SUGER physiology Flashcards
what is GFR determined by?
- balance of hydrostatic and colloid osmotic forces acting across the capillary membrane
- Kf
what are the layers of the glomerular filtration barrier?
- endothelium of capillary
- basement membrane
- podocyte foot processes
which forces promote filtration?
glomerular hydrostatic pressure and the colloid osmotic pressure of bowmans capsule
which forces oppose filtration?
hydrostatic pressure of bowmans capsule and colloid osmotic pressure of the glomerular capillary plasma proteins
what is osmolality?
number of solute particles per kg of solvent
what is osmolarity?
number of dissolved particles per litre of solution
what are the major cations of the ECF and ICF?
ECF= Na+ ICF= K+
how is the proximal convoluted tubule structured to promote reabsorption and what does it reabsorb?
- brush border on luminal membrane
- Na+, Cl-, HCO3-, K+, H2O, glucose, amino acids
what do principal cells do?
- reabsorb Na+ and H20
- secrete K+
what do intercalated cells do (type A and B)?
- type A- reabsorb K+, secrete H+
- type B- secrete HCO3-, absorb Cl-
why is insulin used to measure GFR?
- not reabsorbed or secreted
- so the concentration of insulin reflects the amount of water present in the tubular fluid
what is the effect of parathyroid hormone?
- released in response to a decreased concentration of Ca2+
- increased Ca2+ reabsorption
- stimulates formation of vitamin D and hydrolysis
what is the effect of atrial natriuretic peptide (ANP)?
- controls Na+ reabsorption
- inhibits aldosterone secretion
- causes Na+ secretion
how is ANP released?
when there is more Na+ in the blood, water moves into the blood down its osmotic pressure gradient- so blood volume increases- this stretches the atria releasing ANP
what is the effect of aldosterone?
- increases renal tubular reabsorption, of Na+ and secretion of K+
- increased expression of Na+/K+ ATPase
what is the effect of vasopressin/ ADH?
- secreted in response to ECF osmolarity and hypovolemia
- stimulates thirst centre in hypothalamus
- can trigger vasoconstriction
- acts at collecting ducts by inserting aquaporin II channels by acting on V2R receptors
what is the ammonium buffer?
- tubular cells take up glutamine from GF
- glutamine metabolised- forms NH4+ and HCO3-
- NH4+ secreted into lumen via Na+/ NH4+ anti porter
- HCO3- transported into peritubular capillaries via Na+/ HCO3- cotransporter
what is the law of mass action?
as the end products of a chemical reaction build up in a reacting medium, the rate of the reaction decreases, approaching zero
what is the renin angiotensin aldosterone system?
- decreased BP= decreased perfusion of juxtaglomerular aparatus- results in stimulation of macula dense- secretes renin into the blood stream
- angiotensinogen found in blood
- renin converts angiotensinogen into angiotensin I
- angiotensin I converted to angiotensin II via ACE
- ACE found in lungs and renal epithelium
what are the actions of angiotensin II?
increases blood pressure by:
- increasing ADH secretion (increased blood volume)
- vasoconstriction
- Na+ reabsorption= increased water retention= increased blood volume
- increased aldosterone secretion- acts of Na+/K+ pumps, increased absorption of Na+
what are the layers of the adrenal glands and what is secreted by each?
- zona glomerulosa- secretes aldosterone in response to decreased blood volume
- zona fasciculata- secretes cortisol in response to stress and low blood sugar
- zona reticularis- secretes androgens
- medulla- secretes adrenaline
what is the function of mineralocorticoids?
control salt and water balance- act on distal convoluted tubule and collecting ducts
what are the functions of glucocorticoids?
- immune- increases anti-inflammatory protein expression
- metabolic- gluconeogenesis, inhibits glucose uptake, increases blood glucose levels
- developmental- fetal- long maturation- surfactant production, brain development
what are the 2 main adrenal androgens?
- dehydroepiandrosterone (DHEA)
- androstenedione
what is the function of cortisol?
- lipid soluble- binds to intracellular proteins
- secreted in response to stress and low blood sugar
- decreases inflammation and increases blood glucose levels
what is the effect of adrenaline acting on alpha, beta 1 and beta 2 receptors?
