Diabetes Flashcards
Homeostasis
Disrupted by an imbalance which is detected by a receptor that send an afferent signal to the control center where an efferent signal is sent to the effector that respond by restoring homeostasis
5 basic principles to maintain homeostasis
1- shape= function, change shape and change activity of molecule
2- to move water, move solute first
3- blood pressure= blood volume
4- loss of compartment integrity leads to disease/death
5- Bicarb equation of vital to homeostasis
Normal body parameters
Blood
BPM
BP
PH
5 L
60-80, 70 AVG
120/80
7.35-7.45
RR
BLGLU
O2
TEMP
12-15
100
98% saturated
97 Degrees
What type of feedback loop is homeostasis
Negative feedback loop because the body receives a signal then release a response to stop the signal
Diabetes
Failure to regulate blood glucose by insulin release and reception
Type 1 diabetes
Insulin isn’t produced by the pancreas, insulin-dependent
Type 2 diabetes
Pancreas don’t produce enough insulin
Gestational diabetes
Insulin is less effective during pregnancy
Diabetes symptoms
Frequently urination, dizziness, vision blurred, constant feeling of hunger, fatigue, dry mouth, itching
Metabolism
Refers to anabolic (build up) and catabolic (break down) reactions within the cell
Diet
Carbohydrates and be used to build up amino acids and fats and the reverse can occur
Glycogenesis
Glucose to glycogen
Glycogenolysis
Breaks down glycogen to glucose
Lipogenesis
Excess glucose can be used to make fat stores
Lipolysis
Break down fats to free fatty acid
Gluconeogenesis
New glucose from amino acid
Fed State
Immediately after eating, converted into glycogen and triglycerides, insulin is dominant. Enzymes for glycogen breakdown are inhibited.
Fasted State
Between meals, break down glycogen and triglycerides into glucose, glucagon is dominant. Enzymes for glycogen synthesis are inhibited.
In fed state, triglycerides and cholesterol are absorbed and/or synthesized from glucose
1- glycerol (3C) is made from glucose during glycolysis
2-Fatty acids are when two carbon units from acetyl CoA are linked together
3- 1 Glycerol and 3 fatty acids combine to make triglyceride
In fasted state, glycogenolysis, amino acid catabolism and gluconeogenesis maintain ATP and glucose blood level
-Glycogenolysis is when glycogen is broken down back into glucose by the the liver and kidney
-Glycogenic AA can be broken down into pyruvate then go back to glycolysis and used to reproduced glucose through gluconeogenesis.
-Fatty acids can be beta-oxidized and used to produced ATP. Lipolysis is when triglycerides is broken down into fatty acids
How are protein, carbohydrate or fat metabolized
Acetyl group can be used to make steroid hormones, fatty acids and oxaloacetate to citrate then amino acids are made.
What are some essential nutrients obtained through eating
Acetyl groups C=C
Amino acids (8 essential ones)
Fatty acids (2C)
Vitamins( water, fat-soluble)
Minerals (micro, macro)
Polymers of glucose can be used for energy storage and structural support
Cellulose is fiber that can’t be broken down due to its orientation and is able to pack tightly so we can’t digest it, beta linkage.
Starch and Glycogen are polymers of glucose that can only branch into one direction.
Starch isn’t well branched and glycogen is highly branched, alpha linkage.
Glucose is the primary source for converting the energy stored in chemical bonds into ATP
Hexokinase- phosphorylate the six carbon of glucose by breaking down ATP.
Phosphoglucose- isomerase- catalyze the reversible isomerization of glucose-6-phosphate (G6P) to fructose-6-phosphate (F6P).
Phosphofructokinase- turns fructose 6-phosphate into fructose 1,6- bisphosphate by breaking down fructose.
