Case 7 Flashcards
What is the difference in onset between type 1 and type 2 diabetes?
type one is usually in childhood and adolescence, type two is typically in adulthood.
What is the difference in the weight of people with type one diabetes?
They typically lose weight in the run up to diagnosis.
What is the difference between blood insulin levels in type one and type 1 and type 2 diabetes?
There is a progressive decrease in type 1 whereas in type 2 they start particularly high and then there is a moderate to normal decrease in the later stages
What is the difference in the appearance of the islets of langerhans in type 1 and type 2 diabetes?
There is insulitis (inflamatory infiltrate of T cells and macrophages) in type 1 which is not present in type 2 in type two there is also amyloid deposits in the islets.
What is the mechanism and indication for Thiazides (e.g. bendroglumethiazide) and thiazide like drugs (e.g.indapamide)
They inhibit the sodium-chloride transporter in the distant tubule, this transporter only reabsorbs 5% of filtered Na so is less effective than loop diuretics, they are mostly used in small doses for the treatment of hypertension.
What is the mechanism and indication for loop diuretics (e.g. Furosemide, Bumetanide, Torasemide)
They inhibit the sodium-potassium-chloride transporter in the thick ascending limb, this transporter is responsible for 25% of Na re-absorption so has a strong effect, these drugs are used to treat heart failure and fluid retention in chronic kidney disease.
What is the mechanism for potassium sparing diuretics? (e.g. amiloride, triamterene) What advantage do they pose over loop diuretics
Some antagonize the work of aldosterone in the distal segment of the distal tubule causing more sodium and water to be into the collecting duct and be excreted in urine, the advantage of this is that there is no risk of hypoalkemia as potassium is not unnecessarily lost.
What is the relationship of the kidneys to the peritoneum?
They are retroperitoneal
Which kidney is slightly lower than the other? Why is this?
The right kidney is slightly lower than the left kidney to make up for the space the liver takes up
What vertebral level do the kidneys begin and extend to?
They extend from T12 to roughly L4
What are the rough proportions of the kidney?
10cm long, 5cm wide and 2.5cm thick
What are the three layers of supportive tissue that surround the kidneys? list them from most superficial to deep
The renal fascia, the perirenal fat capsule and the fibrous capsule
What is the purpose of the perirenal fat capsule?
It acts as a shock absorber protecting the kidney from physical blows
How do the shapes and positions of the two kidneys differ from one another?
The left kidney is longer and more slender, it is also closer to the midline. The right kidney is lower than the left due to the space the liver takes up
What is the role of the fibrous capsule of the kidney?
It prevent infection in the regions surrounding the kidney from spreading to it
What is the name of the extensions of the renal cortex that extend into the renal medulla?
renal columns
How do the renal columns effect the shape of the medulla? What structure does this form?
The renal columns divide the medulla into discontinuous triangular sections called renal pyramids
What surrounds each renal pyramid? What makes up a lobe of a kidney?
renal pyramids are surrounded by a shell of cortex that together for each lobe of the kidney
What is at the end of each renal pyramid what surrounds it?
Each renal pyramid has a renal papilla at its apex surrounded by a minor calyx
What is the name for portions of nephron that extend beyond the renal pyramids into the renal cortex?
medullary rays
What forms the renal pelvis?
minor calyxes of the renal pyramids combine to form major calyxes which themselves converge creating the renal pelvis
Name the sequence of arteries that arise originally from the abdominal aorta to supply the kidney from largest to smallest
abdominal aorta, renal artery, segmental, interlobular, arcuate, cortical radiate, afferent arterioles
What are the series of venous vessels that help drain the kidneys, name them from smallest to largest
capillaries, efferent venules interlobular veins, arcuate veins, interlobar veins renal veins
What i the innervation of the kidney?
renal nerves whose fibers are derived mostly sympathetic post ganglionic fibers from the celiac plexus and inferior splanchnic nerves
What is the effect of sympathetic innervation on the kidney?
Modulation of urine production by altering blood flow and pressure at the nephron level. Stimulation of renin release restricting loss of water and salt in urine by stimulating reabsorption
What is the lymphatic drainage of the kidney?
lateral aortic lumbar nodes surrounding the origin of each renal artery
Roughly how many nephrons and collecting ducts are in each kidney?
1.2 million nephrons and thousands of collecting ducts
What proportion of nephrons are cortical nephrons?
85%
What is a cortical nephron?
A cortical nephron is a nephron that is almost entirely within the superficial cortex of the kidney. It has a short nephron loop and its associated efferent arteriole delivers blood to a network of peritubular capillaries
What is a juxtamedullary nephron?
