Renal, Reproductive, Endocrine Physl Flashcards
5 functions of the kidneys?
Regulate blood pressure and volume Maintain acid-base balance Excrete waste Gluconeogensis Secrete various hormones
Waste products excreted by kidneys?
Urea, uric acid, bilirubin, creatinine
3 hormones secreted by the kidneys?
Erythropoetin
Renin
1,25-dihydroxyvitamin D
Which fluid do the kidneys regulate? What are the components of it?
Extracellular fluid: plasma, ISF, CSF
Proportion of body’s intracellular to extracellular fluid
40% intracellular, 20% extracellular (total 60% of body weight is water)
Relative Na, K, Cl, bicarbonate, phosphate concentrations in ECF vs ICF
Na, Cl and bicarbonate have higher concentrations in ECF
K and phosphate..ICF
Aquaporins
Water channels in the plasma membrane, allowing for rapid diffusion of water
What does the water concentration of a solution depend on?
The number of solute particles in that solution
Osmolarity
The number of solutes per volume of solution,expressed in moles per litre
A region with lower osmolarity has a higher or lower water concentration?
Higher water concentration
Diffusion
Solute particles move from an area of higher concentration to an area of lower concentration
Diffusion is due to what?
Random thermal motion
Osmosis
Net diffusion of water across a semi permeable membrane from a region of high water concentration to a region of low water concentration
Semi-permeable membrane
Allows water to cross, not any solutes
Osmotic pressure & why it is important in cells?
Opposing pressure required to stop osmosis completely. It will stop water from flowing into the cell, and prevent the cell from bursting
Tonicity
Determined by the concentration of non-penetrating solutes of an extracellular solution
Non-penetrating solutes
Solutes that do not enter the cell
Isotonic
Intracellular and extracellular solute concentrations(osmolarity) and water concentrations are the same. No net movement of water
Hypertonic
Extracellular environment has a higher solute concentration (osmolarity) than intracellular environment. Water moves out of the cell
Hypotonic
Intracellular environment has a higher solute concentration (osmolarity) than extracellular environment. Water moves into cell.
Movement of fluid in absoption
Fluid moves from ISF to plasma
Movement of fluid in filtration
Fluid moves from plasma to ISF
Capillary hydrostatic pressure
Pressure exerted by fluid against capillary wall causing some of the fluid to move into ISF
Interstitial fluid hydrostatic pressure
Pressure of ISF on the walls of the capillary, causing movement of fluid into capillaries
How do plasma proteins in plasma affect osmotic force?
A lot of plasma proteins in plasma means lower water concentration inside capillary compared to outside, so water tends to be pulled into capillary.
How do plasma proteins in ISF affect osmotic force?
Fluid will tend to be drawn into ISF
Starling forces
The 4 forces (Sum of the 2 outgoing forces minus the 2 ingoing forces) that determines the net filtration pressure
Which end has higher absorption/filtration? Why?
Venous end has more more absorption. Net filtration pressure is negative so fluid moves into capillary.
Arterial end has more filtration. Net filtration pressure is positive so fluid moves out of capillary.
Hilum
Inner concave part of kidney
Ureters
Drain urine from kidneys to bladder
Bladder
Sac that stores urine
Micturation
Releasing urine outside the body; urination
2 regions of the kidney
Outer: cortex
Inner: medulla
Nephron
Functional unit of the kidney. Urine is made here
Renal corpuscle and structure
Bulb-like structure with loops of capillaries
Composed of the glomerulus and Bowman’s capsule
Renal tubule segments
Proximal convolutes tubule
Loop of Henle
Distal convoluted tubule
Collecting ducts
Function of renal corpuscle
Initial filtering of blood
Podocytes
Cells which come in contact with glomelular capillaries; have foot-like processes
Development of renal corpuscle
Nephron develops as a tube that has no opening
Tubule invaginates and basal lamina is trapped between epithelial cells and epithelial layer
Epithelial cell layer differenciates into parietal and visceral layers
Outer layer does not fuse with inner layer, space left between them
Parietal layer flattens into wall of Bowman’s capsule and visceral layer becomes podocyte cell layer
Parietal vs visceral layer
Parietal- outer layer of epithelial cells
Visceral- layer closest to glomelular capillaries; podocytes
Fenestration importance?
Allows for filtration
Basement membrane
Gel like mesh structure composed of collagen proteins and glycoproteins
Purpose of foot preojections
Wrap around capillaries and leave slits in them, allowing for greater SA for filtration
2 types of nephrons
Cortical and juxtamedullary
What parts are found in the cortex?
Tubule segment, collecting duct, DCT, PCT
What parts are found in the medulla?
Loops of henle, ascending limb, renal corpuscles
Difference between cortical and juxtamedullary nephrons
They both perform filtration,absorption and secretion but the juxtamedullary nephrons additionally create osmotic gradients to regulate the concentration of urine.
Afferent arteriole
Brings blood into glomerular capillary network
Efferent arteriole
Blood exits glomerulus through it
Peritubular capillaries
Found around the PCT. They fuse together to form renal vein
Vasa recta
Capillaries found mostly associated with the juxtamedullary nephrons in medulla
Steps in urinary production
Glomerular filtration
Tubular absorption
Tubular secretion
Urinary excretion
Glomerular filtration
Fluid in blood is filtered across capillaries of glomerulus and into Bowmans capsule
Tubular reabsorption
Movement of a substance from tubule to blood
Tubular secretion
Movement of non-filtered substances from capillaries to tubular lumen
Urinary excretion
Blood is filtered at glumeruli and urine excreted from body
What can move from glomerular capillaries to Bowmans capsule? What cannot?
Water, electrolytes, glucose, waste products.
Plasma proteins and blood cells cannot
Ultrafiltrate
Cell free fluid that has come into Bowman’s space. Contains mostly all the substances at the same concentrations as in the plasma and in the filtrate.
Proteinuria
Proteins that weren’t supposed to pass through filtration barrier end up in the filtrate and urine.
Glomerular capillary hydrostatic pressure
Hydrostatic pressure of the blood found in glomerular capillaries. Pushes fluid into Bowman’s space
Bowman’s space hydrostatic pressure
Hydrostatic pressure of fluid in Bowman’s space. Pushes fluid in glomerular capillaries
Osmotic force due to proteins in the plasma
Due to plasma proteins; there is high solute concentration in capillaries due to presence of these proteins and less water, so this causes movement of fluid from Bowman’s capsule to capillaries (water follows solute)
Which forces oppose and favour filtration?
Glomerular capillary hydrostatic pressure favours filtration.
Bowmans space hydrostatic pressure and osmotic force due to proteins in plasma oppose filtration.
How to determine glomerular pressure
Sum of the 3 pressures subtracted
Net filtration is always…?
Positive
Which factor would contribute to increased glomerular filtration rate?
Increased blood pressure
Which factor would contribute to decreased glomerular filtration rate?
Increase in protein concentration in plasma
Fraction of volume entering glomerular capillaries that is filtered?
20%
Volume of fluid excreted?
<1%
Glomerular filtration rate? What are the numbers?
