Hormones of Kidney, Skin, and Heart

1) Erythropoietin (EPO)

2) Calcitriol

Other:

3) Renin

2 main hormones secreted by the kidney & other

1,25-dihydroxyvitamin D3

Calcitriol is also called as

Calcitriol

It plays a crucial role in calcium and phosphate homeostasis by:

* ++ absorption in the intestines

* promotes bone mineralization

* regulates PTH levels.

Calciferol

Calcitriol is derived from ___

Erythropoietin (EPO)

A circulating glycoprotein with a molecular weight of about 23,000

Kidneys (85%)

Liver (15%)

2 sources of EPO (where it is produced)

Kidney: endothelial cells of peritubular capillaries (renal cortex)

Liver: Von Kupffer cells, hepatocytes

Responsible for EPO production in kidneys & liver

* low oxygen levels (Hypoxia)

* Hemorrhage

EPO stimulates red blood cell production in response to what specific stimulus?

Brain

Recently it has been found that EPO is also synthesized in the ____ when oxygen becomes scarce there

helps protect neurons from damage via:

* improving oxygen and nutrient delivery

*encourages the growth and repair of neural tissue

Why is EPO synthesized in the brain during low oxygen levels?

High altitude & anemia

2 main reasons of hypoxia

Transfusion

This is inhibitory to the release of EPO

air pressure is lower

Hypoxia occurs at high altitudes because the ______, reducing the amount of oxygen available for your lungs to absorb

blood oxygen levels, hematocrit

Transfusions inhibit the release of EPO because they increase ___ & ____, signaling the body that there is no need to produce more red blood cells

[!!!]

[!!!] Page 5 Explain RBC Production in Kidney

(From stimulus to effects)

red bone marrow

Erythropoiesis occurs specifically in what part of the bone marrow?

stem cells

the specific target cells of EPO in the bone marrow

proerythroblast

EPO Stimulates stem cells in the bone marrow to differentiate into

hematocrit

Increase in this blood component due to EPO enables more oxygen to flow to the skeletal muscles

Liver

Site of EPO metabolism

[!!!] Page 7. Explain Erythropoiesis

Erythroid precursor cells

EPO stimulates progenitor cells to ___

Basophilic erythroblast

stage in EPO-sis where hemoglobin synthesis starts

normoblast

The stage where the cell nucleus is extruded before formation of reticulocyte

Reticulocyte

An enucleated polychromatic erythrocyte

Calcitriol

Active form of vitamin D

* synthesized in skin exposed to the ultraviolet rays of the sun

* ingested in the diet

Calciferol is synthesized via:

Liver: converted into 25-hydroxyvitamin D₃ (calcidiol*) then transported to kidney

Kidney: converted into calcitriol*. (stimulated by parathyroid hormone PTH).

Calciferol in the blood is converted into the active vitamin in two steps:

binding to a serum globulin

Calcidiol is transported to the kidney due to this process

* Intestine: promotes absorption of calcium from food

* Bone: mobilize calcium from the bone to the blood

2 actions of Calcitriol

Calcium receptors

Calcitriol enters cells & bind to them at this site

[!!!]

[!!!] Page 11. Study Calcitriol production

Liver 25-hydroxylase

Kidnye: 1a- hydroxylase

enzyme that plays a role in calcitriol conversion

Liver: ___

Kidney: ___

T

T/F: Insufficient calcitriol prevents normal deposition of calcium in bone

rickets

In childhood, this produces the deformed bones characteristic of _____

osteomalacia

In adults, abnormal Calcium deposition produces weakened bones causing

* inadequate amounts of vitamin D in the diet

* insufficient exposure to the sun

most common causes of Calcitriol Deficiency disorders

two mutant genes for the kidney enzyme

However, some rare inherited cases turn out to be caused by inheriting ________ that converts 25[OH] vitamin D3 into calcitriol.

two defective genes for the calcitriol receptor

Other cases of inherited rickets (also very rare) are caused by inheriting ______

zinc fingers

Mutations that change the amino acids in one or another of the __ interfere with binding to the DNA of the response element.

Renin

Proteolytic glycoprotein enzyme with MW of about 40,000

a) Low pressure in the afferent arteriole

b) Decreased sodium and chloride flux in the macula densa c) Stimulation of prostaglandins and sympathetic nerve discharge

JG cells produce renin in response to these 3 factors:

vasopressin and angiotensin II

Renin is inhibited by these 2 hormones

angiotensinogen

Renin acts on the circulating glycoprotein of hepatic origin

decapeptide, lungs

angiotensinogen is a ___, its conversion takes place in the ___

aldosterone

Angiotensin II : Stimulates __ secretion from adrenal cortex

* Constrict the efferent arteriole which increases GFR, which aids in the excretion of toxic metabolites even during hypotension

* Stimulates the thirst center in the hypothalamus to increase water intake

* Stimulates vasopressin secretion

Functions of angiotensin 2

distal tubule

Angiotensin 2 Appears to act directly on what part of the tubule to increase sodium and water retention

jejunum and colon

Also been shown to simulate salt and water absorption in the ___&___ and to induce formation of blood vessels

Angiotensin 3

a hepapeptide with lesser vasopressor activity

T

T/F. Although called a vitamin, calciferol and its products fully qualify as hormones because they are made in certain cells, carried in the blood, affect gene transcription in target cells.

Atrial Natriuretic Peptides (ANP)

A hormone Secreted by the secretory granules in cardiac Atrial cell

126 amino acid proANF

Predominant form of ANP is stored in the heart as

28 aa- ANF/ ANP

on secretion, 126AA pro ANF is cleaved, generating the ___ biologically active hormone

pressure increase via:

* Pressor stimulants

* Increase in atrial volume

what stimulates ANP

Pressor stimulants (Epi, vasopressin, angiotensin 2)

These increase blood pressure by causing vasoconstriction

1. A-type Natriuretic Peptide (ANP)

2. B-type Natriuretic Peptide (BNP)

2peptides release by the heart in response to an increase in Pressure:

A-type Natriuretic Peptide (ANP)

Hormone of 28 amino acids that is released from stretched atria (hence the "A")

B-type Natriuretic Peptide

Hormone of 29 amino acids that is released from the ventricles.

First discovered in brain tissue (hence the "B".)

a) Relaxing arterioles

b) Inhibiting the secretion of renin and aldosterone

c) Inhibiting the reabsorption of sodium ions by the kidneys.

ANP & BNP lower blood pressure by

natrium = sodium; uresis

natrium means

a) Prolonged bed rest

b) Prolonged recumbency -> fluids maintain in the body --> edema

c) Increased ANF --> high amount of Na attracts water

d) High salt diet

e) Hypernatremia

Conditions that would lead to natriuresis:

a) Natriuretic and diuretics

b) Stimulates an increase in GFR

c) Increase renal excretion of water, sodium, chloride, magnesium, calcium and phosphate

Effects of ANF on the kidney:

F. blocks

T/F: ANP stimulates the secretion of vasopressin from the neurohypophysis and the angiotensin II, K or ACTHstimulated release of aldosterone from the adrenal cortex

* Generally causes a decrease in blood pressure in both normal and hypertensive animals

*Appears to be a hormone that protects the animal against fluid volume overload and elevated blood pressure

Effects of ANF on Vasculature:

[!!!]

[!!!] Page 26. ANP effects diagram

Neural endopeptides

Metabolism of ANP

* Increase ECF volume in the body

* Increase Na in the body

ANP Regulation of Secretion: