Physiology Exam 3

central nervous system

• brain - cerebrum, cerebellum, brainstem

• spinal cord

peripheral nervous system

cranial nerve, spinal nerves, peripheral nerves

meninges

• covers CNS

• epidural space → dura mater → subdural space → arachnoid mater → subarchnoid space → pia mater

CSF

• clear, colorless liquid (protein and glucose rich)

• provides nourishment and protection and removes waste from CNS

• lateral → 3rd → 4th ventricles

• 80% prodcued by choroid plexus within ventricles (lateral are primary)

how much CSF produced per day

500mL per day; normal 150mL at any time

hormones

chemcial messengers made in glands that travel through blood to target organs, where they trigger specific effects

endocrine glands

pituitary, thryoid, parathyroid, adrenal glands, pancreas, gonads

where does specifcity come from

the receptor, NOT the hormone. only cells expressing receptor respond

what do hormones influence

prolonged processes like growth and metabolism (can be seconds or years)

peptide hormones

chains of amino acids that are water-soluble and cannot cross cell membranes

• bind to cell-surface receptors

• binding triggers chain of reactions inside cell without hormone entering

• preprohormone→prohormone→hormone and then stored in secretory vesicles

examples of peptide hormones

insulin, growth hormones

steroid hormones

derived from cholesterol and lipid-soluble so pass through membranes and bind intracellular receptors

• bind receptors in cytoplasm or nucleus and directly affect gene expression to produce longer-term changes in cell function

are steroid hormones stored

NO because secretion rate=synthesis rate. control acts on synthesis

steroid hormones examples

testosterone, estrogen, cortisol

amino acid derived hormones

• made from single amino acids but differ from peptide hormones in structure and function

• water or lipid soluble

• act on surface receptors or enter cell like steroid hormones

examples of amino acid derived hormones

thyroid hormones: behave like steroids, carrier-bound, acts on nuclear receptors, take days for onset

catecholamines: behave like peptides with surface receptor, fast acting (seconds)

what do intracellular receptors do

they alter gene expression

signal transduction

series of biochemical reactions inside cell that result in specific biologic response

channel-linked (ligand-gated ion channel)

open ion channel upon ligand binding

G protein coupled receptors (GPCRs)

one of most common types; modulate intracellular effectors when ligand binds and activates G proteins in cell membrane

enzyme-linked receptor

possess intrinsic enzymatic activtiy and are associated with enzymes

• tyrosine kinase receptor most prominent - bind phosphorylate proteins in cell to lead to cell function changes

intracellular receptors

located within cytoplasm or nucleus and bind lipophilic ligands

insulin receptors and glucose uptake

• insulin bind to surface receptor (tyrosine kinase) to activate internal signaling proteins via autophosphorylation

• recruitment and translocation of GLUT4 vesicles to membrane to fuse with membrane

• GLUT4 transporters inserted into membrane to allow glucose to enter cell

receptors that repress transcription unless activated (already bound)

• thyroid hormone receptor sits on DNA and represses transcription

• T3 binds to receptor and converts it to activator and stimulates transcription of genes

receptors that cannot be bind unless activated

• steroid receptors cannot bind to DNA in absence of hormones

• found in cytoplasm and nucleus

• steroid hormone binding to receptor (ex. testosterone) allow for complex to bind to DNA and activate gene transcription

primary disorder

target gland itself malfunctions → overproduction or underproduction of hormone

• ex. adrenal tumor produces excess cortisol independently of ACTH

secondary disorder

dysfunction in upstream gland (usually pituitary) → abnormal hormone levels in target gland

• pituitary adenoma overproduces ACTH to stimulate adrenal glands and cause excess cortisol release

teritary disorder

originates directly in hypothalamus, disrupts signals to pituitary gland and affects hormone production by target gland

