CEP Flashcards
Endocrine signalling
Secreting hormone into blood to reach target cell
Paracrine signalling
Hormones secreted to reach nearby cells
Autocrine signalling
Hormones to a local effect (target sites on the same cell)
How is the response to a drug/hormone measured?
Radio ligand binding assay
Amount of radioactivity is proportional to number of receptors
EC50
Effective concentration 50%
The concentration required to make 50% response (effect)
Kd (dissociation constant)
50% of receptors occupied (binding)
Affinity equation
1/Kd (low Kd = high affinity)
Why measure ligand binding?
To see affinity of drug
Endocrinology
The study of hormones
What are the four types of hormone?
Protein (insulin)
Steroid (cholesterol)
Amine/small peptide (tyrosine)
Amino acid derivatives
How are hormones measured?
Bioassays
Immunoassays
Mass spectrometry
What are the anterior pituitary hormones?
ACTH
TSH
GH
LH/FSH
PRL
What are the posterior pituitary hormones?
Vasopressin
Oxytocin
How to treat underactive glands?
Hormone replacement
Can be due to autoimmune
Primary/secondary can effect later on down the line and not appear until then
How to treat over active glands?
Block receptors
Often caused by tumours (surgery)
What are the 4 main types of receptors?
Ligand-gated ion channels (ionotropic)
G-proteins coupled receptors
Kinase-linked receptors
Nuclear receptors (not on plasma membrane)
What is the mechanism of ionotropic/ligand-gated ion channels?
Ion channels open when ligand binds
Causes change in membrane potential as +/- ve charges change
Can cause depolarisation/hyperpolarisation
What is the mechanism of GPCRs?
Ligand binds
G protein activates/changes conformation
Has a postage or negative effect
Causes ions channels to open or enzymes to produce second messenger
Resulting in a signalling cascade
What is the mechanism of kinase-linked receptors?
Ligand bonds directly to enzyme
Conformation change
Phosphorylation cascade occurs
Gene transcription
Protein synthesis
What is the mechanism of nuclear receptors?
Ligand diffuses directly across the membrane
Binds in nucleus to transcriptional factor
Gene transcription
Protein synthesis
What is the fastest receptor?
Fastest: l-g ion channels
GPCRs
Kinase-linked receptors
Nuclear receptors
How does Adenylyl cyclase work?
AC is an effector enzyme activated by a g-protein
It converts ATP into cyclic AMP which is a second messenger
Signal is stopped by cAMP phosphodiesterase
How does phospholipase C work?
It has 2 second messengers
Gq activates PLC
Causes PIP2 to convert to DAG and InsP3
Causes Ca2+ to be released from ER
What does a protein kinase do?
Adds phosphate
What does a proteins phosphatase do?
Removes phosphate
What can mutations in receptor genes lead to?
Inactive (no function or under)
Or over active (tumour/hyper function)
What is the thyroid pathway?
Hypothalamus released TRH
Anterior pituitary TSH
Thyroid released T3, T4
Increases metabolism
TSH resistance
Hypothyroidism
Not enough thyroid activity
Treated by more TSH
Cushing’s syndrome
Adrenal tumor
Benign adenoma
What is the endocrine system?
A system of ductless glands and cells that secrete hormones
Regulates metabolism, homeostasis, reproduction
Exocrine glands
Realise their secretions outside of the body
May be ducted
Not part of endocrine system
Intercrine signalling
Acting within the same cell
Hormones are controlled by…
Feedback (usually negative)
How does negative feedback work?
Senses the change and activated the mechanism to reduce it
The final product of an endocrine cascade acts to inhibit the release of hormones
Axis
How glands communicate
Peptide/protein hormones
Mainly from pituitary
Made from chains of amino acids
Hydrophilic
No carrier needed in blood
Stored in membrane bound vesicles (to be released via exocytosis)
Produce on RER as pre-prohormone which is broken by proteolysis
Steroid hormones
Made from cholesterol
Converted to pregnenolone via CYP11A
This then can differentiate using other enzymes
Hydrophobic (won’t travel in blood)
Can’t store in vesicles so synthesised as required
Where is aldosterone made?
