PHS 3300 - midterm review

what is GERD

gastroesophageal reflux disease

What is celiac disease?

an autoimmune disease in which people cant eat gluten because is damages their small intestine

What is the "Honeymoon Period"?

- a short period after the diagnosis of type 1 diabetes where the pancreas is still able to produce a significant amount of insulin.

What are the cell types in the pancreas

endocrine + exocrine gland cells

acinar cells - exocrine (released into ducts) and produce enzyme rich juice for digestion

Islets of Langerhans - endocrine (released into BS) - cell clusters that produce pancreatic hormones

What are the two main types of Islets of Langerhans cells + function

Alpha cells - release glucagon into blood, 25%

Beta cells - produce proinsulin, 60%

used in fed and fasting states

What is a prohormone?

inactive from of hormone that has to be modified to produce active final product - ex: proinsulin

What is the role and function of glucagon

hyperglycemic hormone = raises blood glucose levels

targets the liver

breakdown gylcogen - > glucose

synthesis of glucose from lactic acid = gluconeogenesis

amino acids stimulate glucagon release

activation of sympathetic NS + stress

What triggers the release of glucagon

low blood glucose levels triggers secretions from alpha cells

SNS + high amino acid levels can also trigger

* suppressed by high blood glucose levels or insulin

What is the role and function of insulin

hypoglycemic hormone = lowers blood glucose

lowers blood glucose

anabolic hormone

promotes cellular uptake of glucose, fatty acids, amino acids

enhances conversion into glycogen, triglycerides and proteins

secretion increased in absorptive state

How does glucose stimulate the release of insulin

glucose enters B cells by facilitated diffusion

Glut 1 and 3 carries it through plasma membrane

glucose stimulates exocytosis of vesicles containing insulin

insulin binds to receptor, triggering glucose uptake through Glut 4 carriers

action of insulin on liver

stores glucose as glycogen

primary role in maintaining blood glucose levels

principal site for metabolic interconversions

action of insulin on adipose tissue

stores glucose

regulates fatty acid levels in blood

action of insulin on muscle tissue

stimulates glucose uptake

primary site of amino acid storage

major energy user

Is the brain affected by the action of insulin?

NO, not directly

brain can only use glucose as an energy source

does not store glycogen

Factors that control insulin secretion

increase blood glucose

rising levels of blood amino acid and fatty acid concentration

rising incretin hormones (GIP + GLP-1 - released after food intake)

parasympathetic NS - rest and digest, store glucose

What is the sympathetic nervous system's effect on insulin secretion

inhibits release of insulin

fight or flight response

blood is released to muscles

energy required

Counter regulatory hormones to insulin

growth hormone, glucocorticoids, adrenaline, epinephrine

stress hormones promote production of glucose in liver, glucagon release and decrease glucose use

can lead to stress hyperglycemia

Effect of exercise on insulin secretion

initially insulin levels drop, glucagon levels increase + production of FFAs + glycogenolysis = glucose meets energy demands

muscle contractions increase insulin sensitivity - maintaining glucose levels

What are factors that increase blood glucose

-Glucose absorption from digestive tract

-Hepatic glucose production through glycogenolysis of stored glycogen and through gluconeogensis

What are factors that decrease blood glucose

-Transport of glucose into cells for utilization for energy production; for storage as glycogen through glycogenesis and as triglycerides

-Urinary excretion of glucose (ONLY when glucose levels are so high it exceeds reabsorptive capacity)

Action of glucagon on liver

increased hepatic glucose production and release = increase in blood glucose levels

Action of glucagon on adipose tissue

antagonizes the actions of insulin with regard to fat metabolism by promoting lipolysis and inhibiting triglyceride synthesis

Action of glucagon on protein

inhibits hepatic protein synthesis and promotes degradation of hepatic protein

What is the structure of insulin

polypeptide hormone stored as inactive hexamer

composed of two chains - A+B linked by disulfide bridges derived from proinsulin

active insulin packaged w C peptide into secretory vesicles and released from B cells

Glucose stimulation of insulin secretion by beta cells

glucose is sensed by glucose transporter Glut 1 that move into beta cells

K channels close causing Ca channels to open and change charge = release of insulin and suppresses glucagon release

What is phase 1 of insulin secretion by beta cells

after eating, the increase in blood glucose and incretin stimulate first phase

3-5 mins after increase in blood glucose, preformed insulin released

What is phase 2 of insulin secretion by beta cells

around 15 minutes after eating, insulin rises a second time and reaches plateau in 2-3 hours

increased synthesis adn release of new insulin

gradual and sustained phase

How does insulin regulate glucose uptake

diffusion of glucose into cells is controlled by glucose transporters

GLUT 1-4

1-3 = insulin independent

4 = insulin dependent - packaged in vesicles

What is the advantage of Glut 4 being located in cytoplasm and packaged into vesicles?

