SUGER Flashcards
where does normal proliferation of the skin occur?
just in basal layer
what are the functions of the skin?
barrier to infection
thermoregulation
protection against trauma and UV
vitamin D synthesis
regulate H2O loss
layers of the skin
epidermis, dermis, subcutaneous tissue
what is the epidermis?
outermost layer - stratum corneum
what is the epidermis made of?
corneo-desmosomes and desmosomes
what do corneodesmosomes do?
adhesion molecules
keep corneocytes together
when are increased numbers of corneodesmosomes seen?
psoriasis - thickening of the stratum corneum
when are decreased numbers of corneodesmosomes seen?
atopic eczema - thinning of stratum corneum, increased risk of inflammation
what does a healthy skin barrier consist of?
filaggrin, corneocytes
what does filaggrin do?
derived from profilaggrin (structural component of the cornfield envelope)
produces natural moisturising factor
what are corneocytes filled with? why?
NMF
maintain skin’s hydration, keeps H2O inside the skin
what is NMF? what does it do?
natural moisturising factor
maintain skin hydration, keep NMF inside skin
maintain acidic environment at outer surface of the stratum corneum
filled with acids
what is desquamation?
mature corneocytes are shed from the surface of the stratum corneum
balance introduction of new cells in basal layer
degradation of extracellular corneodesmosomes under protease enzymes
what enzymes are involved in desquamation?
proteases - degradation of extracellular corneodesmosomes
what is the pH of normal skin? what does this allow?
5.5
proteases remain on skin - enables balance of new cells from basal layers
what does lipid lamellae do?
keeps water inside skin cells
irritants/allergens bounce off surface of skin
what is the brick wall model?
corneocytes are the bricks, corneodesmosomes are the iron rods and lipid lamellae is the cement
iron rods only rusty near surface of skin barrier
what is the role of vitamin D in the skin?
producing the anti-microbial peptides needed to defend the skin from bacteria and viruses
what do irritants and allergens do?
irritants break down healthy skin
allergens trigger flare ups by penetrating into the skin and causing it to react
skin flare ups
caused by allergens - met with lymphocytes which release chemicals to induce inflammation
types of inflammation
red skin - dilation of blood vessels
itchy skin - stimulation of nerves
dry skin - skin cells leaking
cause of increased pH on skin
profilaggrin and filaggrin aren’t present - lack of NMF, so less water retention in corneocytes
effect of increased pH on skin
due to less water retention in corneocytes
damage to skin barrier as corneodesmosomes are damaged -> breakdown of skin and increased risk of infection
what happens in acne?
hypercornification
what does hypercornification lead to?
corneodesmosomes blocking entrance to hair follicles
increased production of sebum by sebaceous glands
sebum trapped in narrow hair follicle
sebum stagnates at pit of follicle where there’s no oxygen
what does the stagnation of the sebum lead to?
anaerobic conditions -> propionic bacteria acnes (p.acnes) multiply in stagnant sebum
what do p.acnes do?
breakdown triglycerides in sebum into FFAs -> irritation, inflammation, neutrophils
pus formation and further inflammation (follicle filled with neutrophils)
what is cosmetically induced acne?
cosmetics and oily hair gel can trigger acne - help plug hair follicle and initiate acne process
where are the kidneys? what are they derived from?
retroperitoneal
mesoderm
T12 - L3
right kidney vs left position
right kidney is lower than left
pushed down by liver
where are the hilums of the kidneys?
right: L2
left: L1
distinct structures of the kidneys
cortex, medulla and pelvis
what does the medulla consist of?
20 upside down pyramids
what does the pelvis contain?
fat and urine collecting system
transitional epithelium
what does the cortex contain?
renal corpuscules (glomerulus and bowman's capsule) and PCT/DCT medullary ray interlobular artery
what is the medullary ray?
collection of loop of Henle tubules
collecting ducts
striated appearance
what does the medulla contain?
no renal corpuscules
no glomeruli
tubules of loop of Henle, collecting duct and blood vessels
how are tubules in the medulla orientated?
radially - point from cortex to medulla
what is the renal pelvis?
space that urine drains into -continuous with collecting ducts proximally and ureters distally
what is the renal pelvis lined by?
transitional - same as in bladder
where does the renal artery come off?
abdominal aorta at L1
division of renal artery
into segmental arteries and suprarenal arteries, lead to radial network of arcuate arteries
what do arcuate arteries divide into?
travel circumferentially at the junction between cortex and medulla
give off interlobar arteries
what do interlobar arteries supply and divide into?
each lobe (medullary pyramid and overlying cortex) and divide into interlobular arteries
what do interlobular arteries divide as?
afferent arterioles
basic functions of the segments of the nephron
renal corpuscle - filter
proximal convoluted tubule -reabsorbing solutes
loop of Henle - concentrating urine
distal convoluted tubule - reabsorbing more water and solutes
collecting duct - reabsorbing water and controlling acid base and ion balance
what is the renal corpuscule?
whole unit of the glomerular tuft and bowman capsule
how thick is the urothelium?
5 cells
what does the surface layer of the glomeruli consist of?
large dome-shaped umbrella cells
what are umbrella cells?
large and cover several underlying intermediate cells
tight junctions to prevent urine going between cells, keep apical membrane components from diffusing to lateral aspects of cells, prevent material diffusing around cells
basal layer of urothelium
cuboidal cells
layers of bladder epithelium
surface, intermediate and basal layer
do ureters have serosa?
no
how is urine propelled along the ureter?
peristalsis
layers of the bladder
lamina propria, muscularis mucosa, submucoas, muscularis propria, subserosa/serosa
what prevents reflux into the ureter from the bladder?
functional valve
what sphincters are in the urethra? what do they do?
internal - smooth muscle from the bladder
external - skeletal muscle from the pelvic floor
total renal blood flow
1L/min
meet their metabolic demands and filter/excrete waste
total urine flow
1ml/min
divisions of renal artery
renal artery, segmental, interlobar, arcuate, interlobular, afferent arteriole, glomerular capillary, efferent arteriole, peritubular capillary
how much plasma filters into Bowman’s capsule from the blood?
