Renal Flashcards
What is the uriniferous tubule - function, components, and where they are located
Uriniferous tubule - microscopic, functional unit of the kidney responsible for blood filtration and urine formation; ultrafiltrate –> forming urine (reabsorption and secretion)
Components:
renal corpuscle= glomerulus + Bowman’s capsule- in renal cortex,
proximal convoluted tubule - in renal cortex,
loop of henle - both cortex and medulla,
distal convoluted tubule - in renal cortex,
collecting duct- both cortex and medulla
What is the difference between nephron and uriniferous tubule?
Nephron - Renal corpuscle (glomerulus + Bowman’s capsule), PCT, loop of henle, and DCT
uriniferous tubule - nephron + collecting duct
Describe the histological components of the kidney
Cortex - has medullary rays (collecting ducts) and cortical labryinth (renal corpuscles)
Medulla - homogenous - only straight bits
What is the glomerulus? What are the components and functions of the glomerular filtration barrier?
1) Glomerulus - modified capillaries of the renal corpuscle
2) Glomerular filtration barrier - goal to keep protein out of the forming urine;
Fenestrated endothelium (retains negative charge), shared basement membrane- lamina rara externa, lamina densa, lamina rara interna (filters large and (-) proteins), foot processes of podocyte ie pedicels (slit diaphragm tight junction between pedicels for materials to cross through)
Describe the arterial and venous components of the kidney
renal artery –> segmental –> interlobar –> arcuate –> interlobular –> afferent arterioles of glomerulus –> glomerulus –> efferent arterioles –> vasa recta –> renal veins –> systemic circulation
Define: kidney lobe renal papilla lobule vascular pole urinary pole area cribosa
1) kidney lobe = medullary pyramid (8-18 in kidney)
2) renal papilla - tip of medullary pyramid, where urine exits into excretory passages (minor calyx –> major calyx –> ureter)
3) lobule- nephrons grouped around single medullary ray and draining into single collecting duct
4) vascular pole - where afferent and efferent arterioles enter and exit from glomerulus
5) urinary pole- where ultrafiltrate leaves
6) area cribosa - holes in the papilla, where collecting ducts terminate
Where does efferent arteriole of glomerulus go?
forms capillary beds around the tubule, returns materials reabsorbed from the forming urine into the blood circulation
2 divisions of peritubular capillaries:
1) cortex - peritubular plexus
2) medulla (loop of Henle) - vasa recta
What are the three types of cells of the glomerulus?
1) mesangial - structural core of glomerulus, secrete matrix, remove debris from filtration apparatus, regulate blood flow
2) endothelial- part of glomerular filtration barrier
3) podocytes- part of glomerular filtration barrier
What is the pathology of the glomerular basement membrane in diabetics?
abnormally thick basement membrane is less effective barrier and allows proteins to get into the urine –> proteinuria
Describe the pathology of nephrin mutation in podocytes
Nephrin - in slit diaphragm that connects adjacent pedicels from different podocytes;
With nephrin mutation - pedicels not as tightly adhered to the basement membrane as they should be –> allow proteins into the urine –> proteinuria
Describe the epithelium of:
1) Bowman’s capsule
2) PCT
3) Loop of Henle
4) DCT
5) Collecting duct
6) Calyces and renal pelvis
1) Bowman’s capsule - simple squamous
2) PCT - simple cuboidal + brush border consisting of microvilli (transition is at urinary pole which is start of PCT
3) Loop of Henle - thick ascending/descending are cuboidal, thin ascending/descending are simple squamous
3) DCT- simple cuboidal without brush border
4) Collecting duct - cuboidal without brush border
5) Calyces and renal pelvis - transitional epithelium
Describe the histology of the:
1) PCT
2) Loop of Henle
3) DCT
4) Collecting duct
5) Calyces and renal pelvis
6) Ureter
7) Urethra
1) PCT - simple cuboidal with brush border that looks like ragged lumen, central nuclei, indistinct cell borders, eosinophilic (lot of mitochondria to fuel transporters), membrane infoldings for extra space to dump absorbed materials which appear as striated line
2) Loop of Henle - region of macula densa where loop passes close by to the corpuscle that spawned it
3) DCT - distinct luminal margin ie no brush border, apical nuclei, less eosinophilic but still striated
4) Collecting duct- 2 cell types, principal for water balance and intercalated for acid/base regulation, distinct cell borders, domed apex juts into lumen
5) Calyces and renal pelvis- uppermost nuclei round, binucleated cells
6) Ureter- star shaped lumen, outer circular and inner longitudinal muscle layers
7) Urethra- U-shaped lumen, outer circular and inner longitudinal muscle layers
How do you distinguish PCT from DCT?
