molecule?
The prohormone.
46
How do you treat Addisonian crisis/acute adrenal insufficiency?
IV hydrocorticoids.
47
What does LOX catalyze?
Lipoxygenase - catalyzes arachidonic acid to 5-HPETE. Moves from cytoplasm to membranes in a calcium dependent manner. Increased activity associated with asthma, allergies, hyper-immune response.
48
Where is the thyroid derived from embryologically?
The endodermal epithelial cells of the pharynx.
49
How do you tell between primary and secondary hypothyroidism?
Both have low T3/T4. Primary has high TSH, secondary has low TSH.
50
What kind of insulin is given for diabetic ketoacidosis or perioperative management of patients who need insulin?
Regular insulin via IV.
51
What is PGF2alpha involved in?
Uterine contractions, bronchoconstriction.
52
Describe regular insulin given as a drug.
Zn-insulin crystals dissolved in a clear liquid. Associate as hexamers in a neural pH aqueous solution. Has about a 45 min lag time.
53
What are the anterior pituitary cell types?
Chromophils - acidophils (somatotrophs + mammotrophs). Basophils (thyrotrophs, gonadotrophs, corticotrophs). Also chromophobe cells.
54
What are the adverse effects of Dinoprostone?
Vominting, transient fever, diarrhea, nausea, headache, chills, transient diastolic blood pressure increase \>20mmHg, possible uterine hyperstimulation.
55
How do you spread out glucocorticoid replacement therapy? When do you need to increase it?
2/3 in the morning, 1/3 in the evening. Increase during stress, infections, surgery.
56
What is 5 alpha reductase?
Converts testosterone to DHT.
57
What are the signals for glycogen breakdown?
Liver - glucagon or E Muscle - E or exercise
58
What is Propiolthiouracil? What's a possible serious side effect?
A thioamide - inhibits thyroid peroxidase and blocks organification and coupling reactions. Slow onset of action, safer than other thioamides, inhivits peripheral deiodination of T34 -\> T3. Can cause agranulocytosis.
59
How is insulin processed?
Starts as preproenzyme, ER cleaves the amino terminus, golgi cleaves C-peptide (1:1 ratio).
60
What is Addison Disease?
Lack of corticosteroids, most often by autoimmune adrenal cortex destruction.
61
What are the symptoms of Addison disease?
Salt craving, skin darkening from MSH, nausea, vomiting, low BP, syncope/presyncope, muscle and joint pain, women have low libido and hair production, hypoglycemia, GI disturbances, weight loss, weakness, postural hypotension, changes in body hair distribution.
62
Describe the Hypothalamic-pituitary-ovarian axis in women pre-menstruation.
Hypothalamus produces GnRH which stimulates the ant. pituitary gonadotrophs to produce FSH and LH. FSH and LH signal the ovary to produce estradiol, which positively affects the hypothalamus and pituitary. Positive feedback loop!
63
Is most Cushing's exogenous or endogenous?
Exogenous.
64
How much exercises should diabetics get?
150mins per day.
65
What are the types of neurons in the hypothalamus?
Magnicellular (1. contain vasopressin and oxytocin - project axons into post. pituitary for hormone release). Parvicellular (2. neuroendocrine-related functional group - project into median eminence and secrete hormones into portal bloodstream. 3. Involved in central autonomic control.)
66
What is spironolactone?
Aldosterone receptor antagonist / K+ sparing diuretic. Used in treatment of primary hyperaldosteronism, also competes with DHT for androgen receptor, can cause gynecomastia to.
67
What type of receptors if the GH receptor?
A JAK-STAT system.
68
Describe thyroid hormone production.
TSH signals transcription of thyroglobulin, cAMP also signals Na/I symporter to bring Iodide into the cell. Pendrin also brings iodide into the lumen by itself. Thyroperoxidase is synthesized and transfers the charge from iodide, then the iodine is conjugated onto thyroglobulin. MIT+DIT=T3, DIT+DIT=T4. The thyroglobulin is endocytosed and degraded.
69
What does natriuretic peptide inhibit?
Adosterone production.
70
What is the cause of endemic goiter?
Iodine deficiency.
71
How do GH and IGF1 affect the muscle?
Both stimulate protein synthesis, AA uptake. GH inhibits glucose uptake.
72
What is the pars intermedia and what does it produce?
Separates the anterior and posterior pituitary. Has cords of basophilic cells, makes alpha-MSH. \*between the pars intermedia and pars distalis are the occasional fluid filled cyst or follicular structure.
73
What are the glucocorticoid drugs?
Hydrocortisone (cortisol), Prednisone (intermediate-acting), Dexamethasone (long-acting).
74
What are most steroid hormones made from?
Cholesterol.
75
Describe an adrenal adenoma.
Benign tumor of adrenal cortical cells, encapsulated, yellow, usually \<5cm and 50g, may have occasional large bizarre nuclei. Mitoses, neuroses, hemorrhage rare.