20%
layers of the glomerular filtration barrier
single-celled capillary endothelium
BM
single-celled epithelial lining of Bowman’s capsule (podocytes)
how does fluid filter through the GFB?
across endothelial cells
BM
between foot processes of podocytes
what do efferent arterioles supply?
peritubular capillaries (supply proximal and distal convoluted tubules)
how is a baby’s skin different to adult skin?
baby skin has naturally thin brick wall
needs very little damage, allergens could break through
why does atopic dermatitis start in babies?
thin brick wall
why does AD start on the face?
thin stratum corneum
epidermal barrier in normal vs eczematous skin
thinner stratum corneum
genetic susceptibility of AD
changes in filaggrin gene -> less NMF and water
degradatory proteases -> degraded corneodesmosomes
abnormal cornified envelope
breakdown lipid lamellae
environment interacting with genetics in AD
soaps/harsh detergents can raise pH of skin, breaking barrier
generates sub-clinical inflammation -> mild AD (intrinsic)
dust mite (produces proteases and acts as allergen)
staphylococcus aureus
saliva, breast milk, nasal secretions, foods, friction
what does inflammation do to filaggrin?
down regulates it
what do allergens do?
Th1 -> Th2, leading to inflammatory response
NA -> allergic
what is sensitisation?
babies develop allergies not through eating, but through topical application
what is tolerance induction?
giving food early can prevent allergy to it later on
what is the atopic march?
first AD, then allows food to get in (food allergy) which changes the immune system to Th2, which can lead to asthma
what chemical messengers does damaged skin release?
cytokines (IL-1, TSLP, IL-25, IL-33) trigger immune system, leads to skin barrier suppression, eosinophilia, pru
effect of inflammation the brain
IL-1, IL-6, TNFalpha increases 5 HTTP, leading to decreased serotonin which can decrease melatonin and depression/anxiety
what is disease modification?
change disease forever
how can we repair the skin barrier in AD?
foundation: emollients to repair barrier
irritants and allergen avoidance
what do lipid bilayers do?
prevents water loss
what do occlusive emollients do?
trap moisture in skin - transiently increase hydration
artificial barrier above stratum corneum
humectants
help retain moisture in skin
why are emollients sometimes not effective?
used in minimal quantities
what proportion does non-compliance leading to therapeutic failure occur?
50%
what is the greatest response in the treatment of AD?
education
what is eczema herpeticum?
herpes simplex 1 or 2
what do people with AD want?
time to listen, explain and demonstrate
steps of AD management
complete emollient therapy
treatment of flareups
role of vit D in skin barrier
filaggrin, dysregulation of AMP LL37, abnormal ceranide levels in lipid lamellae
what shifts Th0 to Th2?
prostaglandins from histamine released by mast cells and basophils
IL-4
what does dupilumab do?
prevents IL-4 from producing excess IgE
what is HbA1c?
glycated haemoglobin
what does HbA1c identify?
average plasma glucose concentration
by measuring it, we can see what our average blood sugar levels have been over weeks/months
when does HbA1c develop?
when haemoglobin joins with glucose in the blood - becomes glycated
HbA1c in diabetes
the higher the HbA1c, the greater the risk of developing diabetes-related complications
how does HbA1c return an accurate average measurement of average blood glucose?
when body processes sugar, glucose naturally attaches to Hb
amount of glucose that combines with Hb is directly proportional to the total amount of sugar in system
long term measurement due to erythrocyte lifespan
what is the HbA1c target for diabetes patients?
48 mmol/mol (6.5%)
HbA1c vs blood glucose level
HbA1c provides a long-term trend of how high blood sugars have been over a period of time
blood glucose level is the conc. of glucose in blood at a single point in time
how often should HbA1c be tested?
at least once a year
what is CKD?
chronic kidney disease
long term condition where kidneys don’t work as well as they should
in who is CKD more common?
black people and people of south Asian origin
symptoms in early CKD
usually no symptoms
may be picked up if blood/urine tests pick up problems
symptoms in advanced CKD
tiredness, swollen ankles/feet/hands, SOB, feeling sick, blood in urine
causes of CKD
often by other conditions that put a strain on the kidneys
high BP, diabetes, high cholesterol, kidney infections, glomerulonephritis, polycystic kidney disease, blockages in urine flow, lithium/NSAIDs
medication for CKD
none specifically for CKD, but they’re used to control conditions causing it
control of BP in CKD
aim for below 140/90, below 130/80 in diabetes
ACE inhibitors used, e.g. Ramipril, enalapril, lisinopril
control of cholesterol in CKD
higher risk of cardiovascular disease
statins e.g. atorvastatin, fluvastatin and simvastatin
side effects of statins
headaches, feeling sick, constipation/diarrhoea, muscle and joint pain
control of water retention in CKD
kidneys can’t remove fluid -> oedema
reduce salt/fluid intake, diuretics e.g. furosemide
side effects: dehydration and hypokalemia/hyponatremia
control of anaemia in CKD
later-stage kidney disease - anaemia often developed
injections of erythropoietin/iron supplements
bone problems in CKD
severely damaged kidneys -build-up of phosphate in body as kidneys can’t get rid of it
important for maintaining bone health, but a too much can upset calcium balance
control of bone problems in CKD
limit high phosphate foods
phosphate binders - calcium acetate and calcium carbonate
vit D - colecalcifeol/ergocalciferol
glomerulonephritis in CKD
medicine to reduce activity of immune system, e.g. steroids or cyclophosphamide
what does dialysis do?
removes waste products and excess fluid from the blood
what types of dialysis are there?
haemodialysis and peritoneal dialysis
what is haemodialysis?
diverting blood into an external machine, where it’s filtered then returned to the body
3 times a week
what is peritoneal dialysis?
pumping dialysis fluid into abdomen to draw out waste products
several times a day/overnight
what determines fetal sex?
SRY gene switches testicular development
what does the SRY gene do?
switches testicular development
testes produce MIF
prevents Muellerian duct development
what happens in absence of Y?
ovaries and Mullerian ducts form
uterus and fallopian tubes form
two X chromosomes required
what are germ cells?
specialised cells that develop into gametes
where do germ cells migrate to?
genital ridge by amoeboid movement
when does mitotic division occur?
rapid, until 20 weeks
what is the kidney surface anatomy?
retroperitoneal
where is the kidney derived from?
mesoderm
nephron in the cortex, medulla and pelvis
cortex: proximal and distal convoluted tubules and renal corpuscles
medulla: loop of Henle and collecting ducts
pelvis: receives collecting ducts
what do the renal corpuscles consist of?
glomerulus and Bowman’s capsule
how many nephrons do we have?