• hypothalamic tumor over-secretes CRH → increased ACTH → increased cortisol

hypothalamus

neuroendocrine organs that is bridge between nervous and endocrine systems

• produces neurohormones that regulate pituitary hormone secretion

corticotropin-releasing hormone (CRH)

released in response to stress, CRH stimulates ant pituitary to secrete ACTH → cortisol in adrenal glands

thyrotopin-rleasing hormone (TRH)

stimulates anterior pituitary to release thyroid-stimulating hormone (TSH) which triggers thyroid gland to produce thyroid hormones

thyrotropin-releasing hormone (TRH)

stimulates anterior pituitary to release thyroid-stimulating hormone (TSH) which in turn triggers thryoid gland to produce thyroid hormones

gonadotropin-releasing hormone (GnRH)

prompts anterior pituitary to secrete LH and FSH which are essential for reproductive processes

growth hormone releasing hormone (GHRH)

stimulates anterior pituitary to release growth hormone (GH) which plays vital role in growth, metabolism, tissue repair

somatostatin

aka growth homrone-inhibiting hormone (GHIH)

• inhibits release of GH and TSH to help regulate growth and metabolism

dopamine

functions as prolactin-inhibiting hormone and inhibits release of prolactin from anterior pituitary

pituitary gladn

master gland; sits in sella turcica under the optic chiasm

anterior pituitary hormones

ACTH, TSH, GH, FSH, LH, prolactin

posterior pituitary hormones

oxytocin, ADH

ACTH

stimulates adrenal gland to produce cortisol

TSH

stimulates thryroid to produce T3 and T4

GH

stimulates growth in tissues, particularly bones and muscles

FSH and LH

control reproductive processes

prolactin

stimulates milk production in breasts

ADH

helps regulate water balance by controlling amt of water reabsorbed

oxytocin

stimulates uterine contraction during childbirth and milk ejection during breastfeeding

pituitary adenomas

benign tumors of pituitary gland that can cause overproduction of certain hormones

acromegaly

caused by excess GH production, leads to abnormal growth of hands, feet, and facial features in adults

prolactinoma

excess prolactin production can cause irregular menstrual cycles in women or reduced libido in men

diabetes insipidus

occurs when posterior pituitary does not produce enough ADH

• excess urination and thirst

• AKA arginine vasopressin deficiency or central diabetes insipidus

• rarely caused by adenomas, usually from trauma/surgery

what hormones does thyroid gland produce

T3/triiodothyronine (more active) and T4/thyroxine (converted into T3 in tissues)

• iodine necessary for synthesis which the thyroid gland absorbs from bloodstream

calcitonin

hormone helps regulate calcium levels

what is thyroid made up of

thyroid follicles

synthesis of thyroid hormone

• follicular cells surround thyroid follicles and produce thyroglobulin (thyroid hormone precursor)

• iodine is absorbed from bloodstream and transported into follicles

• iodine attaches to thyroglobulin to form T3 and T4

• this process is catalyzed by thryoid peroxidase

how does thyroid hormone increase metabolism

1. enhancing cellular energy production - T3 stimulates mitochondra to produce more ATP

2. increasing protein synthesis and breakdown - increases protein synthesis for growth and promtoes protein breakdown for supporting energy needs of body

3. elevating basal metabolic rate (BMR) - T3 raises BMR by increasing heat proudction thorugh stimulating cells to use more oxygen and nutrients

4. stimulating fat breakdown - promotes lipolysis - mobilizing fat stores for energy, contributing to energy expenditure

what are T3 and T4 stores in the follicular lumen as

part of thyroglobulin

• reabsorbed in follicular cells when needed and T3 and T4 are released into bloodstream

conversion of T4 to T3

in peripheral tissues (liver and kidney mainly), T4 converted to T3 by enzyne deiodinase

• T3 binds with higher affinity to thyroid hormone receptors to exert greater metabolic effect on tissues

• esnures that tissues have right amount of active hormone

hyperthyroidism

• weight loss

• increased appetite

• increased heart rate

• palpitations

• nervousness

• tremors

• excessive sweating

• heat intolerance

• exophthalmos - Graves’ disease caused by inflammation and expansion of orbital tissues

hypothyroidism

• weight gain

• decreased appetite

• persistent tiredness

• muscle aches

• sensitivity to cold

• constipation

• hair loss

• myxedema (swelling of skin and tissues especially around eyes and legs from mucopolysaccharide deposits)

goiter

enlargement of thyroid gland that occurs when thyroid is overstimulated

• iodine deficiency - tries to produce more hormones but cannot → chornic stimulation by TSH and hyperplasia

