6.1 Liver & GI Flashcards
Insulin effects
Liver
Glucose uptake
What tissues do not need insulin for uptake
K
Insulin is anabolic in nature and it predominantly inhibits glycogenolysis in the liver (though it also stimulates glycogenolysis) and stimulates glucose uptake in adipose tissues and cellular uptake of amino acids (protein synthesis).
Some tissues do not require insulin for efficient uptake of glucose - important examples are brain and the liver. This is because these cells do not use GLUT4 (a hexose transporter for facilitated diffusion of glucose) for importing glucose, but rather, another transporter that is not insulin-dependent.
Insulin is used for the treatment of hyperkalaemia and hence ‘drives’ K+ back into cells.
Hypocalcaemia - defined as
what other condition causes total reduced calcium
Causes
x6
Features
x7
Hypocalcaemia is defined as a total calcium of less than 2.10 millimoles per litre or an ionised calcium of less than 1.0 millimoles per litre.
In hypoproteinaemia the total calcium is reduced but the ionised portion is normal thus clinical features are absent.
The causes include:
Hypoparathyroidism Disorders of vitamin D metabolism Sepsis Burns Rhabdomyolysis Pancreatitis. Features of hypocalcaemia include:
Muscle cramps Spasm and tetany Seizures Hyperreflexia Paraesthesia Stridor A prolonged Q-T interval on the ECG.
Thyrotoxicosis tends to cause hypercalcaemia.
What causes hyperglycaemia
The catecholamines, corticosteroids, glucagon and growth hormone are counter-regulatory and their secretion results in hyperglycaemia. The only other hormones, like insulin, that promote glycogen synthesis are the corticosteroids.
How does glucose pass to cells what are they called where are they located how many types where are they located
Are they all dependepent on insulin
What is the structure of insulin
how many of the things are there
What is the result of a lack of insulin
The passage of glucose into cells is achieved with the help of glucose transporters. These glucose transporters (GLUT) are proteins located in cell membranes which promote glucose uptake into the cytoplasm by facilitated diffusion or active transport.
There are four glucose transport proteins:
GLUT1: universally distributed
GLUT2: present in gut, liver, and pancreatic islets
GLUT3: present in the central nervous system and brain
GLUT4: present in insulin-responsive tissues, skeletal muscle, adipose tissue, and heart.
GLUT3 is not dependent on insulin.
Insulin is composed of two polypeptide chains (A and B) linked by two disulfide bridges. The A chain typically contains 21 amino acids and the B chain 30 amino acids.
The hyperglycaemia from insulin resistance or lack of insulin is characterised by reduced entry of glucose into the cells.
One physiological action of insulin is to increase the permeability of cell membranes to potassium, magnesium and phosphate ions. This forms the basis of treating life threatening hyperkalaemia with a glucose/insulin infusion.
During fasting, serum insulin and glucose levels fall whilst lipolysis increases.
BMR what is it
Main controlled - secondary
What does it secrete
what reponsed to this
which affect where
factirs ubfkeybce
What is normal adult male bmr
The hypothalamus is the primary controller of the basal metabolic rate by regulating the activity of the anterior pituitary and thyroid glands.
The hypothalamus secretes thyrotropin-releasing hormone (TRH) when it senses low levels of thyroid hormones. The anterior pituitary responds to TRH by secreting thyroid-stimulating hormone (TSH) that in turn stimulates the release of thyroid hormones (T3 and T4) from the thyroid gland. T3 and T4 increase the BMR. The hypothalamus and anterior pituitary gland are subject to feedback loops.
The basal metabolic rate (BMR) is the amount of energy expended per unit time during a period of rest. The units are expressed as calories/m2/hour and are corrected for age and sex under standard conditions of rest.
Factors which influence BMR include:
Exercise
Thyroid function
Catecholamine release/activity of the autonomic nervous system
Food (specific dynamic action)
Pregnancy
Age and sex (higher in children and males)
Pyrexia.
Normal BMR in an adult male is 40 cal/m2/hour. A rough approximation is BMR = 37- (age-20)/4.
Bile salts - do what
reabsorbed from where
vitamins?