Adrenal cortex
Zona glomerulosa
Where is cortisol made?
Adrenal cortex
Zona fasciculata
Where is adrenal androgens made?
Adrenal cortex
Zona reticularis
How are steroid hormone signals stopped?
Inactivated metabolism transformations
Excretion in urine/bile
Amine hormones
From thyroid gland
T4 Contains 4 iodine atoms
T3 contains 3 iodine atoms
Small, non polar -> hydrophobic
Soluble in plasma membrane
Require carrier proteins
What do carrier proteins do?
Increase solubility
Increase half life
Reservoir in blood
Can have specific and non-specific (looser binding) kinds
Where to hormones bind?
Protein- cell surface receptors
Steroid- intracellular receptors
What’s HRE?
Hormone response element
Specific areas for hormones to bind in DNA
Exogenous
Come from sources outside of living things
Endogenous
Come from sources within a living thing
Potency
the strength of an intoxicant or drug, as measured by the amount needed to produce a certain response.
Pharmacology
The study of mechanism or drug action
Drug
Active ingredient in a medicine
What drugs produce an effect by not binding to a receptor? (Physicochemical properties)
Antacids
Laxatives
Heavy metal antidotes (EDTA)
Osmotic diuretics
General anaesthetics
Alcohol
Most drugs have ___ potency
High
So effect at very low concentrations
Biological specifity
Receptor wise
Natural, biological, endogenous receptor/target
Chemical specifity
Drug wise
Artificial, chemical, exogenous ligand/drug/agonist
Stereo selectivity
In vivo razemisation (equilibrate back to both isomers)
So always both forms appear
What can drugs be classified by?
Chemical nature
Symptoms/disease
Organ system effected
Receptor
Duration of action
Generations
Route of administration
Affinity
The binding strength of the drug receptor interaction
Or
Likelihood of binding
Receptor in pharmacology
Anything that causes a physiological effect when interacting with a drug
Law of Mass action
Le chantelier’s principle
A + R <-> AR
E max
Maximum response
Relationship between drug conc and response
Continuous
Saturation
Exhibits threshold
Kd equation
Kd = [A][R] / [AR]
Mol/litre
Langmuir isotherm
P= [A] / (Kd + [A])
Kd vs EC 50
EC 50 is model free equivalent to Kd (has to be the classic curve)
Agonist
Bind to receptor to produce response
Can be endogenous (given from outside also) and exogenous
Antagonist
Binds to receptor but no response
Prevent agonist binding so inhibits
Has affinity but no efficacy
Antagonist vs inhibitor
Inhibitor - enzymes
Antagonist -receptors
Types of antagonists
Competitive- unbind and rebind
Irreversible- covalent binding, same site
Allosteric- alternative site
Channel blockers- plug channel
Physiological- no binding
ADME
Absorption, distribution (drug to target)
Metabolism, Excretion (remove drug)
Effective concentration
The lowest concentration needed to make an effect
Therapeutic window
The concentration window between the toxic and effective concentration
Where can the drug be lost when administered?