1) LM: PAS staining - PC stains positive (dark) and DCT stains negative (light)
2) EM: PCT has brush border (consisting of microvilli) while DCT does not
What is the juxtaglomerular apparatus? Describe tubuloglomerular feedback?
1) Function: regulates filtration rate at the glomerulus, regulates blood pressure
Components: macula densa (end of TAL/start of DCT that passes near glomerulus), JG cells of the afferent arterioles, extraglomerular mesangial cells (middlemen between MD and JG)
2) Tubuloglomerular feedback - higher blood flow –> higher GFR –> high NaCl in macula densa, which is sensed through the apical NKCC2 transporter –> macula densa feeds back on glomerulus to decrease renin release, signals afferent arteriole to vasoconstrict –> decreases blood flow and GFR
(eg if NaCl is low, macula densa signals afferent arteriole to dilate –> increased RBF and GFR + increased renin release by JG cells)
What are juxtaglomerular cells (JG cells)?
JG cells - modified smooth muscle cells, mainly in the walls of the afferent arterioles
regulate GFR minute by minute by constriction and dilation of afferent arterioles in a given glomerulus (autocratic)
also globally regulates blood pressure and GFR on longer time scale through renin secretion (democratic)
Meanwhile, AT1Rs are mostly found in efferent arterioles, AII binds to vasoconstrict to increase GFR
What is the relative distribution of body water? What is third spacing?
1) Intracellular fluid - 67%
2) Extracellular fluid - 33%
- -> blood volume (1st space)- 8%
- -> interstitial fluid (2nd space)- 25%
* decrease in ECF triggers SNS and RAAS system*
3) Third spacing - pathological condition where fluid is where it should not be eg edema
Define:
1) effective solute
2) effective osmolality
3) effective circulating volume ECV (how is this measured)
4) renal clearance C
1) effective solute- solutes which cannot passively diffuse across cell membrane eg Na+, glucose –> sets tonicity to create osmotic gradient
2) effective osmolality - concentration of effective solutes in given weight of H20; = 2[serum Na+] + glucose/18, should be ~290
3) effective circulating volume ECV - blood volume required for adequate perfusion of vital organs *changes moment to moment depending on metabolic factors –> measured as the pressure perfusing arterial baroreceptors in carotid sinus or afferent arterioles
4) Renal clearance C- volume of blood that is completely cleared of solute into urine per unit time (mL/min)
Define glomerular filtration rate GFR
What is the threshold GFR?
When does GFR = clearance?
1) GFR- rate at which solutes are filtered from glomerulus into Bowman’s capsule collecting reservoir; GFR = [[urine] * urine flow (ml/min)] / [plasma]
2) GFR less than 60 - associated with high risk for devlpt of cardiovascular disease
3) GFR = C when solute is freely filtered, neither reabsorbed nor secreted eg inulin
1) What is the relationship between GFR and serum creatinine and BUN (blood urea nitrogen) measured in blood?
2) What is the normal range for creatinine, BUN, GFR, and BUN:Cr?
3) How do the following factors affect serum creatinine?
- black
- hispanic + asian
- kidney disease
- large muscle mass
- eating red meat
- malnutrition
4) What factors will increase serum BUN?
