sugar 1 Flashcards
name the layers of the skin
epidermis
- stratum corneum (anucleate)
- stratum lucidum (anucleate)
- stratum granulosa (2/3 layers)
- stratum spinosum (2/3 layers)
- stratum basale (single layer)
dermis
- papillary collagen type 3
- reticular collagen type 1
- subcutaneous tissue
how are skin cells connected to one another and to the basement membrane?
to each other by desmosomes
to basement membrane by hemidesmosomes
describe the process of skin turnover
loss of skin cells is by desquamation corneodesmosomes anchor the corneocytes together protease enzyme can digest corneocytes break down of skin barrier loss of skin cells
replaced by stem cells in the stratum basale layer.
what is the skin pH?
5.5
describe the healthy skin barrier?
profilaggrin goes to form filaggrin
filaggrin produced Natural moisturing factor which fills the coreocytes
allows them to retain water
keeps skin healthy and surface more acidic.
allergens and irritants repelled
what is the role of vitamin D in the skin?
production of antimicrobial proteins which help to protect against viral/bacterial damage.
what is the cause of red skin, dry skin, itchy skin?
due to allergen entry
red skin, vasodilation, neutrophils causing inflammation
dry skin, corneocyte leakage, poor H20 retention
itchy skin - due to nerve stimulation
what is the role of melanocytes?
absorption of UV light
where do melanocytes originate?
neural crest
found in the basal layer
where is melanin produced?
in melanocytes in melanosomes from tyrosine
what determines skin colour?
darker skinned people have same number of melanocytes but number/size of melanosomes greater
red skin
due to pheomelanin
yellow/black skin
due to eumelanin
how does Acne come about?
blockage of the hair follicle entrance either due to hypercornification of stratum corneum so the corneodesmosome block entrance. Or cosmetics block hair follicle entrance
increased production of sebum, skin feels oily
stagnation of sebum
anaerobic conditions perfect for propionic bacterium which can divide
break down triglycerides in sebum to fatty acids
neutrophils attracted to the area
pus formation
further inflammation
from where does the dermis originate?
mesoderm
what are the resident cells of the dermis?
fibroblasts
macrophages
mast cells
dermal dendrocytes F13A+ CD34+ Langerhans (APC)
what is the function of the skin?
barrier to infection thermal regulation trauma protection UV protection Vitamin D synthesis regulate H20 loss
what happens if there is no profilaggrin?
no filaggrin no NMF less h20 retention ph increases corneodesmosomes damaged increased infection risk as skin barrier damaged
describe the boundaries of the inguinal canal
anterior - aponeurosis external obliique and internal oblique more laterally
posterior - transversalis fascia
roof - transversalis fascia, transversus abdominis and internal oblique
floor - inguinal ligament thickined medially by the lacunar ligament
what is the deep inguinal ring and where is it found?
directly above the midpoint of the inguinal ligament
invagination of the transversalis fascia
describe the hernia formed in the inguinal canal
indirect -when peritoneal sac enters canal via deep inguinal ring. Failure of the processes vaginalis to regress.
direct - when peritoneal sac enters via posterior wall of inguinal canal.
describe the contents of the inguinal canal
male - spermatic cord
female - round ligament
what was the inguinal canal used for?
passage of testes
originally on posterior abdominal wall
movement through canal attached to gubernaculum
which leads to the scrotum
in females gubernaculum attaches ovaries to the uterus and ovaries do not pass down the inguinal canal to the same extent.
describe the layers of the Spermatic cord
processes vaginalis fascia transversalis fascia cremaster cremaster muscle external oblique aponeurosis dartos muscle and colles fascia skin
state the contents of the spermatic cord
Panpaniform plexus Ductus deferens Cremaster artery Testicular artery and vein Artery of the vas deferens Genital branch of the genitofemoral nerve Sympathetic nerves Lymphatics
which is the capsule which contains the testes?
tunica albuginea
what covers the anterior and lateral parts of the testis?
processus vaginalis
describe the layers of the kidney
renal capsule
perirenal fat
renal fascia (suprarenal glands located here!)
pararenal fat
where are the kidneys located?
t12 - l3
retroperitoneal
right lower than left
left slender and more midline
describe the structure of the kidney
outer renal cortex
renal cortex columns project into the inner renal medulla
formation of renal pyramids
apex of pyramid is the renal papilla and drains into the minor calyx
2/3 of these form the renal pelvis and drain into the ureter.
