Biochemistry Flashcards
Water balance in the body is controlled by
Anti-Diuretic Hormone (ADH) (aka Arginine Vasopressin)
ADH is produced by __________ and released by ____________
Hypothalamus
Posterior pituitary
ADH acts specifically in…..
Distal convoluted tubule (DCT) and collecting ducts (CD)
ADH acts through a ______________ to increase the transcription and insertion of ________________ to the apical membrane of the DCT and CD cells causing permeability of DCT and CD to _________
G-protein coupled receptor
Aquaporin–2 channels
Increase
Increased plasma osmolality would cause _______ release of ADH while decreased plasma osmolality would ________ ADH release
Increased
Decreased
Increase in DCT and CD permeability allows water to move ____________________, out of the nephron and back into the bloodstream, thus normalising ________________ and increasing ________________.
Down its concentration gradient
Plasma osmolality
Total blood volume
Large amount of ADH in volume leads to _____________ urine
Small volume of concentrated
Small amount of ADH in volume leads to _____________ urine
Large volume of diluted
Urine concentration/dilution measured as…
Urine osmolality
Concentrated urine has ________ osmolality while dilute urine has _______ osmolality
High
Low
Sodium balance in the body is mainly controlled by….
Mineralocorticoid activity of steroid
Mineralocorticoid activity is….
Na+ reabsorption in the renal tubules in exchange for K+/H+
Give examples of steroids with mineralocorticoid activity
Aldosterone (the main one)
Cortisol
Too much mineralocorticoid activity causes Na _______ while too little mineralocorticoid activity causes Na ______
Gain
Loss
Sodium (Na) is the most abundant cation in the _______________
Extracellular fluid (ECF) compartment
The normal plasma sodium concentration in ECF is __________, while the intracellular fluid (ICF) concentration is approximately _____________
135-145 mmol/L
10-12 mmol/L
Maintaining transmembrane concentration gradient of Na+ is necessary for……
Generating the resting membrane potential and for action potential propagation
Sodium is the main osmotic solute in the ECF, meaning that…..
Water travels in the direction of increasing sodium concentration via osmosis
Na+ intake determined by ____________ and excretion determined by _______________
Dietary intake and absorption in the colon and distal small bowel
Urinary excretion but also insensible losses, particularly in the sweat and faeces
Urinary sodium concentration is highly variable, depending on the……
Amount of reabsorption occurring in the nephrons
Majority of sodium reabsorption occurs in the…
Proximal Convoluted Tubule (PCT)
_______________________ allow for sodium reabsorption in the DCT
Apical Na+/Cl+ cotransporter
At any part in the nephron Na+ is driven across the basolateral membrane via…
Na-K-ATPase pumps
Which transporter is stimulated by aldosterone in order to increase Na reabsorption?
Apical ENaC in the collecting duct
In renal artery stenosis, there is reduced perfusion of the kidneys due to the partial arterial occlusion. Which downstream hormone would increase in quantity as a result of this?
Aldosterone
What are the 2 kinds of stimuli for ADH release
Osmotic → in health
Non-osmotic → in disease
Give examples of non-osmotic stimuli that cause ADH release
Hypovolaemia/hypotension
Pain
Nausea/vomiting
Hypotension and hypovolaemia stimulate _____________________
Activation of the sympathetic nervous system
Renal sympathetic nerve activity causes increased reabsorption of sodium in the PCT by activation of ___________________. This increases ___________, thereby ________________________, maintaining homeostasis.
a1 and a2 adrenoceptors
Fluid retention
Intravascular volume and blood pressure
Reduced renal perfusion and/or reduced sodium delivery to the nephron stimulates ________________________
Renin release from granular cells of the juxtaglomerular apparatus
Renin release leads to the production of ____________, which ____________.
Angiotensin II
Stimulates aldosterone secretion.