1) Increased GFR –> decreased in serum creatinine and BUN and vice versa
2) Pcr less than 1.5 mg/dl; BUN 10-20 mg/dl; GFR 75-125; BUN:Cr 10:1 ratio
3) Black-increase;
kidney disease- decrease;
high muscle mass- increase;
eating red meat - increase;
malnutrition - decrease
4) High protein, volume depletion/dehydration (and thus hypoperfusion) –> manifests as high BUN without increase in creatinine (BUN:Cr > 20:1)
Define:
filtered load
fractional excretion
filtration fraction
1) filtered load - amount of solute x filtered into bowman’s capsule per unit time
2) fractional excretion - ratio of solute excreted : filtered load (% of solute filtered that actually ends up in excreted urine) = [X]excreted / (GFR * [X]plasma)
3) filtration fraction - fraction of renal plasma flow that is filtered across the glomerular capillaries = GFR/RPF
Describe the tubulo-glomerular feedback (TGF) system when there is increased GFR.
What happens during increased volume expansion (pathologic situation)?
1) Increased GFR –> increased NaCl in urine –> depolarize and activate macula densa cells (in TAL, close to juxtaglomerular apparatus embedded around afferent arteriole)–> secrete vasoconstrictors to afferent arterioles –> decreases glomerular pressure –> reduces GFR
2) Increased volume expansion –> increased ECF –> increased GFR –> increased excretion of H20+ Na+ (pressure natriuresis) –> macula densa lumenal Na+ relatively low compared to H20 –> desensitizes TGF –> higher glomerular P and increased GFR –> in order to restore euvolemia, need lots of urine excretion (diuresis)
* Note: ANP decreases sensitivity of TGF mechanism to increase diuresis*
Describe how the RAAS system responds to hypovolemia (how is it turned on and off)
1) low volume –> low blood pressure sensed by baroreceptors (carotid sinus, afferent arterioles)–> activates SNS tone –> activates beta 1 adrenoreceptors on JG cells –> secrete renin –> renin converts angiotensinogen to AI –> ACE converts AI to AII –> AII binds to AT1 receptor on efferent arteriolar vascular smooth muscle –> vasoconstricts efferent arteriole –> increases glomerular pressure (through back pressure) into optimal range –> increased GFR –> increased reabsorption of Na+ from filtrate into renal interstitium and back into circulation (this is also facilitated by lowered capillary pressure due to reduced renal perfusion and lower renal blood flow RBF from AII binding to AT1R)–> increases volume
2) once sufficient volume/MAP/perfusion pressure is reached –> SNS tone downregulated –> Decreased renin secretion –> RAAS turned off
Describe the mechanism of ARBs
ARBs selectively block AT1 receptors:
1) Directly blocks vasoconstriction (reduces glomerular pressure GFR)
2) Directly inhibits Na+ reabsorption (NHE3, NKCC2, NCC, EnaC)
3) Inhibition of aldosterone production and secretion from adrenal cortex
4) Possibly promotes release of bradykinin via AT2R –> vasodilation and natriuresis
Describe the phenomenon of ACE escape and how it explains the limited effectiveness of ARBs and ACE inhibitors in some patients
AII production impaired –> feedback inhibition of renin is lost –> reactive increase in renin –> AII produced through ACE independent pathways
*option is to use combination of renin inhibitors and ARBs
What is the effect of SNS activation?
Postganglionic SNS fibers secrete norepi –> activates alpha1 adrenoreceptors in vascular smooth muscle –> systemic vasoconstriction –> reduction in GFR and renal perfusion –> volume conservation;
Norepi also activates beta1 adrenoreceptors on JG cells to secrete renin
Describe the activation and function of AVP
AVP=ADH=vasopressin=antidiuretic
1) Activation - hyperosmolality detected by osmoreceptors, hypotension detected by baroreceptors (carotid sinus and afferent arterioles) –> induces posterior pituitary to secrete AVP
2) Function: Peptide that binds to V1R receptor in arterioles –> vasoconstriction;
Binds to V2R receptor in nephron –> activates aquaporins –> stimulates H20 + Na reabsorption –> increased volume
Describe the activation and function of ANP
ANP=natriuretic peptide
1) Activation - secreted by atrial myocytes when right atrium is distended (increased right atrial pressure due to increased volume)
2) Function - vasodilation within arterioles, decreases sensitivity to TGF, increases GFR and RBF (Renal blood flow), suppresses renin secretion, increases diuresis
What is the importance of renal perfusion?
Describe the process of autoregulation during low BP?