Aldolase- Breaks down fructose 1,6 biphosphate into 3 carbon molecules with an aldehyde group
Lactic acid formation
Anaerobic when O2 is low
Quick energy use
Glucose broken down through glycolysis and makes 2 net ATP
Glucose makes 2 pyruvate then through fermentation makes 2 lactate
Pyruvate takes one electron NADH for NAD+ which is later used for glycolysis and producing ATP
What is acetyl CoA
acetyl CoA is a 2 enzyme carbon that is made from pyruvate break down. Pyruvate breaks down into 2 carbon molecules and then reacts with Coenzyme A to form acetyl CoA
Steps of cellular respiration
Glycolysis-pyruvate oxidation - citric acid cycle- lactate acid fermentation- electron transport/ATP synthesis- CO2 and O2
Citric acid cycle
Happens in the mitochondria
Acetyl CoA is used to make NADH from NAD+ and CO2 is released twice’; GDP is catalyzed from phosphate and GTP.
FAD is gain 2 electrons to become FADH2; during the last step, NAD+ is reduced to NADH.
3 NADH
1 FADH2
2 CO2 released
1 ATP OR GTP made
Why do we need O2
O2 is necessary for oxidative phosphorylation because it accepts electrons and pick up protons to form water.
Why do we breathe out CO2?
CO2 is a waste product of cellular respiration that is formed when carbon and 02 meet each other. When CO2 accumulates, the blood pH drops because bicarb equation eq shifts to right and increase H+ ions.
Steps of oxidative phosphorylation
1- NADH and FADH2 are oxidized back to NAD+ and FADH.
2- H+ ions are pumped across the mitochondrial membrane to establish an electrochemical gradient
3- electrons are transferred to oxygen causing it to split up and take up H+ ions which forms water
4- H ion flow down the gradient to generate ATP.
Chemiosmosis
The energy from the proton gradient is used to make ATP. As H flows down, ATP synthase use H+ to make ATP.
What does cyanide do?
It inactivates mitochondrial oxidative phosphorylation which inhibits cellular respiration under aerobic conditions which leads to an over production of lactic acid
How much calories is each macromolecules
Fats= 9kcal/g
Carbohydrates= 4
Proteins= 4
Ethanol= 7
Unsaturated vs saturated fatty acid
Unsaturated ones have a C=C so no packing tightly and liquid at room temperature
Saturated fatty acid pack tightly and are solid at room temperature
Complete proteins
Grains and legumes( beans)
Why is glycemic index important for diabetes
It measures how much specific foods increase blood sugar levels very rapidly. It’s important for type 1 diabetic that need insulin pumped into their blood so that their blood sugar levels don’t increase to a life threatening level.
Three broad categories of hormones
Peptide hormones are dissolved in the blood, hydrophilic and the receptor is the cell membrane, it need help going through the plasma membrane. Insulin and parathyroid hormones. They modify existing proteins and induce synthesis of proteins
Steroid hormones are hydrophobic and transported though carrier proteins, they can cross the plasma membrane easily and have receptors in the cytoplasm or nucleus. Estrogen, androgens, cortisol, aldosterone. Induce new protein synthesis
Amine hormones which are tyrosine derivatives, 2 kind. Change the central dogma
Catecholamines
Dissolved in plasma and have receptor on cell membrane, modifies existing proteins. Epinephrine, norepinephrine, dopamine from medula
Thyroid Hormones
Carried in plasma, receptor in the nucleus, induces new protein synthesis by activating genes for transcription and translation
Where are steroid derived from
Steroid are derived from cholesterol
Steroid hormones come from the adrenal cortex
Cholesterol can be synthesized to DHEA which can become androstenedione then testosterones but the active form is DHT which is the male hormone or progesterone can be made which makes cortisol and corticosterone winch can become aldosterone
How does testosterone and androstadiene is converted into female hormones
Aromatase is used to covert androstenedione to estrone and testosterone to estradiol
What are the female hormones
Progesterone, estrone, estradiol
What are the male hormones
DHEA, Androstenedione, testosterone, DHT
What hormones do everyone has
Cortisol and corticosterone
Sex hormones
Androgens
What releases aldosterone
It is released by adrenal gland in the adrenal cortex
How do peptide cross the cell membrane
Peptide hormones are too large and charged so they need surface receptors, hydrophilic so they are fast acting because they can travel fast through blood.