2 million in total - one in each kidney
what does the proximal tubule consist of?
proximal convoluted tubule and proximal straight tubule
what does the loop of Henle consist of?
descending limb of loop of Henle, thin segment of ascending limb of loop of Henle and thick segment of ascending limb of loop of Henle
what does the collecting duct system consist of?
cortical collecting duct and medullary collecting duct
histology of the renal corpuscle
tuft of convoluted tubules with fenestrated walls
glomerular tuft supported by smooth muscle mesangial cells
outside glomerular capillaries is the BM
on opposite side of glomerular BM are podocytes
what is the glomerular tuft supported by?
smooth muscle mesangial cells
what is outside the glomerular capillaries?
glomerular BM
what is on the opposite side of the glomerular BM?
layer of cells called podocytes
what does the glomerular BM consist of?
fusion of 2 BMs: capillary BM and podocyte BM
what is the most proximal part of the urinary tract?
Bowman’s capsule - continuous with proximal convoluted tubule downstream
how can you distinguish mesangial cells from the capillaries?
stain tissue with PAS
PAS in kidneys
stains glycoproteins in glomerular BM - highlighting capillaries and allowing you to see mesangial cells inbetween
what are mesangial cells?
modified smooth muscle cells
what are the functions of mesangial cells?
structural support for the capillary and production of extracellular matrix protein
contraction of them in the glomerulus tightens capillaries and reduces GFR - important in tubuloglomerular feedback where chemical changes in tubules feedback to alter GFR
involved in phagocytosis of the glomerular filtration membrane breakdown products
how are mesangial cells important in tubuloglomerular feedback?
their contraction tightens capillaries and reduces GFR - chemical changes in the tubules feedback to alter GFR
what are the components of the juxtaglomerular apparatus?
afferent arteriole and distal convoluted tubule
how are granular cells formed? what do they do?
endothelium of the afferent arteriole is expanded to form mass of cells (granular cells)
detect BP and secrete renin in response to a reduction in BP
when do granular cells secrete renin?
reduced BP
what is the macula densa? what does it do?
distal convoluted tubule closely aligned to glomerulus and afferent arteriole
expansion of cells at juxtaglomerular apparatus - macula densa
detect sodium levels
what does the macula densa do when filtration is slow?
more sodium is absorbed, and macula densa sends signal to reduce afferent arteriole resistance and increase GFR
what is another group of cells in the juxtaglomerular apparatus?
Lacis cells
what is the proximal convoluted tubule lined by?
cuboidal epithelium
what are the characteristics of the cells in the proximal convoluted tubule?
microvilli - increase SA of cell (fuzzy surface)
increased SA increases absorptive capacity of the cell
many mitochondria for active transport - 2/3 of sodium and potassium
why do cells of the proximal convoluted tubule have a fuzzy surface?
cells have microvilli
what does the proximal convoluted tubule absorb/resabsorb?
actively transport ions from filtrate including 2/3 of sodium and potassium
absorb small protein molecules that got through the glomerulus
reabsorption of NaCl, proteins, polypeptides, amino acids and glucose
what are the black dots in the proximal convoluted tubule? what do they do?
lysosomes - degradation of small protein molecules absorbed from urinary space
which convoluted tubule has more lysosomes?
proximal
what are the thin segments of the ascending and descending limbs of the loop of Henle lined by?
simple squamous
what are the thick segments of the ascending and descending limbs of the loop of Henle lined by?
low cuboidal
what is the loop of Henle supplied by?
rich vasa recta
how do the loops of Henle travel?
each loop dips down far into the medulla and then returns to form the distal convoluted tubule and return to the same nephron it left
what does the loop of Henle transport/receive?
water but not ions passively flow out of the thin descending limb into the high osmolarity interstitium - concentrates urine
ions the body wants back are actively pumped out of the ascending limb, leaving water and waste products
how is the urine concentrated in the loop of Henle?
water but not ions passively flow out of the thin descending limb into high osmolarity interstitium
what is left in the ascending limb of the loop of Henle?
after the ions the body wants back are actively pumped out, water and waste products are left
why is the loop of Henle deep in the medulla prone to ischemia?
vasa recta are quite far from glomerulus (where afferent arteriole enters to supply O2) so before blood has reached it, it’s already lost some of the oxygen it was carrying
what is ischemia?
temporary loss of blood supply/inadequate blood supply
how is the histology of the distal convoluted tubule different to the proximal one?
cells don’t have microvilli - no fuzzy brush border
much shorter - looking at a section of cortex, you’d see more proximal tubule
cells of the distal convoluted tubule
cuboidal
mitochondria
what does the distal convoluted tubule do?
regulating acid-base balance
acidifies the urine by secreting H+ ions into it (derived from intracellular carbonic anhydrase)
exchanges urinary Na+ for body K+ (mediated by aldosterone)
how does the distal convoluted tubule acidify the urine?
secreting H+ ions into it -derived from intracellular carbonic anhydrase
regulates acid-base balance
what process in the distal convoluted tubule is mediated by aldosterone?
exchanging urinary Na+ for body K+
can lead to hypernatraemia and hypokalaemia
what is the collecting duct lined by?
cuboidal epithelium
what is the cuboidal epithelium made up of?
2 cell types: principal and intercalated cells
what do the principal cells in the collecting ducts do?
respond to aldosterone (exchange Na+ for K+) and ADH (increasing water reabsorption by insertion of Aquaporin-2 into apical membrane
what does ADH do?
increase water reabsorption by the insertion of Aquaporin-2 into the apical membrane of the cell
what is Aquaporin-2? where is it inserted into?
membrane channel for water reabsorption in the collecting duct
apical membrane of the cell
what can cause diabetes insipidus?
mutation in the AQP2 gene (aquaporin-2 gene)
what is AQP2? where is it located?
provides instruction for making aquaporin 2 protein
12q12.12
what does mutation of the AQP2 gene usually cause?
aquaporin 2 protein is misfolded into an incorrect 3D shape
misfolded protein trapped within the cell, where it can’t reach the membrane to transport water molecules
what is nephrogenic diabetes insipidus?
disorder of water balance - produce too much urine (polyuria), causing them to be excessively thirsty (polydipsia)
acquired or hereditary
what do intercalated cells do?
exchange acid for base (both ways)
what types of intercalated cells are there? what do they do?
alpha intercalated cells secrete acid
beta intercalated cells secrete bicarbonate
how can collecting ducts be recognised?
plumper epithelium than the loop of Henle with a round central nuclei
what is the renal pelvis lined by? what does it do?
transitional epithelium (urothelium)
transmits filtrate from nephron to the ureters
collecting duct drains into it
what are the ureters lined by?
transitional epithelium
what are the muscles of the ureter?
spiral muscular tubes:
inner - longitudinal
outer - circular
what is the structure of the ureter?
no serosa
loose adventitia
how is urine propelled along the ureter?
peristalsis
what is the bladder lined by?
transitional epithelium
what are the layers of the bladder?
lamina propria, muscularis mucosa, submucosa, muscularis propria, subserosa and serosa
what does the bladder contain to prevent reflux into the ureter?
functional valve
what are the sphincters in the urethra?
internal: smooth muscle from the bladder
external: skeletal muscle from pelvic floor
what is the structure of the female urethra?