RAAS activation causes angiotensin II to stimulate __________________ and aldosterone to _________________
The Na+/H+ antiporter in the PCT
Increases the expression of ENaC in the CD
Raised blood volume stimulates myocytes to release ______ and _______ which promote _______________
ANP
BNP
Natriuresis (urinary excretion of sodium)
ANP and BNP act to reduce aldosterone secretion (from the adrenal glands) and renin secretion (from the juxtaglomerular apparatus), thereby _________________________
Decreasing sodium reabsorption in the DCT and CD
Addison’s caused by ___________ thus not enough _______ made so decreased ________
Adrenal insufficiency
Steroids
Mineralocorticoid
Decreased mineralocorticoid activity in Addisons causes kidneys to be unable to _______ thus Na is loss from _______ decreasing the _______ volume meaning the patient is clinically dehydrated
Retain enough sodium
ECF
ECF
Why do patients with Addisons have excess pigmentation
Excess pigmentation reflects excess ACTH from pituitary
ACTH molecule contains sequence for MSH within it
ACTH is degraded by proteases eventually exposing MSH
ADH secreted in response to non-osmotic stimulus causes slow ___________ that is distributed over _________________ so patients clinical volume status is remarkable
Water retention
All body compartments (ICF as well as ECF)
Diabetes insipidus is a….
Disruption of pituitary or pituitary stalk so ADH not secreted from posterior pituitary
There is no ADH to act on kidneys to cause water to be reabsorbed
Lots of pure water lost in urine so [Na] is high reflecting the H20 deficit
In diabetes insipidus, there is no…
ADH to act on kidneys to cause water to be reabsorbed
Mx of diabetes insipidus
Exogenous ADH (desmopressin) to replace ADH that the pituitary can’t make/release
Pituitary gland function is regulated by the _________ which is connected to it via the _________
Hypothalamus
Pituitary stalk
Pituitary stalk comprises of the….
Portal blood capillaries and nerve fibres
What are the anterior pituitary hormones?
TSH (Thyroid Stimulating Hormone)
ACTH (Adrenocorticotrophic Hormone)
LH (Luteinising Hormone)
FSH (Follicle stimulating hormona)
GH (Growth hormone)
Prolactin
What are the posterior pituitary hormones?
ADH
Oxytocin
Function of TSH
Act on the thyroid gland to elicit secretion of thyroid hormones
Function of ACTH
Acts specifically on the adrenal cortex to elicit secretion of cortisol
Function of LH and FSH
Act cooperatively on the ovaries in women and the testes in men to stimulate sex hormone secretion and reproductive processes
Function of GH
Acts directly on many tissues to modulate metabolism
Metabolic fuels (e.g. glucose, free fatty acids) in turn modify GH secretion
Function of prolactin
Acts directly on the mammary glands to control lactation
Gonadal function is impaired by elevated circulating prolactin concentrations
Prolactin release is inhibited by _______ while its release is most strongly stimulated by_________
Dopamine aka PRL-inhibitory factor (PIF)
Suckling
Prolactin (PRL) is produced by the ___________ of the anterior pituitary gland
Lactotroph cells
Causes of hyperprolactinoma
Stress
Drugs
Seizures
Primary hypothyroidism
Prolactinoma
Idiopathic hypersecretion
Idiopathic hypersecretion of prolactin can be identified through….
A rise in serum prolactin following administration of TRH or metoclopramide
Serum potassium concentration is usually kept within….
3.5-5.3 mol/L
T or F: Potassium loses mirror potassium intake
True
Which 2 factors are important in determining potassium excretion
Glomerular filtration rate
Plasma potassium concentration
Severe hyperkalaemia defined as…
> 7.0 mmol/L
What can cause hyperkalaemia in the body
Decreased excretion of Na+
Increased intake of Na+
Redistribution of Na+ out of cells
Where is potassium most reabsorbed in the body?
Proximal Convoluted Tubule
Which channel is mainly responsible for potassium reabsorption in the thick ascending limb?
NKCC2 transporter
Which channel is mainly responsible for reabsorption of Potassium from the lumen into the cell in the distal convoluted tubule?
H+-K+-ATPase
Which channel is mainly responsible for the transportation of potassium ions into the cell from the bloodstream in the late distal convoluted tubule and collecting duct?