Is it acid/alkalitic
Is it hypotonic
Is there cholesterol in it
how much secreted day ml
how much reabsorbed %
Bile salts are required for emulsification and absorption of fats (not protein) associated with activation of lipases through optimisation of the pH.
They are reabsorbed in the terminal ileum.
They are therefore involved in the absorption of fat soluble vitamins (not vitamin B12).
Normal bile is an alkaline, hypotonic electrolyte solution composed of bile pigments and salts.
A small amount of unesterified cholesterol is excreted in the bile.
Approximately 500 ml is secreted per day (not 125 ml).
Ninety five per cent of bile salts are absorbed from the terminal ileum.
ACTH is secreted by what
regulated by what hormone form where
What does it control
Which is max when/min
Where can it be expressed
when does it rise
what meachism & what turns it off
ACTH is secreted by the pituitary gland and is regulated by corticotropin-releasing hormone from the hypothalamus.
The production of ACTH is governed through the secretion of corticotropin-releasing hormone from the hypothalamic nuclei.
It governs cortisol secretion where cortisol is secreted maximally in the morning and concentrations are at a nadir at midnight.
ACTH can be expressed in numerous tissues besides the pituitary and including the placenta.
ACTH concentrations rise in stress, disease and in pregnancy.
Through negative feedback, glucocorticoids (not mineralocorticoids - aldosterone) switch off ACTH production.
Thyorid
Principle storage - site thyorid gland
Fxn uniit of gland is -
Thyroglobulin is the principal site of storage of thyroid hormones in the thyroid gland.
The functional unit of the thyroid gland is the follicle. These follicular cells surround the follicle and the latter is filled with a fluid called colloid. Suspended within the colloid are pro-hormone complexes, thyroglobulin.
The role of synthesis and storage of thyroid hormones is undertaken by the follicular cell
TSH causes -
oxidation by what
Under the action of thyroid stimulating hormone (TSH), iodide ions (I−) are actively transported against a concentration gradient into the follicular cell.
It is here that it undergoes oxidation to “active” iodine by thyroid peroxidase (TPO). Thyroglobulin itself is synthesised in the follicular cells and contains up to 140 tyrosine residues. Active iodine is incorporated into the tyrosine residues of thyroglobulin to form mono- and di-iodotyrosines (MIT and DIT).
The iodinated thyroglobulin is then taken up into the colloid where it is stored and dimerised. The coupling of two DIT molecules produces thyroxine (T4) and the coupling of one MIT and one DIT molecule produces tri-iodotyrosine (T3). This process is catalysed by TPO.
Stimulated by TSH, thyroglobulin droplets are captured by the follicular cells by pinocytosis to form vesicles. Fusion of these vesicles with lysosomes results in hydrolysis of the thyroglobulin molecules and release of T4 and T3 into the circulation.
GNRH is what
produced where
release where
Is it steroid?
GnRH is a hypophysiotropic hormone, produced in the hypothalamus.
It affects the anterior pituitary gland by being secreted into capillaries in the median eminence of the hypothalamus that then empties into the hypothalamo-pituitary portal vessels, which then transport it to the anterior pituitary. With the exception of dopamine, all the known hypophysiotropic hormones are peptides.
Not a steroid!
GnRH effects
side effects long and short
Effects of gonadotrophin releasing hormone (GnRH) administration include symptoms seen at the menopause. However, it does not cause masculinisation.
Currently available medical treatments for endometriosis act by attempting to mimic periods during which a woman does not menstruate: menopause (GnRH analogues), amenorrhoea (chronic anovulation with danazol) or pregnancy [oral contraceptives or progestins]. The GnRH induce the medical menopause by causing down-regulation of hypothalamic-pituitary GnRh receptors. Treatment is associated with significant hypoestrogenic side effects. Short-term effects include menopausal symptoms, such as hot flashes, vaginal dryness, loss of libido and emotional lability. Long-term use is associated with substantial bone mineral density loss and osteoporosis.
hypothermia - move to appropriate section
Hypothermia is defined as a core temperature less than 35°C, and is associated with:
Hypopituitarism Hypothyroidism Spinal cord trauma, and Alcohol and drug overdose. In hypothermic patients the oxygen dissociation curve is shifted to the left.