Not dissolved
Broken down by stomach acid/intestine
Not absorbed
Secreted into bike
Metabolised
Bound to plasma proteins
Excreted
Tissue bound
Routes of administration
Enteral (oral, rectal)
Parenteral (subcutaneous, intra-muscular, intra-venous)
Percutaneous (inhalation, sublingual, topical, transdermal)
Absorption depends on…
Route
Blood flow at site
Dose
Active vs passive diffusion
Solubility
Chemical nature
Molecular weight
Partition coefficient
Gastric mobility
pH at site
Area of absorbing site
Presystemic elimination
Ingestion with/without food
Bioavailability
The fraction of the total dose administered that reaches the plasma
Factors that affect absorption in GI tract
Dispersal/solubility of drug in gut
Stability in acid/alkali
Lipid solubility
Time available for absorption
Concentration of drug
Blood flow
Interaction with food
Effect of drug (irritant)
Effect of meals
First pass metabolism
Pharmaceutical interventions that effect absorption
Particle size
Dry-powder inhaler
Enteric coated tablets
Slow release
Factors effecting transdermal absorption
Lipid solubility
Formulation
Skin thickness
Hydration
Blood flow
Pinocytosis
Endocytosis of fluid and dissolved molecules (opposite of exocytosis)
Lipophilicity
Likes lipids
Distribution of drugs depend on
Lipid solubility
Diffusion barriers
Tissue binding
Plasma protein binding
Albumin
Family of soluble globular proteins that transport small molecules in the blood
Decreased levels in liver and kidney disease
Alpha-acid glycoprotein
A carrier of basic and neutral lipophilic compounds
Increased in inflammatory conditions
Process of pharmokinetics when drug testing
Lipophilic/hydrophilic
pH value
Active perfusion
Large surface area
Diffusion barriers
Any inactivating enzymes
Diffusion barriers
Block diffusion across membranes
Main types- BBB, placenta
Apparent volume distribution
The notional volume of fluid required to dilute the absorbed dose to the concentration found in plasma
AVD equation
AVD = dose / plasma concentration
High AVD
Tissue bound
Lipophilic and basic
Low AVD
Heavily plasma protein bound
Ion trapping
Passive, semipermeable membrane
Only the unionised molecule will travel across the membrane
So a high concentration of an acidic drug will be concentrated in a compartment with high pH
Metabolism
Mainly liver (first pass), kidney, skin, lungs, microbiome
Basically anything in can do chemically with a drug
Mainly oxidation and conjunction
Unusually inactivated but not always
Oxidation via
Cytochrome p450 enzymes
Conjunction via…
Sulfation pathways
Portal vein
Something that vascularises twice
First pass metabolism
Phase 1- oxidation via cytochrome p450 enzymes
-hydroxyl groups -> more hydrophilic
Phase 11- conjunction reactions
- charged groups are conjugated -> more hydrophilic
Excretion
Kidney
-into urine
Liver
-into bile (enterohepatic circulation)
Lungs
Fluids
-salvia, sweat, milk
Performing a PK study
Dose
Collect samples (blood, urine etc)
Analysed drug
PK data analysis
How to quantitatively measure drugs in excretion?
Mass spec
Liquid chromatography
LC-MS
Dose interval dependent on…
Plasma half life
Hormones in anterior lobe
ACTH (Adrenocorticotropic hormone)
TSH (thyroid stimulating hormone)
GH (growth hormone)
FSH/LH (follicle-stimulating hormone/ luteinising hormone)
PRL (prolactin)
Hormones in posterior lobe
Vasopressin (ADH)
Oxytocin
What is the hypothalamus regulated by?
Hormone mediated signals
Neural inputs
Uses of hypothalamus…
Final common pathway to anterior pituitary
Non-endocrine function (thirst etc)
Sends signals to other parts of nervous system
Posterior pituitary communication
Only through nerves
Secretory granules migrate down axons (supraopyicohypopophyseal)
No hormones produced here only secreted
What does the hypothalamus secrete?
corticotrophin-releasing hormone
dopamine
growth hormone-releasing hormone
somatostatin
gonadotrophin-releasing hormone
thyrotrophin-releasing hormone
What does GHRH stimulate?
Growth hormone
What does somatostatin do?
Inhibit growth hormone
What does GnRH stimulate?
Follicle-stimulating hormone
Luteinizing hormone
What does CRH stimulate?
ACTH
What does TRH stimulate?
TSH
What does dopamine stimulate?
Inhibits prolactin
Growth hormone release
Stimulated by hypoglycaemia, exercise and sleep
Suppressed by hyperglycaemia
Released in pulses throughout the day
What is GH mediated by?
Effects mediated by IGF-1
What does GH stimulate?
Protein synthesis
Lipolysis
Glucose metabolism
Acquisition of bone mass
Regulation of body composition
Well-being
What does FSH and LH trigger?
LH- testosterone production in tested
FSH- oestrogen production in ovaries
What is the secondary effect of FSH?
Estrogen -> breasts, hips broaden, pubic hair, folliculogenesis
What is the secondary effect of LH?
Testosterone ->
penis/scrotum grow
facial hair grows
larynx elongates
shoulders broaden
hair grows
muscle increases in body
spermatogenesis
What does prolactin do?
Lactation
But also inhibits GnRH (less FSH/LH)
What does ACTH do?
