FINAL Flashcards

Question

NSAID action on inflammatory pathway

Answer 1

block cox 2 ezyme ➞ inhibit prostanoids - EETs & HETEs still synthesized - minimize inflammatory response - other inflammation pathways are still active

Answer 2

**decreased pro-inflammatory mols:** prostaglandins & cytokines **decreased cell-mediated immune response**: ↓ vascular permeability, mast cell #s, & antigen-presenting cell #s

Answer 3

**↓ differentiation of antigen-fighting cells** 1. inhibits T & B lymphocytes in circulation 2. inhibits synthesis of immunoglobulins **stimulates lymphocyte apoptosis** ➔ removes antigen-fighting cells from circulation

Answer 4

tyrosine ➔ dopamine (dopamine β-hydroxylase - DBH) ➔ NE (PNMT) ➔ EPI

Answer 5

* synthesized from NE * precursor mol: tyrosine * **produced exclusively by adrenal medulla cells** (main product ~80%) * NE present in CNS, adrenal medulla, & sympathetic neurons

Answer 6

1. lipolysis 2. stimulates glycogenolysis 3. stimulates gluconeogenesis 4. ↑HR & SV 5. peripheral vasoconstriction ➞ blood redirected where it's needed 6. ↑BP 7. dilation of coronary arteries & muscles (↑ perfusion)

Answer 7

1. stimulates HSL enzyme to ↑ lipolysis 2. stimulates glycogen phosphorylase to break down glycogen 3. inhibits glycogen synthesis * 2 & 3 oppose cortisol: EPI is breaking glycogen that cortisol is making

Answer 8

* NE fxs primarily as a neurotransmitter for cardiac effects * both NE & EPI influence vascular tone * EPI affects metabolic processes (e.g carbohydrate metabolism) * ↑ RR * ↑ bf to skeletal muscles * intestinal muscles relax * pupils dilate * ↑BP * ↑BG * ↑HR

Answer 9

β2-adrenergic receptor

Answer 10

⍺2-adrenergic

Answer 11

- ↑ HR & inotropy (β1) - systemic vasoconstriction (⍺1) - muscle & liver vasculatures: - vasodilation at low concentrations (β2) - vasoconstriction at high concentrations (⍺1) - @ low-to-moderate circulating [EPI]: ↑ CO w/ only a small change in MAP b/c systemic vascular resistance falls due to β2-adrenoceptor activation - @ ↑ plasma [EPI]: MAP ↑ b/c of binding to ⍺-adrenoreceptors on bv that offsets β2-adrenoceptor vasodilation

Answer 12

* **catecholamine-secreting tumors from chromaffin cells of adrenal medulla** * relatively rare: ≤0.5% of hypertensive patients * secrete mainly **NE** - episodes of ↑ catecholamine secretion cause **hypertension, palpitation, headache, & sweating**

Answer 13

* mineralocorticoid * synthesized in zona glomerulosa * steroidogenesis pathway: cholesterol (cholesterol desmolase) ➔ pregnenolone (3β-HSD) ➔ progesterone (21⍺-hydroxylase) ➔ 11-deoxycorticosterone (P450c11/11β-hydroxylase) ➔ corticosterone (p450aldo/adosterone synthase) ➔ aldosterone * NO p450c17 (17⍺hydroxylase or 17,20-lyase) * NO 17β-HSD

Answer 14

proximal tutbule & loop of Henle via countercurrent system (~94%) * not under endocrine control * remaining Na will be reabsorbed in the principle cells of the collecting duct in response to aldosterone

Answer 15

* stimulates Na reabsorption in principal cell of collecting duct * facilitates **transcription of Na/K ATPase** pumps in basolateral membrane * stimulates **Sgk1 to inactivate Nedd4-2 channels** → cannot destroy ENaC (Na channels) ∴ Na can re-enter cell via apical membrane * ↑ BP by ↑ ECF volume * ↑ urine excretion of K ➞ stimulates **expression of K channels** in apical membrane

Answer 16

enzyme produced in juxtaglomerular cells on afferent arteriole that converts angiotensinogen ➔ angiotensin I - pathway to ↑BP, ↑[Na], ↑ECF V - control of renin release: 1. baroreceptors in JGC detect renal perfusion pressure 2. macula densa cell chemoreceptors detect levels of Na & Cl in filtrate & communicate with adjacent JGC cells to release renin at low [NaCl] - factors that stimulate renin release: 1. ↓BP 2. ↓[Na]