4-5cm long
proximally transitional epithelium
distally squamous epithelium
what is the structure of the male urethra?
20cm long
prostatic urethra, membranous urethra (transitional epithelium) and penile urethra (pseudostratified epithelium proximally and stratified squamous epithelium distally)
what are the functions of the kidney?
endocrine function
maintain balance of salt, water and pH
excrete waste products
how much of the CO does each kidney receive?
20%
what is total renal blood flow? what is this for?
1L/min (both kidneys)
meet own metabolic demands and filter/excrete metabolic waste products of the whole body
what is the total urine flow?
1ml/min
where are the capillary beds of each nephron?
glomerulus and peritubular area
what connects the 2 capillary beds in the nephrons?
efferent arteriole (blood leaves glomerulus)
afferent vs efferent arterioles
afferent arteriole comes before efferent arteriole as A comes before E
why is the renal circulation unusual?
includes 2 sets of arterioles and 2 sets of capillaries
what is the sequence of blood supply of the nephron?
afferent arteriole comes off of interlobular artery, then becomes the glomerular capillary, then the efferent arteriole, then the peritubular capillary, which join to forms where blood leaves the kidneys
what occurs in the peritubular capillary?
tubular secretion and tubular reabsorption
what does the renal corpuscle form?
filtrate from the blood that is free of cells, larger polypeptides and proteins
what is the filtrate free of? what happens to it?
free of cells, larger polypeptides and proteins
leaves renal corpuscle and enters the tubule
substances are added/removed from it
what forms the urine?
fluid remaining at the end of each nephron combines in the collecting ducts and exits the kidneys as urine
what is Bowman’s capsule?
fluid filled capsule
what constitutes the renal corpuscle?
glomerulus and Bowman’s capsule
how does blood leave the glomerulus?
efferent arteriole
what is the Bowman’s capsule covered by?
parietal epithelium
what filters into Bowmans space?
within capsule
protein free fluid filters from glomerulus into this
what does the filtrate from the glomerulus do?
collects in Bowman’s space before flowing into proximal convoluted tubule
how is the blood in the glomerulus separated from the fluid in Bowman’s space? what does this consist of?
filtration barrier
single-celled capillary endothelium
BM
single-celled epithelial lining of Bowman’s capsule (podocytes)- foot processes
how does fluid filter through the glomerular filtration barrier?
across endothelial cells
BM
between foot processes of podocytes
what supplies the proximal and distal convoluted tubules?
peritubular capillaries
what supplies the loop of Henle?
vasa recti (supplied by efferent arterioles)
what do the peritubular capillaries and vasa recti both supply?
water and solutes to be secreted into the filtrate
blood to carry away water and solutes reabsorbed by the kidneys
what is the proximal convoluted tubule?
longest and most coiled with simple cuboidal brush border
drains Bowmans capsule
convoluted and straight
what is the loop of Henle?
sharp, hairpin like loops consisting of a descending limb coming from proximal tubule
ascending limb leading to next tubular segment
what is the distal convoluted tubule
cuboidal epithelium with minimal microvilli
fluid flows from here into the collecting-duct system
what does the collecting-duct consist of?
cortical collecting duct
medullary collecting duct
what happens when the cortical/medullary collecting ducts merge?
urine drains into kidney’s central cavity (renal pelvis)
what is the outer and inner portion?
outer - renal cortex
inner - renal medulla
what are the types and proportions of nephron?
juxtamedullary (15%) and cortical (85%)
what are the juxtamedullary nephrons? what do they do?
renal corpuscle lies in part of cortex closest to cortical-medullary junction
loop of Henle plunge deep into medulla and generate an osmotic gradient in medulla -> reabsorption of water
what lies in close proximity to the juxtamedullary nephron?
long capillaries (vasa recta) - also loop deeply into medulla and then return to cortical-medullary junction
what are cortical nephrons? what do they do?
renal corpuscles lie in the outer cortex and loop of Henle don’t penetrate deep into the medulla
some don’t have loop of Henles
involved in reabsorption and secretion but don’t contribute to the hypertonic medullary interstitium
what does the juxtaglomerular apparatus consist of?
combination of macula densa and juxtaglomerular cells (granular)
what do granular cells do?
secrete renin into blood, initiating RAAS
what do macula densa cells do?
detect how much NaCl is passing through the distal convoluted tubule
sends signals to the granular cells to produce renin
what is glomerular filtration? what is the SA?
passage of fluid from the blood into Bowman’s space to form the filtrate
SA is 1m2
what is the flow of the glomerular filtrate?
glomerular capsule, proximal convoluted tubule, nephron loop, distal convoluted tubule, collecting duct, papillary duct, minor calyx, major calyx, renal pelvis, ureter, urinary bladder, urethra
what does the male reproductive tract consist of?
testis, epididymis, vas deferens, prostate, seminal vesicle, penis
what are the testis? what is their weight?
paired organ in the scrotum
15-19g
what is the testis bound by? what are its layers?
capsule
tunica vaginalis, tunica albuginea, tunica vasculosa
what is the tunica vaginalis (testis)?
projection of peritoneum
flattened layer mesothelial cells resting on BM
parietal and visceral layer
what is the tunica albuginea (testis)?
thick fibrous capsule containing collagen fibres with some fibroblasts, myocytes, nerve fibres
what is the tunica vasculosa (testis)?
thin innermost layer of loose connective tissue containing blood vessels and lymphatics
where do spermatozoa form? what is their path?
seminephrous tubules
pass through ends of straight tubules, rete testes, efferent ducts and epididymis. from here, they leave the testis and into the vas deferens. pass into ejaculatory duct
where does the ejaculatory duct receive secretions from?
seminal vesicle
where does the urethra receive secretions from?
prostate
what is the parenchyma of the testis?
seminiferous tubules
divided into ~250 lobules
by septa originating from the capsule
1-4 seminiferous tubules per lobule
what do seminiferous tubules contain?
germ cells in varying stages of maturation
Sertoli cells - nuture germ cells
what is the function of Sertoli cells?
nuture germ cells in the seminiferous tubules in the testis
what rests on the BM of the seminiferous tubules?
spermatogonia
what are the types of spermatogonia?