76
What do corticosteroids do in regard to PLA2?
inhibit PLA2 - produces eicosanoic acids.
77
What are the primary functions of phosphate in the body?
Skeletal structure, energy metabolism, phospholipid biosynthesis, regulation through protein modification, component of nucleotides, regulation of blood pH, a deficiency results in fatigue and loss of appetite.
78
What are prostamides?
Eicosanoids that are 5 membered rings with C8 linked to C12 attached to an amide.
79
How do GH affect the adipose?
Stimulates lipolysis, inhibits glucose uptake.
80
What is GLUT5 and where is it?
Transports fructose only. SI, sperm. Some also in brain, kidney, adipocytes, muscle.
81
What is Carboprost and how is it administered?
PGE2alpha analog. IM.
82
What are some things that decrease the binding of thyroid hormone to TBG and therefore will cause the person to require a lower dose?
Glucocorticoids, androgens, acute and chronic illness.
83
Describe glycogenolysis.
Glycogen phosphorylase cleaves the glucoses from the non-reducing ends, yielding G1P. The branch point itself is hydrolyzed to glucose by debranching enzyme.
84
What are the criteria and common presentation for diabetes mellitus?
Polydypsia, polyuria, polyphagia. Fasting glucose \>126. Random glucose \>200 HbA1c \>6.5% Symptomatic = 1 normal value only, asymptomatic =2
85
What kind of drug is Epoprostenol and how is it administered?
PGI2 analog. IV in central line.
86
How is calcium moved through the cells?
Enters via TRPV6 channel, binds calbinding in cell. Goes to blood via primary AT or secondary AT Na+/Ca++ exchanger.
87
What are the symptoms of Cushing disease?
Truncal obesity (and moon face) but low fat from extremities, weak CT, striae, insulin-antagonistic effects. Emotional disturbance, enlarged sella tursica, osteroporosis, cardiac hypertrophy, hypertension, buffalo hump, thin and wrinkled skin, amenorrhea, muscle weakness, purpura, skin ulcers (poor wound healing).
88
What is Alprostadil and how is it administered?
PGE1. Administered intraurethrally, intracavernosally, or IV (if trying to keep patent ductus arteriosus open).
89
What's the recommended weight gain for pregnant diabetics?
11.8kg/26lbs total. 0.9-1.8kg / 1-2 lbs in first trimester, no more than 2.2lbs per every two weeks after.
90
What do you find in the bloodwork of someone with CAH?
Elevated 17-OH-progesterone and 17-ketosteroids. Increased adrenal androgens, increased ACTH, decreased corticosteroids.
91
What kinds of drugs are Latanoprost, Travoprost, Tafluprost, and Bimatoprost and how are they administered?
PGE2alpha prodrug analogs. Intraocular.
92
How do epinephrine and norepinephrine affect insulin secretion?
They inhibit GLP-1 (incretin) action, reducing adenylyl cyclase which decreases PKA potentiation of calcium binding to motor exocytosis proteins.
93
What do PGI2 drugs treat? What are the common adverse effects?
Pulmonary arterial hypertension. Adverse effects - headache, flushing, hypotension, nausea, diarrhea, jaw pain. Iloprost can cause cough and bronchoconstriction.
94
What does acetaminophen do?
Inhibits COX1 and COX2 in neural tissues. AM404 (a metabolite) modulates the reuptake of anandamide by neurons and also binds TPVR1.
95
How do you tell between primary and secondary hyperthyroidism?
Both have high T3/T4. Primary has low TSH, secondary has high TSH.
96
What are two major sites of protein degradation?
Kidney and liver.
97
What is the 21-hydroxylase CAH mutation?
Chromosome 6 CYP21 gene.
98
What are chromaffin cells?
Basophilic cells in the adrenal medulla - stain brown with potassium dichromate.
99
What is Hashimoto disease?
Autoimmune thyroiditis - Most common cause of hypothyroidism. Antibodies to thyroperoxidase, thyroglobulin, and/or TSH receptor - there is lymphocytic infiltration. Myxedema due to overproduced GAGs, thickened dry, coarse skin, puffy face, hands, feet, mental sluggishness.
100
What is StAR?
Steroidogenic acute regulator - feeds cholesterol to desmolase.
101
What is AERD?
Aspirin-exacerbated respiratory disease. Sensitivity.
102
What are the adverse effects and contraindications of Latanoprost, Travoprost, Tafluprost, and Bimatoprost?
Irreversible brown pigmentation of iris and layers, drying of eyes, conjunctivitis. Bimatoprost has increased eyelash growth. No known contraindications.
103
What is the action of PTH? How is it regulated?
Prevents low calcium by stimulating kidney 1alphahydroxylase activity - stimulates calcium absorption by thick aLOH and DT. Also enhances calcium absorption form the intestine indirectly through VitD. It also inhibits kidney phosphate resorption and stimulates osteoblast growth and survival. Also involved in RANKL action Low calcium stimulates it directly and indirectly through calcitriol, high calcium induces low cAMP which decreases PTH. PT cells have CaSR which has a GqGi signalling pathway that decreases PTH gene expression and secretion.