The volume of fluid filtered from the glomerulus into the Bowmans capsule per unit time.
125mL/min or 180L/day
Factors affecting GFR?
Blood pressure
Neural and endocrine control
Permeability of corpuscular membrane
Surface area available for filtration
Autoregulation
Allows GFR to remain relatively constant despite large changes in arterial pressure
Autoregulation is regulated by changes in what?
Myogenic reflex and tubuloglomerular effect
Effect of constriction of afferent arteriole on GFR?
Decreased glomerular capillary hydrostatic pressure, therefore decreased filtration rate
Effect of constriction of efferent arteriole on GFR?
Volume of blood builds up in glomerular capillaries so increased hydrostatic pressure and increased filtration rate
Effect of dilation of efferent arteriole on GFR?
Decreased glomerular capillary hydrostatic pressure, decreased rate of filtration
Effect of dilation of afferent arteriole on GFR?
Increased blood flow, increased hydrostatic pressure increased filtration rate
Mechanisms which change arteriolar resistance?
Myogenic responses (muscle contracting/relaxing due to changes in pressure) Hormones/neurotransmitters Tubular glomerular feedback (controls the autoregulatory processes and affect GFR)
Juxtaglomerular apparatus
Specialized structure formed by the distal convoluted tubule and glomerular afferent arteriole
Next to the glomerulus
3 cell types that regulate GFR
Macula densa
Juxtaglomerular cells
Mesangial cells
Macula densa
Cells on the wall of distal tubule where the ascending limb is beggining to form the distal tubule.
Change afferent arterial resistance by paracrine effects. (adenosine)
What do macula densa sense?
Increase Na load and increased fluid flow through distal tubule
What do macula densa secrete?
Vasoactive compounds
Juxtaglomerular cells
Sit on top of afferent arteriole
Juxtaglomerular cells release what?
Renin, which controls afferent arteriole resistance
Juxtaglomerular cells are innervated by?
Sympathetic nerve fibers
Mesangial cells
Found in the triangular portion between afferent and efferent neurons. Allow podocytes to contract, and control filtration surface area.
Which cells are NOT considered as part of the JGA?
Mesangial cells
Tubuloglomerular feedback mechanism
Increase in GFR
Increase in flow
Flow past macula densa increases
Paracrine factors secreted from macula densa and act on afferent arteriole
Afferent arteriole constricts and resistance increases
Glomerular hydrostatic pressure drops
GFR decreases
Filtered load and how to calculate it
Amount of substance filtered by kidneys per day; how much load is filtered into Bowmans capsule
GFR x concentration of the substance in plasma
If substance excreted in urine is less than filtered load, what occured?
Reabsorption
Is substance excreted in urine is more than filtered load, what occured?
Secretion
What happens when a substance is filtered and secreted?
20% of substance filtered at Bowman’s space, 80% moves in peritubular capillaries. As that small amount was being filtered, most of the substance ended up being secreted into urine. Body did not absorb any of substance.
What happens when a substance is filtered and partially reabsorbed?
20% of substance filtered at Bowman’s space, 80% moves in peritubular capillaries. As that small amount was being filtered, the some was also being reabsorbed back into peritubular capillaries.
What happens when a substance is filtered and completely reabsorbed?
20% of substance filtered at Bowman’s space, 80% moves in peritubular capillaries. As that small amount was being filtered, all of it ended up being reabsorbed by the peritubular capillaries. NONE was excreted in urine.
Inulin
Polysaccharide found in plants
Inulin renal handling
Filtered ONLY. Excreted completely in urine so no secretion or reabsorption
Creatinine renal handling
Filtered for the most part
Electrolytes renal handling
Filtered and partially reabsorbed
Glucose and amino acids renal handling
Filtered and completely reabsorbed
Organic acids and bases renal handling
Substance completely secreted into urine
PAH
Organic acid that undergoes filtration and secretion
Measures renal plasma flow
How much % of water is reabsorbed?
99%
How much % of Na is reabsorbed?
99.5%
How much % of glucose is reabsorbed?
100%
How much % of urea is reabsorbed?
44%
How is glucose vs water and Na reabsorption regulated?
Glucose is not physiologically regulated while the body regulates the reabsorption of water and Na
2 pathways of reabsorption
Diffusion and mediated transport (major component involving transporters)
Transepithelial transport and its pathway
Substance will move from the tubular lumen to the interstitial space and into peritubular capillaries.
How does Na move across luminal surface?
Passively down conc gradient
How does Na move out of the cell across basolateral membrane?
Active transport using ATPase
How does Na move into peritubular capillaries?
Bulk flow
Reabsorption of Na by mediated transport
On basolateral membrane: transport of Na mediated by Na/K pump
On apical membrane: influx of Na caused by diffusion into the cell which has lower conc of NA
Clearance of zero
Refers to NO glucose present in urine because all filtered glucose is reabsorbed
In the proximal tubule glucose is reabsorbed by?
Active transport on luminal side by SGLT
Facilitated diffusion on basolateral side using GLUT
Glucosuria
Above renal threshold glucose appears in urine
How does SGLT work?
Uses the inwardly directed Na gradient as “energy” to move glucose into cell from a low to high concentration. This is secondary active transport
Glucose crosses basolateral membrane using what?
GLUT
Relationship between plasma glucose concentration and filtration rate of glucose?
Linear relationship; proprotional. When plasma glucose concentration increases, filtration rate increases also
Relationship between plasma glucose and reabsorption of substance?
Initially linear, until 300mg/100mL plasma. Then the graph plateaus because it hit the transport maximum. No more glucose can be reabsorbed.
Transport maximum. What does it cause on graph?
All SLGT proteins that transport glucose from lumen to peritubular capillaries are saturated. Binding sites are all occupied therefore no more glucose can be absorbed, resulting in plateau on graph.
Relationship between plasma glucose and excretion rate of glucose?
Normally glucose should not be found in urine. Only happens if the body’s limit for handling glucose has been reached (at 300mg/mL)
So graph starts and is linear once it hits 300 on x axis, since this is the renal threshold
Renal threshold
300 mg/mL
Beyond this value, glucose comes out in the urine; there is no more reabsorption of glucose
Diabetes mellitus and cause
Capacity to reabsorb glucose is normal, but filtered load is greatly increased and is beyond threshold level to reabsorb glucose by tubules.
SGLT functions normally
Has too much glucose in blood due to insulin not functioning properly
Renal glucosaria
Mutation of SGLT results in inability to transport glucose from luminal side to peritubular capillaries
Urea reabsorption is dependant on?
Water reabsorption
Tubular secretion movement
From peritubular capillaries to tubular lumen
Tubular secretion involved mostly what ions?
H and K
Renal clearance
Measures the volume of plasma from which a substance is completely removed from the kidney per unit time
Bascially how well the kidneys remove substances
Renal clearance formula
Concentration of substance in urine x volume of urine passed / Concentration of substance in plasma
What is used to measure clearance?
Inulin, since it is completely excreted and not at all reabsorbed nor secreted.
Measuring clearance of inulin will provide GFR
Why does creatinine slightly overestimate GFR?
