gwen kidneys Flashcards
2 major roles of kidneys in pH balance
resorption of HCO3-, secretion of H+
by what enzyme H2CO3 converted to CO2 and H20?
Carbonic anhydrase
What area of the nephron does most bicarbinate reabsorption occur?
PCT
Why is HCO3- converted to H2CO3 then CO2 and H20 in the lumen to be reabsorbed as HCO3?
HCO3 is impermeable to the apical membrane, CO2 is lipid soluble
in the PCT, H+ or NH4+ is secreted via an active transport cotransporter with …
Na
Explain how glutamine is broken down to generate HCO3- and NH4
Breaks down to form NH3, combines with H+ and cotransported against Na into lumen, also produces a-ketylglutarate which breaks down to glucose then H20 and CO2, H2CO3 and HCO3- which is reabsorbed
Explain what happens to NH4 and NH3 throughout the nephron
becomes trapped in lumen at PCT as not lipid soluble, some excreted, some reabsorbed in Ascending limb by substituting K+ in Na/K+/2cl active transporter and is deposited in medullary interstitial fluid and secreted into collecting duct. NH3+ is lipid soluble and becomes highly concentrated in medullary interstitium so it diffuses back into the lumen where it can combine with H+ sectreted from the a-IC cells
what do a and b IC cells do?
a cells secrete H+, reabsorb HCO3- and reabsorb K+, b cells the opposite
a-IC cells secrete H+ via which 2 transporters
H+/K+ antiporter and H+ ATPase transporter
H+ is excreted as titratable acid throughout the nephron, most significant buffer is …. and also ….. These are not as important as ammonia because ….
H+ is excreted as titratable acid throughout the nephron, most significant buffer is phosphate (HPO4-/H2PO4) and also creatinine. These are not as important as ammonia because they are diet dependent whereas ammonia is in abundant supply
Approx … of H+ is excreted as ammonia and … as titratable acid
Approx 2/3 of H+ is excreted as ammonia and 1/3 as titratable acid
Effect of acid/alkilosis on K+ status
Hypokalemia with alkilosis, hyper visa versa. Extracellular H+ exchanges intracellular K+ and inhibition of tubular K+ secretion
Effect of Hyperkalaemia and hypokalaemia on acid/base status
Hyper inhibits NH4 production causing metabolic acidosis, Hypo increases NH4 production and H+secretion causing metabolic alkilosis
Effect of aldosterone on acid/base status and K+ balance and explain why
Stimulates secretion of H+ in IC cells and exaggarates K+ effect and causes K+ shift into cell (hypokalaemia) Exchanges K+ or H+ for Na
How does PTH affect acid/base balance?
Inhibits Na/H+ exchanger
what is a normal GFR?
90-120ml/min/1.73m2
How can GFR be clinically measured?
Inulin (fructose polymer) clearance measured as it is 100% excreted without being altered/secreted/reabsorbed. Or crudely, creatinin clearance
How can renal blood flow be measured
Para-Amino-Hippurric Acid (PAH), as it is entirely secreted into tubules
Explain autoregulation by the myogenic mechanism in the kidneys
Increased pressure on blood vessel walls open stretch activated cation channels, depolarisation leads to rise in intracellular Ca2+ causing SM contraction and increased vascular resistance
explain autoregulation by tubuloglomerular feedback
luminal component (eg; macula densa cells) sensing movement of Na and Cl, signal sent by extraglomerular mesangial cells, effector acting on JG cells to release vasoconstrictor (eg; AT 11, Adenosine)
Extrinsic influences affecting GFR and RBF
Sympathetic nerves innervating afferent/efferent arterioles via a-1 adrenoreceptors. Activated by stress, cold, fear, haemorrhage, pain,etc
Autoregulation is affective at maintaining RBF/GFR between…
90-180mmHg
Normal RBF is..
approx 25% of cardiac output (1.25l/min)
Potassium is … in the PCT and loop of henle and can be …
Potassium is only reabsorbed and unregulated in the loop of henle and can be either secreted by principle cells or reabsorbed by a-IC cells under hormonal regulaton in the late nephron (DCT and collecting duct)
Effect of catecholamines on K+ status
cause shift of K+ into cell causing hypokalaemia
effect of insulin on K+ status
cause K+ shift into cell with glucose causing hypokalaemia
effect of hyperosmolality on K+ status
causes K+ shift out of cells, hyperkalaemia
Effect of Leaking cells due to trauma/cell lysis/excessive exercise/infecton, etc on K+ status
Causes Hyperkalaemia
Cause of lack of ATP due to hypoxia/drugs/ischaemia, etc on K+ balance
Na/K+ ATPase activity reduced, causes hyperkalaemia as less reabsorption
Causes of Hypokalaemia
met Alkilosis, insulin, catacholamines, aldosterone
Causes of hyperkalaemia
Trauma/cell lysis/infection/exercise, etc, acidosis, hypoglycaemia, hyperosmolality, lack of ATP
Normal Plasma K+ levels
3.5-5-5mmol/l
In principal cells how does K+exchange?