Type A - darkly stained (Ad) and pale stained (Ap)
Type B - differentiating progenitor cells with spherical nuclei and densely stained masses of chromatin
what do Type Ad spermatogonia do?
stem cell population of seminiferous tubule
divide to form further type Ad and Ap cells
what do type Ap cells do?
mature into type B cells
what do spermatogonia eventually become?
spermatogonia -> primary spermatocyte -> secondary spermatocyte -> spermatid -> spermatozooa
what is the histological appearance of Sertoli cells?
columnar cells on BM
send cytoplasmic projections around the germ cells
nuclei are irregularly shaped, folded and have a prominent nucleolus (helps distinguish from germ cells)
eosinophilic, granulated cytoplasm may have lipid vacuoles
what are the functions of the Sertoli cells?
supportive, phagocytic and secretory
structure of spermatozoa
head: acrosomal cap (helps penetrate egg) and nucleus
midpiece: spiral mitochondria wrapped around axoneme
tail: neck -centrioles, axoneme, plasma membrane
what does the axoneme in a spermatozoa do? what is it?
responsible for sperm motility
long specialised cilium, with 9 outer doublet tubules around a single doublet pair
what are Leydig cells? what is their function? what do they do?
present singly and in clusters in the interstitium between tubules
abundant cytoplasm containing lipid
Reinke’s crystalloids
may contain lipofuscin
produce testosterone
where do Leydig cells discharge their contents into?
rete testes
what is the rete testis?
anastomosing network of tubules at the hilum of the testis
what is the structure of rete testis?
lined by simple squamous/low columnar epithelium on relatively thick BM
cilia at luminal surface
what is the function of the rete testis?
mixing chamber for contents of seminiferous tubules
possible secretions
reabsorption of protein from luminal contents
how do the rete testis discharge their content?
efferent ducts
what are efferent ducts?
12-15 convoluted tubules which empty into the epididymis
what is the histological appearance of efferent ducts?
lined by ciliated and non ciliated simple columnar epithelium with interspersed cuboidal cells (basal cells) giving a pseudostratified appearance
what is the epididymis?
a tubular structure 4-5cm long containing a highly convoluted and coiled epididymal duct (5m)
what is the histological appearance of the epididymis?
lined by tall columnar cells with long atypical cilia (stereocilia - non motile)
epithelium supported by thick BM surrounded by a well defined muscular coat
what is the function of the epididymis?
site of absorption of testicular fluid, phagocytosis of degenerate spermatozoa, production of secretions rich in glycoproteins, syalic acid and
where are the contents of the epididymis discharged into?
vas deferens
what is the vas deferens?
30-40cm tubular structure arising from caudal portion of epididymis
distal part enlarged to form ampulla which joins the excretory duct of the seminal vesicle to form the ejaculatory duct
what forms the ejaculatory duct?
distal part of vas deferens is enlarged to form the ampulla, which joins the excretory duct of the seminal vesicle to form the ejaculatory duct
what is the structure of the vas deferens?
lined by pseudostratified columnar epithelium composed of columnar and basal cells
thick muscular wall of 3 layers of smooth muscle
what is the prostate?
pear shaped glandular organ
lies at the base of the bladder
how much does the prostate weigh?
up to 20g in young adult - can enlarge as you get older
what does the prostate surround?
bladder neck and prostatic urethra
what are the divisions of the prostate?
lobes: anterior, middle, posterior and 2 lateral lobes
peripheral, central, transitional and peri-urethral gland regions
what happens in the clinical regions of the prostate?
peripheral - prostate cancer
central - enlargement with age
what is the prostate covered by?
ill-defined fibro-connective tissue capsule
what is the structure of the prostate?
ducts - large primary and small secondary
acini - 30-50 tubuloalveolar glands with convoluted edges
what are prostatic acini lined by?
secretory cells, basal cells and neuroendocrine cells
what are secretory cells? what do they do?
in the luminal side
columnar
secrete citric acid, acid phosphatases, fibrinolysin, amylase, PSA and PAP into seminal fluid
what are the clinical uses of PSA?
to determine if a tissue is prostatic, detect prostate cancer
what is PSA? what is its function?
prostate specific antigen
enzyme
helps liquify semen after ejaculation
what is the stroma of the prostate?
smooth muscle, fibroelastic fibres, blood vessels, fibroblasts, nerves
what is hyperplasia of the stroma and prostate gland?
enlarges with increasing age due to production of new cells
what are seminal vesicles?
paired highly coiled tubular structures/glands posterolateral to the bladder
where do the seminal vesicle ducts drain into?
ejaculatory duct
what are seminal vesicles lined by? what is their structure?
lined by tall non-ciliated columnar epithelium
vacuoles and lipofuscin (within epithelial cells)
mucosa is folded
smooth muscles (2 layers) and adventitia
how much of the ejaculate do seminal vesicle secretions comprise
70-80%
what do seminal vesicle secretions consist of? what is its function?
fructose, prostaglandins, amino acids, proteins, citric acid and ascorbic acid (vit C)
nutrients for spermatozoa
what does the penis consist of?
erectile tissue arranged into 3 components
what is on the dorsal side of the penis?
left and right corpora cavernosa
what is on the inferior side of the penis?
corpus spongiosum (surrounds urethra)
what does the erectile tissue (of corpora cavernosa and spongiosa) of the penis comprise?
irregular vascular spaces separated by fibroelastic tissue and smooth muscle
what are the corpora cavernosa and spongiosa surrounded by?
dense connective tissue - when vascular spaces engorge, it becomes erect
nerves supply of penis
rich
what are the ovaries?
paired organ lying on either side of the uterus close to lateral pelvis wall
what are the attachments of the ovary?
to broad ligament via mesovary
to uterus by utero-ovarian ligament
to pelvic wall by suspensory ligament
what is the ovary covered by?
peritoneum - single layer of modified mesothelium
poorly defined layer of fibrous connective tissue (tunica albuginea)
stroma - divided into cortex and medulla
what is the tunica albuginea in the female reproductive tract?
poorly defined fibrous connective tissue layer covering the ovary - underneath the mesothelium and above the stroma
what can the stoma in the ovary be divided into?
cortex and medulla with indistinct boundaries
what does the hilum of the ovary contain?
where blood vessels, lymphatics and nerves enter/leave the ovary
what does the ovarian cortex consist of?
spindle stromal cells arranged in whorls/storiform pattern - resemble fibroblasts
ovarian follicles
some leutinised cells
what does the ovarian medulla consist of?
loose fibroelastic tissue with blood vessels, lymphatics and nerves
rete ovarii - analogue of rete testes. present at hilum
where are follicles found in the ovary?
at different points, depending on stage of maturation/menstrual cycle
what do follicles begin as?
primordial follicles
where are primordial follicles located?
periphery of cortex
what comprises a primordial follicle?
primary oocyte in resting state
surrounded by a single layer of epithelial cells (granulosa cells)
oocyte nucleus in middle
how many primordial follicles develop in the menstrual cycle?
