Lecture 9: Hormone and Glucose Regulation

Where are hormones released into

Bloodstream

Endocrine organs do what?

Synthesize and secrete hormones

Paracrine hormones

act on other cells than where they are expected

Triggers of hormone secretion

Concentration of specific substances
Neural stimulation
Endocrine sequence

The endocrine system is regulated by:

Negative feedback mechanism

Endocrine function tests

Hormone level or affector substance level
e.g TSH, glucoseE

Endocrine dysfunctions

Hyposecretion or hypersecretion due to primary endocrine disorders, signaling disorders or sequence disorders

Hyposecretion

Congenital defect, disease/infection/inflammation, hypoperfusion, ageing

Hypersecretion

Genetic, tumors, environmental stimuli

Common causes of SIADH

CNS - encephalitis and meningitis, infection, surgery, tumor

S&S of SIADH

Increased BP
Decreased urine output
Diluted electrolytes in circulation
Low Na, K
Low osmolality
Edema
Crackles in lungs
HeadacheM

Management of SIADH

Diuretics - furosemide
Fluid restriction
3% of NaCl
Monitor BW

Diabetes Insipidus

Passing tasteless water
Too little ADH
High urine output
High thirst

TX of diabetes insipidus

Fluids ad lib + synthetic ADH
Desmopressin

Where is TRH released

Hypothalamus

Where is TSH released

Anterior pituitary gland

What percent of hormones are T3 and T4

T3 - 20%
T4 - 80%

Calcitrol

Active form of vitamin D
Supports calcium absorption in GI and deposition in bone

Goal of calcitonin and PTH

Serum calcium homeostasis

Diagnosis of hypo and hyperthyroidism

S&S
BW TSH and T4

Common causes of hypothyroidism

Congenital - newborn screen for TSH and T4
Autoimmune (hashimoto disease) - slow destruction
Iodine absence - dietary iodinea

S&S of hypothyroidism

Associated w slow metabolism and cell fx throughout
Goiter
Myxedema coma - severe metabolic insufficiency if hypo is untreated longterm

Hypothyroidism tx drug class

Hypothyroid agents(synthetic hormone)

Hypothyroidism tx drugs

Levothyroixine (Synthroid, Eltroxin)
Liothyronine (Cytomel)

Attributes of hypothyroidism tx drugs

T4 preference
Long t1/2
High PPB
Slow onset of action at 1st stabilized w BW monitoring/effective longterm

Primary energy sources

Glucose
Fatty acids

Glucose

Readily distributed

Glucose: CNS

Most needy system
requires constant supply of glucose
cannot store it for laterW

What happens with extra glucose

Stored as glycogen (liver and muscles) and triglycerides (adipose cell)

What happens when there is a fall in blood glucose

Fall in blood glucose -> glycogen breakdown via glycogenolysis + formation of more glucose from other sources gluconeogenesis and released PRN

Fatty acids distribution

distributed via lymph to circulation

CNS and RBCs cannot use what energy source?

Fatty acids

What happens to extra fatty acids

Stored as triglycerides
-broken down into 3 fatty acids and glycerol
-Fatty acids are not converted into glucose bc cannot be used by brain for energy

What happens when there is fatty acid metabolism in the liver

Ketone metabolites

Insulin is what type of hormone

PancreaticW

Where is insulin synthesized

Beta cells (langerhans)

Insulin actions

Glucose cellular uptake
Promotes storage information (glycogen synthesis, triglyceride synthesis, protein synthesis): prevents glycogen and fat lysis
Amino acid cellular uptake, triglyceride adipose cell uptake

Glucagon is synthesized where?

Alpha cells

What does glucagon promote

Mobilization of stores:
glycogenolysis
gluconeogenesis
lipolysisW

What is glycogenolysis

Glycogen breakdown

What is gluconeogenesis

Amino acid conversion into glucose

What is lipolysis

Triglyceride breakdown

What is glucagon triggered by

Low plasma glucose levels (btw meals, hypoglycemia) -> mobilize stores and replenish blood glucose for cellular use

Glycemic regulation with high blood glucose

High blood glucose -> pancreas -> releases insulin -> cells take up glucose from blood and liver produces glycogen -> blood glucose falls

Glycemic regulation with low blood glucose

Low blood glucose -> pancreas releases glucagon -> liver breaks down glycogen -> blood glucose rises

Beta cells: insulin synthesis

Stimulant high serum glucoseB

Beta cells: insulin inhibition

Somatostatin (D cell produced)

Beta cells secreting insulin steps

Glucose enters pancreatic beta cell via glucose transporter -> metabolized via glucokinase into ATP -> closes K channels (on beta cell) -> depolarization -> insulin secretion - > insulin from pancreas enters hepatic circulation -> 50% 1st pass metabolized -> metabolites renally excreted

Beta cells: insulin action

Binds to cellular membrane receptor (tyrosine kinase) -> activates kinase enzyme within cell -> stimulates glucose transporter -> channels open to glucose

Synergy hormones released in stress/starvation

Glucocorticoids
Catecholamines
Growth hormones

Synergy hormone: Glucocorticoids

Cortisol
mobilizes utilization of all energy stores

Synergy hormones: Catecholamines

Epinephrine
Stimulates glycogenolysis and later lipolysis

Synergy hormone: Growth hormone

Increased in longterm stress or starvation
Inhibits glucose uptake to increase serum glucose -> stimulates higher insulin secretion