Stimulates cortisol production in adrenal gland
-> regulates blood sugar, increases fat, help defends body against infection, respond to stress
What does TSH do?
Stimulates the thyroid
-> that produces T3 and T4
Where is vasopressin synthesised?
Supraoptic and paraventricular nuclei of hypothalamus
What does vasopressin do?
Determines the rate of free water excretion
By changing the permeability of the luminal membrane of cortisol and medullary collecting tubes
What stimulates ADH?
Hyperosmolality (too much water)
Effective circulating volume depletion (blood loss)
What does oxytocin do?
Stimulates contraction of smooth muscle in Breast and uterus
-> milk ejection reflex
-> parturition (birth)
Pituitary disease manifestations
Neurological
Visual
Hypopituitarism
Hormone hypersecretion from adenoma
Lesion
Damage to tissue
Mass neurological effects of pituitary lesions
Headaches
Brain damage/hypothalamic damage
Nerve damage
Optic nerve damage
CFS leak
Hypopituitarism causes
Tumours
Radiotherapy
Pituitary infarction (Sheehan’s syndrome)
Infiltration of pituitary
Trauma
Isolated hypothalamic hormone deficiency (Kallmann’s)
What is apoplexy?
Bleeding into an organ / loss of blood flow to an organ
Infiltration of pituitary
Lymphatic infiltration causes inflammation
GH deficiency manifestation
Children- poor growth
Adults- more abdominal fat, less muscle strength, impaired cardiac function, decreased bone mineral density
How to diagnose GH deficiency?
ITT
glucagon
GHRH+arginine IGF-1 (blood test)
GH deficiency treatment
Hormone replacement
FSH/LH deficiency manifestations
Delayed puberty
Osteoporosis
Anaemia
Men- libido decreased, infertility, less muscle mass, less mood
Women- libido decreased, infertility m, dyspareunia
FSH/LH deficiency diagnosis
Blood test of hormones
Oestradiol
Menstrual history
Morning testosterone
FSH/LH treatment
Hormone replacement
ACTH deficiency manifestations
Fatigue
Weakness
Nausea/vomiting
Anorexia
Hypoglycaemia
Hypotension
Anaemia
ACTH diagnosis deficiency
9am serum cortisol and ACTH
Dynamic: short synacthen test, ITT, glucagon test
Alpha sub units on G proteins
Ga s
Ga io
Ga q11
ACTH deficiency treatment
Replace what is missing (steroids)
Approximate to the natural rhythm
TSH Deficiency manifestations
Fatigue, weakness
Cold intolerance
Bradycardia
Inability to lose weight
Puffiness
Pale/dry skin
Constipation
TSH deficiency diagnosis
TSH, fT3, fT4 tests
Treatment for TSH deficiency
Hormone replacement (levothyroxine)
Diabetes insipidus
Deficient secretion of ADH
Diabetes insipidus causes
Idiopathic (autoimmune)
Familial (autosomal dominant mutations, Wolfram syndrome)
Tumours
Neurosurgery
Infiltration disorders
Infections
Hypoxic encephalopathy
Hypoxic encephalopathy
When blood doesn’t receive enough oxygen for a period of time
ADH deficiency manifestations
Polyuria (lots of urine)
Causes of polyuria
Osmotic diuresis (DM, renal failure)
Primary polydipsia
Diabetes insipidus
ADH deficiency diagnosis
Urine output
Blood (electrolytes, glucose, urea, creatinine)
Water deprivation test
ADH deficiency treatment
ADH analogues (replacements)
Functioning vs non-functioning pituitary adenomas
Functioning- secrete hormones from tumours
Non- no secretion
GH hypersecretion causes…
Acromegaly
Acromegaly symptoms
Gigantism
Arthritis
Hypertrophy of frontal bones
Hyperhidrosis
Etc
Acromegaly diagnosis
Oral glucose tolerance test
IGF-1
Pituitary Imaging
Acromegaly treatment
Pituitary surgery
Dopamine agonists
Somatostatin analogues
GH receptor antagonists
Radiotherapy
High prolactin causes
Stress, pregnancy, lactation, sex, sleep
Antipsychotics, antidepressants, opiates
Hypothalamic tumours
Prolactinoma manifestation
Hypogonadism (lack of sex hormones)
Galactorrhoea
Mass effects
Prolactionoma diagnosis
Pituitary imaging
Prolactinoma treatment
Dopamine agonists
Surgery
Radiotherapy
Cushing’s syndrome
Too much cortisol