describe the arterial blood supply of the kidneys
renal artery usually branch off around l1/l2
left a little higher than the right
right renal artery must pass posterior to the inferior vena cava to reach right kidney. must travel farther.
as arteries enter the kidney via the hilum, divide into anterior and posterior branches
renal artery segmental artery interlobar branches arcuate branches interlobular branches afferent arteioles glomerular capillary efferent arterioles peritubular arteries
name the narrowings of the ureter
- ureteropelvic junction
2.where the ureters cross common iliac vssels at pelvic brim
3.where ureters enter wall of the bladder.
uterovesical junction
what is relevant about ureter narrowings?
kidney stones can become lodged in them
describe the pathway of the ureter
uteropelvic junction descent anterior to psaos major retroperitoneal cross pelvic brim cross iliac artery bifurcation run down lateral pelvic wall turn and enter bladder obliquely forms a one way valve.
describe uteric innervation
efferent fibres from parasymapthetic and sympathetic.
afferent fibres from t11-L2 spinal cord levels. if distention of the ureter pain is usually referred ti areas supplied by t11-l2.
ie scrotum, labia majora, thigh, posterior and lateral space below the ribs
describe the histology and secretions of the suprarenal glands
cortex:
zona glomerulosa
produces mineralocorticoids
aldosterone
zona fasciculata
produces glucocorticoids
cortisol, corticosterone
little androgens
zona reticularis produces androgens (sex hormones) -dehydroepiandrosterone -androstenedione some cortisol
medulla
produces catecholamines by chromaffin cells
noradrenaline
adrenaline
describe the structure of the suprarenal glands
cortex
- zona glomerulosa
- zona fasciculata
- zona reticularis
medulla
contain chromaffin cells which secrete catecholamines (ie noradrenaline, dopamine) in response to stress. fight or flight
what do the suprarenal glands secrete?
cortex produces 1 dehydoepiandrosterone 2 corticosterone 3 cortisol 4 aldosterone (ONLY by zona granulosa) 5 aldrostenedione (minerolcorticoid)
medulla produces noradrenaline and adrenaline
what is the nervous supply to adrenal glands?
sympathetic by T10 - L1
coeliac plexus and splanchnic nerves
how long is the ureter
25 cm
describe the abdominal aorta
I cant see my right gonad, inferior (or) median (that’s) life
Inferior phrenic T12 coeliac L1 superior mesenteric Middle suprarenal renal artery gonadal arteries inferior mesenteric L3 median sacral lumbar arteries (L1 - L4)
describe the thoraic aorta
By Middle October, Perry Starts Interailing and Sightseeing
Bronchial Mediastinal Oesophageal Pericardial superior phrenic intercostal and subcostal
describe the thorcic aorta
By Middle October, Perry Starts Interailing and Sightseeing
Bronchial Mediastinal Oesophageal Pericardial superior phrenic intercostal and subcostal
what is glomerular filtrate?
the plasma filtration by glomerulus into bowmans space. no cells no proteins but same concentration of substance as in plasma.
other substances can be added to filtrate by tubular secretion or reabsorbed by tubular reabsorption.
define glomerular filtration rate
the volume of fluid filtered from the glomeruli into Bowman’s space per unit time
what determines the GFR? IMPORTANT
net filtration pressure
permeability of renal corpuscle membrane
surface area available for filtration
what does net filtration pressure depend on
depends on hydrostatic pressure differences and protein concentration differences between both glomerular capillary and bowmans space
what is the average GFR?
180 L per day for a 70 kg person
give the equation for GFR
GFR = Kf (P GC - P BS) - (π GC - π BS)
Kf is the filtration coefficient. takes permeability and surface area into account.
describe the filtration barrier
endothelial cell layer with fenestrations glomerular basement membrane slit diaphragm (proteins made by podocytes) foot processes of podocytes leaving filtration slits
give the pressures at the glomerulus
osmotic
πGC 25 increases as you go along capillary as it gets more concentrated
πBS 0
hydrostatic
P GC 45
P BS 10
what is urine production per hour?
0.5 ml per kg per hour
describe ion reabsorption / secretion along the tubule system
PCT bulk
- reabsorption of 60% Na+, Cl-, glucose, AA, HCO3-, water (bulk!)