Because it undergoes slight secretion
Relationship between clearance and GFR
If clearance is greater than GFR of 125, substance is being secreted.
If clearnace is less than GFR of 125, substance is being reabsorbed
Relationship between GFR and conc of plasma for substance X for creatinine
GFR is inversely proportional to the plasma concentration of the substance
Which ion is actively reabsorbed?
Na
Which ion is transorted passively when Na is pumped out?
Cl
Which ion is secreted into tubules by cells of the distal and collecting ducts?
K
PCT major function
Reabsorbs majority of water and non wastes
Solute secretion except for K
Loop of Henle major function
Creates osmotic gradient in interstitial space
DCT major fucntion
Physiological control for water absorption
Homeostatic mechanisms of fine control of water and solute to make urine
Sources of water gain
Ingested liquid
Oxidation of food
Sources of water loss
Sweating
Skin and airways (insensible)
GI tract, urinary tract, menustration
Water reabsorption is dependant on?
Na reabsorption
Which hormone regulated water absobtion?
ADH aka. vasopressin
What does ADH regulate and where does it take place?
Regulates specific aquaporins to allow water absorption in the collecting ducts
Which part of nephron has NO water reabsorption?
Distal tubule
Which parts has ADH control of aquaporins?
Large distal tubule and collecting ducts
Descending vs ascending limbs water reabsorption
Ascending limb has NO water reabsorption while descending does.
Goal of environment of interstitial space?
To generate a hyperosmotic environment on the outside of the tubules (interstitial space)
Where does active transport of NaCl occur?
Ascending limb
Net result of ascending limb active transport and no water movement?
Creates a gradient difference between interstitial fluid and ascending limb. NaCl is allowed to accumulate in interstitial fluid without water moving into it since ascending limb is impermeable to water
Net result of descending limb
Water keeps moving out until equilibrium is reached, and osmolarity in interstitial space and surroundings is the same.
Multiplication
As you move down the descending limb, the osmolarity increases, so the gradient is multiplied as fluid moves down the loop and at the very bottom it is very hyperosmolar
Why is counter current multiplier important?
To keep water in the body and produce a hypersmotic/concentrated urine
Osmolarity at the top of the ascending limb?
Low since NaCl can move out but water cannot
As water leaves collecting duct, osmolarity…?
Increases
What happens to water moving into interstitial space?
Juxtamedullary neurons create hyperosmolar gradient
Short vs long loops of Henle
Short- optimal for environments where lots of water does not need to be conserved
Long- optimal for environments where you need to conserve more water (hyperosmotic gradient is greater to conserve more water)
Vasa recta. Permeable to?
Blood vessels that run parallel to the loop of Henle. Permeable to both solutes and water
Counter current blood flow
Blood flows in through one direction and flows out the other
Why is a hyperosmotic interstitial gradient created?
To absorb water in the interstitial space
Purpose of vasa recta
Maintains the salt gradient at each level that the nephron tubules have created
How does the vasa recta help in countercurrent exchange?
Blood flow in vasa recta serves as countercurrent exchangers by helping maintain the Na Cl gradient. Vasa recta doesn’t create any hyperosmolarity but maintains it because capillaries are freely permeable to ions, urea, water
What does the vasa recta maintain?
The gradient established by the Loop of Henle
How much percent of original amount of urea is excreted?
15%
Importance of minimal uptake of urea by vasa recta and recycling?
Helps in maintaining high osmolarity in medulla
Mechanisms used to maintain hyperosmotic environment of medulla?
Counter current anatomy and opposing fluid flow in loops of Henle
Reabsorption of NaCl in ascending limb
Impermeability of ascending limb to water
Trapping urea in medulla
Hairpin loops of vasa recta
Diuresis
Producing a large volume of urine
Antidiuresis
Reduction/supression of excreting a large amount of urine
What type of hormone is ADH?
Peptide hormone
What type of cells make ADH and where are they found?
Neurosecretory cells in hypothalamus. Found in the supraoptic nucleus.
AQP1
Water channels found in proximal convoluted tubule
AQP2,3,4
Water channels found in the collecting ducts
Which aquaporin types are regulated by ADH?
AQP2 is. AQP3 and 4 are not
ADH binds to receptor on cell, and through what mechanism are transcription factors activated and AQP2 regulated?
G protein coupled mechanism
Water moves across apical membrane through…?
AQP2
Water moves out basolateral membrane through…?
AQP3,4
What happens when there are low levels of ADH?
AQP2 channels are recycled by endocytosis
What happens in the absence of ADH?
Leads to diuresis because theres not enough AQP2 channels in luminal membrane of collecting duct so the cells are almost impermeable to water.
Diabetes insipidus
Large amounts of urine
Central diabetes insipidus
Failure to release ADH from posterior pituitary
Nephrogenic diabetes insipidus
Regular release of ADH but the hormone does not function properly. May be problem with the signalling pathway or cells within nephron
When ADH is increased…
AQP2 levels increase and more water is reabsorbed (pee less)
When ADH is decreased…
AQP2 levels decrease and more water is excreted (pee more)
Osmolarity gradient for dry/water deprived conditions?
Steep gradient, ADH will work to retain water
Osmolarity gradient for excess water conditions?
Not a steep gradient. More water is excreted in urine than absorbed
Water diuresis
Only water is excreted with no extra solutes in urine
Osmotic diuresis
Excess solute in urine is always associated with large amounts of water excretion
Na is never what? What happens instead?
Never secreted into renal tubules. It is EXCRETED
Low Na in plasma: short term regulation?
Baroreceptors regulate GFR
Low Na in plasma: long term regulation?
Aldosterone helps facilitate Na reabsorption
High Na in plasma regulation?
ANP regulates GFR and inhibits Na reabsorption.
Also inhibits aldosterone actions
Baroreceptors
Used for short term regulation of low plasma volume (reflection of low Na levels)
Where are baroreceptors located?
Carotid sinus, aortic arch, major veins, intrarenal
How do baroreceptors work?
Sense changes in blood volume, peripheral resistance,
Where is baroreceptor info processed?
Medulla oblongata
Aldosterone
Steriod hormone that regulates Na reabsorption (acts to conserve it)
Aldosterone is secreted from?
Adrenal cortex
What triggers aldosterone release?
Low plasma volume due to low Na
Aldosterone site of action
Cells of the distal tubule and collecting ducts
How does Na in diet regulate aldosterone secretion?
High amounts of Na: low aldosterone secretion
Low amounts of Na: high aldosterone secretion
Renin
Enzyme that senses low NaCl in blood.
Converts angiotensinogen to angiotensin I
Angiotensin II
Sensor that senses secretion of aldosterone
Angiotensinogen to aldosterone pathway
Angiotensinogen to angiotensin I to angiotensin II (via ACE) and then angiotensin II acts upon adrenal cortex to stimulate release of aldosterone.
ACE inhibitor
Manages high BP by blocking ACE enzyme. Reduces plasma Na concentration by blocking angiotensin I to II conversion and ultimately blocking aldosterone release.
Most important trigger for release of aldosterone?