A metabolic acidosis is commonly seen in hypothermia, and is exacerbated by a reduction in hepatic clearance and renal excretion of hydrogen ions and lactic acid.
Other complications include:
Acute pancreatitis Hyperglycaemia Thrombocytopenia, and A coagulopathy. Passive rewarming is appropriate when the core temperature is above 33°C (not all patients), but active measures are required when the temperature is lower.
Hypotension may be seen as the core temperature rises, as hypovolaemia is revealed and will usually require fluid resuscitation.
Gut Barriers to invading microorganisms
Intraluminal defences:
Gastric acidity Gut motility Intraluminal enzymes Secreted IgA immunoglobulin. Mucosal defences:
Normal flora
Mucous layer in the glycocalyx and
Tight intracellular junctions between the enterocytes.
Gut associated lymphoid tissue:
Lymphocytes that make up 20% of the intestinal mucosa.
Macrophages:
70% are found in the gut, peritoneum and hepatic reticulo-endothelial system.
Insulin - synthesised where
interact with what receptors
What type structure is it
weight
is it in lymph
what does binding do to tyrosine residues
t1/2 IV injection
Increased by
Insulin is synthesised in the beta cells of the islets of
Langerhans, which interacts with cell surface receptors (not the nuclear membrane and so is not like steroids).
It is composed of two polypeptide chains that are linked by disulphide bridges.
It is synthesised as a precursor molecule that is split before secretion.
Insulin is a polypeptide with a molecular weight of approximately 5800Da
Oassage from plasma to interstitium and lymphatics is dependent on the integrity of the capillary endothelium. Insulin can be measured in lymph but concentrations can be up to 30% less than that of plasma.
Insulin binding to its receptor results in receptor autophosphorylation on tyrosine residues and the tyrosine phosphorylation of insulin receptor substrates (IRS-1, IRS-2 and IRS-3) by the insulin receptor tyrosine kinase.
Following intravenous injection it has a half life of less than eight minutes and secretion is increased by:
Beta adrenergic stimulation Vagal stimulation Stress Glucose, fructose, mannose and amino acids Glucagon and other gut hormones Sulphonylureas and Phosphodiesterase inhibitors.
CTZ is where
in or out bbb
what type of receptors
problems with certain anti emitics
does it have input from anything else
The chemoreceptor trigger zone (CTZ) is found in the floor of the fourth ventricle and lies outside the blood brain barrier. It is, therefore, susceptible to blood borne toxins which can induce nausea. The CTZ has dopaminergic (D2), histaminergic (H1), muscarinic (M1) and serotonergic (5-HT3) receptors.
Both ondansetron and all the trons and the butryphenones, (for example, haloperidol) can cause prolonged QT intervals.
Cranial nerve VIII (vestibulocochlear) has input to both the CRTZ and the vomiting centre
Neurokinin 1A is an antagonist in the CTZ, substance P an agonist.
ADH
short or long
syntheitised where
stored where / secreted
how does it travell
action
which is carried out where
How is it secreted
hakf life
Antidiuretic hormone (ADH, arginine vasopressin, AVP) is a nonapeptide hormone that is synthesised in the hypothalamus (paraventricular and supraoptic nuclei) but is stored and secreted by the posterior pituitary gland. It travels from the hypothalamus by axonal streaming
The main actions of ADH are:
Water retention in the face of dehydration. It has an action on the distal convoluted tubule and the collecting ducts.
ADH is an agonist for G-protein coupled V2 receptors on the basolateral memebrane, which regulate the activity of aquaporin water channels. The action of ADH on the V2 receptors opens the aquaporin channels and water flows out of the nephron down a concentration gradient into the interstitium and intravascular space.0
It is also a powerful vasoconstrictor by an action on V1 receptors and it is released to increase blood pressure in severe hypovolaemic shock. But its release occurs at a late stage of hypovolaemia.