• autoimmune disease (ex. Graves’ disease); chronic inflammation can enlarge gland even though it leads to reduced hormone output (Hashimoto’s thyroditis)

where are goitetrs common

in areas where dietary iodine is insufficient

• can occur in hyper or hypothyroidism

nodules

localized growths or lumps within thyroid gland and can vary in size and composition (solid, cystic, mixed)

• can form from localized hyperplasia of thyroid cells

• can be influenced by TSH or genetic mutations

• can be benign or cancerous

radioactive iodine treatment

takes advantage of specificity and destroys overactive thyroid hells

PTU and methimazole

inhibit enzyme thyroid peroxidase (TPO), blocking T3/T4 synthesis

• PTU also reduces T4 to T3 conversion

beta blockers (esp. Propranolol) can be used as adjunctive treatment

• can reduce HR in hyperthyroidism and block conversion of T4 to T3

what are the common causes of hyperthyroidism

• graves disease - autoimmune condition where antibodies stimulate thyroid and cause excess hormone production

• toxic multinodular goiter - enlarged thyroid with multiple nodules that overproudce thyroid hormone

• thyroid adenoma - benign tumor in thryoid that produces excess hormones independently of normal regulation

common causes of hypothyroidism

• hashimoto’s thyroiditis - autoimmune disorder wehre immune system attacks thyroid leading to decreased hormone production

• iodine deficiency - insufficient iodine intake

• post-thyroidecetomy - removal of thyroid gland causes hormone deficiency

what does high TSH indicate

underactive thyroid because pituitary is tyring to stimulate thyroid to proudce more hormones

low TSH suggests

suggests overactive thyroid because body has excess thyroid hormones, reducing TSH production

what is first test ordered when screening for thyroid disorders

TSH because it is a sensitive indicator of thyroid function

parathyroid glands

small glands located on posterior surface of thyroid gland

• play crucial role in regulating calcium levels

parathyroid hormones (PTH)

released when blood calcium is low

• acts on bones, kidneys, intestines to increase blood calcium levels

• magnesium required for PTH secretion and action (hypomagnesemia can cause hypoparathryoidism)

PTH when calcium is low

1. bones - stimulates osteoclasts

2. kidneys - increases calcium reabsorption and decreases phosphate reabsorption; stimulates production of calcitriol (active vitamin D) to enhance calcium absorption in intestines

3. intestines - calcitriol (produced in kidneys because PTH influence) increase calcium absorption

calcitonin

• thyroid gland releases calcitonin when calcium is high

• calcitonin inhibits osteoclast activity, reduces calcium reabsorption, increases calcium excretion in urine

physiology of calcium

• stabilizes nerve membranes

• low levels cause uncontrolled nerve impulses and muscles contraction

• in parathyroid dysfunction, low PTH reduces calcium release within body leading to hypocalcemia

common causes of hypocalcemia

• parathryoid gland removal or damage

• autoimmune disorders attacking parathyroid glands

• vitamin d deficiency

• chronic kidney disease

hypocalcemia clinical manifestations

• muscle spasms, tingling numbness

• Chvostek sign (facial twiching when tapping on facial nerve)

• trousseau’s sign - carpopedal spasm after inflation of BP cuff for 3 minutes

• largyngospasm, seizures

• ECG changes - prolonged QT intervals

hypercalcemia

• raises threshold potential, reducing excitability → hyporeflexia, muscle weakness, lethargy, altered mental status

• primary hyperparathyroidism (usually from parathryoid adenoma) results in excess PTH secretion, which increases calcium reabsorption and bone break down