30-40
what do primordial follicles develop into?
primary follicles
what mediates the maturation of primordial follicles into primary follicles?
cyclic follicle stimulating hormone (FSH) secretion from anterior pituitary
what produces FSH?
anterior pituitary
what effect does FSH have on a primordial follicle?
oocyte enlarges
granulosa cells proliferate/enlarge - squamous to cuboidal
stromal cells become organised into connective tissue sheath
zona pellucida forms directly around oocyte
what is the zona pellucida?
layer of glycoprotein between granulosa cells and oocyte
pink
what does continued action of FSH do to the primary follicles?
develop into secondary follicles
granulosa cells proliferate
spaces form between granulosa cells filled with follicular fluid
cortex differentiates into theca interna and theca externa
how is the follicular antrum formed?
spaces formed between granulosa cells that are filled with follicular fluid coalesce
what are the mature follicles called? how many ovulate?
Graafian
~1
what is the structure of a Graafian follicle?
antrum
ovum surrounded by a thick zona pellucida
layer of granulosa cells surround oocyte - corona radiata
basal lamina
theca interna and externa
cumulus ooferus
how many primordial follicles are present at birth?
about 1 million
what is atresia?
primordial follicles will involute and disappear
how many primordial follicles mature to ovulate?
400-500 - 99% undergo atresia, 1 mature per cycle
what is triggers ovulation?
lutinising hormone
what does LH do?
accumulation of lipid in theca interna cells and granulosa cells
what does leutinisation of granulosa and theca interna cells cause?
enlarge
lipid rich cytoplasm
what happens to the corpus luteum if pregnancy occurs/if it doesn’t?
if it does, it keeps enlarging for support
if it doesn’t, it regresses
what does the corpus luteum secrete?
oestrogen and progesterone
when does regression of the corpus luteum occur if pregnancy doesn’t?
8-9 days after ovulation
what characterises regression of the corpus luteum?
granulosa cells decrease in size, develop small densely haemotoxophilic pyknotic nuclei, and accumulation of abnormal lipid
cells undergo dissolution and are phagocytosed
progressive fibrosis by ingrowth of connective tissue (formed by ovarian stroma cells)
what is the product of the regression of the corpus luteum?
formation of the corpus albicans
what is the corpus albicans? what is its structure?
well circumscribed structure with convoluted borders
almost entirely composed of densely packed collagen with occasional follicles
what eventually happens to corpus albicans?
resorbed/replaced by ovarian stroma
where are the fallopian tubes?
run throughout length of the broad ligament
what are the functions of the fallopian tube?
transports ovum to the uterus
fertilisation occurs here
segments of the fallopian tube
intramural - inside uterine wall
isthmus - 2-3cm, thick walled
ampulla - expanded area
infundibulum - trumped shaped opening to peritoneum, has fimbriae
what is the mucosa of the fallopian tube?
thrown into branching folds (plicae)
what are the cell types in the fallopian tube epithelium?
secretory and ciliated
peg cell - effete secretory
basal - lymphocytes
where are ciliated cells of the fallopian tube more abundant?
infundibular end
where are secretory cells of the fallopian tube more abundant?
uterine end of tube
what is the muscularis of the fallopian tube?
myosalpinx
smooth muscle:
inner circular layer
outer longitudinal layer
what is the serosa of the fallopian tube?
loose fibrous connective tube covered by mesothelium
what are the layers of the body of the uterus?
endometrium, myometrium and serosa
what is the endometrium? what are its layers?
deep basal layer - stratum basalis
superficial functional layer - stratum compactum (towards surface) and stratum spongiosum
what does the deep basal layer of the endometrium act as? what does it do?
not hormonally responsive, not lost in menstruation
acts as a reserve of stromal and endometrial epithelial cells - will be replenished
what does the stratum spongiosum of the endometrium do?
undergoes changes, eventually lost in each cycle
proliferative phase of the endometrium
hormonally responsive - changes according to cycle
oestrogen stimulation - causes proliferation
straight proliferating glands with mitotic activity
no luminal secretions
stromal cells are spindled and compact, mitotic activity
when does the secretory phase of the endometrium occur?
after ovulation
second phase
what influences the secretory phase of the endometrium?
progesterone stimulation
what is the division of the secretory phase of the endometrium?
early, mid and late
what is seen in the early secretory phase of the endometrium?
sub-nuclear glycogen vacuoles
what is seen in the mid secretory phase of the endometrium?
vacuoles above and below the nucleus and later intraluminal secretions
glands more rounded
stroma-oedema
what is seen in the late secretory phase of the endometrium?
elongated and saw-toothed glands with more intraluminal secretions
stroma - spiral arterioles, decidual change
what is the last phase of the endometrium if pregnancy does not occur?
menstrual phase
what causes the menstrual phase in the endometrium?
withdrawal of progesterone stimulation
what characterises the menstrual endometrium?
stromal haemorrhage and granulocytes
stromal and glandular fragmentation
what is the myometrium? what is its layers?
thick muscular wall of endometrium
inner longitudinal, middle circular and outer longitudinal (3 ill defined smooth muscle layers)
what are the components of the cervix?
endocervix and ectocervix
what is the endocervix composed of?
loose fibromuscular stroma lined by simple columnar ciliated epithelium
thrown into crypts
what is the ectocervix composed of?
dense smooth muscle stroma lined by non-keratinised stratified squamous epithelium
site of squamocolumnar junction varies
what is the ectocervix like in postmenopausal women?
atrophic
what is the vagina?
tubular, muscular structure
what is the mucosa of the vagina?
lined by non keratinising stratified squamous epithelium
fibromuscular stroma contains elastic fibres and rich vascular network
what is the muscular wall of the vagina?
smooth muscle cells
inner circular
outer longitudinal
what is the adventitia of the vagina?
loose connective tissue
what often accumulates in epithelium lining vagina and ectocervix? when does it usually occur? what appearance does it give?
glycogen
maximal at ovulation
cytoplasm becomes clear - spongy look
what does the vulva consist of?
mons pubis, labia minora and majora, vulvar vestibula, urethral meatus, Bartholins gland, clitoris, hymen, Skeon’s gland, introitus
what is the labia majora lined by? what does it contain?