makes the process faster

when insulin binds to insulin receptors - signaling cascade occurs that causes vesicles with Glut 4 to translocate to PM

How is insulin degraded

insulin binds to its receptor -> insulin receptor complex which enters cells via endocytosis

degraded in lysosomes

dependent on concentration of insulin

How is type 1 diabetes defined

body destroys the beta cells that produce insulin in pancreas

more glucose in the blood

glucose cannot move into the cells = high blood glucose levels

What is Type 1A diabetes

autoimmune

genetic predispositions + environment factors - autoantigens form on insulin producing beta cells

activation of cellular immunity (T lymphocytes) against beta cells

beta cells are destroyed = less insulin = hyperglycemia

What is the genetic predisposition for type 1A

inherited susceptibility - strongest linkage

- HLA gene in MHC

serological

- associated with IAA, GADA, ZNT8A, IA2A

have one or more of these antibodies in blood = type 1

What are environmental factors for type 1A

diabetogenic viruses

- infection of B cells

- systemic infection with cross reacting immune response ex: chicken pox

- trigger IS to produce antibodies that mimic anti-beta cell antibodies

dietary factors

- cow milk proteins

- wheat (gluten)

- decreased vitamin D

Microbiome

- alterations to gut bacterial population and production of metabolites MAY impact immunity

What age is type 1 diabetes most common

can occur at any age but peaks at ages of 2-6 and 10-14

How is diabetes diagnosed?

based on stages of glucose intolerance

1st signs are of hyperglycemia

above 7 or 11.1 on tests indicate diabetes

auto antibodies are only detected in type 1

What happens when large amounts of insulin need to be degraded?

decreases amount of receptors

body becomes less sensitive to insulin because the receptors are being endocytosed

What is happening to the B-cells during the "honeymoon period"?

the b-cells become hyper productive and compensate for failing insulin response

Type 1 pathogenesis

1. starts with genetic predisposition

2. precipitating event + environmental factors trigger immune response

3. beta cell mass starts to decrease but can still have normal insulin

4. progressive loss of insulin release

5. when 80% of B cell mass stops functioning - signs appear = hyperglycemia

During the "honeymoon period," are insulin injections required?

- in some cases, they are not needed, or injections are reduced

What happens if you succeed in prolonging the "honeymoon period" of type 1 DM?

- it can reduce some complications of type 1 DM long-term

What is the definition of Type 2 Diabetes Mellitus?

- lack of insulin activity due to impaired insulin action and/or insulin resistance

What is the most common initial symptom of TYPE 2 DM?

- weight gain/obesity

What does hyperinsulinemia mean?

- increased plasma insulin concentration

When does hyperinsulinemia occur?

- in response to insulin resistance

Is type 2 DM a gradual or rapid progression?

- gradual

Type 2 DM causes an impairment in carbohydrate utilization and storage because of what?

- a decrease in insulin sensitivity

In type 2 DM, how does the impairment of carbohydrate utilization and storage, affect blood glucose levels?

- carbohydrates help keep blood sugar/glucose levels stable. The impairment allows for the increase of blood glucose and the hyperactivity of insulin secretors, in the long run exhausting and decreasing sensitivity.

What are three other mechanisms linked to type 2 DM that cause excessive weight gain?

- decrease in number of insulin receptors

- abnormalities in signalling pathway

- lipotoxicity

What is metabolic syndrome?

- a cluster of conditions that occur together that can increase risk for several conditions

How does metabolic syndrome relate to type 2 DM?

insulin resistance (one of the conditions) predisposed to the development of Type 2 DM

What is the major consequence of metabolic syndrome?

- cardiovascular disease

What are some of the conditions listed under metabolic syndrome? (5)

- insulin resistance

- obesity

- fasting hyperglycemia

- dyslipidemia

- hypertension

Hypertension can put you at risk for what?

a stroke

What are the risk factors for type 2 DM? (13 possible)

- age 40yrs or older

- family history of type 2 DM

- hypertension

- obesity

- level of physical activity

- stress

- socio-economic factors

- obstructive sleep apnea

- history of prediabetes or gestational diabetes

- birthing a baby over 9lbs

- evidence of complications related to DM

- heart disease

- use of glucocorticoid medication

According to the textbook pathophysiology of type 2 DM, what are the two leading factors contributing to type 2 DM?

- genetic predisposition

- obesity

Adding onto the textbook pathophysiology of type 2 DM, what does obesity and genetic predisposition causes that ultimately leads to Type 2 DM

- loss of b-cell mass and function OR insulin resistance

Which phase of insulin secretion is affected by the condition of type 2 DM?