1) Renal perfusion - maintain adequate 02 delivery, maintain optimal hydrostatic and oncotic pressures for reabsorption
2) Low BP –> sensed by afferent arteriole pressure sensor –> activates vasodilatory prostaglandins (afferent arterioles) + RAS (vasoconstricts efferent arteriole which contain AT1 receptors for AII) –> increased glomerular pressure –> increased GFR + RBF
What happens if BP is too low (outside of range of autoregulation)?
What are some causes of renal hypoperfusion (lack of blood flow to kidney)?
What are the symptoms of renal hypoperfusion?
1) BP too low (pathophysiologic) –> locally produced vasoconstrictors –> act on afferent arterioles –> lower glomerular pressure + GFR –> reabsorptive gradients impaired –> ischemic acute renal failure
2) Causes: anything that impedes blood delivery to the nephron eg impaired CO, renal artery stenosis, volume depletion, prerenal azotemia (increase in BUN)
3) Symptoms: Increased urinary specific gravity, decreased urinary Na+ and urea, BUN:creatinine > 20:1
Describe the ion+glucose reabsorption in:
the proximal tubule (PCT)
majority of Na+ reabsorbed in first half of PCT;
basolateral (bw epithelium and interstitium): Na/K+ ATPase sets favorable gradient, transport also through Na+/HC03- symporter;
transport across apical (bw lumen and epithelium): SGLT1/2 glucose/Na+ transporters, and Na+/H+ exchanger NHE3
passive Ca2+ reabsorption in PCT
Describe the ion+glucose reabsorption in:
Loop of Henle
thick ascending limb (TAL)
1) Na+ reabsorption from thin ascending limb through Na+ pumps
2) diluting segment - impermeable to H20 reabsorption;
basolateral: Na/K ATPase and CL/HC03 exchanger;
apical: ROMK2 secretes K+, facilitates NKCC2 (reabsorbs K, CL, Na), Na/H exchanger NHE3
Describe the ion+glucose reabsorption in:
distal convoluted tubule (DCT)
basolateral: Na/K ATPase, transporters that reabsorb Cl-, K+ into interstitium, Na+ (into cytoplasm)/Ca2+ (out) exchanger;
apical: Na/Cl cotransporter NCC, Na+ transporter ENaC, + another transporter that reabsorbs Ca2+
Describe the ion+glucose reabsorption in:
cortical collecting tubule (CCT)
aldosterone-sensitive distal nephron
basolateral: Na/K ATPase (stimulated by AVP, AII, aldosterone);
apical: K+ secretion by ROMK2 creates positive charge gradient for Na+ reabsorption through ENaC (stimulated by AVP, AII, aldosterone), H+ secretion and bicarb formation through ATPase (stimulated by aldosterone)
Describe the mechanism of the following diuretics, where they act, and whether they are K+ sparing or wasting:
1) Acetazolamide
2) Furosemide
3) HCTZ
4) Amiloride
5) Spironolactone/Eplerenone
1) Acetazolamide - (PCT, weak)- carbonic anhydrase inhibitor, blocks H+ formation and bicarb reabsorption
2) Furosemide loop diuretic- (Loop of Henle, powerful) -blocks NKCC2 transporter –> blocks Na, Cl, K reabsorption –> K+ wasting –> charge gradient leads to Ca2+ wasting
3) HCTZ thiazide diuretic - (DCT, weak) - blocks NCC tranporter –> blocks Na+ and Cl- reabsorption –> charge gradient leads to K+ wasting and Ca2+ sparing
4) Amiloride - (CCT) - blocks ENaC Na+ transporter –> K+ sparing
5) Spironolactone/eplerenone (CCT) - aldosterone antagonist –> K+ sparing, used to treat resistant hypertension
Aldosterone:
1) where is it secreted
2) what stimulates secretion
3) where does it bind
4) Function
1) Zona glomerulosa of adrenal cortex
2) Elevated AII and hyperkalemia (K+ depolarizes outer membrane and activates voltage gated Ca2+ channels to stimulate aldosterone synthesis)
3) mineralocorticoid type steroid receptor in principal cells and VSM
4) combats volume depletion: (acute) stimulates Na+ reabsorption through ENaC –> H20 reabsorption (chronic) stimulates Na/K ATPase, K+ excretion through ROMK2
Describe the aldosterone paradox
1) Hyperkalemia - only increases aldosterone (not AII expression) –> gene changes cause aldosterone to be more attracted to ROMK than ENaC –> promotes K+ excretion without excess Na+ reabsorption/hypervolemia
2) Hypovolemia - RAAS activated –> AII and aldosterone cause Na+ reabsorption –> H20 reabsorption and volume rebalance without hypokalemia
Describe aldosterone escape
Pressure natriuresis - Na+ and H20 excretion even with high levels of aldosterone, bc MAP and blood pressure are too high;
K+ excretion high in distal nephron when aldosterone levels are high;
thus patients with hyperaldosteronism are more likely to be hypokalemic than hypernatremic (bc there is this mechanism of pressure natriuresis which overrides aldosterone if BP is too high); on the flip side, hypoaldosteronism leads to hyponatremia (not bc there is less Na+ reabsorption/more excretion, but because the low volume/BP activates AVP –> more H20 reabsorption compared to [Na+])
Explain the different effects of increased Na+ on renal RAAS vs brain RAAS.
