diabetes pathophysiology pavreen Flashcards
how many glands are in the pancreas?
the pancreas is two glands in one. the digestive gland and the endocrine gland
what is the function of the digestive gland in the pancreas?
digestion. it secretes alkaline pancreatic rich juice digestive enzymes into the duodenum through the pancreatic duct to aid digestion
what does the endocrine gland in the pancreas consist of?
Endocrine tissue of the pancreas consists multiple small clusters of cells scattered throughout the gland called the pancreatic islets or Islets of Langerhans which discharge secretions directly into the bloodstream
what is an islet? and what are they composed of?
small clusters of cells in the gland.
they consist of several different types of cells : alpha beta delta and f cells
what do f cells secrete?
they secrete pancreatic polypeptides
what does the core and the mantle consists of ?
- The core islets for producing beta cells and mantle consists of other cells a,d,f
what are pancreatic acini?
the are multiple cells surrounded by capillaries which allows exchange of larger molecules
where are these acini found most commonly?
in areas that require large exchanges between blood and tissues
what are the 3 main types of cells in the pancreas?
islet alpha, beta and delta
what is the function of islet alpha cells? where is it found?
- secrete glucagon
- raises blood glucose
- Located at the periphery of the islet
what is the function of islet beta cells? where are they found?
- secrete insulin
- lowers blood glucose
- Predominate cell type found in the core of theislets
what is the function if islet delta cells?
- Produce gastrin and somatostatin
* Somatostatin inhibits secretion of glucagon and insulin
what is the difference between type one and type two diabetes? (cause)
- Type 1 Diabetes; cause is insulin deficiency
- Type 2 Diabetes; typically an adult-onset diabetes; cause is inadequate response to insulin; becoming more common in children
what is hyperglycemia?
Manifestation is elevated glucose levels in blood called hyperglycemia
what occurs when there is low blood glucose?
a cells secrete glucagon
they act on hepatocytes to produce glycogenolysis and glycogeneogenesis
this release of glucose by hepatocytes increases blood sugar level to normal
if blood glucose continues to inc hyperglycaemia inhibits glucagon secretion
what hapoens when there is high blood glucose?
stimulates beta cells to secrete insulin
this accelerates faculitated diffusion of glucose into cells
inc conversion of glucose to glycogen- glycogenesis
inc uptake of amino acids and inc protein synthesis
inc synth of fatty acids
dec glycogenolysis and gluconogenesis
therefore dec blood glucose levels
if blood glucose levels continues to drop
what are the regulatory hormones and counter-regulatory hormones for diabetes?
regulatory- insulin
counter regulatory- glucagon, ad, glucocorticosteroids
, growth hormone
what does insulin do?
increases glucose uptake, glycogen synthesis, decrease glycogenolysis and glucogenesis
overal decreases lood glucose
how is insulin made up?
small protein- 551 amino acids which are linked y disulphide bridges
a chain has 21 aa
b has 30 and c is synthesised as a prohormone
what is proinsulin?
long single chain molecule and is processed into beta cells, packed into granules and it is hydrolised into connecting segment called the C peptide
pro insulin is released as insulin and c-peptide
what regulates insulin secretion?
insulin is the main regulator
amino acids, ketones, nutrients and neurotransmitters allso affect the rate
what rate is glucose released from the pancreas?
glucose is released at a low rate from the pancreas and at a higher rate after stimulation such as glucose
what is an insulin secretory burst?
usually in response to a stimulus. rapid first stage preformed insulin from granules in b cells
longer phase is consequence of a newly synthesized insulin,
how does the insulin dependent glucose transporter work?
insulin binds to insulin receptor of the cell membrane
generation of intracellular signal
insertion of GLUT-4 receptor from its active site into the cell membrane
transport of glucose across the cell membrane
why are GLUT transporters needed?
as cell membranes are impermeable to glucose
faster rate than diffusion alone
what are the different types of GLUT transporters?
glut 4,2 1
what is GLUT 4 responsible for?
Insulin dependant glucose transporter for skeletal muscle and adipose tissue. It is inactive and inside the cell membrane; active when insulin causes it to move from its inactive site to the cell membrane
what is GLUT 2 responsible for?
Major transporter of glucose into beta cells and liver cells. It has low affinity for glucose and acts when glucose plasma glucose level are high
what is GLUT 1 responsible for?
