Urinary 1-6 Flashcards
What is the main function of the urinary system?
Control concentrations of key substances in extracellular fluid - homeostasis
What results from failure to control ECF volume?
Changes in blood pressure, tissue fluid and cell function
What reults from failure to control ECF osmolarity?
Cells shrink or swell
What are membranes permeable to?
Very permeable to water, selective to other types of molecules and electrolytes
What is osmolality?
Solute per kg of solvent - functionally the same as osmolarity.
What is osmolarity?
Number of osmoles of solute per litre - total concentration of substances which do not cross the membrane freely
Is potassium concentration higher intra cellularly or extra cellularly?
Intracellularly (sodium opposite)
What are the main anions extra cellularly?
Cl- and HCO3-
What controls the pH of extra cellular fluid?
HCO3
How do the kidneys control homeostasis?
Control volume
Control osmolarity
help to control pH
Excrete some waste products
What substances are 100% reabsorbed?
HCO3, glucose and amino acids
What % of cardiac output goes to the kidneys? (at rest)
25%
What is the functional unit of the kidney?
Nephron - filter unit connected to a long tube for reabsorption
In order, what are the regions of the nephron?
Prox. con. tubule (cortex) -> loop of henle (into and out of medulla) -> dist. con. tubule (cortex) -> collecting duct (passes through the medulla to pelvis)
What is the glomerulus?
Highly specialised filter.
What is filtered through the glomerulus?
Water, electrolytes and small molecules - NOT large proteins
What causes filtration through the glomerulus?
Pressure from the capillaries to the afferent arterioles.
Where is the major site of reabsorption in the kidneys?
Proximal convoluted tubule -
60-70% Na and water
80-90% K
90% HCO3
100% glucose and aa (usually)
reabsorbed materials leave by peritubular capillaries
What are the 2 membranes lining the tubular cell?
Luminal (luminal side)
Basolateral (ECF side)
POLARISED
allow transport across the epithelium
What controls tranport across the tubular cell membranes?
Na-K pump - couple other substances to energy from sodium movement. Water follows osmotically
What is the main function of the loop of henle?
Create a gradient oof increading osmolarity in the medulla by counter-current multiplication - produces concentrated urine as water is reabsorbed
How is the distal convoluted tubule different to the prox.?
Variable reabsorption of electrolytes and water.
What is the function of the dis. con. tubule?
Removes more Na and Cl and actively secretes H ions
What is diluresis?
large volumes of dilute urine
What controls sodium recovery?
Renin angiotensin system - controls ECF volume
What controls water recovery?
Anti diuretic hormone - controls permeability of DCT and collecting duct to water - this controls the ECF osmolarity
How might you gather an image of the renal tract?
Ultrasound
CT scan
MRI
KUB
Micturating Cystogram
Urethrogram
Retrograde Pyelogram
Antegrade Pyelogram
Arteriography
DMSA scan
Where do the kidneys lie?
Each side of the vertebral column betwen T12 and L3
Retroperitoneal
Where are the renal corpuscles found?
Cortex
Where are the tubules found?
Pass from the cortex through the medulla
What is the renal corpuscle?
Glomerulus and bowmans capsule
Produces ultrafiltrate plasma
What is another name for the collecting duct?
Ducts of Bellini
What is the renal papilla?
Location where the medullary pyramids empty urine into the minor calyx
What is at the vascular pol of the corpuscle?
Afferent and efferent arterioles and glomerulous
What dos the urinary pole consist of?
Bowman’s capsule
What are the filtration barriers of the nephron?
Capillary endothelium and visceral layer of Bowman’s capsule
What does the parietal layer of Bowman’s capsule do?
Makes a “funnel” to collect ultrafiltrate which drains into the prox. con. tubule at urinary pole
Describe the capillary endothelium in the nephron
Fenestrated with podocytes investing into it with slits between them.
Endothelium and podocytes share the basement membrane
What type of epithelium lines the prox.con.tubule?
Simply cuboidal with pronounced brush border
What is the longest part of the tubule?
Proximal
What are the 4 parts of the Loop of henle?
Pars recta
Thin descending limb
Thin ascending limb
Thick ascending limb
What is the epithelium of the thin limb of the loop of henle?
Simple squamous
No active transport
No brush border
What is the epithelium in the thick ascending limb of the loop of henle?
Simple cuboidal, no brush border
Active transport
Describe the distal convoluted tubule
Cortical
Makes contact with its parent glomerulus
Contains numerous mitochondria
No brush border adn larger lumen than PCT
What makes up the juxtaglomerular apparatus?
The macula densa of the distal convoluted tubule
Juxtaglomerular cells of afferent arteriole of glomerulus
Extraglomerular meangial cells (aka lacis cells)
What is the collecting duct?
Continuation of the DCT via collecting tube
Similar appearance to the thick limbs of loop of Henle but lumen is larger and tend to be more irregular rather than circular
What are the renal pyramids?
Progressively larger ducts formed by merging of collecting ducts
Emplty at renal papilla
What are the layers of the ureter?
2 layers of smooth muscle - only a third appears in the lower 1/3 of the ureter
Lined by transitional epithelium aka urinary epithelium or urothelium
It is a muscular tube
What are the histological layers of the bladder?
3 layers of muscle
Outer adventitia
Transitional epithelium
What is urothelium?
Stratified epithelium
“umbrella cells” on the surface layer which make the epithelium impermeable
What is the amniotic fluid made of?
Weak urine produced by the metanephric kidney from the end of the first trimester
What function do the mesonephric ducts have in an adult?