104
How is calcitonin given as a drug?
It's salmon calcitonin. Given intranasally.
105
What does GHBP carry?
GH.
106
What is BH4?
Cofactor in many hydroxylases (particularly Tyr and Trp).
107
How are oxytocin and vasopressin matured?
Gly removed in ER. Neurophysin I is monomeric oxytocin transport protein. Neurophysin II dimerizes and carries 2 AHDs. (These are made from preprohormones).
108
What isotope of radioiodine is given for treatment of thyrotoxicosis and which is used to measure iodine uptake for thyroid imaging?
I-131 and I-123.
109
What's the most common pituitary tumor?
Pituitary adenoma.
110
What are the paraventricular and supraoptic nuclei of the hypothalamus responsible for and which hormones does it produce?
Fluid balance regulation, milk letdown, parturition. Paraventricular also does ANS integration and control of anterior pituitary. ADH, Oxytocin. Paraventricular also CRH, TRH.
111
What kind of FAs are eicosatrienoic, arachidonic, eicosapentaenoic acids?
First two are omega-6, last one is omega-3.
112
What are glumepiride and glyburide?
Sulfonylureas - orally active. Bind to and inactivate SUR1 subunit of ATP-sensitive K+ channel and close it. Increases insulin release regardless of glucose levels.
113
What is exenatide?
Incretin memetic. GLP-1 analog - needs glucose before insulin is released. Suppresses glugon secretion, slows gastric emptying, decreases appetite, injectable.
114
What are catecholamines?
E and NorE. Water-soluble amine hormones derived from Tyrosine.
115
What is insulin glargine?
Insulin soluble at pH4 and aggregates in human pH, slowing its release. Peaks much lower and releases slow - is good for a baseline.
116
Describe a partial deficiency of G6P dehydrogenase.
X-linked recessive. Deficiency in RBCs. Hemolytic crisis after exposure to oxidizing drugs, some sulfonamides, antimalarials, fava beans.
117
What's the primary blood glucose source 3-4 hours after fed state ends?
Hepatic glycogenolysis.
118
What is somatropin? Howi is it given?
Recombinant human GH. Given via subcutaneous depot.
119
What is Levothyroxine and how is it given?
T4 - orally (IV in myxedema coma)
120
What is DInoprostone used for?
Uterine contraction at any point in pregnancy (more effective as pregnancy advances) - good to induce labour. Also has direct effects on cervical collagenase, promoting cervical softening. Can also induce abortion, or deal with missed abortion, also benign hydratidiform mole.
121
What are incretins?
GIP/GLP-1, GI secreted hormones whose targets are beta cells - stimulate insulin secretion.
122
What does Carboprost do? What are the contraindications?
Stimulates uterine contractions for 2nd trimester abortion or to treat postpartum bleeding that hasn't responded to anything else. Contraindications are acute PID, active cardiac, pulmonary, renal, hepatic disease.
123
When do you have to increase mineralocorticoid replacement therapy?
Exercise, sweating, diarrhea.
124
What does transcortin carry?
Progestins and glucocorticoids.
125
How do increased amino acids in the blood affect insulin and glucagon secretion?
Increase both!
126
How do you get from cholesterol to progesterone?
Made to pregnolone via desmolase, then 3beta-HSD to Progesterone.
127
What are the effects of galactokinase deficiency?
Elevated galactose in blood glucose, elevated glalactitol.
128
In starvation, how long do carbs, fat, and protein sustain you?
Carbs about 0.5 weeks, fat can last ~5-7 weeks, protein levels gradually drop for those 5 weeks but once the start dropping substantially death is imminent.
129
What does eicospentaenoic acid become through LOX action?
LTB5
130
What inhibits pyruvate kinase?
ATP, Ala, glucagon.
131
What is GLUT2 and where is it?
Transports Glu, Gal, Fru. 'Low affinity, high capacity glucose transporter', glucose 'sensor' in pancreatic beta cells. In pancreatic beta cells, SI kidney.
132
When do people start feeling the symptoms of hypoglycemia?
\<50mg/dL
133
How do you get from progesterone to aldosterone?
21alpha Hydroxylase and 11beta Hydroxylase. Also CYP450.
134
What are the 3 major hormone classes and what is their water solubility?
Amines - hydrophobic or hydrophilic Peptides - usually hydrophilic Steroids - hydrophobic
135
How do GH and IGF1 affect the liver?
GH stimulates protein synthesis, gluconeugenesis, IGF production, secretion. IGF1 has no effect.
136
What does aldosterone do?
Increases apical ENac channels, basal Na+/K+ pumps, apical K+ channels. Increases sodium retention and K+ excretion. Also H+ excretion in kidney.
137
What stimulates and inhibits PEP carboxykinase?
Stimulated by cortisol, inhibited by ADP.
138
What's the adult calcium upper limit?
2.5-3g/day
139
What is mifepristone?