Answer 17

* aldosterone facilitates K removal from ECF * ↑ K stimulates aldosterone synthesis (hyperkalemia) * depolarization of zona glomerulosa cell membrane opens Ca v-gated channels ➞ ↑ in intracellular Ca stimulates expression of P450aldo/aldosterone synthase

Answer 18

* stimulated by: * K * angiotensin II * ACTH (minimal) * inhibited by: atrial natriuretic peptide (ANP) ➔ involved in diuresis

Answer 19

1. macula densa cells in distal tubule detect ↓ [NaCl] & JGC detect ↓BP in afferent arteriole ➔ JGC release renin 2. renin converts angiotensinogen ➔ angiotensin I (precursor) 3. ACE (angiotensin converting enzyme) produced mainly in lungs converts angiotensin I ➔ angiotensin II (potent vasopressor) 4. angiotensin II stimulates: 1. SNS ➔ release catecholamines from adrenal medulla to stimulate vasoconstriction 2. transcription of P450aldo ➔ ↑ aldosterone: reabsorption of Na & Cl in kidney to retain water 3. vasoconstriction ➔ ↑ BP & ↑ renal bf 4. AVP secretion in neurohypophysis ➔ ↑ water reabsorption 5. normal perfusion removes stimulus & acts as ⊖ feedback

Answer 20

maintain normal ECF V & BP 1. ↑ transcription of P450aldo ➞ ↑ aldosterone production 2. vasoconstriction ➞ ↑BP ➞ ↑renal bf 3. release of EPI & NE from adrenal medulla 4. promote release of AVP ➞ water reabsorption in kidneys

Answer 21

* atrial natriuretic peptide secreted by atrial myocytes in response to volume expansion 1. vasodilation 2. hyperfiltration: ↑ GFR 3. natriuresis (Na excretion): inhibits Na & water reabsorption in principal cells of collecting duct 4. **inhibits secretion of renin, aldosterone, AVP, & ACTH**

Answer 22

* primary overproduction of aldosterone with low renin * Conn's syndrome * ↑BP from ↑ retention of NaCl & H2O by kidneys + ↓ serum [K] (hypokalemia) from excess K secretion in urine * causes: - benign adrenal tumor (adenoma) - hyperplasia of 1 or both adrenal glands (idiopathic: unknown cause)

Answer 23

1. **↑ K channels in apical membrane** to excrete more K 2. **↑ Na/K ATPase pumps in basolateral membrane** to pump Na out of cell into blood & K into cell (out of blood) where it can move through channels in apical membrane to be excreted in urine 3. **↑ expression of Sgk1** to inactivate destruction complex for Na channels to keep them in membrane * **ENaC** = epithelial Na channel ➔ brings Na back from lumen into cell * **ubiquitin** = system cells use to recycle mol ➔ tags cells & targets for destruction * **Nedd4-2** = ubiquitin protein that targets & destroys Na channels * **Sgk1** (serum-and-glucocorticoid kinase) phosphorylates Nedd4-2 ➔ inactivates them * aldosterone stimulates Sgk1 ➔ Nedd4-2 cannot destroy ENaC

Answer 24

enzyme that converts cortisol ➔ cortisone (inactive form) * cortisol has good affinity for mineralocorticoid receptor & because plasma [cortisol] > than [aldosterone] cortisol would occupy all MCR * aldosterone ≠ substrate for 11β-HSD

Answer 25

synthesized in ER of thyrocyte & packaged into exocytosis vesicles that fuse w/ apical membrane releasing contents into colloid * contains tyrosyl residues that can be iodinated - stimulated by TSH

Answer 26

reverse T3 = inactive form * control mechanism for TH level regulation * no 5 iodine

Answer 27

* Gq ⍺ subunit GPCR * Ca & PKC involved in activation of transcription of TSH gene * TRH also promotes glycosylation of TSH gene making TSH biologically active

Answer 28

1. iodine uptake via NIS 2. Tg synthesis 3. Tg iodination 4. deposition of Tg in colloid 5. colloid uptake into follicular cells (thyrocytes) 6. proteolysis of Tg (T3/T4 production) 7. immediate release of T3/T4 from colloid storage 8. follicular cell metabolism & cell growth

Answer 29

activated PKA stimulates: 1. **hypertrophy of thyroid cells** 2. activation of iodine pumps (**NIS**) 3. Tg exocytosis 4. TPO activity 5. induces pseudopods to ↑ Tg reabsorption at colloid border 6. lysosome-mediated **proteolysis of Tg**

