Human Phys Exam III

Know this anatomy, label all parts

Know this anatomy, valves of the heart

Know this anatomy, conduction system of the heart

Know this anatomy, basic scheme of the lymphatic system

Exocrine

secretion outside the body (e.g. sweat glands)

Endocrine

secretion into the blood, acting on distant tissues

Paracrine

secretion acting on nearby cells

Autocrine

secretion acting on same cell

glands

Exocrine and Endocrine Cells that secrete chemicals

examples of endocrine glands

feedback loop

How to prove that abnormal loss of a hormone causes a disease?

Connect the circulatory systems of a normal and diseased individual.

How to tell if the diseased person have no hormone receptors

Shared circulation -> no effect on disease

ob/ob mutation

extra stop codon terminates leptin transcript. –> hypoleptinemia

db/db mutation

extra stop codon terminates leptin receptor –> **functional** hypoleptinemia

leptin feedback loop

Hypothalamus tells rat to eat, the fat cells secrete leptin to stop the hypothalamus from telling the rat to eat

ob/ob mutants look identical to db/db mice

**both** over eat, are obese, become diabetic

Parabiotic experiments

shared blood supply

What would happen if db/db blood mixes with ob/ob

db/db blood makes ob/ob anorexic

hypoleptinemia

no leptin hormone, so can’t produce negative feedback signal and keeps putting on fat

functional hypoleptinemia

no leptin receptors, so can’t detect negative feedback signal, and keeps putting on fat

anx mutant parabiotic experiments

Nuclear Receptor Hormones

(Steroids, Thyroid Hormone, & Retinoic acid = lipophilic hormones)

Can pass through membranes and skin due to being lipophilic and can **diffuse** across membrane and bind to receptors **inside** the cell. (can be bounded to carrier proteins in the blood to help move around).

Not easily contained in vesicles. Synthesized from lipid-soluble store by enzymes (so no gene for these hormones, although there are genes for synthesizing enzymes and for their receptors).

Receptors bind to specific sequences (response elements) in gene promoters. Because the nuclear receptors bind to DNA, their effects are necessarily genomic (e.g. not directly on ion channels or second messengers); i.e., they induce protein synthesis.

Tamoxifen

displaces estrogen, inactivates receptor

Polypeptide and Glycoprotein Hormones (Second-Messenger Coupled Hormones)

packaged in vesicles and secreted by endocytosis

Coded for by genes; processed in endoplasmic reticulum & Golgi apparatus; packaged in vesicles and secreted by endocytosis.

Hydrophilic molecules so soluble in blood; circulate and act on plasma membrane receptors (on the surface of the cell) to induce second messenger signaling in the target cells

3 Common Hormone Receptor Signaling Pathways

1\. GPCR linked to cAMP

2\. GPCR linked to phospholipase C and Ca++

3\. Tyrosine Kinase Receptors

GPCP linked to cAMP

1\.Hormone binds to receptor on target cell’s plasma membrane

2\. Hormone-receptor interaction acts by G-proteins to stimulate adenylate cyclase on the cytoplasmic side of the membrane

3\. Activated adenylate cyclase catalyzes conversion of ATP to cyclic AMP (cAMP) in the cytoplasm

4\. Cyclic AMP activates protein kinase enzymes in the cytoplasm

5\. Activated cAMP-dependent protein kinase phosphorylates (transfers phosphate groups) to **activate/inhibit** other enzymes in the cell.

6. Enzyme activity mediates the target cell’s response to the hormone.

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Intracellular Ca++ as a Second Messenger

1\. Hormone binds to receptor on target cell’s plasma membrane

2. Hormone-receptor interaction acts by G-proteins to stimulate phospholipase C enzyme in the membrane

3\. Activated phospholipase C catalyzes the conversion of phospholipids in the membrane to inositol triphosphate (IP3) and diacylglycerol (DAG).

4. IP3 enters the cytoplasm and diffuses to the endoplasmic reticulum, binds to IP3 receptors, and causes Ca++ channels to open

5\. Endoplasmic reticulum has high \[Ca++\]; Ca++ rushes out of endoplasmic reticulum unto cytoplasm.

6. Ca++ in the cytoplasm binds to calmodulin protein.

7. Activated calmodulin activates protein kinases, which phosphorylate (transfers phosphate groups) to activate/inhibit other enzymes in the cell.

8. Enzyme activity mediates the target cell’s response to the hormone.

Tyrosine Receptor Kinases

1\. Hormone binds to receptor on target cell’s plasma membrane


2. Receptors dimerize (form pairs)
3. Receptors phosphorylate each other (the receptors themselves are kinases)


4. Activated receptors phosphorylate target proteins (“tyrosine kinases” because add phosphate groups to tyrosine residues in target proteins)
5. 5. Phosphorylated proteins activate/inhibit other pathways in the cell.
6. 6. Enzyme activity mediates the target cell’s response to the hormone.