- secretion: creatinine, antibiotics, diuretics, uric acid
Loop of Henle
absorption of water, K+, Mg, Ca
HCO3- , Ca, Na
DCT fine tunes
absorption of Na, Ca, H20
secretion of K+/H+/urea
H20
CCD
sodium reabsorption
controlled H20 reabsorption
secretion of K+. HC03- if needed
describe the countercurrent multiplication system
producing a hypertonic medullay interstitium to enable h20 reabsorption via osmosis.
ascending limb solute reabsorption cl- na+
impermeable to water
increase medullary osmolality
h20 drawn out of descending limb, as this is permeable to water but not to solutes.
inc luminal osmolality
fluid flow pushes this hyperosmotic fluid into ascending limb
process repeats itself
what stimulates the renin angiotensin aldosterone system?
juxtaglomerular cells in the afferent arterioles detect changes in blood pressure, secrete renin as a response. Increased blood pressure, inhibition of renin. decrease in blood pressure, release of renin.
macula densa (located between ascending loop and DCT) these detect sodium in DCT. high Na+ = inhibition of renin. low Na+, stimulation of renin.
summarise the renin angiotensin aldosterone system
renin released by juxtaglomerular cells of afferent arterioles.
renin cleaves angiotensinogen produced by liver to angiotensin 1.
angiotensin 1 goes to the liver where it forms angiotensin 2 via ACE.
angiotensin 2 is a vasoconstrictor and causes adrenal cortex to release aldosterone and ADH release.
Aldosterone acts on kidneys to upregulate solute reabsorption.
describe the role of angiotensin 2
vasoconstrictor
vasoconstricts afferent arterioles more than efferent, increasing the hydrostatic pressure gradient by inc P GC. Therefore increase GFR
thirst
inc PCT NA+ reabsorption
acts on adrenal medulla to release aldosterone
acts on pituitary to release ADH/vasopressin
describe the role of aldosterone
acts on the kidneys upregulating Na+/K+ ATPase pump and ENaC (sodium channel).
Increased Na+ reabsorption and therefore water reabsorption, this occurs in the dct
Describe the role of ADH/vasopressin
produced by hypothalamus
stored in pituitary
acts cortical and medullary collecting duct to insert aquaporins into cell membrane and upregulate water reabsorption
urine becomes more concentrated
describe the role of atrial natriuretic hormone
released by atrial myocytes in response to distention
dilate veins and arteries
decrease in cardiac output fue to decrease in ventricular preload
inhibit renin release, aldosterone, Na+ reabsorption.
Increase GFR so more Na+ can be excreted
describe the role of parathyroid hormone
increases ca and phosphate reabsorption in the DCT
stimulate formation of 1,25 dihydorxyvitamin D from kidney by upregulating enzyme 1 alpha hydroxylase which upregulates Ca (and inhibits phosphate) intestinal absorption, 1,25 dihydorxyvitamin D also increases osteoclast activity releasing calcium and phosphate from the bone. It also increases reabsorption in the DCT.
how is release of vasopressin regulated?
baroreceptors detect changes in blood volume and pressure. fire when blood volume is LOW
These are less sensitive but can override osmolality pressure changes.
osmoreceptors (in hypothalamus) are very sensitive. they stretch when hypotonic
stimulated if osmolality INCREASES
regulate release of ADH from post pituitary
blood volume restoration is prioritized
describe the insensible losses
menstrual GI sweat repsiratory airways skin urinary tract
what proteins are found in urine?
tamm horsfall produced by thick ascending limb
also called uromodulin
how if GFR calculated?
GFR = (M conc in urine x urine flow rate) / M conc in plasma
normally 125 ml/min
what can be used clinically to look at GFR?
creatinine (produced by muscle) clearance
it is freely filtered
only tiny amounts secreted
so should be about 125 ml min
give the equation of renal clearance and define it
the volume of plasma from which a substance is completely removed by the kidney per unit time.
clearance = urine conc x urine volume /plasma concentration
how would you calculate the filtration fraction
GFR / renal plasma flow
this is the proportion of renal blood flow that gets filtered.
renal blood flow is 1000ml /min 60% of blood is plasma and 40% is cells so renal plasma flow 600 ml/min GFR is 125 ml/min so filtration fraction 120/600 about 0.2% urine flow is 1 ml/min
what is the filtered load
filtered load = GFR x plasma conc of substance
gives you the rate at which something should be filtered
what is the role of mesangial cells
surround glomerular capillaries
no role in filtration
controlled by neural/hormones
contraction can cause decrease in glomerular capillary surface area
decrease in GFR regardless of filtration pressure
structural support and production of extracellular matrix
involved in phagocytosis of breakdown products
what are the causes of metabolic and resp acidosis?