Explain how the brain is potentially involved in the pathophysiology of hypertensive disease through the cardiotonic steriod ouabain.
1) Renal RAAS: increased plasma Na+ –> increased Na+ and H20 retention –> increases plasma volume –> increases blood pressure –> once BP/perfusion pressure/MAP is achieved, SNS downregulated –> renal RAAS turned OFF
2) Brain RAAS for salt-sensitive populations: increased plasma Na+ –> increased NaCl in CSF –> brain RAAS turns ON –> production of ouabain –> vasoconstriction –> decreased pressure natriuresis –> vicious cycle of chronic HTN direct association with dietary NaCl and induction of hypertension in salt-sensitive population
What factors stimulate the reabsorption from interstitium into capillaries (and thus the blood plasma/ECV)?
Filtration = Pcap - Pif + PIif - PIcap
Reduced flow in capillaries reduces Pcap, while the Pif is high bc it is related to the pressure of forming urine
Glomerular filtration increases PIcap, while PIif is low
Overall, filtration # is low –> favors reabsorption
Describe the condition, causes, and presentation for:
1) Euvolemic hyponatremia
2) Hypovolemic hyponatremia
3) Hypervolemic hyponatremia
1) Euvolemic hyponatremia - inordinate water retention + normal Na+ content;
cause: SIADH;
presentation: otherwise healthy patient
2) Hypovolemic hyponatremia - both H20 and Na+ loss, but more Na+ lost proportionally;
cause: (intrarenal) diuretics, aldosterone deficiency, (extrarenal) intravascular fluid loss through diarrhea, vomiting, sweating, hemorrhage;
presentation: (intrarenal) increased urine Na+ (extrarenal) decreased urine Na+, increased BUN due to hypoperfusion, tachycardia, flattened neck veins
3) Hypervolemic hyponatremia = dilutional hyponatremia due to H20 retention
cause: heart failure, renal failure, drinking lots of water while exercising
presentation: heart failure- decreased urine Na+ (conserve H20 to raise volume and perfusion pressure), renal failure - increased urine Na+ (renal function and thus Na+ reabsorption impaired)
Describe the condition, cause, and presentation for:
1) Mineralocorticoid hypertension
2) Pseudohypoaldosteronism
1) Mineralocorticoid hypertension - aldosterone excess hyperstimulates ENaC;
cause: primary (Conn’s disease e.g. tumor, would have high PAC:PRA) or secondary (e.g. renal artery stenosis) hyperaldosteronism;
presentation: hypertension bc increased aldosterone –> increased Na+ reabsorption –> increased blood volume –> increased venous return –> increased CO –> increased BP (=COxTPR), hypokalemia (aldosterone promotes K+ excretion through ROMK)
2) Pseudohypoaldosteronism - disruption in ENaC leading to Na+ excretion (natriuresis) and K+ accumulation;
cause: mutation in SCNN1 gene for ENac;
presentation: hypotension (increased PRA), hyperkalemia, metabolic acidosis, can have high plasma aldosterone
Describe the causes (neurogenic and nephrogenic) and presentation for:
1) Diabetes insipidus
2) SIADH
1) Diabetes insipidus - loss in AVP production (neurogenic) or AVP resistance bc of V2R or AQP2 mutation- (nephrogenic);
presentation: polyuria- large volumes of dilute urine (*dilute aspect differentiates this from DM, where there is glucose in urine)–> hypovolemia, polydispia (reduced plasma volume and hyperosmolality triggers osmoreceptors to activate hypothalamic thirst centers), hypotension (reduced ECV), hyper/hyponatremia (ion imbalance due to immense water excretion);