- alpha- vasoconstriction of arterioles
- beta 1- positive chronotropic and inotropic effect
- beta 2- bronchodilation
what is the secondary messenger theory?
intracellular signalling molecules released by cell to trigger physiological changes after an initial stimuli on the outside of the cell- e.g. a hormone
where is EPO synthesised?
peritubular cells in the interstitial space of the renal cortex
what are the 5 epidermal layers?
- stratum corneum (keratin)
- stratum lucidum (not always present)
- stratum granulosum (contains keratohyaline granules)
- stratum spinosum (keratonocytes)
- stratum basale (keratinocytes, melanocytes and Merkel cells)
where are rete ridges found?
derma-epidermal junction
what are the 2 layers of the dermis?
papillary and reticular
what is the function of profilaggrin?
- precursor for filaggrin
- filaggrin produces natural moisturising factor
what causes desquamation?
shedding of mature corneocytes via protease enzymes breaking don corneodesmosomes
what is the function of the lipid lamellae?
keeps water inside cells and protects skin from irritants and allergens
what is the effect on an increased pH on the skin?
corneodesmosomes are broken down- increases risk of infection
what causes an increased pH of the skin?
lack of filaggrin- results in less NMF, so less water retention
what is the effect of decreased pH on the skin?
desquamation will not occur- as protease enzymes denature- so skin thickens
what are the 3 main cell types in the Islets of Langerhans and what do they secrete?
- alpha cells- glucagon
- beta cells- insulin and amylin
- delta cells- somatostatin
what is the function of insulin?
- lower blood glucose levels
- suppress glycogenolysis, gluconeogenesis, lipolysis and ketogenesis
- promotes glucose uptake into insulin-sensitive tissues
what is the function of glucagon?
- raise blood glucose levels
- increases hepatic glucose output via glycogenolysis and gluconeogenesis
- stimulates uptake of gluconeogenic precursors (e.g. fatty acids, glycerol and amino acids)
- reduces peripheral glucose intake
what is the function of somatostatin?
- inhibitory
- depresses action of insulin and glucagon
- decreases motility of stomach, duodenum and gallbladder
- decreases secretion and absorption in GI tract
how is insulin secreted?
- GLUT 2 transporters have low affinity- so glucose only enters when concentration is high
- glucose broken down via hexokinase- produces ADP
- ADP converted back into ATP
- ATP binds to K+ ATP channel- closes it
- prevents K+ leaving cell- depolarises membrane
- depolarisation causes voltage gated Ca2+ channels to open- Ca2+ influx
- Ca2+ binds to granules containing insulin- released via exocytosis
how is insulin stored?
- proinsulin- precursor for insulin
- proinsulin has alpha and beta insulin chains joined by C peptide
- proinsulin is cleaved- releasing alpha and beta insulin
- packaged into insulin- secretory granules
how does insulin act at cells?
- binds to insulin receptor on muscle and fat cells
- triggers intracellular cascade- mobilisation of GLUT 4 vesicles- inserted into membrane
- results in increased rate of glucose uptake by facilitated diffusion- therefore reducing blood glucose levels
where does glucose sensing occur?
Islets of Langerhans, ,medulla, hypothalamus and carotid bodies
what are incretins?
- amplify insulin response to glucose
- secreted by endothelial cells in GI tract
what are the 2 major incretins?
- glucagon- like peptide 1
- glucose- dependent insulinotropic peptide
where are C cells found and what is their function?
- between follicles in the thyroid gland
- secrete calcitonin
what is the colloid in the thyroid gland filled with?
thyroglobulin
what is iodide trapping?
- iodide transported from blood into thyroid glandular cells
- via sodium-iodide cotransporter
- sodium concentration maintained via K+/Na+ ATPase
how are thyroid hormones produced?
- iodide transported and oxidised into iodine
- binds to tyrosine residues of thyroglobulin via thyroid peroxidase
- iodine can attach to either of 2 positions or both on tyrosine
- coupling results in formation of T4
what are the chemical names for T3 and T4?
T3= triiodothyronine T4= thyroxine
how is T4 converted into T3?
via iodinase
what are the functions of thyroid hormones?
- activate nuclear transcription of large numbers of genes
- increase expression of oxidative enzymes, mitochondrial proliferation, sugar transport, Ca2+ ATPase activity, increased Na+ transport in muscles, increase Na+/ K+ membrane activity
- results in increased heart rate, BMR, cardiac function, ventilation and SNS activity
what nerve causes contraction of the detrusor muscle?
pelvic nerve (S2-S4)- parasympathetic
what is the function of the pudendal nerve (S2-S4)?