metabolic dilutional failure of hydrogen ion excretion hypoalosteroidism (decreased aldosterone) excess H+ load acid ingestion HC03- loss diarrhoea
resp
co2 retention
what are the causes of metabolic alkalosis?
alkali digestion
vomiting
renal acid loss
resp
hyperventilation
type 1 resp failure
how is HCO3- reabsorbed?
inside lumen H20 + Co2 –> H2C03- –> HCO3- + H+
H+ exchanged for Na+ with lumen
H+ combines with HCO3- in lumen to form H2CO3 which forms H20 and CO2 which can be taken into cell.
the HCO3- is transported into interstitial fluid co transport with Na+.
how is HCO3- reabsorbed?
inside lumen H20 + Co2 –> H2C03- –> HCO3- + H+
H+ exchanged for Na+ with lumen
H+ combines with HCO3- in lumen to form H2CO3 which forms H20 and CO2 which can be taken into cell.
the HCO3- is transported into interstitial fluid co transport with Na+.
all HCO3- is absorbed unless alkalosis
how is new HCO3- generated?
All filtered HCO3- is absorbed
non bicarbonate buffers such as HPO4 2- filtered.
inside cell H20 + co2 –>h2c03–>Hco3- + H+
H+ combines to form H2PO4 which is excreted
HCO3- added into blood, new.
new HCO3- can also be produced by glutamine metabolism, producing HCO3- and NH4+.
NH4+ secreted into lumen via Na+ exchange
this occurs in response to acidosis
what happens in diseases such as psoriasis and eczema?
In psoriasis there is an increase in number of corneodesmosomes resulting in thickening of the skin.
In eczema there is a decrease in corneodesmosomes resulting in thinning of the skin and increase risk of inflammation.
how thick should the cortex be in a health adult?
7mm
what is the renal corpuscle?
glomerulus and bowmans capsule
what gives the cortex of the kidney a striated appearance?
medullary rays (tubules looping)
what epithelium lines the renal pelvis?
transitional
how would you distinguish the mesangial cells?
periodic acid shift PAS
stains glycoproteins in basement membrane
what is the juxtaglomerular apparatus composed of?
Afferent arteriole granular cells detect blood pressure
distal convulted tubule - macula densa detect sodium
also LACIS CELLS are involved. (be aware of existence)
describe the epithelium of the proximal convoluted tubule?
cuboidal
microvilli
many mitochondria
lysosomes
describe the epithelium of the thick and thin segments of the loop of henle
thin simple squamous
thick low cuboidal
why is the loop of henle prone to ischemia?
because the vasa recta are far from the glomerulus where afferent arterioles supply with oxygen. quite deoxygenated.
descibe the epithelium of the DCT
cuboidal
NO microvilli
how would you describe high sodium and low potassium?
hypertraemia
hyperkalaemia
could be mediated by aldosterone
describe the epithelium of the collecting duct
cuboidal epithelium
principal cells - respond to aldosterone (inc Na+/K+ ATPase and EnaC) and ADH (inc aquaporins) into apical membrane.
intercalated cells - responsible for exchanging acid for base both ways. ALPHA intercalated cells secrete acid and BETA intrecalated cells secrete bicarbonate.
describe transitional epithelium/urothelium
stratified 5 layer epithelium. Has a surface later, intermediate layer and a basal layer. Basal layer is CUBOIDAL
able to stretch in 3 dimensions going from cuboidal to flat, volume of cells stay same but thickness and diameter can change.
surface layer has UMBRELLA cells. these have tight junctions (ZONA OCCLUDENS) whcih prevents urine getting in between the cells.
describe the histology of the ureter
spiral muscular tube, inner is longitudinal muscle and outer is circular (opposite in GI).
no serosa
loose adventitia
describe the bladder histology
transitional epithelium lamina propria muscularis mucosa submuscosa muscularis propria subserosa and serosa
have a functional valve to prevent reflex into ureter
describe the sphincters of the urethra
internal sphincter - smooth muscle from the bladder
external sphincter - skeletal muscle from the pelvic floor
describe the differences of the urethra in men and women.
men 20cm made up of 3 segments prostatic urethra membranous urethra (transitional) penile urethra (pseudostratified epithelium proximally and stratified squamous epithelium distally)
women
4-5 cm long
proximal transitional epithelium
distal squamous epithelium
how much cardiac output is received by EACH kidney?