treatment - (central) AVP analog, (nephrogenic) thiazide diuretic
2) SIADH - increased AVP production (neurogenic) or increased AVP response eg gain of function mutation in V2R (nephrogenic);
presentation: euvolemic hyponatremia (although AVP causes both Na+ and H20 reabsorption, more water is reabsorbed leading to a low Na+ concentration); presents normally, NO hypertension (bc the increased fluid is ICF, not ECF, so does not affect blood volume/pressure); blood labs show concentrated urine (high specific gravity), increased urine [Na+], hypoosmolality
How do the following mechanisms regulate NaCl transport:
1) Glomerular-Tubule balance
2) RAAS
3) SNS-norepi
4) ANP, prostaglandins, bradykinin, dopamine
1) GT balance - PCT can absorb constant fraction of filtered load –> as more Na+ is filtered, more is reabsorbed
2) RAAS - Na+ reabsorption through upregulation of NHE3 in PCT, ENaC in DCT, aldosterone secretion
3) SNS - Na+ reabsorption by stimulating RAAS via beta1 adrenoreceptors on JG cells, activating NHE3 and Na/K
ATPases via alpha adrenoreceptors ; reduces GFR and RBF
4) ANP, prostaglandins, bradykinin, dopamine- all impair Na+ reabsorption and decrease plasma [Na+]
Explain how H+ is secreted through:
1) lumenal buffers
2) protein metabolism
3) NH3-NH4+ buffer system
- both occur in PCT
1) H20 dissociates into OH- and H+ in the peritubular epithelial cytoplasm –> H+ is excreted as H2P04 and OH- combines with C02 to make HC03-
2) Glutamine is metabolized in epithelial cytoplasm into NH4+ (excreted) and alphaketoglutarate (used to make bicarb)
3) In PCT, NH3 + H+–> NH4+ which travels with forming urine to TAL where it is reabsorbed into epithelium and then dissociates;
NH3 diffuses into interstitium –> recycled in PCT to make more NH4+ (thereby buffering low pH) OR secreted as NH4+ from collecting tubule in distal acidification (thereby reducing acid load) –> end result is removing H+ from circulation
Explain the relationship between kalemic and acid/base status
in order to maintain electroneutrality:
Hyperkalemia —> Metabolic acidosis, and
hypokalemia –> Metabolic alkalosis
low K+ –> gradient for K+ to move from intracellular to extracellular interstitium–> H+ moves from extracellular to intracellular –> intracellular acidosis –> H+ secretion/HCO3- reabsorption –> metabolic alkalosis
When do you calculate urine AG? Why is it negative if the kidneys are healthy?
1) Calculate with normal AG metabolic acidosis; UAG = Na+ + K+ - Cl-
2) When pH is low, healthy kidneys reduce acid load by secreting NH4+ in the form of NH4Cl –> urine has high [Cl-]
–> UAG negative;
When kidneys are not healthy, cannot acidify the urine –> lower [Cl-] in urine –> UAG positive
1) How does hyperaldosteronism lead to hypokalemic metabolic alkalosis?
2) How does hypoaldosteronism lead to hyperkalemic metabolic acidosis? common cause is congenital adrenal hyperplasia
1) Hyperaldosteronism –> increased activity of H+/K+ and H+ ATPases –> increased H+ secretion in collecting duct –> increased HC03- reabsorption –> increased pH –> decreased extracellular H+ –> gradient for H+ to come out of cells, K+ to go into cells –> hypokalemic metabolic alkalosis
2) Hypoaldosteronism –> decreased aldosterone –> decreased H+ secretion –> decreased HC03- generation –> decreased pH –> H+ goes into cells, K+ comes out of cells –> increased extracellular K+ –> hyperkalemic metabolic acidosis
What is the renal response to alkalinity?