Could be due to too much ACTH or adrenal disease/steroids
Cushing’s disease
Excess ACTH from corticotroph adenoma
Cushing’s syndrome symptoms
Weight gain
Slow healing of cuts
Fatigue
High risk of infections
Glucose intolerance
Moon face/ buffalo hump
Red marks (striae)
Cushing’s diagnosis
24hr UFC (cortisol in urine)
Midnight serum cortisol
Overnight/low dose dexamethazone suppression test
9am ACTH
Imagining
Cushings treatment
Pituitary surgery
Radiotherapy
Drugs
Bilateral adrenalectomy
TSHoma (mani, diag and treat)
Mani-
Thyrotoxicosis
Diag-
Hormonal tests
Imaging
Treat-
Surgery/meds/radiotherapy
FSHoma
Mani-
Menstrual irregularities
Ovarian hyper stimulation
Testicular enlargement
Infertility
Diag-
hormonal tests
Imaging
Treat-
Surgery
Radiotherapy
What protein hormones made up of?
An alpha and beta subunit
What do TSH, LH, FSH and hCG all share?
The same type of alpha subunit
Thyroid gland embryology
Proliferation on pharyngeal floor (foramen caecum)
Descends through thyroglossal duct then duct obliterates (or becomes thyroglossal cyst)
Thyroid gland location
Anteriorly: strap muscles
Sternohyoid, sternothyroid
Laterally: sternocleidomastoid muscle
Can only palpate isthmus
Thyroid blood supply
Superior thyroid artery (first brand of external carotid artery)
Inferior thyroid artery (from thyrocervical trunk)
Superior (into jugular vein)
Middle (into jugular vein)
Inferior thyroid veins (into brachiocephalic vein)
All together- venous plexus
The aortic arch extends to…
Left subclavian artery
Left common carotid artery
Brachiocephalic artery-> right subclavian and right common carotid
Parathyroid glands secrete… and their functions
PTH - regulator of serum calcium
Targets kidneys intestine and bone
Describe parathyroid glands
Small, flattened oval shaped glands
Normally 4 glands
On POSTERIOR of thyroid gland
Parathyroid gland embryology
Superior parathyroid derived from 4th pharyngeal pouch
Inferior derived from 3rd pharyngeal pouch
Glands descend with thymus but stop earlier
Parathyroid glands blood supply
inferior thyroid artery
Superior/middle/inferior veins
Adrenal glands location
Superomedial aspect of kidneys
Retroperitoneal
Level t11-12
Surrounded by Perirenal fat
Separated from kidneys by fascia
Retroperitoneal
anatomical space located behind the abdominal or peritoneal cavity
Adrenal glands structure and secretions
Distinct inner medulla (noradrenaline and adrenaline) and outer cortex (cortisol)
Adrenal glands blood supply
Superior adrenal artery (branch of inferior phrenic)
Middle adrenal artery (branch of abdominal aorta)
Inferior adrenal artery (branch of renal artery)
Right adrenal vein (into inferior vena cava)
Left adrenal vein (into left renal vein then IVC)
Adrenal gland innervation
Directly by preganglionic sympathetic fibres (from mostly greater splanchnic nerve)
Adrenal medulla acts as a specialised sympathetic ganglion
Endocrine pancreas function
Islets of langerhans
Release insulin and glucagon
Exocrine function of pancreas
Acinar cells
Digestive enzymes
Endocrine pancreas embryology
Begins as two buds that develop rotate and fuse (=2 ducts)
Endocrine pancreas location
Head -attached to duodenum to the right
anterior to IVC, right renal artery and vein and left renal vein
Bile duct is embedded in its posterior surface
Neck- overlies superior mesenteric vessels
Formation of portal vein occurs posteriorly
Body- left of superior mesenteric vessels
Posterior surface in contact with aorta, SMA left Kidney and adrenal
Tail- enters lienorenal ligament
Related to splenic hiking and left colic flexure
mesentery
Fold in membrane that attaches the intestine to the abdominal wall
Dirty drugs
Bind to more than one receptor
Side effects
The nature of drug receptors
Enzymes
Ion channels
Transports
Physiological receptors
DNA/RNA
Substrates, metabolites and proteins
Monoclonal antibodies