ADH is secreted in response to changes in plasma osmolality. The osmoreceptors are located near the hypothalamus (subfornical organ and vascular organ of the lateral terminalis). These are capable of maintaining a plasma osmolality between 280 and 303 mOsm/kg. Secretion of ADH has a diurnal pattern. The osmoreceptors shrink in response to an increase extracellular osmolality leading to an increase in ADH secretion. ADH has a relatively short half-life of 10-15 minutes. In normal individuals, plasma ADH levels are virtually undetectable when the plasma osmolality falls below 280 mOsm/kg.
Plasma half life is approximately 18 minutes (not 60 minutes).
Aldosterone
Produced where -
acts how
regulated by what
Aldosterone is produced in the zona glomerulosa of the adrenal cortex, and it acts via intracellular steroid receptors to increase sodium reabsorption.
It is regulated by the renin/angiotensin system. Its release is therefore stimulated by hypovolaemia and blood loss, and is inhibited by increased sodium intake/hypertension.
H2RA
do what to seceetios
do they effect pancreas
effect on vasculature
do they cause sedation
Histamine type 2 (H2) receptor antagonists reduce acid secretion (thus lower the volume) and cause an increase in pH (not decrease).
The exocrine pancreas has H2 receptors and the use of H receptor antagonists potentially reduce pancreatic secretion
Vasodilatation is associated with histamine type 1 (H1) and H2 receptor agonists (not antagonists).
Sedation is more a feature of the older H1 antagonists (not H2 antagonists) which can cross the blood brain barrie
What is the stimulus to for PTH
how much calicum is non bound
Is i affected by pH
Calcitonin causes what
Where is 25 hydroxy for cholecalciferol
A fall in ionised plasma calcium levels causes the chief cells of the parathyroid glands to secrete parathyroid hormone (PTH).
Fifty percent of extracellular calcium occurs as non-ionised, protein- (albumin-)bound calcium.
The degree of ionisation increases inversely with pH.
Calcitonin causes increased renal calcium excretion.
Cholecalciferol is 25-hydroxylated in the liver
Anti-insulinic hormones include
They lead to:
Growth hormone
Adrenaline
Glucagon, and
Corticosteroids (not mineralocorticoids like aldosterone).
An anti-insulin hormone (the four listed above) reduces the uptake of glucose into cells, increases gluconeogenesis, and increases glycogenolysis, whereas insulin reduced these two processes. Thyroxine enhances insulin-dependent entry of glucose into cells and increased gluconeogenesis and glycogenolysis to generate free glucose.
Where are the parathyroid in releation to thyroid
where is the RLN
What is it composed of
What does it weigh
The parathyroids lie posteriorly to the thyroid gland and the recurrent laryngeal nerves lie posteromedially.
The gland is composed of follicles and iodine is internalised by an active transport system - the iodide symporter.
The normal weight of the gland is approximately 30 grams.
Krebs cycle
what is it
where does it occur
can it be anaerobic
oxidation of what to form what
Krebs’ cycle (tricarboxylic acid cycle or citric acid cycle) is a sequence of reactions in which acetyl coenzyme A (acetyl-CoA) is metabolised to carbon dioxide and hydrogen atoms.
The sequence of reactions only occur in the mitochondria (not cytoplasm) of eukaryotic cells. The cycle requires oxygen and does not function under anaerobic conditions.
It is the common pathway for the oxidation of carbohydrate, fat and some amino acids, required for the formation of high energy phosphate bonds in adenosine triphosphate (ATP).
Sequence of reaction
Krebs cycle
Pyruvate enters the mitochondria and is converted into acetyl-CoA, which represents the formation of a 2 carbon molecule from a 3 carbon molecule (with the loss of one CO2 and the formation of one NADH molecule). Acetyl-CoA is then condensed with the anion of a 4 carbon acid, oxaloacetate, to form citrate which is a 6 carbon molecule.
Citrate is subsequently converted into isocitrate, alpha-ketoglutarate, succinyl-CoA, succinate, fumarate, malate and finally oxaloacetate.
Alpha-ketoglutarate is the only 5 carbon molecule in the cycle.
Vit D deficiency a/w :
Vitamin D deficiency is associated with
low plasma calcium and phosphate together with elevated alkaline phosphatase and parathyroid hormone as a secondary response.
Proximal myopathy occurs, together with reduced growth and softening of the long bones resulting in deformities, for example, rickets and osteomalacia.