Renin-angiotensin mechanism
Renin-angiotensin mechaism initiated in reponse to..?
Sympathetic stimulation of renal nerves
Decreased filtrate osmlarity
Decreased BP
Juxtaglomerular cells
Mechanoreceptors on the wall of afferent arteriole.
Sense plasma volume
Secrete renin
Macula densa
Chemoreceptors on wall of DCT
Sense NaCl load of filtrate
What do macula densa do when Na concentration decreases in the filtrate?
They sense it and release signalling molecules, which stimulate renin release by juxtaglomerular cells
3 factors affecting renin release?
Sympathetic input from extrarenal baroreceptors
Intrarenal baroreceptors
Signals from macula densa
ANP
Synthsized and secreted by cardiac atria.
Important for regulating high levels of Na
Site of ANP action?
On cells of several tubular segments
What does ANP do?
Inhibits aldosterone, so inhibits Na reabsorption
Increases GFR and Na excretion
What stimulates ANP secretion?
Increased Na concentration
Increased blood volume
Atrial distension
K concentration is regulated where?
Cortical collecting ducts
Hyperkalemia
Excessively high concentration of K in blood
K levels physiologically regulated by? How?
By aldosterone. When there is a high extracellular K concentration, aldosterone acts to increase secretion of K in urine.
ADH secretion is directly sensitive to what?
Extracellular K level
What can happen with pH changes? (4)
Changes in shape of proteins
Neuronal activity changes
K ion imbalances
Irregular cardiac beats
Volatile acid vs non volatile
Volatile acids can be converted into gases and then eliminated by exhaling
Volatile and non volatile acids produced in our body?
Volatile: CO2
Non: phosphoric and sulfuric acid
Sources of H gain?
Generation of H from CO2
From non volatile acids
Loss of bicarbonate in diarrhea
Loss of bicarbonate in urine
Sources of H loss?
Vomiting
In urine
Hyperventilation
Buffer
Substance that binds to H and forms a H buffer conjugate
Weak acid+its conjugate base
Extracellular buffer example
Bicarbonate
Intracellular buffers examples
Phosphate ions
Hemoglobin
Acid base balance formula
CO2+H2OH2CO3H + HCO3-
What happens when respiration rate is not high enough?
Passage of blood through peripheral tissues generate H
Which organ plays a short term role in pH regulation?
Lungs
Increased H conc causes what?
Stimulates ventilation
Decreased H conc causes what?
Inhibits ventilation
Which organ plays a long term role in pH regulation?
Kidneys
When one H ion is lost from body…what happens
One HCO3 is gained
Alkalosis. What happens after
Decrease of plasma H. Kidneys excrete more bbicarbonate
Acidosis. What happens after
Increase of plasma H.
Kidneys make new bicarbonate and send it to blood
Reabsorption of HCO3: mechanism I
Extra H binds to intracellular buffer HPO4
HCO3 is still generated by tubular cells and diffuses into plasma
Net gain of HCO3
Reabsorption of HCO3: mechanism II
Only cells from proximal tubule are involveed
Uptake of glutamine
NH4 and HCO3 are formed
NH4 is actively secreted by counter transport into lumen
HCO3 is added to to plasma
Initial buffer and what happens when its depleted (acidosis)
Biacarbonate. Then phosphate and then glutamine metabolism
Respiratory acidosis caused by? How does kidney compensate?
Result of decreased ventilation. Increase blood PCO2.
Kidney secretes H and lowers plasma H conc.
Respiratory alkalosis caused by? How does kidney compensate?
Result of hyperventilation. Decrease blood PCO2. High altitudes. Kidney excretes HCO3
Metabolic acidosis
Occurs in diarrhea, severe excersise. Results in increased ventilation and increased H secretion
Metabolic alkalosis
Occurs after prolonged vomiting
Results in decreased ventilation and increased HCO3 excretion.
Functions of the reproductive system
Provides gametes for procreation
Mating
Fertilization
Function of gonads
Produce the gametes
What are the gonads of the male reproductive system?
Testis
Scrotal sac & what is contained in it?
Found outside the body. Contains testes, blood vessels, nerves
Importance of countercurrent blood flow?
Cools the blood before it enters testes. Heat from arterial blood is passed to cooler venous blood
Why are testes housed outside the body?
So that the temperature is maintained at least 2 degrees below core body temp. This is necessary for optimal spermatogenesis.
Spermatic cord
Passes through a slit in the abdomen down into scrotal sac.
Combination of vas deferens, blood vessels, nerves
Testes during gestation period
Present in abdominal cavity at 8 weeks
Testes first phase of descending
During 8-12 weeks testes will move down towards inguinal canal
Second phase of testes descending
Between month 7-9 testes pass through inguinal canal and rest in the scrotum
Seminiferous tubules
Site of sperm production
Contain a lumen and many spermatogenic cells
Mumps virus
Causes the lumen to become much bigger making the spermatogenic cells appear small. This affects spermatogenesis
Leydig cells/interstitial cells
Found in connective tissues surrounding seminiferous tubules.
Produce testosterone
Sertoli cells
Epithelial cells lining the circular seminiferous tubule
Help in sperm development
Smooth muscle cells of testes
Muscle like
Contractile properties which help move sperm forward
Tight junctions of testes
Do not let infections or anything that may harm sperm through
Create and invisible ring-like structure that is impermeable.
Helps in forming the blood-testis barrier
Sertoli cells: 11 functions
Support sperm development
Secrete luminal fluid for sperm housing
Secrete androgen binding protein under influence of FSH
Androgen buffer
Maintains androgen concentration in lumen
Target cells for testosterone and FSH
Secrete paracrine factors that stimulate spermatogenesis
Secrete inhibin
Negative feedback loops for FSH
Phagocytosis of old sperm
Site of immunosuppression (Blood testes barrier)
Testosterone and where is it produced?
Lipophilic, steroid hormone synthesized by cholesterol.
Principally produced by the testes in males
Progesterone
Intermediary hormone synthesied from cholesterol. May be converted to mineralcorticoids, glucocorticoids, or androgens depending on enzymes present.
Action of testosterone?
Influences gene transcription and protein synthesis to produce response in target cell
DHT
Maintains sexual characteristics and tissues, like prostate gland and secondary male sex characteristics
How is testosterone converted into estrogen? Where does this happen?
By aromatase
In the brain, testes, adipose tissue, liver
Plasma testosterone levels before birth
High peak of testosterone and then levels decrease until birth
Plasma testosterone levels after birth
Right after birth there is a peak but then levels decrease through childhood
Plasma testosterone levels from adolescence to adulthood
Slowly increase and remain high throughout adulthood.
Slowly start declining around age 40
What is pulsatile secretion and why is it necessary?
Secretion of GnRH every 90 min causing the pulsatile release of hormones. Occurs at the onset of puberty in males.
Important because cells of the anterior pituitary will not respond to constant GnRH, only pulsatile.
High frequency pulses of GnRH results in predominant secretion of?
LH
Low frequency pulses of GnRH results in predominant secretion of?
FSH
LH
Acts on Leydig cells to stimulate testosterone secretion
How is testosterone a negative feedback regulator?