Kidneys do NOT upregulate HCO3- excretion (by reducing bicarb resorption bicarb is not secreted, only filtered and reabsorbed. Instead they downregulate NH4+ excretion (which is combined with HC03- reabsorption when glutamate is broken down in the process of protein metabolism) –> decreases HC03- reabsorbed –> lowers blood pH
Explain how urea recycling promotes H20 absorption
PCT - 50% filtered load reabsorbed
Loop of Henle - 110% filtered bc lot is secreted
Collecting duct - urea reabsorbed into interstitium, final excreted is 20% of filtered load
high concentration of urea in medullary interstitium creates favorable oncotic gradient for H20 reabsorption esp when AVP is activated and aquaporins open up
What are cells in the endocrine pancreas are responsible for secreting?
Islets of Langerhans = endocrine pancreas
alpha cells - glucagon (increases plasma glucose through glycogenolysis and gluconeogenesis, acts in the liver)
beta cells - insulin (decreases plasma glucose)
delta cells - somatostatin (inhibits GH to decrease plasma glucose)
Define:
1) glycogenesis
2) glycogenolysis
3) gluconeogenesis
4) lipogenesis
1) glycogenesis - glucose uptake and storage as glycogen
2) glycogenolysis - metabolism of glycogen into plasma glucose
3) gluconeogenesis - synthesis of glucose from other substrates
4) lipogenesis - formation of FFA and uptake of FFA into cells
When is insulin synthesized?
What is the result of a decrease in insulin?
1) Synthesized when plasma glucose > 100 mg/dl (max insulin release at 300), circulates in bioactive form and binds to receptors that mediate rapid influx of glucose by facilitated diffusion
2) Normally, insulin leads to lipogenesis. With low insulin, glycolysis shifts to lipolysis –> FA oxidation –> ketone bodies –> oxidative fuel
* if ketoacid production > usage –> can lead to diabetic AG ketoacidosis*
What is the function of insulin in:
1) skeletal muscle
2) fat
3) the liver
4) protein
5) bone
- insulin at low levels is v good at cellular K+ uptake i.e. reducing plasma K+ levels*
1) Skeletal muscle: promotes glucose uptake and glycogenesis major site of post-prandial glucose uptake (opposite action of GH and cortisol, which suppress glucose uptake by muscle)
2) Fat: stimulates lipogenesis (FFA uptake for combination with glucose to produce triglycerides), blocks lipolysis (opposite action of GH, which promotes lipolysis to produce FFA for skeletal muscle fuel)
3) Liver: promotes glucose uptake and glycogenesis, inhibits gluconeogenesis and glycogenolysis, stimulates fatty acid synthesis (opposite action of GH, which stimulates gluconeogenesis)
4) Protein: impairs protein catabolism –> anabolic (in conjunction with GH)
5) Bone: anabolism (in conjunction with GH)
What are the 3 P’s of DM (DMI and diabetes insipidus) and what are their pathologies?
1) Polydispia - increased glucose –> hyperosmolality –> activates thirst centers in the hypothalamus (increased levels of AII trigger thirst)
2) Polyuria - more glucose in forming urine –> draws Na+ and H20 out (mainly in PCT) –> osmotic diuresis –> decreases ECF volume –> decreased blood pressure, triggers SNS and RAAS; DI polyuria is due to lack of AVP –> more dilute urine excreted
3) Polyphagia - loss of insulin which is an anabolic hormone leads to weight loss and increased appetite
What are treatment options for DMII?