Present in all tissues . Does not require actions of insulin and important for transport of glucose into the cells of the nervous system.
how is diabetes aetiology classified?
Type 1 (β-cell destruction usually leading to absolute insulin deficiency)•Autoimmune T-cell mediated (type 1A)•Idiopathic (type 1B)
Type 2 (ranges from predominantly insulin withrelative insulin deficiency secretory defect with orwithout insulin)
other
what is the insulin dependent glucose transporter process?
1-binding of insulin to insulin receptor on the surface of the cell membrane
2-generation of intracellular signal
3-insertion of GLUT 4 receptor from its inactive site into the cell membrane
transport of glucose across cell membrane
what are the clinical features of type 1 diabetes?
beta cell destruction islet cell antibodies present strong genetic link age onset usually less than 30 faster onset of symptoms insulin must be administered body weight normal or low extreme hyperglycaemia causes diabetic ketoacidosis
what are the clinical features of type 2 diabetes/
no beta cell destruction no islet cell antibodies present very strong genetic link age of onset usually greater than 40 slower onset of symptoms diet control and oral hypoglycemic agents body weight usually obese extreme hyperglycemia causes hyperosmolar non-kenotic hyperglycaemia
what is the mechanism of islet
beta cell destruction ?
t cells react against beta cell antigens resulting in cell damage
t helpers activate macrophages directed at beta cells
cytotoxic t cells directly kill beta cells
locally produced cytokines damage b cells
autoantibodies against beta cells and insulin are detected in 70-80% of patients
what are the factors involved in the development of type 1 A diabetes?
genetic predisposition
hypothetical triggering event involving an environmental agent that incites an immune response
immunologically mediated beta cell destruction
what are the factors involved in the development of type 1 b diabetes?
cases of beta cell destruction in which no evidence of autoimmunity is present
strongly inhertied
episodic ketoacidosis due to varying degrees of insulin deficiency
what does lack of insulin cause?
decreased anabolism
increased catobolism
increased sec of glycagon, cortisol, GH and catecholamines
what does a decrease in anabolism cause
hyperglycaemia ( fatigue)
glycosuria ( vulvitis balantis)
osmotic diuresis ( poly polysipsia)
salt and water depletion ( tachycardia and hypotension)
what does increased catabolism cause?
inc in glycogenolysis increase glyconeogenesis-wasting inc lipolysis- weight loss hyperketonaemia acidosis- hyperventilation and peripheral vasodilation diabetic ketoacidosis
what factors cause a suboptimal response to insulin in type 2 diabetes?
obesity, genetic predisposition, physical inactivity
what is the difference between metabolic syndrome and type 2 diabetes?
metabolic syndrome: –Triglycerides–HDL–Hypertension–Systemic inflammation–Fibrinolysis–Abnormal function ofthe vascularendothelium–Macrovascular disease
t2 diabetes: Obesity and insulinresistance
•Increased resistance tothe action of insulin
•Impaired suppressionof glucose productionby the liver
•Hyperglycemia andhyperinsulinemia
how do you diagnose diabetes?
the three polys of diabets
Polyuria
–Excessive urination•Polydipsia–Excessive thirst•Polyphagia–Excessive hunger
WHO method- glucose concentrations in blood
when do you initiate for oral glucose test?
Fasting plasma glucose 6.1-7.0mmol/l (110-126mg/dl)
Random plasma glucose 7.8- 11.1 mmol/l (140- 199mg/dl)
what is HbA1c and how is it used in diabetes?
Elevatedglycated haemoglobin levels (HbA1c)- key test used to monitor long –term glycaemia control in diagnosed patients
good to check compliance and long term control
what is hypoglycaemia?
- Occurs in those treated with insulin and occasionally in those with a sulphonyl urea drug and rarely with metformin.
- Decreased glucose in serum (< 3.5 mmol/l or 63mg/dl) is termed as hypoglycemia.
- Excessive treatment of hyperglycaemia may result inhypoglycaemia.
what are the symptoms of Hypoglycaemia?
Autonomic: •Sweating •Trembling •Tachycardia •Palpitations
•Pallor
Neuroglycopenic: •Faintness •Loss of concentration •Drowsiness •Visual disturbances •Abnormal behaviour (agitation, aggressiveness) •Confusion •Coma
Other
•Hunger
•Headache
•Tiredness
what are the causes of hypoglycaemia and what action should you take to combat it?