• can also be from malignancy

clinical manifestations of hypercalcemia

• dependent on how severe, can be asymptomatic

• muscle weakness, neuropsychiatric symptoms, confusions, arrhythomias, acute renal failure, constipaition, congitive dysfunction, short QT intervals

hyperparathyroidism

resultant hypercalcemia

• bone pain, kidney stones, abdominal discomfort

• treatment - surgical removal of overactive glands or medications to control calcium levels

hypoparathyroidism

underactivity results in low blood calcium

• muscle cramps, tingling, spasms

• treatment of calcium and active vitamin D supplements

adrenal cortex/outer layer

produces steroid hormones (mineralcorticoids, glucocorticoids, androgens)

mineralcorticoids

produced in zona glomerulosa

• control BP by regulating sodium and potassium balance

• secreted in response to RAAS and high potassium

• ex. aldosterone

glucocortiocoids

produced in zona fasciculata

• regulate metabolism, immune response, stress response

• ex. cortisol

• released in resopnse to ACTH

• has diurnal and pulsatile pattern (peaks in morning, declines throughout day)

androgens

produced in zona reticularis

• start as precuroses to androgens such as DHEA and contribute to development of secondary sex characteristics

adrenal medulla/inner layer

produces catecholamines - epinephrine and norepinephrine

increase HR, BP, blood glucose levels

aldosterone function

acts on distal tubules and collecting ducts of kidneys to increase reabsorption of sodium and water to raise BP and blood volume

• promotes excretion of potassium and hydrogen ions

functions of glucocorticoids

1. increases blood glucose through gluconeogenesis (producing glucose from non-carb sources) in liver

2. promotes protein breakdown in muscles to provide amino acids for gluconeogenesis

3. stimulates lipolysis - breaking down fat stores to release free fatty acids

4. anti-inflammatory effects of suppressing immune system by reducing release of pro-inflammatory cytokines and inhibiting white blood cell activity

5. mobilizing energy resources and adjusting cardiovascular function during stress

6. indirectly influences sodium and potassium by enhancing action of aldosterone

cushing’s syndrome/hypercortisolism

often from pituitary adenoma/Cushing’s disease, adrenal tumors, prolonged use of exogenous steroids

• hyperglycemia, muscle wasting, central obesity

• immune suppression

• hypertension because aldosterone activity

• decrease bone density and increased risk of fracture

• reduction of collagen synthesis → thnning of skin and striae

• mood swings, memory, congitive function alterations

androgen functions

development of secondary sex characteristics

• development of body hair and may impact libido

• adrenal andorgens significant source of testoerone-like activity in females but only minor in males

catecholamines physiological effects

• increase HR, BP, CO

• bronchodilation

• glycogenolysis in liver

• relaxation and constriction of smooth muscles

pheochromocytoma - adrenal meduall tumor that cause excess catecholamine production

primary adrenal insufficiency (addison’s disease)

adrenal glands damaged and cannot produce cortisol or aldosterone

• kidneys do not reabsorb sodium so sodium is lost in urine → hyponatremia

• aldosterone normally increases renal potassium excretion so body can’t get rid of potassium → hyperkalemia

• low BP, dehydration, dizziness, muscle weakness

• hyperpigmentation - increased ACTH = increase melanin production

• impaired gluconeogenesis → increased insulin sensitivity and reduced vascular tone → hypoglycemia and hypotension

secondary adrenal insufficiency

problem within pituitary itself

causes:

• panhypopituitarism - damage to pituitary tissue → diminished secretion of pituitary hormones, including ACTH

• isolated ACTH deficiency

• genetic casues

• TBI

aldosterone is PRESERVED so NO hyperkalemia

NO hyperpigmentation because low ACTH

teritary adrenal insufficiency

from exogenous steroid use = suppression of HPA axis

decreased CRH → decreasing ACTH → adrenal cortex atrophies

• can be from stopping steroid abruptly (need to be tapered slowly)

aldosterone production UNAFFECTED and NO hyperkalemia

NO hyperpigmentation because low ACTH

pancreas has what kind of function

endocrine (islet of langerhands) and exocrine (digestive enzymes) function

cushing’s disease

specific type of cushing’s syndrome due to pituitary tumor overproducing ACTH

hormones produced by pancreas

insulin, glucagon, somatostatin (from delta cells, inhibits release of insulin and glucagon)

does regulation of blood glucose levels work with the HPA

no, it works independently of hypothalamus-pituitary axis

insulin effects

encourages fat storage and prevents lipolysis

• lowers blood potassium by moving potassium from blood into cells by stimulation of Na/K ATPase pump, primarily in skeletal muscles

what if we don’t have enough insulin

• breakdown of fat → FAs converted into ketone bodies for alt energy source

• occurs in diabetes; most often Type 1 DM

• can cause ketoacidosis