Decreases the amplitude of pulsatile secretion, which results in down regulation of receptors for GnRH so less release of LH
Effects of androgens (6)
Stimulate spermatogenesis
Promote development and maintenance of secondary sex characteristics
Increase sex drive
Proetin synthesis
Stimulate growth hormone secretion
Development of male reproductive structures
What happens in spermatogenesis when the spermatogonium undergoes mitosis?
One cell remains as a spermatagonium to prevent depletion.
The other is called the primary spermatocyte and progresses on to become mature sperm
What happens to primary spermatocyte?
Meiosis occurs and produces 2 secondary spermatocytes from that one.
Chromosome number is halved
Each secondary spermatocyte gives rise to…?
2 spermatids, each with haploid number of chromosomes
Final sperm are called? How many are formed?
Spermatozoa. 4, each with haploid chromosomes
Where exactly does spermatogenesis occur in the sertoli cells?
From the basement membrane to the lumen, and occurs in the space between Sertoli cells
Spermiogenesis
Last stage in spermatogenesis where spermatids mature into motile spermatozoa by aquiring flagella and cytoplasm is shedded to make a sperm shape
Parts of sperm head
Nucleus
Acrosome
Acrosome
Vesicle close to plasma membrane at tip of sperm head
Contains enzymes needed for fertilization
Mid piece of sperm contains many..?
Mitochondria needs for movement of tail
Tail of sperm movement
Whip like movements
Where are sperm stored until ejaculation?
Vas deferens
3 male accessory glands
Seminal vesicles, prostate glands, bulbourethral gland
Seminal vesicles
Secrete alkaline fluid with enzymes, fructose, and prostaglandins
Why is the fluid secreted by semincal vesicles alkaline?
To neutralize the highly acidic environment of female genital tract
Prostaglandins function
To contract the female tract to to help sperm move forward
Prostate gland
Secretes enzymes like PSA, and citrate
PSA
Protease that breaks down proteins in the seminal clot making semen more fluid
PSA is also a biomarker for detection of abnormal growth of prostate tissue
Bulbourethral glands
Secrete viscous fluid with mucous
Male sexual response is controlled by?
ANS
Function of seminal fluid?
Dilution of sperm
Erection phase is mainly controlled by?
Parasympathetic nervous system
When the penile tissue is not erected (relaxed state) what is the dominant control?
Sympathetic nervous system
Emission phase is controlled by?
Sympathetic nervous system (thoracolumbar division)
Muscle contraction to move sperm to mix with seminal fluid
Ejaculation phase is controlled by?
Somatic nervous system since its skeletal contraction
What happens during erection?
When parasympathetic nerve is stimulated, NO is released, stimulating production of cGMP
cGMP acts to dilate smooth muscle
cGMP is broken down by phosphodiesterase and erection ceases
How is erectile dysfunction treated?
Viagra, which acts as an inhibitor for phosphodiesteraase
Site of fertilization?
Fallopian tube
Site of sperm maturation?
Epididymis
Capacitation
Physiological maturation of sperm cell membranes before fertilization can occur.
Acrosomal reaction
Sperm must penetrate the zona pellucida of egg.
Acrosomal reaction is triggered by the binding of the sperm to zona pellucida, and pores are created so acrozomal enzymes can pass through and allow sperm to create a path through zp
Fertility in men vs women
In men: sperm are always fertile
Women: only during ovulation
Female gonads
Ovaries
Uterine tubes
Transport ova from ovaries to uterus
Contain hair like structures called fimbrae to help with movement
Movement of ovum through tube
Intially: peristaltic contractions
And then mostly ciliary actions
Ectopic pregnancy
When cilia do not mvoe properly in ovi duct, resulting in fertilized egg in in uterine tube
Perimetrium
Outer layer of uterus
Epithelial cells, connecting tissues
Protective
Myometrium
Middle layer of uterus
Muscular
Endometrium
Inner layer of uterus
Contains connective tissue and glycogen
Cyclic change every month
Cervix
Canal leading to vagina
Birth canal
Cervix and vagina
Follicles
Densely packed shells of cells containing an immature oocyte at all stages prior to ovulation
Ovary
Contains follicles in different stages of growth
Primidorial, primary, and mature follicles?
Primadorial- very small
Primary- medium
Mature- large, with a fluid filled cavity
Ovarian cycle
Development of ovarian follicle, rupture, and degeneration
Uterine cycle
Menstral cycle
Essentially preparing endometrium for possible embroyo in case of fertilization
Hormonal cycle
Controlled by FSH and LH, causing ovarian changes during monthly cycle
Ovarian cycle phases
Follicular phase: First 14 days Development of follicles Ovulation: On 14th day Luteal phase: Next 14 days Egg is released
Uterine cycle phases
Mentrual phase:
Bleeding, shdding of endometrial layer for about 5 days
Proliferative phase:
Layers of endometrium widen
Functional layer of endometrium develops
Secretory phase:
Further vascularization and development of uterine glands
Which phases coincide?
Menstrual and proliferative phases of uterine cycle coincide with follicular phase of ovarian cycle.
Secretory phase coincides with luteal phase of ovarian.
Oogenesis
Development of female gamete
Primidorial follicles
Single oocyte surrounded by a single layer of epithelial cells
How does follicle grow?
By mitosis of granular cells
Primary follicle stage
Growth stage
Grnaular cells secrete proteins and glycopreoteins which forms a thick layer around the oocyte (zona pellucida)
Preantral follicle
Mitosis of granula reult in many layers around oocyte
Early theca cells develop
No antrum
Early antral follicle
Fluid filled spce in antrum begins to fill
Mature follicles
Major growth due to growth of antral space
Cumulus oophorus
Corpus albicans
Empty structure which functions as temporary endocrine structure. Eventually dissapates
Which follicles become the dominant ones?
The one that secretes the highest amount of estrogen
Hormonal cycle phases
Estrogenic phase: first 14 days
Predominant hormone is estrogen
Progestational phase: after ovulation
Prodominant hormone is progesterone
FSH effect on granular cells
Increases rate of mitosis
Zona pellucida
Seperates the oocyte from the inner layer of granulosa cells
2 cell compartment theory
LH acts on its receptors in theca cells and androgens are secreted
Theca cells convert cholesterol to progesterone to androgens
Inside the granulosa cells, androgens are converted to estrogen
How does FSH help with making estrogen?
Stimulates aromatase production, which helps convert androgens to estrogen in granulosa cells
Granulosa cells secrete…?
Antral fluid Paracrine factors Inhibin Estrogen Substance that forms zona pellucida
Estrogen and feedback in the axis
Negative feedback- estrogen can dampen the amplitde of pulse generator or reduce responsiveness of pituitary to GnRH
Positive feedback- estrogen can act on hypothalamus to increase amplitude of pulse generator or increase responsveness
Progesterone and feedback in the axis
Only has negative feedback- in the lack of estrogen it produces negative feedback on level of both the anterior pituitary and hypothalamus
When does the second meitotic division occur?
After ovulation and only if the secondary oocyte is fertilized by male gamete
Net result of oogenesis?
