17 - Endocrine

Glucocorticoids

• Keep blood glucose levels relatively constant

• Maintain blood pressure by increasing action of vasoconstrictors

• Cortisol (hydrocortisone)

  • Only one in significant amounts in humans

• Cortisone

• Corticosterone

Cortisol

• a Glucocorticoids

• Released in response to ACTH, patterns of eating and activity, and stress

• Prime metabolic effect is gluconeogenesis— formation of glucose from fats and proteins

  • Promotes rises in blood glucose, fatty acids, and amino acids

• “Saves" glucose for brain

• Enhances vasoconstriction → rise in blood pressure to quickly distribute nutrients to cells

• Inhibit inflammation, depress immune system

Homeostatic Imbalances of Glucocorticoids

1. Hypersecretion—Cushing's syndrome/disease

2. Hyposecretion—Addison's disease

Cushing's syndrome/disease

• Hypersecretion of Glucocorticoids

• Depresses cartilage and bone formation

• Inhibits inflammation

• Depresses immune system

• Disrupts cardiovascular, neural, and gastrointestinal function

Addison's disease

• Hyposecretion of Glucocorticoids

• Also involves deficits in mineralocorticoids

• Decrease in glucose and Na+ levels

• Weight loss, severe dehydration, and hypotension

Gonadocorticoids

• Sex Hormones

• Most weak androgens (male sex hormones) converted to testosterone in tissue cells, some to estrogens

• May contribute to

  • Onset of puberty

  • Appearance of secondary sex characteristics

  • Sex drive

  • Estrogens in postmenopausal women

Gonadocorticoids Homeostatic Imbalance

• Hypersecretion

  • Adrenogenital syndrome (masculinization)

  • Not noticeable in adult males

Adrenal Medulla Causes

• Responses brief

• Epinephrine stimulates metabolic activities, bronchial dilation, and blood flow to skeletal muscles and heart

• Norepinephrine influences peripheral vasoconstriction and blood pressure

Adrenal Medulla

• Medullary chromaffin cells synthesize epinephrine (80%) and norepinephrine (20%)

• Effects

  • Vasoconstriction

  • Increased heart rate

  • Increased blood glucose levels

  • Blood diverted to brain, heart, and skeletal muscle

Adrenal Medulla homeostatic imbalances

• Hypersecretion

  • Hyperglycemia, increased metabolic rate, rapid heartbeat and palpitations, hypertension, intense nervousness, sweating

• Hyposecretion

  • Not problematic

  • Adrenal catecholamines not essential to life

Pineal Gland

• Small gland hanging from roof of third ventricle

• Pinealocytes secrete melatonin, derived from serotonin

Melatonin may affect

• Timing of sexual maturation and puberty

• Day/night cycles

• Physiological processes that show rhythmic variations (body temperature, sleep, appetite)

• Production of antioxidant and detoxification molecules in cells

Pancreas

• Triangular gland partially behind stomach

• Has both exocrine and endocrine cells

Type of Cells in Pancreas

• Has both exocrine and endocrine cells

  • Acinar cells (exocrine) produce enzyme-rich juice for digestion

  • Pancreatic islets (islets of Langerhans) contain endocrine cells

    • Alpha (α) cells produce glucagon (hyperglycemic hormone)

    • Beta (β) cells produce insulin (hypoglycemic hormone

Glucagon

• Major target—liver

• Causes increased blood glucose levels

• Effects

  • Glycogenolysis: breakdown of glycogen to glucose

  • Gluconeogenesis: synthesis of glucose from lactic acid and noncarbohydrates

  • Release of glucose to blood

Effects of insulin

• Lowers blood glucose levels

• Enhances membrane transport of glucose into fat and muscle cells

• Inhibits glycogenolysis and gluconeogenesis

• Participates in neuronal development and learning and memory

• Not needed for glucose uptake in liver, kidney or brain

Insulin Action on Cells

• Activates tyrosine kinase enzyme receptor

• Cascade → increased glucose uptake

• Triggers enzymes to

  • Catalyze oxidation of glucose for ATP production – first priority

  • Polymerize glucose to form glycogen

  • Convert glucose to fat (particularly in adipose tissue)