Glucocorticoid receptor antagonist (also progesterone). Used in Cushing's for control of hyperglycemia specifically.
140
How is galactose metabolized?
Converted to Gal1P by galactokinase, then reacts with UDP glucose via galactose 1P uridyl transferase to make G1P and UDP-galactose (which can be turned to UDP-glucose by an epimerase).
141
What are thromboxanes involved in?
Vasoconstriction, increased platelet expression of glycoprotein IIa and IIb (promote clotting).
142
How are steroids hydroxylated? Why is this done?
With NADPH and an H+ and an O2. P450 as a cofactor. It's done because it changes their affinity.
143
What is secondary hyperparathyroidism associated with?
Decrease of kidney function.
144
Describe the venous drainage of the adrenal gland.
Blood from both cortical and medullary veins empty into single large central vein. Right suprarenal vein drains into the IVC. Left suprarenal vein drains into the left renal vein which drains into the IVC.
145
What are the vasopressin receptors?
V1 is Gq, producing smooth muscle contraction. V2 is Gs, causes antidiuresis. It is more sensitive.
146
What are some potential gluconeogenesis precursors?
Lactate, Ala (made straight to pyruvate in liver), Gln (preferred by kidney), glycerol.
147
How is calcitriol synthesized?
Precursor steroid has OH on C3. Liver adds OH on C25 and then kidney adds OH on C1. From the sun you get 7-dehydrocholesterol, which you convert to Pre-D3 and heat turns into D3.
148
What's the primary blood glucose source 1-3 days after fed state ends?
Almost entirely gluconeogenesis, hepatic glycogen is depleted. Ketone body formation from fat begins. Muscle and fat breakdown continues.
149
What are prostacyclins or thromboxanes?
Eicosanoids that are 5 membered rings with C8 linked to C12 with a cyclic peroxide attached to it.
150
What is the major energy source when dietary glucose is depleted?
Fatty acids.
151
How does increased blood glucose affect somatostatin release by pancreatic tissue?
Stimulates.
152
What is the major crystalline salt of bone?
Hydroxyapatite - key components are calcium and phosphate.
153
Are steroids water soluble or lipid soluble?
Lipid.
154
What does PP1 do?
Dephosphorylates phosphorylase kinase (inactivates), glycogen phosphorylase (inactivates), glycogen synthase (activates). Also counteracts glucagon/E signalling by cAMP degradation.
155
What causes CAH?
A deficiency in any of the regulated enzymes from cholesterol to testosterone, or in CYP450, particularly 21-hydroxylase of 11-hydroxylase.
156
What is FGF23 and what stimulates its secretion?
Peptide hormone secreted by osteocytes and osteoblasts a little. Impairs Na+ dependent PO4 transport in both intestinal and renal brush border membrane vesicles. Inhibits calcitriol and PTH production/secretion. PTH and calcitriol stimulate its secretion.
157
What's the primary blood glucose source \>3 days after fed state ends?
Ketone bodies (everything but RBCs use). Gluconeogenesis, muscle and fat breakdown continue.
158
What is PGI2 involved in?
Vasodilation, bronchodilation, inhibits platelet aggregation.
159
What are prostaglandins?
Eicosanoids that are 5 membered rings with C8 linked to C12.
160
Describe hereditary fructose intolerance.
AR aldolase B deficiency. Fructose in blood and urine, F1P accumulates in liver, ATP production affected. Presents at time of weaning, aversion to sweets, hypoglcermia and nausea after eating fructose containing foods, risk of liver damage (fructose tends to accumulate there).
161
What comes from phosphorylating PFK2/FBP2?
Reduces F2,6BP (which stimulates glycolysis).
Gluconeogenesis direction.
162
What does a BH4 deficiency result in?
Decreased levels of catecholamines and serotonin. Also elevated Phe (often misdiagnosed as phenylketonuria).
163
What are eicosanoids?
Cell signaling molecules - unsaturated molecules made from arachidonic acids or other PUFAs or 20 carbons.
164
What is the result of increased use of the polyol pathway?
Reduction in NADPH levels so makes cell more subject to oxidative stress.
165
What inhibits F1,6bisphosphatase?
AMP and F2,6bisphosphate.
166
What are the adverse effects of actreotide?
Abdominal cramps, steatorrhea, diarrhea, malabsorption, gall stones, B12 deficiency, cardiovascular problems - sinus bradycardia (25%), conduction disturbances (10%).
167
Describe thyroid hormone.
Iodinated tyrosine. Largely water insoluble. T3 has 3 iodines, T4 has 4.
168
What is octreotide and how is it given?
A somatostatin analog. 45X more potent than somatostatin in suppressing GH secretion. Given subcutaneously 3x a day and also slow-release depot preparation or IM once monthly.
169
What are leukotrienes?
Eicosanoids with no ring, may have a Cys attached at C6.
170
What are the effects of galactose 1P uridyl transferase deficiency?
Galactosemia in blood and urine, galactose 1P accumulates in cells, P depleted, feeding difficulties/vomiting shortly after birth.