One primary oocyte with n number of chromosomes
Net result of spermatogensis?
4 spermatozoa with n number of chromosomes
Estrogen has an inhibitory effect on..? When?
Gonadotropin, when plasma concentrations of estrogen are low
During early proliferative stages what happens with estrogen levels?
Estrogen levels increase
Rapidly increasing estrogen causes sharp rise in?
LH, causing LH surge
Estrogen at high levels causes?
Positive feedback effect on gonadotropins
When is there a large increase in progesterone?
After the corpus luteum is formed
Where does the estrogen in LH surge come from?
As dominant follicles secrete more and more estrogen, , estrogen levels increase
Proliferative phase prepares for what?
Fertilized ovum
What happens during proliferative phase?
Endometrial lining grows and develops
Smooth muscle layer thickens
Mucus secreted from cervical glands
What happens during the secretory phase?
Blood supply increases
Glands enlarge and secrete glycogen-rich fluids
Cervical secretions are more sticky
Effects of estrogen on ovaries?
Increased growth of follicles
Increased receptors for LH, FSH, estrogen, progesterone
Effects of progesterone on ovaries?
Decreased FSH induced estrogen production
Decreased receptors for estrogen
Effects of estrogen on uterus?
Increased growth of endometrium and myometrium
Increased blood flow and contractibility
Increased sensitivity to oxytocin
Effects of progesterone on uterus?
Increased endometrial secretions
Decreased contractility
Decreased sensitivity to oxytocin
Effects of estrogen on breasts?
Increased duct growth, fat deposition, size of areola
Effects of progesterone on breasts?
Increased alveolar growth
Zygote
Fertilized egg cell resulting from the union of male and female gametes
Polyspermy
Multiple sperm fertilze one egg
Pronucleus
Pair of gametic nuclei before their fusion leads to a formation of a nucleus of the zygote
Morula
Made of many cells, and develops into blastocyst. Cells are totipotent at morula stage
Identical twins arise from?
Division of totipotent morula cells
Fraternal twins arise from?
Fertilization of 2 separate oocytes released during the same cycle
Blastocyst
Cells lose their totipotency and start to differenciate
No zona pellucida
Outer cell layer of blastocyst will become?
Fetal placenta
Inner cell layer of blastocyst will become?
Embroyo
What happens when blastocyst enters uterine site?
Inner cell mass has lost its totipotency and will develop into embroyo
How does implantation occur?
Blastocyst will anchor itself to the wall of the endometrial lining
Sticky trophoblast cells anchor themselves the the endometrial lining
Trophoblast cells divide into what 2 parts?
Syncytiotrophoblast and cytotrophoblast layers
Syncytiotrophoblast layer
Outer trophoblast cells enter deep into the endometrial layer and start dividing and become fused. They form a syncytium (multiple nuclei but no cell membranes)
Cytotrophoblast layer
Trophoblast layer closest to the inner cell mass becomes cytotrophoblast layer. These cells release hormones for the growing embroyo
Decidual response
Response of the endometrial tissue where there is the appearance of blood vessels and glycogen secreting glands for the newly anchored embroyo or blastocyst/
Fetal placenta develops from?
Develops from the same blastocyst that forms the fetus
Maternal placenta develops from?
Maternal uterine placenta
Amnion
Innermost membrane that encloses the embroyo
Chorion
Embroyonic derived portion of placenta
Chorionic villi
Finger-like projections on chorion that allow for faster transfer of materials between maternal and fetal blood
Umbilical arteries
Carry deoxygenated blood from fetus to placenta
Umbilical veins
Carry oxygenated blood from placenta to fetus
Functions of the placenta
Temporary endocrine gland
Exchange tissue for gases, nutrients, waste
Filter/immunological barrier
hCG during pregnancy released from? Level during pregnancy? Function?
Released from chorionic part of placenta.
Initial peak at 2 mo, then decreases and stays low during pregnancy.
Helps maintain corpus luteum
hPL
Human placental lactogen
Anti-insulin like actions in mother, it allows plasma glucose levels to remain high, helping fetus take up more glucose through placenta
Progesterone during pregnancy
Once corpus luteum degenerates, prog is released
Decreases uterine contractions
Inhibits secretion of LH or FSH
Stimulates growth of alveolar ducts
Estrogen during pregnancy
Once corpus luteum degenerates, est is released
Causes growth of myometrium and mammary ducts
LH and FSH inhibited
Positive feedback loop of oxytocin release
During childbirth, pressure of fetus head against cervix causes oxytocin release via anterior pituitary
Oxytocin acts on myometrial layer, binding to the tissue and causing more contractions
Myometrial contractions are increased by…?
Oxytocin, prostaglandins, estrogen, stretch
Cervical ripening
Process that makes the cervix soft, allowing for easier expansion
Hormones influencing cervical ripening? how?
Relaxin and prostaglandins
Relaxin relaxes the cervix while progesterone inhibits contractions if mother is not ready to deliver yet
Prolactin
Released from ant pit
Stimulates production of milk/lactation
Lactogenesis
Cells in the breast tissue start making milk
Oxytocin role in lactation?
Needed for milk ejection/ let down
Galactapoesis
Maintenance of lactation while mother is breast feeding
Alveolar epithelial ducts
Synthesize milk but CANNOT release milk
Myoepithelial cells
Muscle like and have contractile properties to expel the milk
Myoepithelial cells have receptors for?
Oxytocin
Suckling process
Suckling stimulates mechanoreceptors (tactile receptors) in breast, signal sent to hypothalamus and oxytocin is released.Contraction occurs in myoepithelial cells of breast and milk is ejected.
Dopamine role in suckling
Inhibits prolactin secretion
2 Hormones that impose male characteristics?
Testosterone and AMH
SRY gene
Present in males because of the Y chromosome
Allows testes to develop
Klinefelter syndrome
XXY
Infertile
Turners syndrome
Lack of X chromosome
XO
Streaked ovaries (flattened)
Double genital duct system in males vs females
Wolffian ducts persist and Mullerian ducts regress in males
Mullerian ducts persist and Wolffian ducts regress in females
MIH
Mullarian inhibiting hormone
Hormone present in only males that causes Mullerian duct to regress
What causes development of the male internal genitalia?
Testosterone secreted from Leydig cells
Teststerone is converted to what?
DHT by 5 alpha reductase
What does DHT do?
Causes masculisation of male external genitalia
Congenital adrenal hyperplasia
Genetically female (XX) but phenotype is male
Caused by too much androgens produced in fetal stage
Decreased cortisol, so increased ATCH, so adrenal androgens, so increased mascularization
Androgen insensitivity disorder
Genetically male (XY) but phenotype is female Tissues were unresponsive to testosterone during development so Wolffian ducts cant develop Male internal and external genitalia do not develop
What triggers onset of puberty?