Anterior Lobe of pituitary gland

contains endocrine cells that secrete tropic hormones into the circulation that stimulate target organs in the body.

Posterior Lobe of pituitary gland

contains axon terminals of ADH and oxytocin neurons that originate in the hypothalamus; releases ADH (water retention) and oxytocin (uterine contractions, milk release) into the blood stream

Where is ADH and oxytocin created?

Antidiuretic Hormone & Oxytocin synthesized in hypothalamus

anterior pituitary gland

Transection of infundibulum

decrease of all pituitary hormones except prolactin increases.

releasing hormone

hypothalamus→ pituitary gland

tropic hormone

pituitary gland → target gland

examples of Hypothalamic Pituitary Axes

Immediate Endocrine Response to Stress

Long-Term Response to Stress

Enhanced Stress Response

Depressed women with Posttraumatic Stress Disorder (childhood abuse) show enhanced cortisol release in response to social stress.

If cortisol synthesis is **blocked**

(by drug that blocks synthetic enzyme, or by a disease that damages adrenal cortex), then ACTH levels stay **elevated** (trying to elevate cortisol levels)

If excess glucocorticoids are administered

HPA detects high negative feedback, so then ACTH and cortisol levels should **fall**

Dexamethasone suppression test

administers an artificial glucocorticoid to confirm that HPA responds to negative feedback

metyrapone blocks conversion of 11-deoxycortisol -> cortisol; so cortisol levels fall;

pituitary responds by increasing ACTH levels

Addison’s Disease

autoimmune destruction of adrenal cortex causes loss of corticosteroids, but excess ACTH

Pheochromacytoma

Tumors can oversecrete hormones. Tumors of adrenal medulla -> elevated epinephrine

Cushing’s Syndrome: elevated cortisol

Tumors of Pituitary Gland (adenoma) or Lung (lung carcinoma) can produce too much ACTH

Tumors of Adrenal Gland can produce too much cortisol

anatomy of pituitary gland

Dexamethasone suppression test

preRX with artificial GC (dexamethasone) suppresses cortisol response to CRH injection

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iodine is important because

the thyroid needs it to create T3 and T4

Obesity: After the circulatory systems of two mice are surgically connected, one mouse remains obese while the second mouse becomes anorexic. One mouse is _____ and the anorexic mouse is _____.

db/db; wildtype

Hormone Receptors: Steroid hormones must dissociate from _________ in order to pass through the cell membrane. Inside the cytoplasm, steroid hormones bind to the __________ of receptor proteins in order to influence gene expression.

carrier proteins; ligand binding domain

Obesity: ____________, excreted by adipocytes, serve as negative feedback to the ________ in order to reduce feeding behavior.

Leptin; hypothalamus

Obesity: Which of the following is **NOT** a characteristic of a db/db mouse?

No leptin hormone

Hormone Receptors: This second messenger molecule releases Ca++ from the endoplasmic reticulum after it is converted from phospholipids by phospholipase C.

IP3

Pituitary: After transection of the infundibulum, the secretion of most pituitary hormones goes down, but secretion of _____________ increases.

prolactin

Lidocaine

blocks voltage-gated Na+ channels

Propranolol

beta blocker”: blocks norepi from binding beta-adrenergic receptors

Verapamil

blocks the voltage-gated Ca++ channels

The ______________________ is the origin of the action potential that spreads from the pacemaker cells located at the top of the right atria. Due to the fibrous skeleton of the heart, this action potential must then pass through the _________________________ in order to depolarize the ventricles of the heart.

sinoatrial node; atrioventricular node

The auditory sound referred to as a heart beat is produced by pressure differences between the ____________________ that closes the AV valve. Likewise, the pressure difference between __________________________ closes the semilunar valves

atria and ventricle; the ventricles and aorta/pulmonary artery

The pacemaker cells are different than neurons because (choose the best answer):

in pacemaker cells, depolarization results from voltage-gated ion channels that open in response to hyperpolarization, as opposed to depolarization in neurons.

The opening of _____________________ channels result in the rapid depolarization of myocardial cells in the ventricles; whereas the opening of ________________channels results in the slow plateau of the action potential. __________________ efflux then hyperpolarizes the cell.

Fast Na+ channels; slow Ca2+ channels; K+

According to an electrocardiogram, the ____ wave is created by atrial depolarization, the ______ wave is due to the spread of depolarization to the ventricles, and the S-T interval is due to the _______________.

P; QRS; plateau phase of the cardiac action potential

A fenestrated capillary is _________________ to compounds found in the blood; however, the majority of capillaries in the brain have _______________.