171
Describe the relative secretion rates and plasma concentrations of cortisol and aldosterone.
Cortisol secreted ~100X greater, ~200X greater plasma concentration.
172
What is metacroplamide?
A D2 antagonist targeted to CTZ and gastric emptying. Treats drug-induced hyperproactinemia.
173
How do the catecholamines affect adipose tissue?
Stimulate FA and glycerol release.
174
What are the contraindications of radioiodine?
Pregnancy and lactation.
175
What is octreotide given for?
Acromegaly, suppression of ectopic hormone production, bleeding esophageal varices.
176
What is MCR?
Metabolic clearance rate - the volume of plasma cleared of a hormone per minute.
177
What happens is sorbitol accumulates?
Sorbitol is not membrane permeable so it increases the intracellular osmolarity. Can lead to cataracts, perpipheral neuropathy, retinopathy, nephropathy.
178
What are the symptoms of 5alpha reductase deficiency?
External ambiguous genitalia in males, sometimes virilization at puberty.
179
What are the secondary endocrine glands?
Hypothalamus, pineal glands, right atrium, liver, stomach, kidney, adipose tissue, small intestine.
180
What does eicosatrienoic acid become through LOX action?
LTB3
181
How do Acetylcholine and free fatty acids affect insulin secretion?
They stimulate a Gq pathway in beta cells, increasing calcium release from the ER.
182
Describe insulin release by pancreatic cells.
Glucose enters beta cells by GLUT2 receptors. ATP/NADH levels in the cell rise, closing ATP sensitive K+ channels. Closing of these channels result in the opening of the VG Ca++ channels, Ca++ enters from the ER and binds motor exocytosis proteins.
183
Whati is most thyroid hormone bound to?
TBG.
184
What is the relative amount of glucocorticoid and mineralocorticoids in the blood?
600X more glucocorticoids.
185
What do Latanoprost, Travoprost, Tafluprost, and Bimatoprost treat?
Increased intraocular pressure (by increase aqueous humour outflow from anterior chamber in uveoscleral pathway). Bimatoprost also treats eyelash hypotrichosis.
186
What is the arcuate nucleus of the hypothalamus responsible for and which hormones does it produce?
Controls the anterior pituitary. GHRH, GHIH, GnRH, DA.
187
What types of hormones typically have the shortest half lives?
Small water soluble ones.
188
What kind of drug is Iloprost and how is it administered?
PGI2 analog. Usually inhaled 6-9X/day.
189
What is the EC and IC amount of calcium in the body?
EC is ~1300mg, IC is ~13,000
190
What are the effects of cold, pregnancy, and illness on thyroid hormone?
Elevated in cold and pregnancy (activate TSH, HcG activates TSH), decreased in illness.
191
What is rosigliatazone?
A thiazolidinedione. Selective agonist of PPARgamma - heterodimerizes with RXR receptor and activates insulin-responsive genes. Primary action is in fat but also works in muscle and liver.
192
What is RANKL?
AKA Juxtacrine. PTH and calcitriol stimulate osteoblasts to produce it - it binds RANK on preosteoclasts and matures them.
193
How does Cinacalcet work?
Alters synthesis of CaSR (changes its set point so there's less PTH release). Treats hyperparathyroidism, sometimes parathyroid carcinoma. Watch for hypocalcemia!
194
What is mecasermin?
Recombinant human IGF1. Often given with IGFBP-3. Most important side effect is hypoglycemia.
195
What are the zones of the adrenal gland? Describe them.
Outermost is zona glomerulosa, filled with stem cells (cells in rounded or arched clusters). Zone fasciculata is a broad zone of cels in straight cords 1-2 cells thick, running perpendicular to the surface of the gland. Lightly stained, frothy. Zona reticularis stain deeper, arranged as an anastomosing reticular or net-like cords.
196
Where is somatostatin produced?
Pancreatic delta cells, GI tract, hypothalamus.
197
What is McArdle Syndrome?
Defect in muscle glycogen phosphorylase. Temporary weakness after exercise, chronic and relatively benign.
198
What does arachidonic acid become through LOX action?
LTA4, LTB4, LTC4, LTD4, LTE4, LTF4
199
How does IGF1 respond to high protein and fasting states?
Elevated in high protein, decreased in fasting.
200
Describe an adrenocortical carcinoma.
Malignant tumor of adrenal cortical cells, most \>5cm and 50g. Capsular invasion, venous invasion, mitoses, necroses, diffuse architecture common.
201
What is the pars nervosa?
The posterior pituitary AKA neurohypophysis. Cell bodies are glia, has Herring bodies (eosinophilic) that are secretory. Stains much more. Releases oxytocin and vasopressin.
202
What is NPH insulin?
Insulin with Zn and protamine - the protamine is enzymatically digested to release the insulin. Slower acting.
203
Describe the Hypothalamic-pituitary-liver axis.