Increased secretion of GnRH causes more LH and FSH secreted
Kisspeptin
Neuropeptide that acts on the cells that release GnRH
Hormonal changes in menopause
Follicular depletion
Ovulation ceases eventually
Decreased estrogen and inhibin and progesterone
Increased FSH:LH ratio
Nervous system vs endocrine system
Nervous system is rapid and short term regulation while endocrine system is slower but more sustained control over long term processes
Exocrine glands
Glands that empty their secretions directly into body cavities or onto body surfaces via tubular ducts
Endocrine glands
Ductless system that release secretions directly into bloodstream
Endocrine signaling
Hormone released into bloodstream and acts on distant target sites
Nervous signalling
NT is released into synapse close to target site
Neuroendocrine signalling
Release secretions into a blood supply
Hormone characteristics
Regulate homeostasis
High potency
Actions are mediated through specific receptors
Delay of response
Secreted irregularily in phases
Most are carried in blood by binding proteins
Steroid hormones are derived from?
Cholesterol
Protein hormones include?
Amines
Peptides
Proteins
How does cholesterol enter the cell?
Bound to LDL
What happens once cholesterol is in the cell?
Moves to mitochondria to eventually form pregnenolone and and be further modified into different steriod molecules.
How is mRNA converted to a hormone?
mRNA, pre hormone, pro hormone, hormone
Secretory vesicle
Vessel that mediates transport of cargo like NTs or hormones
Secretory vesicle roles?
Protects hormone from degredation Resevoir Provides a transport mechanism along microtubules and microfilaments Release mechanism (exocytosis) Provide for quantal release
Roles of binding proteins?
Increase solubility and concentration of lipid soluble hormones
Increases size of hormone, protecting against degredation
Inactivates free hormones
Negative feedback in regulating hormone secretion
Inhibits hormone secretion when circulating levels are high and increases when they are low
Positive feedback in regulating hormone secretion
Rare, but there is a participation of negative feedback inhibitory signals that will terminate secretion rates
Requirement for hormonal action
Binding of a hormone to specific receptor
Nuclear receptors
Receptors located in nucleus
Produce effects by altering protein synthesis
Cytoplasmic receptors
Receptor is found in intracellular transport
Provide a resevoir of the hormone within target site
Protein hormones cannot cross the …? What must they do?
Cant cross the cell membrane. They must bind to membrane bound receptors
Sensitization
Increase in affinity of a receptor
Down-regulation
Cells down-regulate receptors in response to high hormone concentrations in the blood
Up-regulation
Cells up-regulate receptors in response to low hormone concentrations in the blood
Defects in rate of hormone synthesis is due to?
Problems with endocrine gland
Defect in regulation of hormone is due to?
Problem in hormone action because hormone action requires feedback
Defect in hormone action is due to?
Problem with target tissue
Neurohypophosis/posterior pituitary
Down growth from the brain or hypothalamus
Neural tissue
Anterior pituitary/adenohypophysis
Non neural tissue
Results from invagination of roof of mouth
Intermediate lobe
Between the ant and post pituitary
Infundibulum
Contains the axons of neurons in the hypothalamus and blood vessels
Where is ADH produced?
Supraoptic nuclei
Where is oxytocin produced?
Paraventricular nuclei
Neurophysins
Transport ADH to neurosecretory granules or vesicles in the nerve
Main stimuli for ADH secretion
Decrease in blood volume
Increase in blood osmolarity
ADH secretion increased by?
Stress, heat, nicotine, caffeine
ADH secretion decreased by?
Cold, alcohol
Hypothalamic diabetes insipidus/central DI
Problem of ADH production
Nephrogenic diabetes insipidus
Problem of ADH action
SIADH
Excess ADH due to problem of ADH production, feedback failure
Poluria
Large amounts of dilute urine
Polydipsia
Excessive fluid intake
Hyponatremia
Excess ADH and decreased aldosterone
Median eminence
Capillary bed which recieves axons from nuclei in the hypothalamus
Hypothalamal-hypophyseal portal vessels
Venous or portal blood vessels which run into the anterior pituitary
Short portal vessel
Blood vessel which comes from the capillary bed in the posterior pituitary
Parvocellular neurons
Have small cell bodies and short axons
Produce neural secretions that are released into blood vessels down to anterior pituitary
Magnocellular neurons
Large neuroendocrine cells located in hypothalamus
Synthesize ADH and oxytocin
GnRH
Stimulates release of FSH and LH
GHRH
Stimulates release of growth hormone(GH)
TRH
Stimulates release of TSH and prolactin
PRFs
Stimulate release of prolactin
CRH
Stimulate corticotropin release
SRIF
Inhibits release of GH and TSH
PIFs. Example?
Inhibit release of TSH and PRL
Dopamine
TSH
Stimulates thyroid gland
Secretes T3 and T4
ACTH
Stimulates adrenal cortex
Secretes cortisol
Somatomedins
Induce growth effects on soft tissues and bone
How is GH release inhibited?
By Somatomedins
GH inhibits its own release
By products of lipolysis and glucose
How do certain meals affects GH release?
Meals high in glucose or fatty acids supress GH release
Meals high in amino acids increase GH release
Dwarfism
Due to GH deficiency in juveniles.
Isolated growth hormone deficiency (Type I)
Defect in GH production
Laron type dwarfism
Defect in GH action due to problem with GH receptors
GH dwarfs vs thyroid dwarfs
GH dwarfs have normal body proportions just shorter in height, while thyroid dwarfs have body proprtions of an individual much younger than themselves
Somatopause
GH deficiency in adults.
Decrease in lean muscle tissue and increase in fat tissue.
Thymic atrophy
Acromegaly and symptoms
Excess GH in adults. Adult does not grow in height, but hands, bones of face, etc widen and enlarge Protruding jaw Hirsutism (hair growth excessive) Due to GH secreting tumour Enlarged breast tissue in males
What hormone inhibits prolactin secretion?
Progesterone
Hyperprolactenemia. How to treat it?
Excess prolactin resulting in decreased libido, amenorrhea, gonadal dysfunction
Dopamine agonist for treatment
Hypoprolactenemia
Deficiency in prolactin
Gonadal dysfunnction and impairment of lactation
Pituitary diabetes
Excess of all anterior pituitary hormones
Hypopituitarism
Deficiency in pituitary hormone production
What do thyroid hormones do?
Increase metabolic rate and heat production
Enhance grwoth and CNS development
Enhance sympathetic activity
Glycoprotein hormones
Contain sugar residues
Made of alpha and beta subunit
Promote receptor recognition and prevent degredation
Basic unit of the thyroid gland?
Follicle
Thyroglobulin, where is it synthesized and secreted?
Precursor for thyroid hormone biosynthesis
Synthesized in the follicular cells of rough ER
Secreted into the colloid
Contains numerus tyrosine residues
The 2 thyroid hormones. Which is more active?
T3 (triiodothyrinine) and T4 (thyroxine)
T3 more active
How is T4 a precursor hormone?
Degraded by deiodinase to T3 where iodine is lost from thyroxine
Monoiodotyrosine
Produced by addition of 1 iodine attached to tyrosine
MIT
Diiodityrosine
Addition of 2 iodines attached to tyrosine (DIT)
Thyroid peroxidase
Responsible for attaching iodine to tyrosine on thyroglubulin, and for oxidizing iodides
DIT on TG+MIT=?