Na/K+symporter and K+/Cl- cotransporters on apical membrane, 2K+/3Na ATPase on basolateral membrane, diffusion either way
how will the body normally respond to increased plasma K+
Directly act on adrenal cortex to release aldosterone, will act on apical membranes of principal cells to increase permeability to Na and K and basolateral membrane to increase Na/K+ ATPase activity. Will also directly act on principal cells to increase Na/KATPase activity… increased K+ secretion. Decreased plasma K+ will act on a-IC cells to do opposite. Changes can directly act on aldosterone release rather than relying on RAAS
Where is the main site for reabsorption in the kidneys and what are its histological features
PCT, tight junctons, large SA, microvilli with brush border for enzymes (CA, etc)
Basic principles of Na reabsorption in the nephron
Actively transported by 3Na/2KATPase on basolateral membrane setting up EC gradient, Passive movement down conc gradient.coupled with different substances along nephron. Approx 70% Na+ and H20 reabsorbed in PCT, 25% in loop, 5% distal nephron.
In the early PCT, how does Na transport
In the early PCT, around 30-60% Na is reabsorbed linked to indirect HC03- reabsorption and Na+/H+ exchange, around 10% is coupled to other solutes (Glucose,PO4, aa’s), and the rest is down concentration gradients para/intracellularly
How does Na transport across the late PCT?
mostly Cl-, preferential reabsorption of solutes and HCO3- in earlier PCT, Cl/HCO3- exchanger, Na/H+ exchanger, passive movement Na/Cl- across membrane
The DCT, there is an …… in the apical membrane, luminal fluid is… and the basolateral membrane contains a …. Also, ……
The DCT, there is an Na/Cl cotransporter in the apical membrane, luminal fluid is -ve promoting Cl- reabsorption and the basolateral membrane contains a Na/Ca antiporter. Also, PTH stimulates Ca2+ reabsorption.
thiazide diuretics, example, mechanism of action, and side effects
eg chlorothiazide,Inhibit Na/Cl cotransporter in DCT, hypercalcaemia, hypovolaemia, hypercalcaemia, hyperkalaemia, reduced uric acid clearance, increased in blood, don’t use in gout
Loop diuretic mechanism, example, side effects
Furosemide, competes with Cl binding site K+/Na+/2CL- cotransporter in thick ascending limb of loop of henle, causing increased Na conc and tonicity in distal tubule and collecting duct so less reabsorption of Na and water. SEs, hypokalaemia, hypomagnesia, ottotoxicity, hypovolaemia
K sparing diuretics side effects and mechanism and eg
Spironolactone, aldosterone receptor antagonist, SE gynacomastia
explain the mechanism of ADH
reduced plasma osmolarity, osmoreceptors in anterior hypothalamus stimulate, increase ADH production from post pituitary, increase H20 permeability in principle cells, increased H20 reabsorption, increased urine osmolarity, decreased urine volume
Explain how the loop of henle and vasa recta set up osmotic gradient by the countercurrent mechanism
the descending limb of the LOH is largely inpermeable to Na+, Cl- and urea, no active transport but very permeable to H20 as it contains many aquaporin proteins. The thick descending limb is visa versa containing no aquaporins and Na/K/2Cl actve transporter. Na/Cl out of lumen(reabsorbed) Urea in, Also, usual 2K/3NaATPase transporter. Also, basolateral membrane permeable to Cl- and cotransporter with K+ driving small cation reabsorption (NH4+, Na+,Mg2+,Ca2+) Tubular fluid becomes increasingly concentrated in descending limb and increasingly diluted in ascending limb, Meanwhile, vasa recta blood vessels maintain osmotic gradient in kidney. Blood flows down descending vasa recta limb, salts and urea diffuse from highly concentrated medullary interstitium into vasa recta meaning solute conc in medulla blood is very high, in ascending limb, osmolarity reverses, solutes flow back out nto interstitium which is less concentrated towards the cortex
solute concentration in kidney blood is ….