Answer 30

expression of (synthesis via transcription): * Tg * thyroid peroxidase (TPO)

Answer 31

Na/I symporter = pump that actively transports I (& Na) into thyrocyte across the thyrocyte **basolateral membrane** * activated by binding TSH to its receptor * disorders of NIS associated w/ **hypothyroidism** * inactivating mutation of the NIS gene: **congenital hypothyroidism** * autoimmune disease = antibiodies against NIS: **acquired hypothyroidism**

Answer 32

inactivating mutation of the NIS gene

Answer 33

autoimmune disease where the body produces antibodies against NIS

Answer 34

1. oxidation of iodine 2. iodination (organification) of thyroglobulin 3. coupling of MIT & DIT to form T3 & T4

Answer 35

T3 & T4 made of iodinated Tg 1. iodine is oxidized by TPO activity 2. tyrosine residues on Tg are iodinated (iodination/organification) 3. **iodination** of tyrosines yields MIT & DIT: adding iodines 4. **coupling** = binding of MIT & DITs (catalyzed by TPO) to get T3 & T4 5. **pendrin channels** in apical membrane transport I into colloid (not TSH-dependent − always there on a [gradient])

Answer 36

transported via plasma carriers: **thyroid-binding globulin (TBG)**, **albumin**, **transthyretin** 1. occupy space on TH ∴ only free portion of TH not bound to carrier is available to enter target cell & become metabolically active 2. extend TH half-life by protecting from degradation 3. maintain large circulating pool of TH

Answer 37

* thyroid gland can modify its activity **independent** of TSH to adapt to changes in iodine availability * in response to **iodine deficiency**: * ↑ iodine transport efficiency * T3 preferentially synthesized over T4 * in response to **iodine excess**: inhibit NIS i.e. **Wolff-Chaikoff effect** aka **iodide block**)

Answer 38

1. **monocarboxylate transporter (MCT8)** = highly specific transporter ➞ carries TH across PM 2. **binding of T3 dislocates co-repressors & activates co-activators** (or vica-versa) - **co-regulator proteins** = co-activators (CoA) & co-repressors (CoR) - CoR bind to TR inactivating it - T3-binding exchanges CoR with CoA - sometimes TR has a CoA bound already & is actively transcribing ➞ T3 binding changes CoA ➔ CoR so binding represses gene transcription 3. modulation of gene expression in target cells

Answer 39

* THRs binding to DNA is **independent** of hormone binding * THRs bind to DNA as: * **homodimers**: combination of TR isoforms (⍺, β) * **heterodimers**: associated w/ other nuclear receptors − most commonly retinoid X receptor (RXR)

Answer 40

1. hormone synthesis can autoregulate depending on iodine availability 2. T4 converted to T3 on demand 3. multiple carrier proteins ensure that TH is stable in circulation: **thyroid-binding globulin (TBG), transthyretin, albumin** 4. **deiodinases** are present in a variety of tissues

Answer 41

synergistic response with cortisol: * maintaining/↑ levels of glucose * stopping immune system in response to stressor

Answer 42

**hyperadrenocorticism** - **excess circulating cortisol or glucocorticoids** - **ACTH-independent**: ↑ cortisol but not from adrenal gland being overstimulated - most commonly iatrogenic: induced by tx given to animals by humans - **ACTH-dependent**: pituitary or non-pituitary tumors secreting ACTH or CRH ➔ **Cushing's disease** -

Answer 43

excess circulating cortisol or glucocorticoids from tumors **ACTH-dependent hyperadrenocorticism** - **pituitary-dependent:** pituitary tumor producing ACTH ➔ hyperstimulation of adrenal gland - ectopic ACTH expression by nonpituitary tumor cells: POMC precursor incorrectly cleaved to release ACTH - bilateral hyperplasia of zona fasciculata & zona reticularis **ACTH-independent hyperadrenocorticism** from adrenal tumor secreting excess cortisol/glucocorticoids

Answer 44

- **atrophy of epidermis & connective tissue** ➞ skin thinning & alopecia - **centripetal obesity**: visceral fat accumulation ➞ pendulous abdomen - dehydration - osteoporosis - muscle weakness - **polyphagia**: feeling of extreme insatiable hunger - **exophthalmos**: bulging eyes - bruising & poor healing - pruritus: itching - acne - hyperpigmentation