- somatic voluntary
- contracting pelvic floor and striatal sphincter
what is the function of the gastric nerve (T10-L2)?
- sympathetic
- relaxes bladder and contracts bladder neck
what is the mechanism of bladder storage?
- sympathetic and parasympathetic
- inhibits contraction of detrusor muscle
- distention of bladder
- sends low level signals to CNS
- triggers guarding reflex- pudendal outflow- causes contraction of pelvic floor and striatal sphincter
what is the voiding mechanism?
- spinobulbospinal reflex- periaqueductal gray
- passes signals to pontine micturition centre- increased parasympathetic outflow via pelvic nerve
- contraction of detrusor muscle= emptying of bladder
what is stress incontinence?
- loss of urine with exertion (sneezing or coughing)
- caused by urethral hypermobility or by intrinsic sphincter deficiency
what is urgency incontinence?
leakage accompanied by urinary urgency- detrusor overactivity
what is mixed incontinence?
loss of urine associated with urgency and also exertion, effort, sneezing or coughing
what is overflow incontinence?
overflow due to urinary retention (occurs due to detrusor underactivity or bladder outlet obstruction)
what is total incontinence?
complaint of continuous leakage
what connects the anterior and posterior pituitary?
pars intermedia
where does the anterior pituitary develop from?
Rathkes pouch
where does the posterior pituitary develop from?
it develops as a neural tissue outgrowth from the hypothalamus
what does the anterior pituitary gland secrete?
- growth hormone
- adrenocorticotropin
- thyroid stimulating hormone
- prolactin
- follicle stimulating hormone
- lueteinizing hormone
what does the posterior pituitary gland secrete?
- vasporessin
- oxytocin
what is the main difference between the production of hormones in the anterior and posterior pituitary?
posterior pituitary hormones are produced in the supraoptic and paraventricular nuclei of the hypothalamus and then transported to the posterior pituitary, wheres anterior pituitary hormones are produced and secreted there
what cell types produce each hormone secreted by the anterior pituitary?
- somatotropes- GH
- corticotropes- ACTH
- thyrotropes- TSH
- gonadotropes- LH and FSH
- lactotropes- PRL
what is the blood supply to the anterior pituitary gland?
portal circulation from hypothalamus- NO ARTERIAL BLOOD
what is the function of growth hormone?
- promotes increased cell size and mitosis
- increases rate of protein synthesis and mobilisation o fatty acids
- decreased rate of glucose utilisation throughout the body
what is the function of adrenocorticotropin?
- stimulate production of glucocorticoids and androgens
- maintains size of zona fasciculata and zona reticularis of adrenal cortex
what is the function of thyroid stimulating hormone?
production of thyroid hormones by the thyroid follicular cells
what is the function of follicle stimulating hormone?
- development of ovarian follicles (F)
- regulates spermatogenesis (M)
what is the function of luetinising hormone?
- ovulation and formation of corpus luteum (F)
- stimulates production of oestrogen and progesterone by the ovaries (F)
- stimulates testosterone production by the testis (M)
what is the function of prolactin?
- milk secretion and production
- prevents further ovulation
what is the function of vasopressin?
controls rate of water excretion- by acting on V2R receptors on the distal convoluted tubule and the collecting duct of the nephron
what is the function of oxytocin?
helps express milk from glands of the breast to the nipples and assists with delivery of the baby
what regulates the secretion of the anterior pituitary hormones?
- thyrotropin releasing hormone- TSH
- corticotropin releasing hormone- ACTH
- gonadotropin releasing hormone- FSH and LH
- GH releasing hormone- GH
- dopamine- inhibitory effect on prolactin
which is the only anterior pituitary hormone that does not have a negative feedback loop?
prolactin
what is the function hCG?
- stimulates oestrogen and progesterone production in the ovary
- diminishes once placenta is mature enough to take over production
- causes persistence of corpus luteum
what is the function of oestrogen?
- produced throughout pregnancy
- regulates progesterone levels
- prepares uterus for baby
- prepares breasts for lactation
what is the function of progesterone?
- prevents miscarriage- builds up endometrium for support of placenta
- prevents uterine contractions
what is the function of relaxin?