Missed , delayed or inadequate meal↓ carbohyrate intake, ↓ glucose level
↑ dose of insulin↑ uptake of glucose into cells ; ↑ storage of glucose as glycogen
↑ Exercise ↑ uptake of glucose into cells
increased alcohol consumption: Impaired gluconeogenesis
Liver disease Impaired gluconeogenesis & glucogenolysis
Introduction of other blood lowering drugs to oral agents Enhanced hypoglycaemic effect
how do you treat hypoglycaemia?
- Early treatment carbohydrate meal.•10-20g of rapidly absorbing carbohydrates
- Process repeated in 15-20 minutes if glucose concentration remains <60 mg/dl or if patient is symptomatic.
what is the recommended iv dextrose to be given to children?
•The recommended dose of i.v. dextrose in children is0.2g/kg.
what are the cardinal biochemical features of Diabetic Ketoacidosis?
- Hyperglycaemia
- Hyperketonaemia
- Metabolic acidosis
what are the signs and symptoms of diabetic ketoacidosis?
Polyuria, thirst
Weight loss Weakness Nausea, vomiting Leg cramps Blurred vision Abdominal pain
Dehydration Hypotension Cold extremities Tachycardia Air hunger Smell of acetone Hypothermia Confusion, drowsiness, Coma
how is ketoacidosis managed?
Fluid replacement•0.9% sodium chloride •Fluid volume expansion •Infusion of Insulin •Correction of hyperglycaemia and presence of ketones •Potassium •Prevention of hypokalemia •None in first hour unless <3.0mmol/l •Treatment for any associated infection
what is Hyperosmolar non-ketotic hyperglycaemia?
•No ketone production or severe acidosis •Due to severe osmotic diuresis •Causing dehydration •Increase blood viscosity •May lead to thromboembolism associated with type 2 diabetes
how does HNKH Differ from diabetic ketoacidosis (DKA)?
•In the degree of insulin deficiency (more profoundin (DKA)•The elevation of glucose levels and degree of fluiddeficiency (more marked in HNKH)
what are the Synergistic factors of HNKH?
- Insulin deficiency
- Increased levels of counter-regulatory or stresshormones
- Increased gluconeogenesis and glycogenolysis
- Inadequate use of glucose by peripheral tissue
what is HNKH characteristed by?
- Characterized by a lack of ketosis
- Proinflammatory mediators (TNF-α, IL-6, IL-1 also promote insulin resistance and release of counterregulatory hormones insulin resistance and hyperglycaemia
- Because of this the amount insulin required to inhibit fat breakdown is less than that needed for effective glucose transport
what are the diagnostic features of HNKH?
- Non-ketotic hyperglycaemia (often in a regionof 55mmol/l)
- Mild acidosis without ketone production
- Slight confusion to coma
- Sometimes seizures
- Plasma Na+and K+usually normal
- Creatinine is high
- Fluid deficit is 10L; lead to circulatory collapse
what is the treatment for HNKH?
- Fluid replacement
- Stabilize BP ; improve circulation and urineoutput
- Sodium Chloride 0.9% or 0.45%
- Potassium added if required
- Insulin given but not aggressive
- Because fluid replacement also lowers plasmaglucose levels
- Prophylaxis treatment for thromboembolism
what are some of the diabetic complications?
reinopathy- impaired vison neuropathy- impared renal function cornary heart disease peripheral vascular disease cerebrovascular disease
what is the drug treatment for diabetes?
1- single non-insulin blood glucose lowering therapy
2- 2 non-insulin blood lowering therapies in comb
3- 3 non0insulin therapy or any treatment combination containing insulin
what if HbA1c rises to 48mmol/mol?
standard release metformin- if not tolerated try MR
what happens if HbA1c rises to 58mmol/mol?
add sulfonylurea add pioglitazone add DPP4 inhibitor add SGLT 2 inhibitor support the person to aim to 53mmol/mol
what is triple therapy?
1SGLT2 2sulfonlyurea SGLT2 3 sultonylurea SGLT2
or insulin based treatment
what if metformin not tolerated?
DPP-4i, pioglitazone or SU