very high in the medulla, low towards cortex
explain how urea recycling further concentrates urine
Recirculates between CD and inner medullary interstitium adding to interstitial solute concentration, keeps high solute conc in medulla, ADH enhances this effect
what is the effect of angiotensin 2 and aldosterone on the kidneys
AT2 stimulates Na+ reabsorption in proximal tubule, aldosterone stimulates Na+reabsorption in late DT and CD
what effect does PTH have on the kidneys
inhibits P04/Na+ cotransport in PT, decreasing Tm for phosphate reabsorption, stimulates Ca2+ reabsorption in early DT
characteristics of Acute Renal Failure
Pre/intra/postrenal origin, majority of nephrons stop working, oliguria or anuria. Causing uremia, can be reversible by reestablishing blood flow but can progress to CRF. Polyuria usually follows removal of injury
Explain features of kidney disease
metabolic abnormalities, such as anemia(reduced erythropoetin but due to other issues in CRF such as B12/Fe deficiency,etc) acidemia, hyperkalemia (inability to secrete) osteopathology, hyperparathyroidism(reduced 1,25OHvitd3,hyperphosphataemia, reduced Ca absorption from LI) malnutrition, and hypertension, can occur.Uremia usually develops only after the creatinine clearance falls to less than 10mL/min but can be symptomatic at higher in ARF, hypertension, increased vascular volume, heart failure, uremia which can cause pericarditis, impaired immunity, skin disorders, GI, neurologic disturbance, sexual dysfunction
explain what occurs in CKD
Progressive loss of nephrons, kidney function reserve is high, poor GFR causing retention of nitrogenous waste products demonstrated by rising serum creatinine levels,
causes of prerenal kd
Reduced blood flow, eg; hypovolaemic shock, sudden hypotension (shock, MI, haemorrhage) leading to poor kidney perfusion
Causes of Intrarenal kidney disease
Poorly perfused glomeruli due to pre-renal, glomerular disease where capillaries are occluded (no blood flow to PCT and DCT), infection of tubules/interstitium (pyelonephritis), acute tubular necrosis
what is the most common cause of intrarenal KD and describe
Acute tubular necrosis, poorly perfused glomerulus causing death of epithelium, especially DCT/PCT, dead cells shed and block tubules. Clinically, oliguria/uremia and fluid overload, casts in urine, recovery phase, polyuria due to phagocytosis of necrotic cells, tubules open again but epithelia too underdeveloped to be fully functonal, replace electrolytes, etc
chronic renal failure is associated with a GFR of 15-29mmol/l/minute, end stage renal failure <15
15-29mmol/l/minute <15
Describe the juxtaglomerular Apparatus
specalisation of aa and dct of nephron acting as baroreceptor and chemoreceptor. macula densa cells of DCT, specialised, lining DCT, sense reductions in systemic bp, Na and GFR. Juxtoglomerular cells in aa, smooth muscle specialised cells, sense pressure and major secretors of renin. Extraglomerular mesangial cells near macula densa also involved but unclear how
characteristics of nephrotic syndrome
increase in permeability of glomerular BM and mesangium, loss of albumin and proteins, proteinuria, oedema, hyperlipidemia leading to increased atherosclerosis and lipidurea, Ig loss so infection, pleural odema, low thyroid hormones and ions (iron/zinc) due to increased binding proteins, increased thromboembolitic events due to loss of balance of coagulation/anticoagulation factors
4 descriptions of glomerular disease
diffuse, global, segmental, focal
characteristics of nephritic syndrome
haematuria, retention of waste products, uremia, activation of RAAS, hypertension, proliferation of endothelial cells and mesangial cells leading to occlusion of capillaries
define one nephritic syndrome
Nephritic, acute post-infectious glomerulonephritis, swelling and proliferation of endothelial cells and mesangial cells occluding lumen and allowing infiltration of RBCs, usually post-strep or staph or viral mumps, infiltration of neutrophils and monocytes, immune complexes accumulate post-infection(approx 1-4 weeks) and deposit BM and mesangium. Oliguria, mild hypertesion, cola urine (blood) more often children and prognosis good in children
define one nephrotic synd
minimal change, podocyte effacement, children, proteinuria, oedema, only dx under microscope, doesn’t progress to renal failure, treat with steroids
what drugs can cause pre-renal nephrotoxicity
reduced perfusion, loop diuretics, laxatives, ACEis and NSAIDS (alter renal haemodynamics)
What drugs can cause intra-renal nephrotoxicity
Glomerular, NSAIDS, penicillin, thiazides, accumulation of antigen-antibody complexes, inflammation, reduced GFR, water and Na retention, hypertension, proteinuria, nephrotic syndrome, tubular, NSAIDS, lithium, tubular, NSAIDs, Gent
What drugs can cause post-renal problems?
cytotoxic drugs, eg;methotrexate, uric acid, renal calculi
what other problems occur with PCKD
aneurisms of the brain, cysts in liver, usually asymptomatic, diverticular disease
what is the pathogenesis of PCKD?
The renal cysts originate from the epithelia of the nephrons and renal collecting system and are lined by a single layer of cells that have higher rates of cellular proliferation and are less differentiated than normal tubular cells (1). Abnormalities in gene expression, cell polarity, fluid secretion, apoptosis, and extracellular matrix have also been described in PKD, but the mechanism of cyst formation remains incompletely understood