A nephron with a long nephron loop that extends deep into the medulla and have peritubular capilaries that are connected to vasa recta
What is the other name for a glomerular capsule?
Bowman’s capsule
What are the two layers of the Bowman’s capsule?
An external parietal layer that helps contain the glomerular filtrate and a visceral layer that clings to the glomerulus helping filtration
What type of cell composes the visceral membrane of the glomerular capsule?
modified branching epithelial cells called podocytes
What is the name for the openings between the foot processes of podocyte?
filtration slits
What is the name for the supporting cells that have actin like filaments surrounding adjacent capilaries in glomeruli that can contract under the stimulation of various hormones helping to modify capilary diameter/blood flow
mesangial cells
What are the three main hormones that effect the contractility of mesangial cells?
angiotensin II, vasopressin and histamine
What are the three layers of the ultrastructure of the glomerrular membrane?
capillary membrane, basement membrane and Bowman’s visceral epithelium
The capillary membrane of the glomerulus is fenestrated with capilaries how large?
70-90nm
What composes the basement membrane of the glomerulus?
thick glycoproteins and mucopolysaccharides
How large are the filtration slits?
25nm
How long is a typical renal tubule?
3cm
What are the three main parts of a renal tubule, what does it drain into?
proximal convoluted tubule, loop of henle, distal convoluted tubule. it drains into a collecting duct
What is the role of the proximal convoluted tubule?
To reabsorb organic nutrients, ions water and if present plasma proteins from the glomerular filtrate and to secrete them into the peritubular fluid where they can be returned to the blood
What type of epithelium linesthe proximal convoluted tubule?
a simple cuboidal epithelium with microvilli on its apical surface
Both the descending and ascending limb of the loop of Henle have thick and thin segments how do the epithelium of each of these differ from one another?
Thick segments have cuboidal epithelium thin segments have squamous epithelium
What is the role of the thick segments of the loops of henle?
They pump sodium and chloride ions out of the tubular fluid
What is the role of the thin segments of the loops of henle?
They are permeable to water but not ions, water moves out of these into peritubular fluid condensing the tubular fluid
What are two ways the distal convoluted tubules are different in structure from proximal convoluted tubules?
They have a smaller diameter and their epithelial cells lack microvilli
What are the three processes that happen in the distal convoluted tubule?
Active secretion of ions, acids, drugs and toxiins into the tubule, the selective reabsorption of Na ions and calcium ions from the tubular fluid and the selective re-absorption of water from the tubule helping to concentrate the tubular fluid
Where are the epithelial cells of the DCT tallest? what other other unique arrangement do they have in this area?
near the renal corpuscle (the region is known as the macula densa) they also have their nuclei clustered together
What is the name of the unusual smooth muscle fibers in the afferent arterioles?
juxtaglomerular cells
What composes the juxtaglomerular complex? what does it secrete?
juxtaglomerular cells and the macula densa. It secretes the the hormone erythropoietin and the enzyme renin
Which convoluted tubule has leaky tight junctions between its cells?
proximal
Which convoluted tubule has tight tight junctions between cells?
distal
What is the difference between leaky tight and tight tight junctions?
leaky tight junctions allow the passave of water and solutes across them, tight tight do not
What do several collecting ducts converge to form before they become a minor calyx?
a papillary duct
What type of epithelium typically lines collecting ducts?
columnar
What are the three distinct processes that help the kidneys control the content of urine?
glomerular filtration, tubular reabsorption and tubular secretion
Apart from size selectivity how else can the glomerulus effect its filtrate
Charge selectivity (negativly charged molecule are filtered less easily than positively charged molecules of the same size
What provides the glomerulus with charge selectivity?
proteoglycan rich in sialic acid in the capillary wall give it a negative charge repelling other negative molecules
What is the normal capillary hydrostatic pressure?
60mmHg
What is the normal hydrostatic pressure within the Bowman’s capsule?
18mmHg
What is the normal glomerular oncotic pressure?
32mmHg
What is the normal bowmans capsule oncotic pressure?
0mmHg as it contains no proteins
What is oncotic pressure/colloid osmotic pressure?
The osmotic pressure exerted by proteins
What is a normal healthy GFR?
125ml/min or 180L/day
What would an increase in pressure in the Bowman’s capsule do to GFR?
decrease it
What would an increase in capillary colloid osmotic pressure do to the GFR?
Decrease it
What would an increase in glomerular capillary do to the GFR?
Increase it?
Why does sympathetic stimulation decrease the GFR?
It constricts renal arterioles decreasing renal blood flow
What is the effect of epinephrine and norepinephrine on GFR?
it decreases it via the reduction of renal blood flow
What is the effect of angiotensin II on GFR how does it achieve this?