- high in early pregnancy
- limits uterine activity and softens cervix
- cervical ripening in preparation for delivery
what is the function of prostaglandins?
initiation of labour
what does hCG cause?
- persistence of corpus luteum
- prevents menstruation
- secreted by syncytial trophoblast cells
what are examples of maternal adaptations during pregnancy?
- weight gain
- BMR increases
- increased protein and lipid synthesis
- increases cardiac output and blood volume
- increased minute ventilation
- decreased total vascular resistance
- skin- increased pigmentation
what are linea nigra and striae gravidarum?
- linea nigra- dark central line on abdomen
- striae gravidarum- stretch marks in lumbar abdominal regions
what happens to the oestrogen: progesterone rate during partuition?
- increases
- progesterone levels drop- progesterone inhibits uterine contractility
- oestrogen increases number of gap junctions between uterine smooth muscle cells- so increases contractility
what are the stages of labour?
- latent phase- little cervical dilation
- active phases- 1- stronger, higher frequency contractions, 2- full dilation, foetal expulsion, 3- placental expulsion
- post-partum phase
what are the layers of the uterus?
- perimetrium
- myometrium
- endometrium
what is the perimetrium a continuation of?
abdominal peritoneum
what is the myometrium?
- thick smooth muscle layer
- hormone sensitive
- cells can undergo hypertrophy and hyperplasia during pregnancy
what are the layers of the endometrium?
- deep stratum basalis- not shed at menstruation, provides cellular reserve so a new functional layer can develop
- superficial stratum functionalis- hormone responsive- proliferates in response to oestrogens, becomes secretory in response to progesterone, shed during menstruation
what is cervical ripening?
- growth and remodelling of cervix prior to labour
- occurs under influence of placental hormones and relaxin
what are the layers of the placentas transport barrier?
- maternal endothelial cells
- maternal connective tissue
- endometrial epithelial cells
- chorionic epithelial cells
- foetal connective tissue
- foetal endothelial cells
what is the primordial follicle?
oocyte surrounded by a single layer of granulosa cells
what is the primary follicle?
oocyte fully grown, zona pellucid forms, single layer of granulosa cells
what is the prenantral follicle?
mitosis of granulosa cells, early theca (interna and externa) form
what is the early antral follicle?
antrum begins to form in the midst of granula cells due to the fluid they secrete
what is the dominant follicle?
many layered theca and granulation cells, large antrum, oocyte surrounded by granulosa cells- cumulus oophoros
what is the function of the zona pellucida?
contains glycoproteins- role in binding sperm cell to surface of egg
what is the role of granulosa cells?
secrete oestrogen, small amounts of progesterone pre-ovulation and secrete inhibin
what occurs in the follicular phase?
- days 4-15/16
- FSH stimulates ripening graffian follicle
- oestrogen secretion from follicle granulosa cells initiates proliferation of endometrium
- endometrial proliferation maintained by increased oestrogen secretion from enlarging follicle
what occurs in the ovulation phase?
- days 14-16
- initiated by LH surge- caused by rise in estradiol produced by dominant follicle- increases anterior pituitary’s sensitivity to GnRH- so more LH is released
- early progesterone secretion of luteinising follicle stimulates early secretory changes in endometrium
- granulosa and theca cells converted into progesterone secreting cells- so rate of secretion of oestrogen decreases, increased progesterone concentration- so reducing uterine contractions
what occurs in the luteal phase?
- days 16-25
- LH secretion induces luteinisation of granulosa and theca cells
- progesterone maintains secretory change in endometrium
- LH and FSH secretion ceases- corpus luteum involutes
- corpus luteum secretes progesterone and androgens
what causes accelerated growth of primary follicles?
- increased concentration of FSH and LH- causes rapid proliferation of granulosa cells
- theca forms:
- theca interna- can secrete additional steroid sex hormones (oestrogen and progesterone)
- theca externa- develops into highly vascular connective tissue- forms the capsule of the developing follicle
how does oestrogen effect granulosa cells?
form increases FSH receptors- amplifying the effect
what does the LH surge cause?
- rapid secretion of follicular steroid hormones containing progesterone
- theca externa releases proteolytic enzyme- allows follicle to swell
what occurs during involution of the corpus luteum?