keratinising stratified squamous epithelium
skin adnexae
what are the labia minora lined by?
mostly non keratinising stratified squamous epithelium
what are Bartholin’s glands?
tubuloalveolar glands
acini lined by mucus secreting epithelium
what are minor vestibular glands?
simple tubular glands lined by mucus secreting epithelium
what are Skein’s glands? what are they lined by?
periurethral glands - analogous to prostate
lined by pseudostratified columnar epithelium
what is the hymen lined by?
non keratinising squamous epithelium
what is the clitoris?
erectile tissue rich in blood vessels and nerves
female analogue of penis
what are common features of glands?
glandular epithelium
richly vascularised
secrete a variety of hormones directly into circulation
controlled by +ve and -ve feedback loops
what is the pituitary? what are its functional components?
coordinates endocrine organs through feedback loops
posterior pituitary (downgrowth of hypothalamus) anterior pituitary (epithelial structure
what is the posterior pituitary? what is its neural tissue?
downward extension of the hypothalamus
axons and glial cells
what does the posterior pituitary store/secrete?
oxytocin and antidiuretic hormone/vasopressin
what is the anterior pituitary? what is its structure?
nested epithelial pituicytes
richly vascular fibrous stroma
several different types of pituicyte, not distinguishable on H&E
how do we determine individual secretions of pituicytes?
immunohistochemistry
what are the pituicytes of the anterior pituitary? what are their proportions?
somatotrophs (50%) lactotrophs (25%) corticotrophs (15-20%) gonadotrophs (10%) thyrotrophs (1%)
what do somatotrophs secrete?
growth hormone
what do lactotrophs secrete?
prolactin
what do corticotrophs secrete?
ACTH, alpha-MSH, beta-lipotrophin and beta-endorphin
what do gonadotrops secrete?
FSH and LH
what do thyrotrophs secrete?
thyroid stimulating hormone
what stain is used to see nests in anterior pituitary?
reticulin
where are somatotrophs found?
lateral wings of anterior pituitary
throughout gland
immunohistochemical staining of somatotrophs
diffuse cytoplasmic positivity
growth hormone +
what are lactotrophs?
polygonal cells
cytoplasmic processes wrap around other cells (hug their neighbours)
staining of lactotrophs
variable prolactin staining - stains cytoplasm brown
what are thyrotrophs?
angular chromophobes
elongated cytoplasmic processes (don’t hug neighbours)
staining of thyrotrophs
immunohistochemical staining
cytoplasm stains brown
targets TSH
what are gonadotrophs?
scattered round/oval cells
how do gonadotrophs stain?
alpha subunit (common to LH and FSH)
beta LH
beta FSH
what are corticotrophs?
round basophilic cells
median of gland
large cytoplasmic vacuoles
how are pituicytes supported? how are they stained?
sustentacular cells, surround normal follicles
S100(protein) +ve - stains them brown
what are benign tumors of the pituitary gland?
pituitary adenoma
what happens as the pituitary adenoma expands?
expands out of sella tursica
becomes pituitary adenoma macro - presses on optic chiasm
what is the HandE staining of an adenoma?
rosettes with capillary in the middle
changes in reticulin in an adenoma
nests become expanded in hyperplasia, in adenomas the normal architecture has been lost and reticulin only surrounds the blood vessels
where is the pineal gland located?
just below posterior end of the corpus callosum. covered by meninges
what is the equation for pH?
-log1{H+}
what is the normal range of pH for blood?
7.35-7.45
acid vs base
acid - donates H+ ions
base - accepts H+ ions
what is acidosis/alkalosis?
acidosis: blood more acid than normal
alkalosis: blood more alkaline than normal
what is acidemia/alkalemia?
low blood pH
high blood pH
what is an anion gap?
difference between measured anions (negative and cations (positive)
[Na+] + [K+] - [Cl-] - [HCO3-]
what is the normal anion gap?
10-16
what is a wide anion gap caused by?
lactic acidosis, ketoacidosis, ingestion of acid, renal failure
what is a narrow anion gap caused by?
GI HCO3- loss, renal tubular acidosis
what are types of urinary phosphate buffers?
urinary phosphate buffer and ammonium urinary buffer
both in proximal tubule
what is the urinary phosphate buffer?
alkaline phosphate (HPO4 2-) - most common urinary buffer
acts in proximal tubule
what does alkaline phosphate (HPO4 2-) do? what happens to it?
when all of filtered HCO3- has combined with secreted H+, the additional H+ secreted starts combining with filtered non bicarbonate buffers
H+ (from dissociation of H2CO3) combines with HPO4 2- to form H2PO4-, which is excreted in the urine
what happens with the HCO3- with the phosphate buffer?
enters the interstitial fluid - no absorption from tubular lumen
net gain of HCO3- in interstitium and blood plasma -> alkalinises it
when do significant amounts of H+ combine with filtered non bicarbonate buffers?
only after the filtered HCO3- has all been reabsorbed
formation of ammonia and bicarbonate in the proximal tubule
proximal tubular epithelial cells take up glutamine from glomerular filtrate and peritubular plasma and metabolise it to form NH3 (ammonia) and HCO3- (bicarbonate)
how is glutamine transferred into the tubular epithelial cell?
with Na+
what is the fate of the NH3 formed from glutamine in the tubular epithelial cell?
reacts with H+ in the cell (either derived from dissociation of H2CO3 or that absorbed due to Na+ reabsorption) to form NH4+ (ammonium ion)
what is the fate of the ammonium ion formed from NH3?
actively secreted via Na+/NH4+ countertransport into the lumen and excreted
what is the fate of the HCO3- formed from glutamine in the tubular epithelial cell?
moves into peritubular capillaries and increases HCO3- levels (net gain of HCO3-) -> alkalinising blood plasma
what is respiratory acidosis?
failure to get rid of CO2 resulting in a decrease in pH as CO2 builds up
what are the causes of respiratory acidosis?
hyperventilation
COPD
any cause of respiratory failure (pulmonary embolism: type 1, hypoventilation: type 2)
what is the renal compensation for respiratory acidosis? how long will it take?
the kidneys will increases H+ secretion in form of NH4+ and release more HCO3- into the plasma which increases pH, via the ammonium buffer
will take days
what is respiratory alkalosis?
too much CO2 lost resulting in an increased pH
what are the causes of respiratory alkalosis?