Tyrosine
include dopamine, epi, norEpi which arecatechloamine
Tyrosine is elastic, two of them make dityrosine and is found in gluten
Makes melanin and Poppy which makes morphine
Tryptophan makes melatonin
What is insulin structure?
Insulin is a quaternary protein, has subunits, sulfur-sulfur bond
Hypothalamus-pituitary axis center of endocrine control system in the body
Anterior side is portal system and posterior side is neurohormones
Anterior pituitary
Neurons synthesizing neurohormones that release them into capillaries of portal system then the portal veins carry them to the anterior pituitary, where they act on the endocrine cells and they release peptide hormones into the second set of capillaries for distribution to the rest of the body.
Posterior pituitary
Neurohormone is made and packaged in cell body then vesicles are transported down the cell, vesicles containing neurohormone are stored in posterior pituitary then released into blood like vasopressin and oxytocin
What releases in the cortex of the adrenal gland and the medulla
Adrenal gland releases corticoids and sex hormones, aldosterone and the medulla releases catecholamines
Cortisol is release at the HPA and increase glucose activity while decreasing immune activity
The hypothalamus gives CRH which releases ACTH that stimulates the release of cortisol which is secreted by the adrenal cortex. Cortisol suppresses the immune system function
liver leads to gluconeogenesis which breaks down AA to make new glucose
muscle leads to protein catabolism
adipose tissue leads to lipolysis which breaks down fats and move it to unusual part of the body.
common mechanism for control in the body is negative feedback
The hypothalamus secretes CRH( corticotropin-releasing hormone) which then makes the anterior pituitary release ACTH( adrenocorticotropin hormone) and then in the adrenal cortex secretes cortisol then target tissue and response.
half life
Water based hormone have a short life like insulin and adrenaline
Steroid hormone have high half-life
Endocrine pathologies involve
either hypo- or hyper secretion. Primary, secondary and tertiary in origin
Primary in origin
Problem in the adrenal cortex which make cortisol and can hyper or hypo secretes.
Low CRH, low ACTH
Secondary in origin
Problem in the pituitary gland leads to an overproduction of ACTH and cortisol
Low CRH
High ACTH, Cortisol
Tertiary origin
Problem in the hypothalamus leads to an overproduction of CRH, ANCH and Cortisol
High CRH, ANCH, Cortisol and the negative feedback fails
Hyposecretion pathologies
SAD and melatonin
Male menopause and testosterone
Hypersecretion
Cushing’s disease and glucocorticoids
Androgenetic syndrome and androgens
Chemicals that mimic endocrine structure can act as endocrine disrupters
DES, DDT, PCB, BPA, Soy which disrupt the endocrine system
Estrogen receptors accept any keys and go into the nucleus and affect translation and transcription.
Obesogens
endocrine disrupters that may specifically affect cortisol activities.
How can obesegens and other endocrine disruptors could play a role in type 2 diabetes
Obesegens lead to fat accumulation and lead to obesity which is a big factor for type 2 diabetes
Insulin resistance can happen due to the endocrine disruptors that can interfere with insulin signaling pathways
What type of cells release glucagon and insulin
Pancreatic alpha cells release glucagon and beta cells release insulin
Low BGL leads to glucagon release
High BGL leads to insulin release
Step of insulin release requires gradients of glucose, potassium and calcium( ATP)
High blood glucose makes glucose enter in the cell through GLUT transporters, Metabolism increases with high rates of glycolysis and citric acid cycle and ATP increases. High concentration of ATP closes potassium channels; Potassium leads to depolarization which calcium channels open. Ca2+ enter the cell and bind to the vesicles then snare protein with insulin will exocytose out of the cell.
Insulin release is no nerve or hormone dependent.