It increases it through the constriction of efferent arterioles
What is endothelial derived effect on GFR?
Increased GFR through the reduction of vascular resistance
What effect do bradykinin and prostaglandins tend to have on GFR?
increase
Decreased GFR leads to lower flow rate in the loop of Henle how might this effect the efferent arterioles of the glomerulus?
slower flow rate in the loop of Henle leads to increased reabsorbtion of Na and Cl in the ascending loop of Henle. This increases NaCl conc in the macula densa which raises glomerular hydrostatic pressure and increases renin release which catalises the formation of angiotensin I therby increasing the amount of angiotensin II produced causing increased efferent arteriole constriction
How is calcium involved in the myogenic autoregulation of GFR?
When vessels walls are stretched then increase their release of Ca into the extracellular fluid causing the vessels to constrict and resist distention
How much Na re-absorption happens at the PCT, loop of Henle and DCT respectively?
67% at PCT, 25% at loop and 8% at DCT
What pump provides the majority of the force for re-absorption in the PCT?
Na+K+ATPase
Co-transporters using Na are particularly useful for reabsorbing what?
organic nutrients such as amino acids and glucose
What is the NHE-3 transporter? What makes it particularly useful?
It is a counter-transporter mechanisms which absorbs sodium while secreting H+. It is particularly usful at removing bi-carbonate ions from the tubule as the secreted H+ ions combine with it to form carbonic acid that degrades into water and CO2
What is the difference in the uptake mechanisms for Na in the first and second half of the PCT membrane?
In the first half it is mostly co-transported with glucose and amino acids, in the second half there is little of these left so sodium is mostly absorbed with Chlorine
What allows the concentration of Na and the overall osmolarity of the tubular fluid to stay near constant throughout the PCT despite the large amount of Na uptake?
The proximal convoluted tubule is so permeable to water that it is caried across the resulting osmotic gradient at such a rate that it compensates for the Na being caried accross
What substances are secreted into the tubular fluid at the PCM?
organic acids and bases such as bile salts, oxalate, urate and catecholamines, also para-aminohippuric acid (PAH)
How much of the water in the glomerular filtrate is reabsorbed in the loop of henle?
about 20%
As well as Na Cl and K what other substances are reabsorbed in considerable amounts in the thick segtion of the loop of henle?
Calcium, Bicabonate ions and magnesium
Roughly how much of the Na CL and K in the glomerular filtrate is reabsorbed in the thick part of the ascending loop of Henle?
25%
What is the basolateral membrane allow chloride to be efficiently moved into the renal interstitial fluid?
Chlorine channels that capitalize on the electrochemical gradient created by the removal of Na and other ions
What are the two cell types the second half of the distal collecting tubule are made of?
principle and intercalated cells
What is the role of the principle cells of the second half of the DCT?
reabsorption of sodium and water from the lumen and secretion of potassium ions into the lumen
What is the role of the intercalated cells of the second half of DCT?
Reabsorbtion of potassium ions and the secretion of H+ ions
The medullary collecting site is the final site for the processing of urine how much of the filtered water and sodium is reabsorbed here?
less than 10%
What function of the medullary collecting duct allows it to help control the acid base balance of the body?
It is able to secrete H+ ions against a strong concentration gradient
What urea transport protein is activated by ADH?
UT-AI
How does the permeability of the medullary collecting ducts to urea help to concentrate the urine?
It allows urea to diffuse into the interstitium and increase it osmolarity
What osmotic concentration does tubular fluid arriving at the DCT have?
100mOsm/L
Urine reaching the minor calyx has a concentration of what?
around 1200mOsm/L
What part of the brain secretes ADH?
The posterior pituitary
What cells in the hypothalamus are the sensors that help regulate ADH release?
osmoreceptor cell
Where in the brain are the osmoreceptor cells?
in the anterior hypothalamus near the supraoptic nuclei
How do osmoreceptor cells respond when they cells react when they shrink in size what does this cause?
When osmorecepto cells shrink they increase action potentials, sending signals to the supraoptic nuclei which are relayed down the stalk pituitary gland to the posterior pituitary causing ADH release
The effects of ADH are opposed by what?
natriuretic petides (ANP and BNP)
Where is the thirst center of the brain? Where is the other are of the brain that promotes drinking?
the anterolateral wall of the third ventricle. The other drinking promoting area is located in the preoptic nucleus
What pump is stimulated by Aldosterone? Whaet other effect does Aldosterone have?
the sodium-potassium ATPase pump on the basolateral side of the cortical collecting duct, it also increases the permeability of the luminal membrane
What are the three ways Angiotensin II helps keep BP and extracellular fluid volume by increasing water and sodium re-absorbtion?
directly stimulates sodium potassium ATPase and sodium hydrogen exchange pumps. Constricts efferent arterioles and stimulates aldosterone secretion
What receptor does ADH bind to in the late distal tubule what effect does this have?