20% of the cardiac output
what is the TOTAL renal blood flow
1L / min
what is the total urine flow and outut?
1 ml /
urine output is 0.5ml/kg/hour
ie in a 64kg man it would be 32ml an hour
where are the 2 sets of capillaries in the nephron?
glomerular capillary bed
peritubular capillary bed
connected via efferent arteriole
how much of the blood flowing through the glomerulus is filtered?
20 %
what type of epithelium if found on the glomerulus surrounded by bowmans capsule?
parietal
what do the efferent arterioles supply?
peritubular capillaries which supply PCT and DCT
long vasa recta which supply loop of henle
what are the 2 types of nephron?
15% are juxtamedullary - renal corpuscle lies in the cortex close to the cortico medullary junction
85% are cortical so renal corpuscles lie in outer cortex. loop does not penetrate as deeply into medulla. some cortical nephrons do not even have a loop of henle so do NOT contribute to hypotonic medullary interstitium.
at what point is the macula densa located and the afferent granular cells of the juxtaglomerular apparatus?
where the ascending loop passes between the afferent and efferent arteriole of its own nephron.
what is glomerular filtration
passage of fluid from blood into bowmans space to form filtrate
what is the meaning of ultra filtrate?
has the same concentrations of all substances as in the plasma, except for later proteins.
*some low weight substances that would be in ultrafiltrate stay in blood if they are bound to plasma proteins. ie, all of the plasma fatty acids and half plasma calcium bound.
how is albumin kept our of the glomerular filtrate?
glomerular basement membrane is negatively charged and repels negatively charged molecules.
why does microalbuminuria show diabetes?
diabetes damages the filtration barrier
albumin normally not in urine
at any given net filtration pressure, GFR will be directly proportional to…
surface area
membrane permeability
how does afferent arteriole constriction and efferent dilation effect the GFR?
P GC decreases
GFR = kf ( P GC - P BS - pi GC)
when using marker substance to measure GFR, what are the properties of this marker substance?
freely filterable
not secreted or absorbed by tubules
not metabolised
describe the role of each segment of the nephron
PCT - bulk reabsorption Na Cl glucose AA HC03-
secretion of organic ions
LOF - na reabsorption urinary dilution and generation of medullary hypertonicity.
DCT fine tuning regulation of na, k, ca, Pi
ALSO separation of Na from H20.
CCD similar to DCT also acid secretion and regulated H20 reabsorption concentrating the urine
how is Na+ transported into PCT cells
na+/K+ ATPase pump is basolateral membrane
Na+ in co transport SYMPORTER with glucose / phosphate / AA
antiporter with H+
how is hco3- reabsorbed
inside cell h20 and co2 form h2c03. H+ secreted in exchange for Na+
Hco3- out via basolateral membrane into blood
H+ combines with filtered HCO3- to generate co2 and h20 in lumen which then diffuse into tubular cells.
what is the TRANSPORT MAXIMUM
the limit of amount of material that can be transported per unit time, by mediated transport systems. this is because binding sites on membrane transport proteins become saturated.
describe how urea is involved in the countercurrent medullary interstitium
urea is freely filtered
50% is reabsorbed in PCT therefore increasing medullary intersitium osmolality.
50% enters loop of henle
urea that has accumulated in interstitium is secreted back into tubular lumen via F diffusion
What is the role of nerves in the bladder system?
The Pelvic splanchnic S2-S4. (parasympathetic) causes detrusor muscle contraction.
the Hypogastric nerve. T1-L2 is sympathetic. It causes contraction of the internal urethral sphincter. It also causes relaxation of the detrusor muscle
The somatic motor nerve - the pudental nerve S2-S4 causes contraction or relaxation of the external sphincter.
what allows urinary retention?
the hypogastric sympathetic nerve causes relaxation of detrusor muscles and contraction of the internal sphincter.
the pudental nerve causes contraction of the external urethral sphincter.