Answer 45

**hypoadrenocorticism**: - associated w/ mineralocorticoid deficiency - primary hypoadrenocorticism = **glucocorticoid deficiency at adrenal level** - **congenital adrenal hyperplasia** = deficiency of enzyme P450c21 → not producing enough GC - causes: - autoimmune - infectious - congenital - iatrogenic - symptom: hyperpigmentation

Answer 46

activates T3 (converrs T4 ➞ T3) - D1: - kidney, liver, skeletal muscle (& small amount in the thyroid gland) - most abundant - in PM of cells ➞ ensures adequate circulating levels of T3 - D2: - brain & pituitary gland - in ER close to nucleus - ensures adequate cellular levels of T3 w/in CNS - sensitive to Δ circulating levels of T4

Answer 47

removes the I at position 5 to convert it into rT3 & inactivate it - highly expressed in fetal tissues, placenta, CNS - inactivates T4 by conversion to rT3 - inactivates T3 by conversion to T2 - ↑ in hyperthyroidism - ↓ in hypothyroidism

Answer 48

- roles in terminal differentiation of brain cells & neural development (mediated by TR⍺) - **congenital hypothyroidism** = genetic/iodine deficiency: impairs terminal differentiation process ➔ severe mental & growth retardation (cretinism) - development of the auditory system: human TH resistance syndrome (Refetoff syndrome) = mutation in TRβ ➔ deafness - development of sensory systems (auditory, visual) - neurogenesis - neural transmission (myelin sheath formation)

Answer 49

1. stimulates protein expression & turnover 2. ↑ metabolism secondary to thermogenesis (↑ basal body temp) 3. stimulate expression of β-adrenergic receptors & ↑ adrenergic activity 4. ↑ BMR accompanied by ↑ energy expenditure & ↑ need for O2 in tissues to support ↑ activity

Answer 50

1. enhances O2 absorption by resp system 2. ↑ expression of erythropoietin to enhance RBC production 3. enhances β-adrenergic receptor-mediated effects in the heart (inotropic & chronotropic effects)

Answer 51

1. ↑ GI motility tract 2. ↑ GI absorption efficiency 3. stimulate lipolysis 4. ↑ appetite ➔ stimulate CNS satiety/hunger centers - full signamls in POMC neurons in Arc use ⍺MSH to signal PVN to secrete TRH & begin TH cascade - insulin & leptin inform brain that body has enough nutrients to ↑ metabolic rate

Answer 52

**non-shivering thermogenesis** by UCP1 (uncoupling proteins) in mitochondria of brown adipose tissue - located in inner mitochondrial membrane - redirect H+ flow from the ATPase ➞ dissipates energy in the form of heat instead of ATP

Answer 53

autoimmune hypothyroidism: body produces antibiodies against TPO, Tg, & TSHR * progressive destruction of the thyroid gland * symptoms: fatigue, weight gain, joint/muscle pain, feeling cold, bradycardia, slow metabolism * may present w/ goiter

Answer 54

**continuous activation of TSHR by antibodies** - autoimmune hyperthyroidism - LATS: long-acting thyroid stimulating antibody - symptoms consistent with hyperthyroidism: insomnia, weight loss, heat intolerance, tachycardia, exopthalmos - commonly presents with goiter

Answer 55

* iodination occurs at apical colloid border * iodination of the tyrosyl residues (iodotorosines) forms monoiodotyrosine (MIT) & diiodotyrosine (DIT) * these are coupled to form T3/T4 * iodide must be oxidized by TPO to be able to iodinate tyrosine residues

Answer 56

- kidney, liver, skeletal muscle (& small amount in the thyroid gland) - converts T4 to T3 - most abundant - in PM of cells ➞ ensures adequate circulating levels of T3

Answer 57

- brain & pituitary gland - in ER close to nucleus - ensures adequate cellular levels of T3 w/in CNS - very sensitive to changing circulating levels of T4 - low levels of T4 ↑ [5'-deiodinase] - high levels of T4 ↓ [5'-deiodinase]

Answer 58

**↑** 1. PEPCK, myostatin, lipase 2. circulating AA 3. BG (↑ 50%) **↓** 1. body weight (visceral fat accumulation) 2. muscle mass 3. endogenous cortisol

Answer 59

brattleboro rat has a genetic mutation in neurophysin II ➔ cannot fold AVP protein properly ∴ cannot synthesize AVP (neurogenic)

FINAL Flashcards

(83 cards)