It binds to specific V2 receptors increasing the formation of cyclic AMP, activating protein kinases stimulating the movement of aquaporin 2 to the luminal side of the cell
What is sympathetic innervation’s effect on water and Na reabsorbtion?
it increases it
Where in the distal convoluted tubule membrane would you find aqua porins 3 and 4?
the basolateral side
What are the normal pH’s of arterial and venous blood respectively, why are they different?
7.4 and 7.35, venous is more acidic because it contains more CO2
What are the two main contributors to H+ production what do each contribute?
metabolism producing 40mmols and Gut uptake of 30mmols a day. 70mmols a day
What are the three primary systems that regulate pH?
the chemical acid base buffer system, the respiratory system and the kidneys
What are the two constituents of an acid base buffer system?
A weak acid and a salt of that acid that is a strong conjugate base
A larger value for K indicates what?
more dissociation and a stronger acid
What is the weak acid and strong conjugate base used for the pH homeostasis of the blood?
Carbonic acid and sodium bicarbonate
The pH of the blood must be kept within what boundary in order to sustain life?
6.8 and 8.0
What are the two components of the phosphate buffer system?
phosphoric acid H3PO4 and sodium phosphate NaH2PO4
Where is the phosphate buffer system most important, why is this?
the tubular fluid of the kidneys as it is greatly concentrated in the tubules and usually has a considerably lower pH than the extra cellular fluid bringing the pH of the buffer closer to the pH of the system
How can the respiratory center help modulate pH
It can stimulate increased alveolar ventilation reducing alveolar and blood CO2 this accelerates the recombination of H+ and HCO3-
Carbonic anhydrases in the kidney mainly what element? how many isoforms are there?
Zinc, there are at least 16 isoforms
What are the two most important isoforms of carbonic anhydrase in the kidney? where are they found?
CAII soluble in the cytoplasm and CAIV extracellular linked to the membrane by GPI anchor
What are the three main causes of metabolic acidosis?
Production of a large number of fixed acids or organic acids, inability of the kidneys to secrete hydrogen ions and severe bicarbonate loss
What three things cause a release of renin from juxtaglomerular cells?
Baroreceptors, sympathetic stimulation and stimulation from the macula densa in response to decreased glomerular filtration rate`
What are extraglomerular messengial cells/lecis cells?
connective tissue cells in the juxtaglomerular apparatus that hold to gether juxtaglomerular cells and the macula densa
angiotensin I is made up of how many amino acids?
10
ACE (angiotensin converting enzyme) is present more predominantly in the endothelium of the blood vessels of which organs?
The lungs and kidneys
Angiotensin II stimulated what protein in smooth muscle cells? What is the effect of this?
It activates the Gq protein raising intracellular calcium ultimately causing contraction
What are the three mechanisms by which Angiotensin II increase blood pressure?
stimulation of vasocontriction, stimulation of aldosterone thereby enhancing Na and water reabsorption and stimulation of thirst
Aldosterone activates whatreceptors? What effect does this have
the nuclear mineralcorticoid receptors in the principle cells upregulating and activating the basolateral Na/K pumps
What are the three main causes of extracellular oedema?
abnormal leakage of fluid, decreased plasma oncotic pressure or failure of lymphatics
Give an example of a carbonic anhydrase inhibitor, might it be used for?
acetazolamidethey are often used for tthe prophylaxis of mountain sickness and glaucoma
NO causes vasodilation through the activation of what?
guanylyl cyclase
What is the effect of the increased activity of nuclear factor kappa B (NF-kB) caused by a decrease in NO?
Leukocyte adhesion molecules are form along with chemokines and cytokines, promoting monocyte and vascular smooth muscle cell migration and the formation of macrophage foam cells. These effects all are characteristic of the first morphological changes in artherosclerosis
What are the main two factors in diabetes that decrease the amount of NO in the body?
Intracellular hyperglycemia induces cellular events that increase the production of reactive oxygen species inactivation NO. Insulin stimulates NO production so a resistance to insulin or lower levels reduces NO production
What are the largest and second largest causes of death in diabetics? name them in order
myocardial infartion and renal failure
What is postural hypotension?
A fall in systolic bp upon standing in excess of 20mmHg
What respiratory infections happen more frequently in diabetes?
staphylococcus aureus, mycobacterium tuberculosis, streptococcus pneumoniae, influenzavirus and gram negative organisms
What are the two types of dialysis?
haemodialysis and peritoneal dialysis