T3
DIT on TG+DIT=?
T4
Thyroid binding globulin
Binds both T3 and T4 to be carried into blood
Membrane bound receptors
Receptors that are linked to channels within the membrane
Binding of the hormone to the receptor opens the channel allowing glucose to enter
Cytoplasmic receptors
Act as a resevoir of thyroid hormone in the target tissue
Nuclear receptors
Affect gene transcription and protein synthesis
Hyperthyroidism
Caused by excess T3 and T4, due to problem with thyroids gland, pituitary gland or hypothalamus
Primary problem caused by thyroid gland
Produces excess T3 and T4
Toxic goiter
Secondary problem caused by pituitary gland
Increased TSH
Goiter
Tertiary problem caused by hypothalamus
Increased TRH
Goiter
Grave’s disease and symptoms
Most common type of hyperthyroidism caused by autoimmune disease in which antibodies develop against TSH receptor
Characteristics include goiter in neck, bulging of eyes, increased BMR, increased sympathetic nervous system activation, palpilations
Hypothyroidism and symptoms
Caused by deficiency of I in diet
Primary thyroid dysfunction
Decrease in thyroid hormone leading to increased TSH and goiter
Hashimoto’s thyroiditis
Autoimmune disease where antibodies are created against T3 and T4; goitre
Secondary hypothyrodism
Low levels of TSH are produced in pituitary gland
Tertiary hypothyroidism
Low levels of TRH
Cretinism
Hypothyroidism in utero
Myxedemia
Hypothyroidism in adults due to accumulation of edema and hyaluronic acid under skin
Steroid hormones are produced by?
Adrenal cortex
Precurser hormone for aldosterone?
Corticosterone
Only hormone to produce feedback inhibition is?
Cortisol
Steroidogenesis
Cholesterol is converted to biologically active steroid hormones
Adrenocorticotropin (ACTH)
Stimulates adrenal blood flow, adrenal growth, steroidogenesis
ACTH and Beta LPH are made from?
POMC (propriomelanocortin)
Increased POMC activity results in?
Increased MSH activity and increased skin pigmentation
Glomerular zone of adrenal cortex
Produces aldosterone, no metabolism
outer zone
Fascicular zone
Produces cortisol, intermediate metabolism
middle zone
Reticular zone
Produces androgens; sex characteristics
inner zone
Conn’s syndrome
Excess aldosterone leads to increased Na retention, therefore increased water retention leading to hypertension
How does cortisol increase blood glucose?
Through anabolic effects on liver (glucogenesis) and catabolic effects on peripheral tissues
Levels of cortisol throughout the day?
High first thing in the morning, decrease throughout the day and are lowest at the end of the day, rise during sleep
Addisons disease
Defect in adrenal cortex. Cortisol is not made and there is no feedback inhibition
Levels of ACTH are very high
Increased skin pigmentation due to high POMC activity
Secondary adrenal insufficiency
Defect at pituitary level…it does not make ACTH
Does not have increased POMC levels
Primary adrenal insufficiency
Reduced cortisol secretion and reduced gluconeogenesis so hypoglycemia
Cushing’s syndrome
Prolonged exposure to cortisol caused by tumour
Adrenal gland tumour
Produces high levels of cortisol adn cortisol inhibits ACHT production via feedback regulation
Ectopic tumour
Can produce ACTH which stimulates cortisol production
DHEA
Weak androgen synthesized in the zona reticularis
Can be converted into estrogen or testosterone
Andrenogenital syndrome and symptoms
Biosynthetic pathways that make aldosterone and cortisol are deficient, and instead all the precursors that enter the pathway that makes DHEA
Masculiniation of female genitals
Hirsuitism
2 hypercalcemic hormones that regulate Ca and P
PTH and vitamin D
Act to increase Ca levels in blood
Hypocalcemic hormone that regulates Ca and P
Calcitonin
Acts to decrease Ca levels in blood
Parathyroid hormone acts to
Increase plasma Ca at the expense of plasma phosphate
PTH effect on kidney
Increased Ca reab, decreased P reab, increased vit D activation
PTH target sites
Kidney
Bones
GIT
Low levels of plasma Ca levels causes (what regarding PTH)
Stimulation of PTH secretion
High levels of plasma Ca levels causes (what regarding PTH)
Inhibition of PTH
Causes of hyperparathyroidism
Problem with parathyroid gland itself
Low blood Ca
2 conditions that result in low blood Ca
Rickets (in children) and osteomalacia (adults)
Trousseau’s sign
Hypoparathyroidism
Involuntary contraction of carpal muscles due to hypercalcemia and tetany
Chvostek’s sign
Hypocalcemia
Trigeminal nerve along neck
Tetany and snarl
Pseudohypoparathyroidism
Tissue insensitivity to PTH action (PTH receptors in tissue arent working)
As concentration of blood plasma increases what happens to calcitonin secretion?
Increases
Calcitonin in GIT
Calcitonin will directly inhibit Ca uptake
Where is calcitonin made?
Thyroid gland in parafollicular cells (C cells)
Photoisomerization occurs in response to?
UV light
How is vitamin D synthesized?
By the addition of hydroxyl groups in the liver and then in the kidney to inactive state
Effects of vitamin D
Increased plasma Ca and P concentration
Vitamin D deficiency in kids vs adults
Kids: rickets
Adults: osteomalacia
Vitamin D toxicity
Excess VD can result in tissue calcification which can lead to aneurysm
Where is the endocrine gland found?
Within the organ called Islet of Langerhans or pancreatic islets
Alpha cells secrete?
Glucagon
Beta cells secrete?
Insulin
Somatostatin
Made in the delta cells and acts as a hypothalamic releasing factor to inhibit secretion of TSH and GH
Also inhibits secretion of glucagon and insulin
What happens when beta cells release insulin?
Inhibits alpha cells
What happens when alpha cells release glucagon?
Stimulates alpha cells and delta cells
Which nerves are involved in pancreatic islet stimulation?
From parasympathetic: vagus nerve
From sympathetic: splanchnic nerve
Sympathetic stimulation effect on glucagon and insulin?
Increased glucagon decreased insulin
Parasympathetic stimulation effect on glucagon and insulin?
Increased glucagon and insulin
Insulin actions. Anabolic or catabolic?
Lower blood glucose
Promotes conversion of nutrients to stored form
Anabolic
Glycogen actions. Anabolic or catabolic?
Increases blood glucose
Promotes breakdown of stored energy
Catabolic
What happens regarding insulin when you ingest food?
Parasympathetic release of insulin
What happens regarding insulin when you are stressed?
Sympathetic stimulation will inhibit insulin release
Primary stimulus for insulin release?
High plasma glucose levels
Primary stimulus for glucagon release?
Low plasma glucose levels
Diabetes mellitus
Insulin deficiency and glycogen excess
Type I diabetes mellitus
Autoimmune disease…body attacks beta cells
Treated with insulin injections
Type II diabetes mellitus
Insulin resistance…body cant respond to insulin
Obesity occurs
Treated by regulating diet
Insulin excess
Due to insulin secreting tumour
Reactive hypoglycemia