- inhibin is secreted
- inhibits FSH and LH- causes corpus luteum to involute
why do progesterone levels increase after ovulation?
to prevent uterine contractions
when must the egg be fertilised?
24-48 hours after ovulation
what is the acrosome reaction?
- binding triggers acrosome reaction in bound sperm
- plasma membrane of head is altered- underlying membrane bound acrosomal enzymes exposed to zona pellucida
- enzymes digest path through to zona pellucida
what changes does the first sperm to penetrate the zona pellucida induce?
- cortical reaction
- fuses with the eggs plasma membrane
- Changes the membrane potential
- prevents additional sperm binding
- head of the sperm drawn into cytosol of egg- completes meiosis II
what is the cortical reaction?
- cytoplasmic secretory vesicles located around eggs periphery release contents
- enzymes present inactivate sperm binding sites and harden the zona pellucida
what occurs on day 1 of fertilisation?
syngamy- pronuclei migrate tot centre, synthesise DNA, chromosomes organise at equator
what occurs on day 2 of fertilisation?
- cleavage
- ooplasm divides
- activation of embryonic genome
what is present on day 3 of fertilisation?
8 totipotent cells
what occurs on day 4 of fertilisation?
- compaction
- cells flatten and maximise intracellular contacts
- tight junctions form
- polarisation of outer cells
what occurs on day 5 of fertilisation?
- cavitation and differentiation
- tight junctions between outer cells form trophectoderm
- fluid-filled cavity expands
- blastocyst- 60% trophectoderm, 40% inner cell mass
what occurs in day 5/6 of fertilisation?
expansion of the cavity, diameter increases, zona pellucida thins
what happens on day 6 of fertilisation?
embryo hatches from zona pellucida
what is apposition?
- synchronisation of embryo and endometrium
- hatches blastocyst orientates via embryonic pole
- receptive endometrium
what occurs during the attachment stage of implantation?
- apical surfaces of hormonally conditioned endometrial cells express integrin subunits
- trophoblastic cells express integrins
- attachment occurs
what is the decidual reaction?
- progesterone- primed endometrial cells differentiate into decidual cells
- endometrial glands enlarge and local uterine wall becomes highly vascularised
- growth factors and nutrients secreted
what are the 2 phases of the endometrium?
- proliferative- thick, glandular tissue, myometrial and endometrial growth, oestrogen increases progesterone receptors on endometrial cells
- secretory- increased number of blood vessels and glycogen storage, decreased contraction of myometrium, mucus plug forms- preventing pathogens entering
during spermatogenesis, what does mitosis form?
- type A daughter cells- remain outside of blood testis barrier- produce more daughter cells
- type B daughter cells- differentiate into primary spermatocytes- pass through tight junctions between Sertoli cells
what are the products of meiosis during spermatogenesis?
4 spermatids
what is the final stage of spermatogenesis?
spermeiogenesis- differentiation of spermatids into spermatozoa
what is capacitation?
- functional maturation fo spermatozoon
- acrosomal cap altered to allow acrosome reaction to occur
- hyperactivity- tail motility increases
how many efferent ductules are present?
12
what is the function of the efferent ductules?
transport sperm from rete testis to epididymis
what is the function of the epididymis?
site of sperm maturation and storage
what is vas deferens?
- arises from epididymis
- muscular tube
- produces peristaltic contractions
- passes up scrotum through inguinal canal to posterior surface of bladder
what is the seminal vesicle?
- combines w/ vas deferens to form ejaculatory duct
- secretes alkaline fluid with clotting factors
where does the ejaculatory duct pass from and to?
from prostate into the urethra
what is the function of leydig cells?
- secrete testosterone
- found between seminiferous tubules
- circulates in blood- bound to albumin or androgen- binding globulin
what is the function of Sertoli cells?
- nourish sperm
- form blood-testis barrier- due to tight junctions between cells
- secrete inhibin- stimulated by FSH- negative feedback action on anterior pituitary
- also secrete androgens for spermiogenesis
what does mitosis during oogenesis produce?
primary oocyte
in oogenesis, when does meiosis 1 occur and what does it produce?
- puberty- at the end of meiotic arrest
- forms secondary oocyte (takes most of cytoplasm) and polar body- apoptoses
in oogenesis, when does meiosis II occur and what does it produce?
- fertilisation
- forms ovum (takes most of the cytoplasm) and polar body- apoptoses