Factors that Influence Insulin Release

• Elevated blood glucose levels – primary stimulus

• Rising blood levels of amino acids and fatty acids

• Release of acetylcholine by parasympathetic nerve fibers

• Hormones glucagon, epinephrine, growth hormone, thyroxine, glucocorticoids

Homeostatic Imbalances of Insulin

1. Diabetes mellitus (DM)

2. Hyperinsulinism

Diabetes mellitus (DM)

• Due to hyposecretion (type 1) or hypoactivity (type 2) of insulin

• Blood glucose levels remain high → nausea → higher blood glucose levels (fight or flight response)

• Glycosuria – glucose spilled into urine

• Fats used for cellular fuel → lipidemia; if severe → ketones (ketone bodies) from fatty acid metabolism → ketonuria and ketoacidosis

• Untreated ketoacidosis → hyperpnea; disrupted heart activity and O2 transport; depression of nervous system → coma and death possible

Diabetes Mellitus: Signs

• cardinal signs of DM

  1. Polyuria—huge urine output

  • Glucose acts as osmotic diuretic

  2. Polydipsia—excessive thirst

  • From water loss due to polyuria

  3. Polyphagia—excessive hunger and food consumption

  • Cells cannot take up glucose; are "starving"

Hyperinsulinism

• Excessive insulin secretion

• Causes hypoglycemia

  • Low blood glucose levels

  • Anxiety, nervousness, disorientation, unconsciousness, even death

• Treated by sugar ingestion

Ovaries and Placenta

• Gonads produce steroid sex hormones

  • Same as those of adrenal cortex

• Ovaries produce estrogens and progesterone

  • Estrogen

  • Maturation of reproductive organs

  • Appearance of secondary sexual characteristics

  • With progesterone, causes breast development and cyclic changes in uterine mucosa

• Placenta secretes estrogens, progesterone, and human chorionic gonadotropin (hCG)

hCG

Pregnancy hormone (what tests test for)

Testes

• produce testosterone

  • Initiates maturation of male reproductive organs

  • Causes appearance of male secondary sexual characteristics and sex drive

  • Necessary for normal sperm production

  • Maintains reproductive organs in functional state

Other Hormone-producing Structures

1. Adipose tissue

2. Enteroendocrine cells of gastrointestinal tract

3. Heart

4. Kidneys

5. Skeleton (osteoblasts)

6. Skin

7. Thymus

Adipose tissue Hormone-producing Structure

• Leptin – appetite control; stimulates increased energy expenditure

• Resistin – insulin antagonist

• Adiponectin – enhances sensitivity to insulin

Enteroendocrine cells of gastrointestinal tract as Hormone-producing Structure

• Gastrin stimulates release of HCl

• Secretin stimulates liver and pancreas

• Cholecystokinin stimulates pancreas, gallbladder, and hepatopancreatic sphincter

• Serotonin acts as paracrine

Heart as Hormone-producing Structure

• Atrial natriuretic peptide (ANP) decreases blood Na+ concentration, therefore blood pressure and blood volume

Kidneys as Hormone-producing Structure

• Erythropoietin signals production of red blood cells

• Renin initiates the renin-angiotensin-aldosterone mechanism

Skeleton (osteoblasts) as Hormone-producing Structure

• Osteocalcin

  • Prods pancreas to secrete more insulin; restricts fat storage; improves glucose handling; reduces body fat

  • Activated by insulin

  • Low levels of osteocalcin in type 2 diabetes – perhaps increasing levels may be new treatment

Skin as Hormone-producing Structure

• Cholecalciferol, precursor of vitamin D

Thymus as Hormone-producing Structure

• Large in infants and children; shrinks as age

• Thymulin, thymopoietins, and thymosins

  • May be involved in normal development of T lymphocytes in immune response

  • Classified as hormones; act as paracrines

Overall Layout of the Cardiovascular System

The circulation is necessary because diffusion to and from the environment is ____

too slow

Anatomy of the CV system

The circulatory system consists of the pulmonary circulation and the systemic circulation

