Endo Exam 2 review

The thyroid is the largest

purely endocrine gland

what lobes make up the Thyroid?

Two lobes make up the Isthmus and the third smaller lobe is the Pyramidal lobe (aka the Thyroglossal duct)

Thyroid deals with _________ through __________

basal metabolic rate through rich sympathetic nerve supply

blood flow is controlled with vasodilation with B2 receptors or vasoconstriction with alpha1 receptors

In the thyroid, what cells produce T3/T4?

cuboidal epithelial cells called Thyrocytes

How do thyrocytes show how much Thyroid hormone is present in them?

Flat cells = INACTIVE STATE due to too much hormone already present

Thick cells= ACTIVE STATE, looking to produce more hormone

Thyroids have follicles referred to as thyrocytes. When these follicles increase in number it is referred to as ________

when they increase in size it is referred to as _______

Follicle increase in number= Hyperplasia

Follicle increase in size = Hypertrophy

thyroglobulin goes through ________ of _______ to get __________

Thyroglobulin goes through Iodination of Tyrosine residues to get T3/T4

iodide trapping

active transport of iodide from plasma across the thyroid follicular cell membrane, followed by diffusion of iodide into the colloid of the follicle

what is the role of pendrin in iodide trapping?

Pendrin protein helps iodine ion enter the lumen, people without pendrin cannot make T3/T4 because iodide is not able to enter the lumen, so they experience hypothyroidism

What are biogenic amines?

they come from mast cells, have TSH effects

include histamine and serotonin (lack of serotonin leads to hypothyroidism)

Iodide controls some of thyroid function, what different compartments can it be found in?

ECF, from dietary means, and from the Thyroid

Wolff-Chaikoff Effect

1. Excess of Iodine intake
2. Inhibits TSH
3. So thyroid is inhibited
4. If thyroid is inhibited, person has hypothyroidism

what antibodies are formed to help the TSH receptor?

Ig[stim]- mimics actions of TSH, causes Graves Disease Hyperthyroidism because of an excess of T3 and T4 (there is no negative feedback mechanism here to regulate this)

Ig[block]- blocks stimulation of TSH and causes hypothyroidism

What is a goiter?

hypertrophy and hyperplasia of thyroid follicles, thyrocytes are enlarged
This can be due to bother hypothyroidism (endemic goiter) and hyperthyroidism (toxic goiter)

What are some competitive inhibitors of iodine and thus of T3/T4?

ClO4, ClO3, ScN ⇒ block T3/T4

Propylthiouracil ⇒ also inhibitsT3/T4

Methimazole drug ⇒ works like prophyiorcil and also inhibits T3/T4, used to treat hyperthyroidism

What are Goitrogens and Antithyroid agents?

they are inhibitors of thyroid transport including:
-thiocyante
-perchlorate
-chlorate

Antithyroid agents include:
sulfonamides, thionamides, sulfonylureas... they cause hypertrophy

Dietary goistrogens

Cause endemic goiter in certain geographical regions

foods that depress iodide uptake

Consuming foods like tapioca, yucca, almonds, etc in high quantity, causes thiocyanates to form and block T3/T4 formation, leading to Hypothyroidism

What does basal metabolic rate depend on?

Depends on buddy surface area

Small body = larger surface area when compared to volume.. Ex: mouse has high BMR

Larger body= smaller surface area compared to volume... Ex: elephant has low BMR

What are some effects of having too much T4

Hyperthyroidism=
Feel warm
Cardiac rate is faster
Hypertension

What are some causes of hyperthyroidism ?

-overstimulation by Ig[stim]
-ectopic production of TSH
-excessive secretion of hCG
-thyroidal adenoma or carcinoma

what is Exophthalmos

eyes bulging out, ppl that have hyperthyroidism... due to accumulation of ECM/ connective tissue, can lead to dryness of cornea

what are some causes of hypothyroidism?

-athyreotic cretinism= congenital thyroiditis in infants/children
-thyroid dysgenesis
-physical and mental retardation
-failure to produce T3/T4

What is myxedema?

puffiness around the eyes, this is indication of hypothyroidism

Idiopathic myxedema (no goiter) =

unknown cause of hypothyroidism

Hashimoto's thyroiditis (goiter) =

common in US, lymphocyte infiltration - hypothyroidism

Athyreotic hypothyroidism =

(no thyroid present)

Iatrogenic hypothyroidism =

due to medication intervention, some medicine that person is taken (ex drug like Amiodarone that has iodine, so person has excess Iodine and experiencing hyperthyroidism, excess T3/T4 so low TSH)... on the flip Amiadarone can lead to high Iodine which down regulates sodium/iodine symporter leading to low (I) in thyroid so hypothyroidism

Euthyroid Graves disease (with or without goiter) =

normal T3/T4

Graves disease (goiter) =

hyperthyroidism due to Ig [stim]

Thyroid function can be evaluated by

either administer T4 and wait 4-6 weeks, then observe T4 and TSH levels

T4 norm/TSH norm= Euthyroidism
T4 Low/TSH high= Primary hypothyroidism
T4 Low/TSH low or normal= administer TRH

then:
normal response= hypothalamic problems, secondary hypothyroidism

no response= pituitary problem, secondary hypothyroidism

excessive response= thyroid problem, primary hypothyroidism

what are the function of ionic calcium?