Hypothalamus produces GHIH and GHRH - if GHRH wins out, somatotrophs in ant. pituitary secrete GH. GH stimulates liver to secrete IGF1. High IGF1 negatively feedbacks the pituitary. Short-loop feedback: GH stimulates somatostatin, which decreases GnRH and GH.
204
What stimulates and inhibits pyruvate carboxylase?
Stimulated by AcCoA, inhibited by ADP.
205
What are the adverse effects of Carboprost?
Diarrhea, vomiting, nausea (33-67% of patients), CV events, pulmonary edema, endometritis, septic shock, incomplete abortion, uterine rupture, uterine hemorrhage, hypersensitivity reaction, anaphylactic shock.
206
What is the ventromedial nucleus of the hypothalamus responsible for?
Anterior is female sexually dimorphic center, posterior is satiety center.
207
How does ADH work?
At the distal tubule and collecting tubule via Gs and increases aquaporins on the blood side.
208
What is diabetes insipidus?
Can't produce ADH.
209
Describe the Hypothalamic-pituitary-thyroid axis.
Hypothalamus produces TRH which stimulates the thyrotrophs to produce TSH. TSH signals the thyroid to make T3 and T4 which negatively feedback the HP (mostly T3).
210
What is insulin lispro?
Insulin modified so it doesn't aggregate - has a very fast onset of action and is the one used in current pumps.
211
What is conivaptan?
A nonpeptide vasopresin antagonist with high affinity for the V2 receptor. SIADH is an indication.
212
What receptors do the catecholamines target?
E prefers beta but can do both alphas. NorE prefers alphas but can do beta1.
213
What is Propanolol?
A beta blocker. The prototype but no longer the drug of choice. Controls symptoms, may also prevent deiodination of T4.
214
What does arachidonic acid become through COX action?
PGD2, PGE2, PGFalpha2, PG!2, TxA2
215
What are the two 'hormone-like' classes?
Prostanoids and gases.
216
What is made from propiomelanocortin?
gamma-MSH. ACTH (makes alpha-MSH and CLIP). beta-lipoprotein (makes gamma-lipoprotein and beta-endorphin (makes beta-MSH and met-enkephalin)).
217
What is the exchange food system?
A list showing which foods can be switched to have the same amount of carbs (used for diabetics).
218
What are the adverse reactions of somatropin?
Increased intracranial tension/headache, scoliosis, diabetes mellitus.
219
What does transthyretin carry?
Thyroxine.
220
What is PGE2 involved in?
Softens cervix, termination, keeps ductus arteriosus open, dilation of BVs, decrease gastric secretion, GI tract SM relaxation (Gs) or constriction (Gi or Gq), lipolysis inhibition, increased neurotransmitters, increased platelet expression of glycoprotein IIa/IIb, promote clotting, increases atherothrombosis, hyperalgesia, pyrogenic.
221
Describe hypothalamo-hypophyseal portal circulation.
Axon terminals go to capillary loops at the external zone of the medial eminence, then blood goes to the long portal vessels which branch again into another capillary bed. \*there are also short portal vessels.
222
What are the primary endocrine glands?
Thyroid, parathyroids, pituitary, thymic gland, adrenal glands, pancreas, gonads.
223
Describe glycogenesis.
G6P made into G1P with phosphoglucomutase, then to UDP glucose. Glycogenin adds 2 glucoses onto Tyrs through UDP-glucoses via glycogen synthase. Branching enzyme makes the alpha1-\>6 branches.
224
How do you get from progesterone to cortisol and testosterone/androgens?
17alpha Hydroxylase and CYP450 takes it to 17 OH progesterone. 17-20 lyase takes it to androstenedione and then 17betaHSD takes it totestosterone. / 21alpha Hydroxylase takes it to deoxycortisone and 11beta Hydroxylase (+CYP450) takes it to cortisol.
225
What is bromocriptine?
A dopamine analog - D1 and D2 agonist, prototype drug. Adverse GI effects, D2 activates CTZ.
226
What are the main effects of thyroid hormone?
Increases BMR, necessary for brain development, stimulates mitochondrial production and increases Na+/K+ pumps. Important for stimulation of skeletal growth, maintenance of fertility.
227
How do iodides treat hyperthyroidism?
Therapeutic effects primarily due to increase of extracellular iodide - inhibits hormone release and organification, devreases size and vascularity of hyperplastic gland. Has a transient effect - good for thyroid storm and surgical prep, contraindicated in pregnancy. May delay ability to use radioactive iodide.
228
What are the regulated steps of gluconeogenesis?
Pyruvate to OAA via pyruvate carboxylase (needs B7 and ATP) - done in mitoch. Then PEP carboxykinase - in cytosol, uses GTP. F1,6BP to F6P by F1,6bisphosphatase. G6P to glucose by G6phosphatase.
229
What is Graves' disease?
Toxic diffuse goiter - IgG antibody to TSH receptor so hyperthyroidism. Colloid depletion and papillary proliferation of follicular epithelium. Ophthalmopathy with exophthalmos.