Permeable; tight junctions

Blood pressure, measured by mm Hg, is lowest in the _______________ ; however, blood is prevented from back flow by ________________ .

veins; valves

Lidocaine and Verapamil are different from Propranolol in which of the following ways?

Lidocaine and Verapamil directly influence ion channel permeability; whereas Propranolol indirectly influences ion channel permeability.

HCN channels open ______________ in response to Acetylcholine; which ________ heart rate due to the opening of more ______channels.

Slower; slows; K+

Damage to Pukinje fibers due to ischemia can result in:

Death,

Circus rhythms

Lack of proper coordination of refractory periods,

Out of synch heart contractions

Venous Return

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Increased blood in the ventricles of the heart results in greater strength during contraction (Frank Starling Law) because

The actin and myosin in the sarcromere have less overlap due to the stretch

A healthy heart has an ejection volume that is maintained at _____ of end-diastolic volume (EDV)

60%

After lying down, you sit up and notice that your vision starts turning black. You come to the conclusion that your blood pressure was too low to adequately supply your brain with oxygenated blood. Which of the following is NOT a part of orthostatic regulation of blood pressure?

osmoreceptors in the hypothalamus

Which of the following does not contribute to an increase in end-diastolic volume?

tissue-fluid volume and urine volume

Which of the following is true about the lymphatic system?

lymph is dumped into subclavian veins via he thoracic duct and right lymphatic duct

Exercise ______________ blood flow to skeletal muscles, _______________ blood flow to the gastrointestinal tract and liver, and _______________________ blood flow to the brain.

Increases; decreases; does not change

An increase in the following will decrease the resistance of a blood vessel.

radius

Baroreceptors detect changes in _________________; whereas osomoseceptors detect changes in_________________________.

Blood pressure; blood concentration

Arteries (arterial blood)

vessels carrying blood from heart towards the capillaries. Thick muscular walls to keep pressure up. High in oxygen (except for pulmonary arteries)

Veins (venous blood)

vessels carrying blood from capillaries back to heart. Very thin flabby walls with low pressure, but have one-way valves to prevent blood from backing up. Low in oxygen (except for pulmonary veins).

How does blood flow through the cardiac system

lub

closing of AV valves = S1

dub

closing of semilunar valves = S2

Diastole

chambers are relaxed, blood can flow in

Atrial Systole

atria contract, pushing blood into ventricles

Ventricular Systole

ventricles contract with high pressure, pushing blood into the lungs and systemic circulation

Diastolic pressure (bottom number)

arterial pressure when ventricle is relaxed

Systolic pressure (top number)

arterial pressure when ventricle contracts and pumps

Action Potential starts from pacemaker cells in

sinoatrial node (SA node) HCN channels open when hyperpolarized (Hyperpolarization-activated Cyclic Nucleotide-gated channels)

Myocardial Action Potential is longer than neural action potential

fast Na+ channels -> fast depolarization slow Ca++ channels -> plateau phase voltage-gated K+ channels cause repolarization

\[P wave\]

AP spreads rapidly across atria to cause depolarization and atrial systole (contraction)

\[QRS wave\]

Ventricles depolarize and contract

\[T wave\]

Ventricles repolarize

how the action potential spreads across the heart

From SA node to AV node, from AV node through bundle of His and along Purkinje fibers in the walls of the ventricles

P-R/ P-Q

time for AP to spread from atria to ventricles

cardiac muscle contraction

"Excitation-contraction coupling in cardiac muscle. Depolarization of the plasma membrane during action potentials, when voltage-gated Na+ channels are opened, causes voltage-gated Ca2+channels to open in the transverse tubules. (1) This allows some Ca2+ to diffuse from the extracellular fluid into the cytoplasm, which (2) stimulates the opening of Ca2+ release channels in the sarcoplasmic reticulum. This process is called Ca2+-stimulated Ca2+release. (3) **The Ca2+ released from the sarcoplasmic reticulum binds to troponin and stimulates contraction**. (4) A Ca2+ (ATPase) pump actively transports Ca2+ into the (5) cisternae of the sarcoplasmic reticulum**, allowing relaxation of the myocardium** and producing a concentration gradient favoring the outward diffusion of Ca2+for the next contraction

abnormal EKG

degrees of AV blocks

Sympathetic NS raises HR

sympathetic chain ganglia -> norepinephrine release onto pacemaker cells -> beta-adrenergic receptors -> increased cAMP -> open HCN channels, open Ca++ channels.

Parasympathetic NS slows HR

Vagus nerve -> acetylcholine release onto pacemaker cells -> muscarinic receptors -> decreased cAMP -> close HCN channels, open K+ channels