Glucose concentration draws release of insulin
How does hyperkalemia affect homeostasis insulin release
High potassium in blood means high potassium in cells so high membrane potential closer to threshold which makes it easier for cell to depolarize and more calcium will enter the cell and insulin will release in high levels
How does hypocalcemia affect homeostatic insulin release
Low calcium in blood which means less calcium coming into the cell which lead to the low release of insulin out of the cell.
How is diabetes diagnosed?
By testing the homeostatic mechanisms of endocrine control, someone with diabetes take larger to bring down their blood sugar down
Normal glucose blood fasting level?
100 mg/dL
Hypoglycemia, hyperglycemia
Low blood sugar
High blood sugar
HBA1C
Hemoglobin being bound by glucose, the higher the number then the closer to diabetes you are.
Blood pressure can increase
SGLT
Has a maximum reabsorption rate
1-Glucose falls into the bowman’s capsule and is reabsorbed
2-Glucose clearance should be zero
3-Hyperglecemia cause increased filtration and transported overload
Renal threshold and transport maximum
Renal is 300 and the SGLT transport is lower than 300
Glucosuria
Glucose in urine
Albuminuria
Albumin in protein
Ketonuria
Ketone bodies in urine
Hematuria
Blood in urine
Type 1 diabetes
Associated with hyperglycemia and acidosis
destruction of beta cells
Flowchart of hyperglycemia
Leads to ketone production which leads ketoacidosis which leads to metabolism acidosis and an increase of lactic acid production
Renal threshold being exceed leads to glusoria which can lead to dehydration by water following solute which decreases blood pressure and volume.
Why does metabolic acidosis cause rapid breathing, lactic acid production, ketoacidiosis
Trying to expel C02 as fast as possible which leads to Kausser breathing
Lactic acid production is increased because NAD+ is needed in the citric acid cycle, ETC and glycolysis
Ketoacidosis- due to acetly CoA forming and making ketone bodies that are acidic and drop the blood pH
Insulin flow in beta cells vs regular cells
Pancreatic beta cells have permeability to insulin which lets glucose directly flow into them and regular cells need insulin to let glucose into them.
Type 1 diabetes symptoms
Skinny due to breaking down fatty acids
Insulin deficiently
Thirst and hunger increase
Frequent urination
Faulty pancreatic beta cells
Type 2 diabetes symptoms
90% of diabetic, hyperglycemia
Visceral obesity
Fasting blood sugar above 110
Insulin resistance
frequent urination
Diabetic foot
Retinopathy
Loss of vision due to sugar blocking blood in blood vessels
Angiogenesis- increase of blood vessels in the eye
Neuropathy
Loss of sensation
Gestational diabetes
Insulin is less effective due to pregnancy hormones affecting the pancreas
Exercise can increase glucose efficiency
Muscles cell will use glucose to perform actions and decrease it in the blood
Muscles cell will increase insulin sensibility
Extensive exercise use up Carbs
How to treat type 2 diabetes
Stimulate beta cells to produce insulin
Slow digestion and absorption of carbs by reading the glycemic index
Inhibit gluconeogenesis
Increase target tissue response like in the muscles cells
Decrease glucose reabsorption in the kidney by inhibiting SGLT
Type 1 diabetes treatment
Insulin replacement
Invokane
Inhibit SGLT in kidney, decrease glucose concentration in blood
Invokana- weight loss
Glucose being secreted and water follows it so that decrease weight. Fats will be burned for energy
Invokana- increased urination
Glucose is excreted and water follows along
Hypotension and invokana
Too much loss of glucose decreases the blood glucose level which decreases blood pressure .
Yeast infection
Urine in the urinary tract leads to bacteria buildup
Hypoglycemia
Too much glucose lost in urine
Anion gap under DKA
Anion gap widens due to the addition of ketone bodies and decrease of HCO3 because it tries to absorb the H+ being released in the blood and that release CO2 and leads to kausser breathing.