General Layout of the Circulation System

Most circulatory beds are arranged in parallel

Flow through the CV system

• Pressure drives flow through the vascular system

• Vessels are characterized by a compliance

Blood Composition

• Fluid connective tissue

• Plasma – non-living fluid matrix

• Formed elements – living blood "cells" suspended in plasma

  • Erythrocytes (red blood cells, or RBCs)

  • Leukocytes (white blood cells, or WBCs)

  • Platelets

Spun tube of blood yields

• three layers

  1. Plasma on top (~55%)

  2. Erythrocytes on bottom (~45%)

  3. WBCs and platelets in Buffy coat (< 1%)

Hematocrit

Percent of blood volume that is RBCs

Physical Characteristics of Blood

• Sticky, opaque fluid with metallic taste

• Color varies with O2 content

  • High O2 - scarlet; Low O2 - dark red

• pH 7.35–7.45

• ~8% of body weight

• Average volume

Functions of Blood

1. Distributing substances

2. Regulating blood levels of substances

3. Protection

Distribution Functions of Blood

• Delivering O₂ and nutrients to body cells

• Transporting metabolic wastes to lungs and kidneys for elimination

• Transporting hormones from endocrine organs to target organs

Regulation Functions

• Maintaining body temperature by absorbing and distributing heat

• Maintaining normal pH using buffers; alkaline reserve of bicarbonate ions

• Maintaining adequate fluid volume in circulatory system

Protective Functions of blood

• Preventing blood loss

  • Plasma proteins and platelets initiate clot formation

• Preventing infection

  • Antibodies

  • Complement proteins

  • WBCs

Blood Plasma

• 90% water

• Over 100 dissolved solutes

  • Nutrients, gases, hormones, wastes, proteins, inorganic ions

  • Plasma proteins most abundant solutes

    • Remain in blood; not taken up by cells

    • Proteins produced mostly by liver

    • 60% albumin; 36% globulins; 4% fibrinogen

Plasma proteins and ions buffer changes in plasma _

pH

• Bicarbonate – carbonic acid is the primary buffering system

• Phosphate buffer system plays a role in plasma and erythrocytes

Albumin

• 60% of plasma protein

• Functions

  • Substance carrier

  • Blood buffer

  • Major contributor of plasma osmotic pressure

Formed Elements

• Only WBCs are complete cells

  • RBCs have no nuclei or other organelles

  • Platelets are cell fragments

  • Most formed elements survive in bloodstream only few days

  • Most blood cells originate in bone marrow and do not divide

Erythrocytes

• Biconcave discs, anucleate, essentially no organelles

• Diameters larger than some capillaries

• Filled with hemoglobin (Hb) for gas transport

• Contain plasma membrane protein spectrin and other proteins

  • Spectrin provides flexibility to change shape

• Major factor contributing to blood viscosity

Erythrocytes Structural characteristics

• contribute to gas transport

  • Biconcave shape—huge surface area relative to volume

  • >97% hemoglobin (not counting water)

  • No mitochondria; ATP production anaerobic; do not consume O2 they transport

  • Superb example of complementarity of structure and function

Cytoskeleton of erythrocytes

Erythrocyte Function

• RBCs dedicated to respiratory gas transport

• Hemoglobin binds reversibly with oxygen

• Normal values

  • Males - 13–18g/100ml; Females - 12–16 g/100ml

Hemaglobin Structure

• Globin composed of 4 polypeptide chains

  • Two alpha and two beta chains

• Heme pigment bonded to each globin chain

  • Gives blood red color

• Heme's central iron atom binds one O2

• Each Hb molecule can transport four O2

• Each RBC contains 250 million Hb molecules

Hemaglobin Loading vs Unloading

• O2 loading in lungs

  • Produces oxyhemoglobin (ruby red)

• O2 unloading in tissues

  • Produces deoxyhemoglobin or reduced hemoglobin (dark red)

• CO2 loading in tissues

  • 20% of CO2 in blood binds to Hb → carbaminohemoglobin

Hematopoiesis

• Blood cell formation in red bone marrow

  • Composed of reticular connective tissue and blood sinusoids

• In adult, found in axial skeleton, girdles, and proximal epiphyses of humerus and femur