Muscle contraction
Neurotransmission
Blood coagulation
Brain functions/ neuronal functions
Skeletal formation
Reproduction
Cardiovascular function

what bodily effects does ionic calcium have?

bathmotropic effect= Ca effects sodium channels

Dromotropic effect= speed of conduction

Chronotropic effect = force, calcium increases the force of contraction

what is the general distribution of calcium in the body?

99% of calcium is in the bone and 1% elsewhere
50% of our calcium is ionic calcium

What hormones are involved in calcium regulation?

PTH= parathyroid hormone, hypercalcemic agent, responsible for minute to minute regulation of Ca

PTHrp= parathyroid related peptide

CT= Calcitonin, hypocalcemic agent

CGRP= calcitonin gene related peptide

Vitamin D3= calcium absorption in intestine

What cells play a role with parathyroids?

Chief cells produce PTH in the parathyroid and oxyphil cells are the precursors

describe PTH quantitation

Lets say you have C terminus, develop antibody against it.. These will be in stationary phase

Also have N terminus, also develop antibody against it...these will be in mobile phase

Any time a C terminus shows up it gets blocked

How does PTHrP come to be?

Comes from prepro → to pro PTHrP → to PTHrP

Where is PTHrP secreted from?

Secreted from several tissues:
-tumors in the breast and lungs
-Also comes from placenta, using Ca crosses placenta to fetus
-Also from epithelial cells from the teeth that make enamel

How do PTHrP and calcium interact?

PTHrP is needed for calcium to milk transfer
Helps with bone resorption and without can lead to tooth eruption

While PTHrP is a _________ agent, Calcitonin is a ___________agent

PTHrP is a hypercalcemic agent
Calcitonin is a hypocalcemic agent

calcitonin is

a hypocalcemic agent, it inhibits bone demineralization (maintains bone health)

calcitonin is produced by

parafollicular cells (sometimes called C or clear cells) in thyroid gland

Calcitonin also comes from neurons in brain

Postprandial hyperglycemia =

happens after you eat, calcium levels rise... this is fixed by calcitonin which brings calcium levels back to normal

Clacitonin gene (CALC1) deals with

deals with alternate splicing

If parafollicular cell = gene makes calcitonin
If sensory neuron = gene makes alpha-CGRP

Calcitonin gene (CALC1) is the source of

alpha-CGRP

describe alpha-CGRP

Can come from dorsal root ganglia- this effects pain transmission

So if Alpha-CGRP is there, there is increased pain perception

Alpha-CGRP also helps with regeneration of injured nerve tissue

alpha-CGRP is a vasodilator

Calcitonin gene (CALC2) is the source of

beta-CGRP

describe beta-CGRP

If visceral neurons = gene makes beta-CGRP

Beta-CGRP is depressed in GI tract

This causes visceral pain and irritable bowel syndrome

Another hormone comes from the stomach = Gastrin

Gastrin causes release of calcitonin and inhibits appetite, so the calcitonin in turn while inhibit Gastrin (Zollinger-Ellison Syndrome)

Things involved in calcium metabolism?

calcitonin gene related peptide (CGRP)

CALC1 CALC2 fom ^^^

Vitamin D3

Osteoprogenitor cells give rise to

chondroplast and osteoplast

Chondroplast →

deposits new cartilage
This leads to ossification into bone (except for skull)

Osteoplast →

deposits new bone by depositing:

1. osteoid (organic portion of the bone include collagen, osteocalcin, etc which give bones tensile strength)

2. Mineral (inorganic portion, Hydroxyapatite gives hardness to the bone)

Osteoclast cells

Come from monocytes and
Dissolve old bone (bone resorption)- this is used for bone remodeling
These cells are inhibited by calcitonin

What is clastogenesis?

clastogenesis is Bone resorption (the process by which osteoclasts break down tissue in bones in order to release minerals)

describe clastogenesis

HCl helps to dissolve the bone

PTH activates the cell and then HCl is released, bone is dissolved, and calcium is released causing hypercalcemia

Describe osteoblast cells

Osteoblast secretes collagen fibers to help with tensile strength of bones (outside) and then secretes the matrix (which is hydroxyapatite) that contributes to the hardness of the bone (inside)

describe the process by which osteoclasts aid in bone resorption

RANK-ligand binds to RANK-receptor and activates Osteoclast to secrete HCL and activate bone resorption

If calcitonin binds to osteoclast, inhibition is initiated and there is no bone resorption so calcium levels fall

collagen

is what makes the bone tensile, not brittle

type(1) collagen is found in

bone, tendons, skin

type(2) collagen is found in

cartilage

type(3) collagen is found in

reticular tissue in bone marrow, liver, lymphoid tissue

type(4) collagen is found in

lens, basement membrane

type(5) collagen is found in

placenta, hair, fetal tissues

Bone formation needs

alkaline pH 9-10

Bone resorption needs

acidic pH

ROLE OF PTH

Hypercalcemic, increases calcium levels by dissolving the bone

Also decreases phosphate levels

PTH upregulates alpha hydroxylase in intestine/kidneys → vitamin D3 synthesis in kidneys, causing calcium absorption in intestine