which type of muscle is found in the bladder
detrusor - smooth
internal urethral sphincter - smooth
external urethral sphincter - skeletal
what is the bladder stretch reflex
bladder fills
activates stretch receptors
synapse with interneurones in the spinal cord
stimulate with parasympathetic neurones (pelvic splachnic s2-s4) which cause contraction of detrusor muscles.
micturition occurs.
this does not happen past childhood as we learn to exert voluntary motor control via descending pathways.
describe the process of bladder filling
parasympathetic input (pelvic splanchnic S2-S4) to the detrusor muscle is minimal, hence it is relaxed. due to muscle fibre arrangement, relaxation of detrusor means internal sphincter is passively closed.
sympathetic input (hypogastric T1-L2) also aids closure of the internal sphincter.
describe the process of micturition
bladder fills and pressure increases
detected by stretch receptor in bladder wall
afferent input to spinal cord
synapse via interneurones with parasympathetic nerves (pelvic splanchnic S2-S4) which cause contraction of detrusor muscle.
Contraction causes passive opening of the internal sphincter.
inhibitory interneurones synpase with the sympathetic nerves (hypogastric T1-L2) and somatic motor nerve (pudental S2-S4) which causes inhibition and relaxation of internal and external sphincter
how is osmolality regulated?
vasopressin secreted by the posterior pituitary
release controlled by osmoreceptors in the hypothalamus.
osmoreceptors respond to osmolality (effectively to sodium)
what is significant about vasopressin having a half life of only 15 minutes?
can adapt very quickly to osmolality changes
how does alcohol, MDMA and nicotine affect vasopressin release?
alcohol decreases secretion
MDMA and nicotine both increase secretion
how sensitive are osmoreceptors?
respond to 1-2% changes
describe the baroreceptor reflex and the effect on ADH secretion?
baroreceptors measure pressure, effectively monitoring blood volume. they are less sensitive than osmoreceptors but when stimulates cause a greater release of ADH and are therefore more potent.
baroreceptors are located in the carotid sinus and aortic arch. increase firing due to increased stretch, increased impulses to the hypothalamus, increase ADH secretion and release from the posterior pituitary.
what is the transport maximum?
refers to the point at which increases in concentration of a substance do not result in an increase in movement of a substance across a cell membrane.
what results in glucosuria?
transport maximum reached
means that blood glucose never exceeds 150mg/100ml
what 2 cell types are found at the collecting duct?
principal cell
have EnaC ion channels. these allow Na+ into cell
have Na/K+ ATPase ion channels. Aldosterone can stimulate increased transcription of these.
respond to ADH and can increase aquaporin insertion into membrane.
intecalated cell
secrete acid into duct
how does ADH stimulate insertion of aquaporin 2 channels into the membrane?
ADH binds via the adenylyl cyclase coupled vasopressin receptor. activation of Kinase which facilitates insertion.
what is the pH of the intracellular fluid?
7
what is the ph of the extracellular fluid?
7.4
what is the plasma osmolality range? How is this calculates?
285 - 295 mOsM 2 x (Na+ + K+) + glucose + urea
how is fluid movement controlled?
sodium movement
how is tonicity controlled?
water movement
where does sodium reabsorption occur along the tubule?
PCT 60%
LOH 25%
DCT 10%
CCD 4%
where is aldosterone secreted?
zona glomerusola
adrenal cortex
acts on principal cells of the collecting duct
what is the role of parathyroid hormone?
released in response to low calcium in the blood. Increases calcium and phosphate in the blood.
negative feedback to prevent levels getting too high.
describe the response to low calcium
in the skin:
7 dehydrocholesterol → vitamin D3
in the liver:
vitamin D3 → 25 hydroxyvitmain D3
enzyme 25 hydroxylase
in the kidney
25 hydroxyvitmain D3 → 1,25 dihydroxy vitamin D
enzyme 1 hydroxylase
enzyme upregulated by parathyroid hormone in response to low level calcium.
1, 25 dihydroxyvitamin D does many things
- increases release of calcium and phosphate from bone
- increased absorption of phosphate and calcium from the intestine
- inhibits parathyroid gland from producing parathyroid hormone.
- increased kidney reabsorption of calcium and phosphate
describe HCO3- reabsorption
all HCO3- is reabsorped inside the cell H2O + CO2 forms H2CO3- dissociates, HCO3- pumped into intersitial space in exchange for calcium ions. H+ is secreted into the lumen in exchange for sodium H+ combines with excreted HCO3- formation of H2CO3- forms H20 and CO2 diffuse into cell
describe kindey response to metabolic acidosis
- all hco3- reabsorbed
secretion of extra H+ via same mechanism
combines with non bicarbonate buffers such as HPO42- to form H2PO4 and is excreted
HCO3- still taken up into interstitial fluid.