Sodium-Potassium ATPase
What is the mechanism of the NKCC2 cotransporter in the nephron?
It pumps Na+, K+ and 2Cl- into the cell from the lumen
What effect do renal outer medullar K+ (ROMK) channels have on K+ in the nephron?
Allow for movement of K+ into the lumen by creating a positive voltage which provides a driving force for the passive reabsorption of K+
Which metabolic abnormality is seen as a consequence of potassium depletion?
Hypokalaemia alkalosis
ECG changes seen with hyperkalaemia
Tall tented T waves
Widening of the QRS complex
Increased PR interval
Flattened/absent P waves
What can cause decreased excretion of potassium
Renal failure
Hypoaldosteronism → e.g. Addison’s disease
High tubular K+ concentration stimulates _________________ which leads to an __________ of K+ channel on apical membrane. This results in an ___________ of K+ into the lumen
Na+/K+-ATPase
Increased permeability
Increased secretion
____________ stimulates ____________ in the basolateral membrane which stimulates ____________ & ____________ in the apical membrane, leading to increased K+ secretion.
Aldosterone
Na+/K+-ATPase
K+ channels & ENaCs
What can cause redistribution of potassium out of cells
Metabolic acidosis
Potassium released from damaged cells
Insulin deficiency
Psudohyperkalaemia
Hyperkalaemic periodic paralysis
Redistribution of K+ causes…
H+ is reabsorbed into the cells to try and decrease the pH, so K+ is excreted to maintain electrical equilibrium thus causing hyperkalaemia
What effect will alkalosis have on K+ in the extracellular fluid (ECF)?
Decrease in the concentration of K+ in the ECF
Where does insulin act in order to exert its effect on potassium levels in the blood?
Na+/K+-ATPase
Clinical features of hypothyroidism
Lethargy / tiredness
Weight gain
Cold intolerance
Dryness and coarseness of skin and hair
Constipation
Bradycardia
Subfertility
Galactorrhoea
Causes of hypothyroidism
Autoimmune destruction of the thyroid gland (Hashimoto’s disease)
Radioiodine or surgical treatment of hyperthyroidism
TSH deficiency
Congenital defect
Iodine deficiency
Primary hypothyroidism is the…
Failure of the thyroid gland itself
T or F: The demonstration of an elevated TSH concentration is usually diagnostic of primary hypothyroidism
True
How to differentiate between primary and secondary hyperlipidaemia
Primary → Not due to an identifiable underlying disorder
Secondary → Disorder is the manifestation of some other disease
Thyroid gland is responsible for…
Regulating the body’s metabolic rate via hormones it produces
Metabolic processes increased by thyroid hormones include….
Basal Metabolic Rate
Gluconeogenesis
Glycogenolysis
Protein synthesis
Lipogenesis
Thermogenesis
How does thyroid glands increase metabolic processes
Increasing the size and number of mitochondria within cells
Increasing Na-K pump activity
Increasing the presence of β-adrenergic receptors in tissues such as cardiac muscle
What are the steps of thyroid hormone synthesis (ATE ICE)
Active transport of iodide into follicular cell
Thyroglobulin is formed in follicular ribosome
Exocytosisof thyroglobulin into the follicle lumen
Iodination of the thyroglobulin
Coupling of MIT and DIT
Endocytiosis of iodinated thyroglobulin back into follicular cell
T or F: T3 and T4 are fat soluble
True
T3 and T4 are mostly carried by…
Thyronine binding globulin (TBG) and albumin → which are plasma proteins
What are the effects of cortisol?
Immunosuppression
Anti-inflammatory
Protein and afat metabolism
Regulate mood, behaviour and cognition
Lipolysis in adipose tissue
Increase plasma glucose by breaking proteins into amino acids
Stimulate gluconeogenesis in the liver
Bone metabolism
Regulate calcium absorption from GI tract
Cortisol MoA
Binds intracellularly to the glucocorticoid receptor (GR) in the cytoplasm