230
What are 'free' foods in regards to diabetes?
Foods with \<5g of carbs.
231
What is short-loop feedback?
Anterior pituitary is the one that produces the negative feedback signal.
232
What is the difference between primary and secondary adrenal insufficiency?
Primary has high plasma ACTH, secondary has low ACTH and high CRH.
233
Where is dehydroepiandrosterone produced?
ZR and ZF from adrenal gland.
234
How do you convert T4 to T3 and T4 to reverse T3?
DIO1/2 DIO3
235
What is the suprachiasmatic nucleus of the hypothalamus responsible for?
Sleep cycle regulation.
236
What does eicospentaenoic acid become through COX action?
PGE3, PGI3
237
What is adaptation?
It lets cells respond to changes in hormone levels by up or downregulating the receptor number.
238
When do you get ectopic calcification?
When the calcium/phosphate solubility product exceeds the critical solubility solubility product.
239
What is the goal of diabetes treatment? What measurements do you want to have?
Want to keep glucose between 80-140mg/dL, HbA1c between 4.4 and 6.5%, LDL \< 100mg/dL, HDL \> 40mg/dL, TGs \>150mg/dL.
240
What is acarbose?
Alpha-glucosidase inhibitor.Inhibits starch and oligosaccharide breakdown to monosaccharides. Slows absorption of carbs, blunts postprandial rise in plasma glucose. Relatively small effect on glucose levels, has GI side effects.
241
What is Pompe disease?
Defect in lysosomal alpha 1-\>4 glucosidase. Glycogen accumulates in the lysosomal vacuoles leading to cardiomegaly and heart failure.
242
What is the difference between type 1 and 2 diabetes mellitus?
Type 1 - B cell destruction (lymphocyte infiltration). Type 2 - Peripheral insulin resistance, amyloid accumulation.
243
What is GLUT1 and where is it?
Transports glucose with high affinity, and also galactose. In many cells (brain, RBCs, endothelial cells, fetal tissues).
244
What is calcitriol? How does its receptor work?
A steroid hormone - action is slow to start and slow to stop. It is not in the normal range of regulation! It's primary effect is to increase intestinal calcium and phosphate reabsorption. It also increases kidney calcium and phosphate reabsorption. In emergencies , it can stimulate bone breakdown - regulates calcium only in extreme conditions, can cause hypercalcemia. It's the ligand for the VitD receptor - which heterodimerizes with RXR.
245
What is PGD2 involved in?
Asthma development, cytokine signalling for Th2, eosinophils, basophils.
246
What is the difference between adrenal cortical and medullary arteries/arterioles?
Cortical ones branch into capillary beds within the cortex then turn into veins at the cortico-medullary junction. Medullary ones penetrate the cortex without branching, then form capillary beds in the medulla.
247
Describe the PPP/HMP.
G6P to G6glyconate via G6P dehydrogenase - makes NADPH. (Committed step). G6P glyconate made into Ribulose-5-P, makes NADPH and CO2.
248
What is ketaconazole?
Treatment for Cushing's - inhibitor of steroid synthesis! Can cause some feminization symptoms in males (gynecomastia).
249
Why do type I diabetic patients tend to have low muscle mass?
Because they use their AAs for gluconeogenesis instead of muscle building.
250
How do you treat thyroid storm?
Beta blockers - them thioamides, iodides, glucocorticoids (release T4 -\> T3).
251
What does PTHrP do?
Plays a role in lactation and may be important in fetal development. Also stimulates calcitriol production.
252
What kind of receptor is the thyroid receptor?
A transcription factor. CoR is displaced, CoA is recruited. \*yeah, I know! Even though its not a steroid hormone!
253
How does insulin activate glycogen synthase?
Activates PP1 which dephosphorylates and activates it. Activates PKB/Akt which phosphorylates GSK (inactivates) so it can't phosphorylate glycogen synthase.
254
What can the liver do with G6P?
Store it as glycogen or convert it to glucose.
255
What is the lateral complex nucleus of the hypothalamus responsible for?
It's the feeding center - lesion results in starvation.
256
What kind of receptors is the insulin receptor?
Tyrosine kinase.
257
How does cold stress affect thyroid hormone?
Stimulates NE neurons which stimulate TRH neurons.
258
What is desmopressin? How is it administered?
Synthetic vasopressin selective for the V2 receptor. Orally (\<1% bioavailability), intranasally (3-4% bioavailablility), parenterally.
259
What is the preoptic area of the hypothalamus responsible for and which hormones does it produce?
Controls ovulation and sexual behaviour. ADH, oxytocin, GnRH.
260
What are the transporters in skeletal muscle, cardiac muscle, and adipose that bring in glucose?
GLUT1 basally, GLUT4 in response to insulin.
261
Describe the polyol pathway.
Glucose to Sorbitol via aldolase reductase (NADPH used), Sorbitol to Fructose via sortibol dehydrogenase (NADH made).
262
What is GLUT3 and where is it?
Glucose with high affinity, also galactose. Brain, placenta, tissues.