2.glutamine taken up from filtrate metabolised to form NH3 and HCO3- H+ added to form NH4+ excreted by exchange with sodium HCO3- moves into the plasma
what does the kidney secrete?
erythropoietin
this stimulates formation of erythrocytes in the bone marrow.
increases in response to poor renal perfusion, anaemia.
decreases in response to polycythaemia (Hb abnormal), renal failure.
what is the blood supply of the adrenal glands
superior adrenal artery - comes from the inferior phrenic artery
middle adrenal gland - from aorta
inferior adrenal gland - from renal artery
venous, right adrenal drains into IVC
left adrenal drains into left renal vein.
what is the innervation of the adrenal gland?
coeliac plexus
abdominopelvic splanchnic nerves.
Sympathetic innervation T10 to L1
what is the role of cortisol
1.maintains normal homeostasis in absence of stress. Secretion increases in response to stress.
2. reduces production of prostaglandins and ;eukotriene to prevent inflammatory response
3. stabilizes lysosomal membranes to prevent leakage of enzymatic contents.
4.immune brake
4, permissive effects on smooth muscle cell receptors to increase sensitivity to andrenaline and noradrenaline.
5.vital for surfactant production in embryo
6. important for growth of neural, adrenal gland tissue in embryo
7. helps to maintain cellular concentrations of hepatic enzymes which control blood glucose between meals.
8. mobilise fatty acids, proteins, glucose during times of stress.
9. reduces capillary permeability in some areas to avoid leakage.
why is cortisol useful in the stress response?
reduction in inflammatory response protects against potential damage linked with inflammation.
increased ability of smooth vascular muscle to contract, improves CV performance, maintains bloop pressure.
increased organic metabolism, useful in starvation. Amino acids are readily available in case of tissue damage.
why is chronic stress negative?
high level cortisol
weakening of bones
poor immune function
reproductive fertility affected
describe the process of ‘stress’
stress stimulus
transmitted to the hypothalamus via neurones
hypothalamus secretes hormone: corticotropin releasing hormone CRH
via hypothalami hypophyseal portal veins
- anterior pituitary responds by secreting adrenocorticotropic hormone ACTH into the blood.
-reaches adrenal glands
-cortisol released from the zona reticularis
-90% travels bound to corticosteroid binding hormone
-5% bound to albumin
-5% free
cortisol has a neg feedback of CRH and ACTH release !!! long loop negative feedback
what are the androgens called which are produced by the adrenal glands and describe their function?
androstenedione
dehydroepiandrosterone
quite weak androgens
androstenedione is a major androgen source in females. can be converted to stronger androgens in peripheral tissue.
what does the adrenal medulla secrete? what ratio
80% adrenaline
20% noradrenaline
when are catecholamines released by adrenal medulla?
under flight or fight situations
cortisol release has a permissive effect on its actions
what is stress
The sum of the bodies responses to adverse stimuli
what do catecholamines do
gluconeogenesis in liver and muscle
lipolysis in adipose tissue
Tachycardia and cardiac contractility
Redistribution of circulating volume
name the muscles of the bladder
detrusor muscle
internal urethral sphincter
external urethral sphincter
what is the nerve supply of the bladder
symapthetic - pelvic splanchnic S2/S4
parasympathetic - Hypogastric T1-L2
somatic motor - prudental nerve S2/S4
what causes contraction of each of the 3 bladder muscles?
detrusor - pelvic splachnic
internal sphincter - hypogastric
external sphincter - somatic motor
how is the hypothalamus connected to the pituitary gland
infundibulum
describe the embryological development of the anterior and posterior pituitary gland?
anterior pituitary gland develops as a protrusion of the ectoderm from the mouth known as Rathke’s pouch. it grows upwards to form the anterior pituitary.
posterior pituitary gland is an extension of the diencephalon.
the two become tighlt apposed.
name the hypophysiotropic hormones released by the hypothalamus.
hypophysiotropic hormones travel to anterior pituitary via the hypothalami hypophyseal portal system.