1) Weight loss and exercise
2) metformin - inhibits liver gluconeogenesis, enhances insulin receptor signaling
3) thiazolidenediones - insulin sensitizer
4) sulfonylurea - promotes endogenous insulin production in pancreatic beta cells
5) insulin replacement - injectables, pump
Describe the regulation of Ca2+ and P04 during
hypocalcemia
Hypocalcemia –> chief cells of the parathyroid glands secrete PTH:
1) resorption of bone –> increased plasma Ca2+ and P04
2) renal Ca2+ reabsorption (distal nephron i.e. TAL, DCT, collecting tubules)
3) impairs renal P04 reabsorption (proximal tubule)
4) stimulates Vitamin D/calcitriol synthesis –> Ca2+ reabsorption (distal nephron) + small intestine
* Vit D also promotes renal P04 reabsorption, but PTH wins out so end result is increased phosphaturia*; Vit D feeds back and inhibits PTH secretion
Describe the countercurrent exchange mechanism in the vasa recta
Vasa recta - loops of capillaries with low blood flow that run parallel to loop of henle;
Maintain hypertonicity of the medullary interstitial osmotic gradient by recycling NaCl, H20, urea from medullary interstitium –> systemic circulation;
nephron (loop of Henle)- countercurrent multiplier - sets up osmotic gradient for diffusion
What is one watchout for providing insulin therapy to diabetics (eg for diabetic ketoacidosis)?
Hypokalemia - need to monitor K+ status when giving insulin;
Although metabolic acidosis (e.g. ketoacidosis) is associated with hyperkalemia, in diabetics: increased glucose –> hyperosmolality –> osmotic diuresis –> increased aldosterone –> loss of total body K+ (through ROMK);
Insulin leads to further cellular K+ uptake (decreased plasma K+) –> so when administering insulin therapy, watch out for hypokalemia
What is the function of glands and their general histology?
Glands - synthesize, modify, and secrete products;
cuboidal or columnar epithelial cells surrounded by basement membrane
Define: 1) Exocrine glands 2) Endocrine glands 2A) endocrine action 2B) autocrine action 2C) paracrine action
1) Exocrine- maintain contact with tissue surface; secrete products into ducts eg salivary, sweat, mammary glands
2) Endocrine - lose contact with tissue surface, secrete into blood stream via fenestrated capillaries
A) endocrine action - tissues are far removed from site of secretion
B) autocrine action - secretions activate secreted cell itself
C) paracrine action - secretions activate adjacent cells
What are four types of products produced by endocrine glands? Give examples
1) modified AA eg adrenaline from adrenal medulla
2) Peptide hormones eg AVP from posterior pituitary (produced in hypothalamus)
3) Glycoprotein hormones eg FSH, LH, TSH, GH- all from anterior pituitary
4) Steroid hormones eg aldosterone from adrenal cortex
T/F:
1) Many peptide hormones require post-translational modifications to produce active hormone
2) All hormones bind to cell surface receptors to activate second messenger systems
3) Hormone activity is regulated by negative feedback loops
1) True
2) False- protein/peptide hormones do this bc they are hydrophilic, but steroid hormones are hydrophobic and can diffuse through plasma membrane and into nucleus to bind to nuclear receptors and directly regulate gene transcription
3) True
Describe the histologically/functionally distinct lobes of the pituitary gland (ie hypophysis) and their embryology
1) Adenohypophysis= Pars distalis (Anterior lobe) + Pars intermediate + Pars tuberalis – glandular tissue, from oropharynx ectoderm (called Rathke’s pouch)
2) Neurohypophysis = Pars nervosa (Posterior lobe) + infundibulum – axon terminals and pituicytes, from neuroectoderm/neural secretory tissue
Describe the hypophyseal portal system that links the hypothalamus and the pituitary
Hypothalamic peptides that regularly pituitary secretion collect at fenestrated primary capillary plexus (located at median eminence of hypothalamus) – formed by superior hypophyseal artery –> portal veins –> secondary plexus at anterior pituitary which bathes cells of the anterior lobe;
inferior hypophyseal artery supplies posterior lobe
Describe the three histologically distinct cell types that can be observed in the anterior pituitary
1) Acidophilic - stain light pink, contain somatotrope GH, lactotrope PRL prolactin (non-glycosylated)
2) Basophilic - stain dark pink, contain thyrotrope TSH, corticotrope ACTH, gonadotrope FSH, LH (glycosylated)
3) Chromophobe - don’t stain bc don’t have secretory granules