- first phase = beginning with the stimulation of insulin receptors

As the type 2 DM progresses with time, is It possible for phase 2 of insulin secretion to deplete?

yes

What is chronic hyperglycemia?

- glucose build-up in the blood stream due to lack of insulin or other drugs to lower it

What are some examples of conditions that can cause chronic hyperglycemia? (4 possible)

- decreased insulin sensitivity

- increased glucose reabsorption of the kidney

- decreased dependent glucose uptake by adipose tissue

- decreased b-cell insulin and amylin secretion

What are some consequences of chronic hyperglycemia? (9 possible)

- retinopathy

- cataracts

- neuropathy

- hypertension

- heart disease

- decreased cognition

- immunosuppression causing increased risk for infection or cancer

- gastroparesis

- kidney disease

What are some long-term complications of chronic hyperglycemia? (4)

- metabolic syndrome

- hypertension

- cardiovascular disease

- stroke

What are the "Three p's"?

- Polyuria

- polydipsia

- polyphagia

What does polyuria mean?

- increased urination due to the increased amounts of glucose in the glomerular filtrate

What does polydipsia mean?

- excessive thirst due to decreased blood volume from excessive urination

What does polyphagia mean?

- hunger due to the inability of intracellular stores to maintain levels of nutrients

In type 1 DM, polyphagia occurs alongside what other response?

- weight loss

why is weight loss associated with polyphagia of type 1 DM?

- glucose is unable to get into the insulin cells

What is acute hyperglycemia caused by? (3)

- alterations in nutrition

- inactivity

- inadequate use of antidiabetic medications

What are some symptoms of acute hyperglycemia? (4)

- three p's

- nausea

- fatigue

- blurred vision

How does acute hyperglycemia affect your susceptibility to infections?

- more prone to infections

What is the dawn phenomenon?

- rise in glucose in the early morning hours

What is diabetic ketoacidosis?

- the body does not have enough insulin to allow blood sugar into your cells for use as energy

Diabetic ketoacidosis is most common in what type of DM?

- type 1

What causes diabetic ketoacidosis?

- increased lipolysis and conversion to ketone bodies

What are the 3 consequences of diabetic ketoacidosis?

- hyperventilation

- hypothermia

- hypotension

How do you manage diabetic ketoacidosis? (5)

- carefully supplement with potassium

- insulin for hyperglycemia

- keep warm

- administer fluids

- treat with antibiotics

What is nonketotic hyperglycemic hyperosmolar syndrome? (NKHHS)

- extremely high blood glucose levels

NKHHS is most common in what type of DM?

Type 2

In NKHHS, what symptoms are most common in older adults?

- coma

- severe hyperglycemia

- dehydration

how do you manage NKHHS?

- slow rehydration

- small amounts of insulin to start

What is hypoglycemia?

- low blood glucose levels

What are the symptoms of hypoglycemia?

- increased adrenaline hormone causing anxiety, tremor, paleness and sweating

- hunger response

- decreased brain function causing confusion, drowsiness, staggering gait and emotional change

- convulsions/coma

What is the Somogyi effect?

- blood glucose levels drop in the early morning hours

What are some risk factors for long-term complications of DM?

- duration of diabetes

- age of onset

- high glycated hemoglobin

- degree of control

- hypertension

- obesity

- smoking

What is the major prognostic factor "degree of control"?

how high is the blood sugar and for how long, as well as other comorbidities

What are the two categories of long-term complications related to DM?

- vascular (micro and macro)

- neuropathic

Persistent hyperglycemia can lead to what? (4)

- oxidative stress

- accumulation of AGEs that lead to structural defects in basement membrane

- activation of complex metabolic pathways that cause tissue damage

- inflammation

What is oxidative stress?

- increased production of oxygen free radicals leading to activation of metabolic pathways resulting in damage to blood vessels

How can the activation of the PKC pathway affect a person with diabetes?

- levels of the signalling molecule that regulate vascular function are increased and therefore cause vascular damage

What happens in the macrovascular complication of "atherosclerosis"?

- damage to the large blood vessels supplying the brain, heart and extremities

What are some consequences of atherosclerosis?

- celiac disease

- peripheral vascular disease

- stroke

True or false: DM is a risk factor for coronary artery disease (CAD).

True

True or false: 80% of people with diabetes will die from cardiovascular complications such as heart disease or stroke

True

The microvascular complications of retinopathy and nephropathy are due to what?

- abnormal thickening of the basement membrane in capillaries

what can retinopathy and nephropathy lead to?

- blindness and renal failure

What does hyperglycemia do to the basement membrane?

- disrupts platelet function and growth

What is the leading cause of blindness in adults?

- retinopathy

What can occur in more severe cases of retinopathy?

- vascular sprouts, glaucoma, and cataracts