263
Describe the major routes for phosphate absorption and secretion.
~1000mg taken in in diet, SI absorbs ~650, excretes 350/ Kidney excretes about 650mg. Bone takes in and gives off about the same amount ~250mg.
264
What are some things that increase the binding of thyroid hormone to TBG and therefore will cause the person to require a higher dose?
Estrogen, pregnancy, liver disease, HIV.
265
What is the blood supply of the thyroid?
Superior thyroid artery from external carotid, inferior from subclavian.
266
How is a ductus arteriosus kept open in vivo and through drugs?
In vivo via PGE2, with drugs through alprostagil (PGE1).
267
What are the effects of glucocorticoids in regards to immune function?
Repress COX2 and stimulate annexin1 (suppresses PLA2).
268
What is Andersen Disease?
Glycogen branching enzyme deficiency. Liver version rare, found in infancy. Muscle version varies in severity.
269
What is Cushing Disease?
Excess glucocorticoids (often ACTH secreting tumor in pituitary).
270
How is glucokinase regulated?
Fasting, GKRP keeps it inactive in the nucleus. With glucose or F1P it is released and goes to the cytoplasm. AMP activates glucokinase (phosphorylates GKRP). F6P inhibits GK - promotes binding to GKRP.
271
What are he causes of hyperaldosteronism?
60% idiopathic (associated with bilateral nodular adrenal hyperplasia), 35% adrenal cortical tumor - mostly adenomas (Conn syndrome). Rarely it's glucocorticoid-remediable (mutation causes aldosterone production from ACTH stimulation).
272
What is MCT8?
Brings thyroid hormone into the cell from the interstitium. (once it's free)
273
What is the pars distalis?
The anterior pituitary AKA the adenohypophysis.
274
What's different in COX2 in the nervous system?
Made in the response to cytokines - not inflammation/injuries/infection like in other tissues.
275
What are some dietary changes that should be undertaken for diabetics?
Increase regularity of eating, reduce consumption of foods that raise blood sugar quickly, reduce alcohol consumption. Reduce sodium intake to 2300 mg/day, 1500 if hypertension present, reduce fats that lead to high atherosclerosis and elevated LDL and cholesterol.
276
What is liraglutide?
Incretin memetic. GLP-1 agonist/analog - needs glucose before insulin released. A slower release, can be injected once a day or week.
277
What are some macro and microvascular complications of diabetes mellitus?
Macro - atherosclerosis early and severely. Micro - accumulation of advanced glycation end products (AGEs) in capillary BM. Is thick - nephropathy, retinophathy, peripheral neuropathy.
278
What is a 'hot nodule'?
A thyroid adenoma that is full of extra iodine.
279
How is prolactin controlled?
Mammotrophs under tonic inhibition by hypothalamic dopamine.
280
What kind of hormones are insulin, GH, vasopressin?
Protein/peptide derived.
281
Where in the adrenal gland are mineralocorticoids, glucocorticoids, sex steroids synthesized?
Aldosterone (mineralocorticoids) in ZG, cortisol (glucocorticoids) in ZF. Sex steroids in ZR.
282
What is the effect of ethanol on glucose metabolism?
Creates high NADH - converts pyruvate to lactate, converts OAA to malate.
283
Which glucose receptor are insulin dependent and where is it found?
Only GLUT-4. Found in skeletal and cardiac muscle, also adipocytes.
284
What besides corticosteroids an make arachidonic acid?
DAG lipase.
285
Where besides the pituitary is prolactin synthesized?
The CNS, immune system, uterus, mammary glands.
286
What are the Kms of GLUT1-4?
GLUT2 - 20 GLUT1/4 - 5 GLUT3 - 1.6
287
What's the primary blood glucose source 4-24 hours after fed state ends? What else is going on?
Hepatic gluconeogenesis. Muscle begins to provide alanine for gluconeogenesis, cortisol starts to be involved. Adipose starts to break down triglycerides.
288
What are leukotrienes involved in?
Paracrine and autocrine signaling in immune response, secretion accompanied by histamine and prostaglandin secretion.
289
What specifically does ACTH trigger?
Cellular proliferation, hormone production and release from ZF and ZR.
290
Describe the Hypothalamic-pituitary-adrenal axis.
Hypothalamus produces CRH which stimulates the ant. pituitary corticotrophs to make ACTH. ACTH signals the adrenal gland to produce cortisol which negatively inhibits the hypothalamus and pituitary.
291
What is Misoprostol and how is it administered?
A PGE1 analog. Administered orally but can also be intravaginally.
292
What kind of drug is Treprostinil and how is it administered?
PGI2 analog. IV or subq.
293
What is fludrocortisone?
A mineralocorticoid replacement drug.
294
What kind of hormone are catecholamines, serotonin, thyroxine, triiodothyroxine?
AA derived.
295
What is SGLT1 and where is it?
Transports 1 glucose or galactose with 2 sodiums. In intestinal mucosa and kidney tubules.