Beta cell destruction

Dysfunction of glucose, fat, and protein metabolism

Immediate effects of beta cell destruction

Disabled transport of glucose into cells

Beta cell destruction pathophysiology sequalae:

Increased glucose in plasma -> high solute concentration -> osmotic shift of fluid into circulation = cellular dehydration -> high solute concentration into renal tubules -> osmotic shift into filtrate = high urine production -> metabolic shift to use fat for energy -> breakdown of triglycerides and glycerol -> hepatic metabolism of fatty acids -> ketone bodies -> metabolic acidosis

What are outcomes of beta cell destruction

Hyperglycemia
Polydipsia
Polyuria
Glycosuria
Ketonuria
Changes in LOC
Metabolic acidosis
Coma
Death

Consequences of reduced glucose uptake: energy substitutes

Proteolysis -> weight loss and muscle wasting
Lipolysis -> fatty acid breakdown, liver metabolism fatty acids (fatty acid oxidation) = ketones and ketonuria

Consequences of reduced glucose uptake

altered cellular function
endothelial dysfx + decreased angiogenesis + increased oxidative stress

Consequences of reduced glucose uptake: Organ injury

Retinopathy
Neuropathy
Nephropathy
CV

Type 1A DM

Genetic predisposition + triggering event (infection, trauma) -> immune reaction to beta cell antigens = autoimmune

Type 1B DM

Idiopathic (familial), rare

DM dx

Fasting glucose >7mmol/L (normal =

What happens in DM

total destruction of beta cells: IDDM (insulin dependent)

TX of DM

Insulin

No tx of DM

Diabetic ketoacidsosis = death

Basal endogenous insulin level

5-15IU/mL
-clinically normal glucose level = 4-8

Peak rise of endogenous insulin levels

60-90IU/mL

Goal of tx with insulin

Restore normal glucose patterns
Minimize risk of hypoglycemia

Basic preparation categories of insulin

Rapid acting
Long acting
Short acting ('regular')
Intermediate acting

Administration route of insulin

SC
-needle injections
-portable pen injectors
-insulin pumps: basal and bolus delivery

7 right considerations when administering insulin

Dose double checked by 2 RN's
Measured in units = U
Patient learning and education

Rapid Acting Insulin: onset, peak and duration

Onset - 10-15 minutes
Peak - 1-2 hr
Duration- 3-5hrs

What is rapid acting insulin ideal for

Meal time bolus; pts eat right away
In insulin pumps, not IV

Rapid Acting Insulin Drug examples

Humalog (Lispro)
Novorapid (Aspart)
Apidra (Glulisine
Fiasp (Aspart) - onset 4 min

Rapid acting insulin in pumps

Achieve boluses
Customize basal insulin requirements

Long acting insulin: onset and plateaus

Onset: 90 min
Plateus: 24 hrs

What is long acting insulin ideal for

Background
Admin 1-2 x daily
MUST have separate syringe for injection
Never IV

Long acting insulin drug exampels

Levemir (Detemir)
Lantus (Glargine)
Tresiba (Degludec) - ultra-long acting (>30 hrs)

Short acting insulin: onset, peak and duration

onset: 30 mins
Peak: 2-3hr
Duration: 6.5 hrs dose dependentW

What is short acting insulin ideal for

Meals (30-45 min pre-meal)
*issues w hypoglycemia and balancing dose w intake
Pt eats
Use IV if ketoacidosis

Short acting insulin 'regular' drugs

Novolin ge Toronto
Humulin R
Entuzity (Kwikpen) - 5x more concentrated, for high daily insulin requirements

Intermediate acting insulin: onset, peak, duration

Onset = 1-3hrs
Peak = 5-8hrs
Duration = up to 18 hrs dose dependent

What is intermediate acting insulin ideal for

Background replacement
Admin 1-2x daily
If patient on steroids - can match sugar peaks, monitor for night hypoglycemia, night snack IMPORTANT
Never IV

Intermediate acting insulin drugs

Humulin N
Novolin ge NPH

Humalog mix 25

25% rapid
75% longH

Humalog mix 50

50% rapid
50% intermediate

NovoMix 30

30% rapid
70% long - protamines increase duration of action

Why are pre-mixed insulin formations good?

Decreased injection frequency and multiple doses per pen

Intensive insulin tx requirements: DM1 requirements

Total daily insulin req't (U) = 0.55(U) x pt wt (kg)
1/2 = background requirement (basal)
Other 1/2 = mealtime and high blood sugar requirement (bolus)

information required for insulin therapy and dosing

plasma glucose
carbohydrate meal content
diabetic dietw

what is the goal of insulin therapy

normal plasma glucose

Bbit

basal (long acting insulin) in A.M

bBit

bolus (short/rapid acting insulin) at meals

bbIt

Insulin correction (short/rapid) if necessary

bbiT

titrate doses to achieve glucose levels 5-8 (monitor glucose)

When should you be checking blood glucose

Pre-each meal
Post meals if new dx
Bed time

How many times per day should you be checking blood glucose

4x per day is minimum requirement
8x for newly dx

Basal insulin

Long acting insulin in A.M
Given in A.M to avoid night hypoglycemia
Tweak the long acting based on blood sugar at 12 hr mark (bedtime glucose remark)

Diabetes diet

Carb counting - 45-60g/meal
-carb total-fibre = total count
-15 g of carb = 1 unit rapid acting formula
Regular meals and snacks
Regular activity/exercise