Corticotropic releasing hormone CRH Growth hormone releasing hormone GHRH Thyrotropin releasing hormone TRH Gonadotropin releasing hormone GRH Dopamine
what does each of the hypophysiotropic hormones bring about?
Corticotropic releasing hormone CRH causes release of adrenocorticotropic hormone ACTH from anterior pituitary.
Growth hormone releasing hormone GHRH causes release of growth hormone from the anterior pituitary
Thyrotropin releasing hormone TRH causes release of thyroid stimulating hormone TSH from anterior pituitary
Gonadotropin releasing hormone GRH causes release of LH and FSH from anterior pituitary
Dopamine causes INHIBITION of prolactin release from anterior pituitary.
where are each of the anterior pituitary hormones stored
FSH and LH in gonadotrophs prolactin in lactotrophs ACTH in corticotrophs TSH thyrotrophs GH somatotrophs
what is the short loop negative feedback?
prolactin acts on hypothalamus to stimulate release of dopamine which inhibts prolactin release from anterior pituitary.
what is stored in the posterior pituitary
ADH/vasopressin
oxytocin
what is the role of oxytocin
stimulate contractions throughout
induce pregnancy
stimulate smooth muscle of the breasts to contract resulting in milk ejection during lactation.
what is the role of vasopressin
vasoconstriction
insertion of aquaporins into cell surface membrane to increase water absorption in the DCT (?)
increases water reabsorption
released in response to decreased blood volume, increased osmotic pressure of the blood, trauma, stress, increased blood co2 / decreased 02
axons of which two nuclei pass down via the infundibulum and terminate in the posterior pituitary?
supraoptic (synthesizes ADH)
paraventricular (synthesizes oxytocin)
when does pancreatic exocrine and endocrine functions begin to work?
exocrine after birth (bile salts, amylase, trypsin)
endocrine from 10-15 weeks gestation
describe the pancreatic cells
98-99% of cells are small clusters of glandular cells called acini, these perform exocrine functions.
1-2% of cells (islets of langerhans) do the endocrine function. alpha cells secrete glucagon, beta cells secrete insulin and delta cells somatostatin.
how many amino acids are in the peptide hormone insulin?
51
how many amino acids are in the peptide hormone glucagon?
29
what is the role of insulin
decreases glycogenolysis and gluconeugenesis
increases fatty acid synthesis in adipose and muscle
increase protein synthesis in muscle
suppresses lipolysis and ketogenesis
what is the role of glucagon
increases glycogenolysis and gluconeogenesis
reduces peripheral glucose uptake
stimulates lipolysis and ketongenesis (protein breakdown in the muscle) producing gluconeogenesis precursors.
how is insulin stimulated to be released from the beta cell
insulin formed from proinsulin (alpha and beta chains joined by C peptide. cleaved to remove C peptide)
GLUT 2 receptor on beta cell membrane is low affinity
only high glucose will allow binding
glucose enters the cell
glucose -> glucose 6 phosphate via hexokinase
ATP broken down into ADP
ATP reformed
ATP binds to K+Atpase, blocking it
no K+ can exit
depolarisation
voltage gated Ca2+ channels open
Ca2+ bind to vesicles containing vesicles causing them to be release via exocytosis
how does insulin effect peripheral tissues
binding of insulin to a receptor causes intracellular signalling cascade. GLUT4 ion channels in vesicles fuse to membrane. increase glucose intake into the cell
decrease in blood glucose
what are 2 phases of insulin release
first phase - insulin is rapidly released
second phase - if glucose is still high more insulin produced but this takes time as it must be synthesised
what senses glucose levels
primary glucose sensors are located in the pancreatic islets of langerhans
also in the medulla, hypothalamus and carotid bodies
input from nose, eyes, taste buds
sensory cells in the gut walls stimulate insulin via release of INCRETINS
what are incretins
these are secreted by endothelial cells of the GI tract in response to eating. it amplifies the insulin response. major types:
glucose dependant insulinotropic peptide GIP
glucagon like peptide 1 GLP1
what is the relevance of c peptides
can see if insulin is naturally produced or synthetic
where does ingested glucose go?
60% to the periphery (mostly muscle)
40% to the liver
glycogen stores are replenished and excess is used for lipid or protein synthesis
what happens during fasting
the liver does glycogenolysis (short term) and gluconeogenesis (long term)
glucose is then delivered to INSULIN INDEPENDENT tissues which are the brain and red blood cells.
muscles use free fatty acids as an energy source