Efficacy relative to endogenous agonist scale=
Full inverse agonist
Partial inverse agonist
Silent antagonist
Partial agonist
Full agonist
Super agonist
Ways to regulate cell function
Alter membrane potential
Alter enzyme activity
Alter gene expression
GABA a receptor
Ligand gated choride ion channel
Benzodiazepine binds to allosteric site and increased affinity of binding
Glutamate gated chloride receptors
Common channels in nervous system
Important targets for anti parasitic drugs
Spare receptors/super agonists
Some ‘super agonists’ can produce maximal response without binding to all available receptors
Emax > 100%
Partial agonists
Low efficacy, cannot produce maximal response even when bound to all receptors
Competitive antagonist
Bind reversible
Parallel shift of dose/response curve
Irreversible antagonist
Being covalently
Decrease the maximal response
Can still produce max response -> evidence for spare receptors
Allosteric antagonism
Being reversibly at different site to agonist
Decrease agonist affinity
Reduced likelihood of agonist binding
Channel blockers
Bind inside and prevent passage of ions
Tend to be enhanced by receptor activation
Physiological antagonist
Not binding to receptor
Desensitisation
Prolonged exposure can reduce response to drug
Allosteric effects on receptors
Change shape for good or bad
Two types of acetyl choline receptors
Nicotinic
Muscarinic (GPCR)
How to get drugs/signals across a membrane?
Integral ion channels
Integral tyrosine kinases
Steroid receptors/nuclear receptors
GPCRs
Cytokine receptors
Nuclear receptors location
Act In nucleus
But mostly located in the cytoplasm
When steroid bound then conformational change
DBD
DNA binding domain mediates binding of nuclear receptors
Types of G subunit
Gs stimulating cAMP pathway
Gi inhibiting
Gq stimulating PLC pathway
Diabetes diagnosis
Random >11.1mmol/l
Fasting glucose >7mmol/l
HbA1c >48mmol/mol
Need to repeat test if no symptoms
HbA1c
Reflects previous 10 weeks of ambient circulating glucose
65% or 48mmol/mol
Can be to diagnose
Or measure how well diabetes is being treated
Oral glucose tolerance test
Gold standard
Fasting state
Measure glucose (>7)
Drink 75g of glucose
Wait 2 hours then measure glucose (>11.1)
Cause of diabetes
Insulin deficiency or resistance
Insulin anabolic function
Maintain supply of glucose to tissues
Regulates metabolism in muscles
Promotes protein synthesis
Inhibits breakdown of fat
Symptoms of diabetes
None
Weight loss
Tiredness
Infection
Candidiasis
Urine
Osmotic symptoms
Polyuria
Thirst
Blurred vision
Coma
Proinsulin
Cleaved by proteases
Can be measured as is always produced with each insulin molecule
Urinated out
Types of diabetes
Type 1 immune system attacks and destroys the cells that produce insulin
Type 2 cells don’t respond to insulin
Gestational
Monogenic
Cause of type 1
T cells attack insulin beta cells in islets of langerhan
Treatment of type 1
Lifestyle- lower glucose levels when they are exercising
Insulin
Insulin delivery system (midlands hybrid closed loop pilot outcomes)
Glucose level sensing
Sends signals to machine
Diffuses insulin into body
Treatment of type 2
Lifestyle
Give drugs that Reduce insulin resistance (metformin, sitagliptin, liraglutide)
Give insulin (gliclazide, insulin injections)
Give something that will Increase glucose excretion (SGLT2 inhibitors: dapagliflozin)
Diabetes treatment not for glucose
Blood pressure- ACE, beta blockers, ca channel blockers, diuretics
Lipids- statins, fibrates
Uncontrolled diabetes
Hypoglycaemia- shaky, sweaty, dizzy, hungry, nervous, upset, tired, weak
Hyperglycaemia- dry mouth, thirst, weakness, headache, blurred vision, urination
Long term-
Mental health
Vascular
Cancer
Lack of insulin on fat
Triglycerides to glycerol/fatty acids
Fatty acids to acetoacetate
To urine ketones/blood ketones/ hydroxybutyrate
Or to acetone (smell in breath)
Why lower blood glucose?