CO2 depletion due to hyperventilation
hypoxia
type 1 respiratory failure: pulmonary embolism (decrease in O2 and decrease/no change in CO2)
what is the renal compensation for respiratory alkalosis?
kidneys decrease H+ secretion - retain it and help it return to normal
decreased H+ secretion -> decrease in HCO3- reabsorption (more excretion) - increases pH
what is metabolic acidosis?
excess acid production (intercalated cells release acid) leading to a decrease in pH
what are the causes of metabolic acidosis?
renal failure
GI HCO3- loss
dilution of blood - the more H20 in blood, the more acidic it gets
failure of H+ excretion (hypoaldosteroneism)
excess H+ (ketoacidosis)
what effect does diluting blood have on acidity?
more H2O in blood, the more acidic it gets
what is hypoaldosteroneism?
insufficient aldosterone is released so less Na+ reabsorbed and less H+ secreted (Na+/H+ countertransporter)
what is the respiratory compensation for metabolic acidosis?
decrease in pH stimulates chemoreceptors of the lung -> enhanced respiration -> fall in CO2 -> increase in pH
what is metabolic alkalosis?
pH of a tissue is elevated above 7.45
what are the causes of metabolic alkalosis?
increase in pH
vomiting, volume depletion alkali ingestion, hyperaldosteronism, hyperkalaemia (increased aldosterone release)
how does hyperkalaemia affect aldosterone release?
increases it
what is the respiratory compensation of metabolic alkalosis?
increase in pH inhibits chemoreceptors -> reduced respiration -> increased CO2 -> decreased pH
where is EPO produced?
kidney - in peritubular cells in interstitial space of renal cortex
what does EPO do?
stimulates bone marrow maturation of erythrocytes
what increases EPO?
anaemia, altitude and cardiopulmonary disorders
what decreases EPO?
polycythaemia (abnormally increased Hb in blood), renal failure
what is the first step in vitamin D metabolism?
absorbed in skin from solar UVB light as 7-dehydrocholesterol, converted into D3 (cholecalciferol)
what is vitamin D3?
cholecalciferol
what does the liver do in vitamin D metabolism?
converts cholecalciferol into calcidiol (25 hydroxy vitamin D) via vitamin D3 -25- hydroxylase
what is calcidol?
25-hydroxy-vitamin D
where is vitamin D obtained from?
skin as 7-dehydrocholesterol
dietary intake as vitamin D3 (cholecalciferol): oily fish, meat, eggs, fortified foods
what does the kidney do in vitamin D metabolism?
converts calcidol (25-hydroxy-vitamin D) to calcitriol (1,25-dihydroxy-vitamin D) via 25(OH)D3-1-alpha-hydroxylase
what are the effects of calcitriol?
intestine: increases Ca3(PO4)2 absorption
bone: inhibits bone resorption
kidney: increases Ca3(PO4)2 reabsorption
parathyroid: inhibits parathyroid hormone
where are the adrenals located?
above kidneys - retroperitoneal
what is the arterial supply of the adrenals?
superior adrenal artery - from inferior phrenic
middle adrenal artery - from abdominal aorta
inferior adrenal artery - from renal artery
what is the venous drainage of the adrenals?
right adrenal vein drains directly into the IVC
left adrenal vein drains into the left renal vein
what is the nerve supply of the adrenals?
splanchnic nerves
what is the structure of the adrenals?
cortex and medulla
what are the hormones secreted by the adrenal cortex?
aldosterone cortisol corticosterone dehydroepiandrosterone (DHEA) androstenedione
what is the adrenal cortex divided into?
from outside in:
zona glomerulosa - mineralocorticoids e.g. aldosterone
zona fasiculata - glucocorticoids e.g. cortisol and small amounts of androgens
zona reticularis - androgens (sex hormones) and small amounts of cortisol
GFR - Makes Good Sex
what is important for glucocorticoids and mineralocorticoids?
negative feedback
what controls the adrenal medulla?
sympathetic control
what does the adrenal medulla secrete?
2 hormones belonging to catecholamine family - adrenaline and noradrenaline, which cause cortex to secrete further hormones
what does the adrenal medulla respond to? how?
stress - dilates pupils, increases glycogenolysis, increases lipolysis, increases sweating, increases heart rate and inhibits insulin release
what is the precursor to all corticosteroids?
cholesterol
what are corticosteroids?
lipid soluble - can pass through biological membranes
bind to specific intracellular receptors
alter gene expression directly or indirectly
exact action depends on structure
what does the zona glomerulosa secrete?
mineralocorticoids
what is the role of mineralocorticoids? give an example?
secreted by zona glomerulosa of the adrenal gland
regulates body electrolytes
aldosterone (due to aldosterone synthase)
what does aldosterone do? how is it released?
maintains salt balance and BP
triggered by release of renin by juxtaglomerular cells in afferent arterioles of kidney - problems with kidney affect release
what does the zona fasiculata release?
glucocorticoids e.g. cortisol and corticosterone
what does cortisol do?
affects metabolism of glucose - actions on most tissues
facilitates bodies response to stress and regulation of immune system
where is cortisol synthesised?
zona fasiculata and zona reticularis
what is stress?
real/perceived threat to homeostasis - any change in temperature, water intake or other factors are designed to prevent a significant change in a variable
what are examples of threat that cause stress?
physical trauma, prolonged exposure to cold, prolonged heavy exercise, infection, shock, decreased oxygen supply, sleep deprivation, pain, emotional stress
what does threat trigger?
increase in cortisol
what also increases in response to stress?
sympathetic nervous system activity and the release of hormone adrenaline from the adrenal medulla increases
what is the process of stress and its effects?
stress detected and transmitted neutrally to the hypothalamus
stimulates secretion of corticotropin-releasing hormone (CRH) from hypothalamus
hormone carried by hypothalamic-hypophyseal portal vessels to anterior pituitary - stimulates release of adrenocorticotropic hormone (ACTH)
ACTH circulates through blood and travels to adrenal cortex, stimulates cortisol release
where is stress transmitted to?
hypothalamus
what does stress stimulate in the hypothalamus?
secretion of corticotropin-releasing hormone (CRH)
what does CRH do?
released from hypothalamus - corticotropin-releasing hormone (CRH)
carried by hypothalamic-hypophyseal portal vessels to anterior pituitary - stimulates release of ACTH
what does ACTH do?
released by anterior pituitary - adrenocorticotropic hormone
travels to adrenal cortex and stimulates cortisol release
what is secretion of ACTH stimulated by?
CRH from hypothalamus
(lesser extent) vasopressin - increases in response to stress
forms of cortisol in circulation
90% bound to corticosteroid-binding globulin (CBG)
5% bound to albumin
5% free
only free cortisol is bioavailable