PTH effects in INTESTINE

PTH upregulates to help get more Vitamin D3

Vitamin D3 induces calbindin to help calcium go from our food, through intestine, into the blood (in exchange for sodium)

Phosphate will be lost with feces, PTH decreases phosphate absorption (same effect in kidneys and intestines)

PTHrP is

-hypercalcemic

-helps with placental transfer of calcium to fetus

-regulates development of mammary glands, hair follicles, and islets

-suppresses vitamin D3 formation

-causes tooth eruption

CALCITONIN (CT)

Has a hypocalcemic effect

CT suppresses bone resorption (bone breakdown)= when this happens blood Ca levels go down
^^^^ can also say it causes/helps/promotes bone mineralization

how does calcitonin effect appetite

CT is a satiety hormone, suppresses food intake

What happens if the chief cells (of parathyroid) have the calcium sensing receptors (CaR) →

If there is hypocalcemia- calcium is detected, and CaR is activated, PTH is activated

If there is hypercalcemia,no calcium in chief cells, so no PTH

KHRSP can cause dephosphorylation or phosphorylation. Describe what each indicate in regards to PTH

If dephosphorylated then mRNA is not stable and there is no PTH

If phosphorylated then mRNA is stable and translated, and get PTH

Primary hyperparathyroidism

-elevated PTH levels and vitamin D3 levels (so high plasma calcium)

-due to hyperplasia or neoplasia (adenoma)

-symptoms: high plasma calcium levels= demineralization, hypertension, osteoporosis

Secondary hyperparathyroidism

excesive PTH
Hypocalcemia of chronic kidney disease due to decreased Vitamin D3

symptoms: painful bones and joints, neurologiclal effects

Chvostek's sign=

tapping of facial nerve leads to twitching, this happens as a result of hypocalcemia due to low PTH

Trousseau's sign =

blood pressure cuff inflated, this causes ischemia to the forearm, when this happens the fingers are going to flex

what are the components of the pancreas

Exocrine portion is the Acinii which produces pancreatic juice

Endocrine component= Islets of Langerhans

The Dorsal anlage of the pancreas =

gives rise to anterior portion of pancreas, body, and tail

The Ventral anlage of the pancreas =

gives rise to posterior portion

Alpha cells =

source of glucagon

Beta cells =

source of insulin

Delta =

source of somatostatin (SST)

F cells or PP cells =

source of pancreatic polypeptide

what are cytoxic agents

used in differential staining to observe cells in the pancreas

Alloxan and Stretostic are B cytotoxic selective and target destruction of B cells

Synthalin A and CoCl are A cytotoxic

Mering and Minkowski

saw that pancreatectomy in dogs led to diabetes

Bauting and Best

provided islet extract, (when put into the diabetic dogs, had hypoglycemic effect, was named insulin)

Insulin causes a postprandial rise, what does this mean?

this means that insulin levels rise up after eating (goes up to 10x of basal levels)

Insulin secretion starts about 8-10 minutes after eating
Peak levels are at 30-45 min
And it goes back to basal levels after 2-3 hours
Pretty fast acting hormone

INSULIN FUNCTION IN THE BODY

Regulates blood glucose level

Tries to maintain a normal glycemia aka Euglycemia = 90-110mg/Dl

Cell growth and differentiation

Glucose homeostasis

insulin is the only ________ agent in the body

the only hypoglycemic agent

describe how insulin reacts to different blood sugar levels

If levels of glucose go down less than 85mg then no insulin secreted

If less than 70mg, sugar is too low, so glucagon will be secreted → epinephrine secretion

If levels are 40-50mg then the person is lethargic

If levels are 30 mg person slips into coma

15mg is too low, here there is brain damage

Describe glucose resorption in the kidneys

This is limited
Depends on the number of transporters
Transporters in kidneys → SGLT-1,2 and Glut

What is osmotic diuresis?

when glucose is excreted in the urine, water follows (indicates diabetes)

(glucose is usually absorbed, but in this case it comes out through the urine)

glucose tolerance test

A test of the body's ability to metabolize glucose that involves the administration of a measured dose of glucose to the fasting stomach and the determination of blood glucose levels in the blood or urine at intervals thereafter and that is used especially to detect diabetes.

describe the insulin receptor

Dimeric protein with alpha and beta subunits

Ligand binding leads to receptor dimerization

Intracellular phosphorylation leads to an enzyme cascade and cellular response

Mutated insulin receptor → leads to stunted growth

where is GluT1 glucose transporter found?

found in RBCs, fetal tissues, astrocytes

where is GluT2 glucose transporter found?

found in beta cells, liver, kidneys, and intestine

where is GluT3 glucose transporter found?

found in the neurons and placenta

where is GluT4 glucose transporter found?

found in skeletal and cardiac muscles, and adipocytes

where is GluT5 glucose transporter found?

fructose transporter

where is GluT6 glucose transporter found?

found in the spleen, white blood cells, and veins