Irritates endothelial cells
Causes furring
Blocking
Complications of diabetes
Micro vascular:
Eye
Kidneys
Neuropathy
Macro vascular:
Brain
Heart
Extremities
Why does t2 causes more cancer?
High levels of insulin
Causes increased growth as stimulates to all cells
Care of diabetic patient
Lifestyle advice
Glucose control
BP
cholesterol after 40, 4mmol/l
Regular screening
Empathy and engagement
Apparent volume of distribution
The notional volume of fluid required to dilute the absorbed dose into the concentration found in the plasma
Bio transformation of drugs
Phase 1
Oxidation/ hydroxylation/ dealkylation/ deamination/ hydrolysis
Phase 2
Conjugation
Endocrine cells 3 distinct anatomical distributions are:
Grouped into an endocrine gland
Forming discrete clusters
Dispersed singly among other cells known as diffuse neuroendocrine system
What are endocrine cells? (Types)
Epithelial cells mainly
But some are neuroendocrine cells
Neuroendocrine cells
Secrete amines that are decarboxylated
Form a secure link with the ANS
Neural crest cell derivative
APUD cells
Amine precursor uptake and decarboxylation
= neuroendocrine
Chromogranin
Core protein expressed by neuroendocrine (associated with hormone)
Synaptophysin
Membrane glycoprotein found in neuroendocrine vesicles
How to see if neuroendocrine cells are present?
Stain chromogranin or synaptophysin
Or directly stain their specific hormone
Where are Neuroendocrine cells normally found?
Respiratory
GI Tract
However not readily seen as scattered
Larger endocrine glands composed of neuroendocrine cells…
Adrenal medulla
Pancreatic uslets
Thyroid gland anatomy
Thin fibrous capsule of connective tissue
Made up of follicles
Follicles are made of..
Thyroid epithelial
C-cells
Colloid
Use of thyroid hormones
Control of metabolism
Regulation of growth
Multiple roles in development
What is the active thyroid hormone?
T3
What’s the difference between t3 and t4?
T4 has 4 iodines
T3 has 3
What cells produces thyroid hormones?
Follicular thyroid cells
What are thyroid hormones synthesised from?
Thyroglobulin precursor
Tyrosine
Thyroperoxidase function
Binds iodine to tyrosine residues in thyroglobulin molecules
Forms MIT + DIT
T3 is made of…
MIT
DIT
T4 is made of…
DIT x2
Thyroid hormone synthesis mechanism
- TSH binds to TSHR
- I- uptake by Na/I symporter
- Iodisation of Tg tyrosyl residues by thyroperoxidase
- Coupling of iodotyrosyl residues by thyroperoxidase
- Export of mature Tg to colloid where it is stored
Which thyroid hormone is more abundant?
T4
How is t3 converted from t4?
By deiodinase enzymes
Tests of thyroid function
Serum TSH (best)
Serum free T4
Serum free T3
Hormone levels of hyperthyroidism
Low serum TSH
High serum free T4 and free T3
Hormone levels of hypothyroidism
High serum TSH
Low free t4
Low free t3
Main causes of hyperthyroidism
Graves hyperthyroidism
Toxic nodular goitre
Thyroiditis
Others:
Exogenous iodine
Factitious
TSH secreting pituitary adenoma
Neonatal hyperthyroidism
Distribution of drugs into the CNS depends on?
Lipid diffusion
What are the different method of elimination?
Toxicology is the study of…
Unwanted or deleterious effects of drugs or chemicals in the body
Diabetes is a metabolic disease that is characterised by…
High blood glucose concentration
People with diabetes are at a greater risk of what conditions?
Neuropathy
Nephropathy
Cardiovascular disease
Stroke
Retinopathy
Hearing impairments
Polyphagia is…
Increased hunger