Male - reproductive function
Female - receed in development of the feotus - non-existant in adult life
What might cause abnormally low amniotic fluid volume?
Renal agenesis
What is another name for an ectopic kidney and how might this occur?
Pelvic kidney
Failure to ascend. Maintains fetal blood supply from iliac vessels or distal aorta
How might a horse shoe kidney occur?
Developing kidneys make contact in their ascen, fusion occurs. Most common in lower poles. Bridge of parenchyma called isthmus. When it reaches the inferior mesenteric artery it can rise no further.
What does a horseshoe kidney increase the risk of?
Hydronephrosis, kidney stones and renal cell carcinoma
Explain the embyological basis for the presence of accessory/supermumerary renal arteries.
Remain attached following ascent of kidneys and continues to supply kidney
What might cause duplication of the ureter?
Division of the ureteric bud
Why might a patient with ectopic ureteral orrifices suffer from incontinence?
No sphincter to control release of urine from ectopic ureteral orifice
Which nephrons have the longest loop of henle?
Lower nephrons (juxtamedullary), closer to the medulla penetrate further into the medulla with longer loop of henles.
What is the capillary arrangement of the nephrons?
Cortical - random
juxtamedullary - organised and structured. loops counter flow to loop of henle
How much blood is filtered throughn the glomeruli?
20% of the flow
Where are the glomeruli found?
Cortex
What are the 3 filter layers of the kidney?
Capillary endothelium
Basement membrane
Podocyte layer
Describe the basement membrane.
Acellular gelatinous layer of collagen/glycoproteins
Permeable to small proteins
Why do proteins not pass through the basement membrane?
Glycoproteins (- charge) repel protein movement
Describe the podocyte layer of the filtration barrier.
Pseudopodia interdigitate and form filtration slits
What causes proteinuria?
In many disease processes the negative charge on the filtration barrier is lost so that proteins are more readily filtered
What type of forces are involved in filtering plasma to form ultra filtrate?
Only physical forces:
- Hydrostatic forces in the capillary (regulated). Favours filtration
- Hydrostatic pressure in bowmans capsule. Oopposes filtration
- Osmotic pressure difference between the capillary and tubular lumen. Opposes filtration
What is tubular secretion and how does it work?
Transfer of materials from peritubular capillaries to renal tubular lumen.
Caused mainly by active transport.
What is usually secreted in tubular secretion?
Usually only a few substances which are in great excess or are natural poisons
What drives reabsorption in the PCT?
Sodium uptake - pumped across basolateral membrane by 3Na-2K-ATPase. Na moves across luminal membrane down conc gradient. This utilises a membrane transporter or channel. Water follows osmotically.
What sodium transporters are in the PCT?
Na-H antiporter
Na-Glucose symporter
What sodium tansporters are in the Loop of Henle?
Na-K-2Cl symporter
What sodium transporter is in the early DCT?
Na-Cl symporter
What sodium transporter is in the late DCT and CD?
Epithelial Na channels
How might a substance move against its concentration gradient?
Co-transport eg. SGLUT moves glucose against its concentration out of the PCT by co-transport with sodium via a symport.
What is the renal threshold for glucose?
200mg/100ml - plasma conc of a substance at which Tm is reached and the substance starts spilling into the urine
What is Tm for glucose in men and women?
Men = 375mg/min
Women = 300mg/min
How does organic cation secretion occur?
Passive carrier-mediated diffusion across the basolateral membrane down favourable concentration and electrical gradients created by the 3Na-2K-ATPase pump.
Secretion into the lumen occurs by a H+-OC+ exchanger that is driven by the H+ gradient created by the Na-H antiport (anions are the same)
Define renal plasma flow.
The amount of plasma that perfuses the kidney per unit time.
usually 605ml/min
What is haematocrit?
Percentage of a volume of blood sample occupied by cells
What is filtration fraction?
Proportion of a substance that is actually filtered - 605ml of plasma enters the glomerulus and only 20% is filtered. Therefore 125ml is filtered through into bowman’s space, 408ml passes into peritubular capillaries
(GFR/RPF)
What is glomerular filtration rate and how is it measured?
The quantity of filtrate formed each minute
Need to be able to measure a substance as it is filtered and use this as an indication of how well the kidney works. Chosen substance must not be altered in any way as it travels through the nephron - completely cleared from the plasma that is filtered, not reabsorbed or secreted
Define clearance
The volume of plasma from which a substance X can be completely cleared to the urine per unit time
eg clearance for urea in a normal kidney is about 665ml/min so the kidenys remove all the urea from 65ml of plasma per min.
(Urine concentration of substance x urine flow rate) / (plasma conc of the substance)
How is filtered fluid different to the remaining plasma fluid?
Filtrate in bowman’s capsule is identical to normal plasma, - proteins
Remaining plasma fluid contains the cells and proteins not filtered
How is filtration regulated?
autoregulation by myogenic responses. Decrease in pressure in the glomerular capillay (blood pressure) causes afferent resistance to increase by constriction of the afferent arteriole. Increase in pressure of glomerular capillary causes a decrease in afferent resistance by relaxation of the afferent arteriole wall
This maintains the GFR when blood pressure is within physiological limits (80-180 mmHg)
What cells recognise and respond to changes in the amount of NaCl reaching the distal tubule?
Macula densa cells NaK2Cl cotransporter. ATP can be released and converted to adenosine. This is recognised by A1 receptors on extraglomerular mesengial cells triggering a rise in intracellular calcium. This causes contraction of the smooth muscle in the walls of the arterioles - vasoconstriction and decrease of GFR. Prostaglandins are released for vasodilation.
What region of the loop of henle reabsorbs salts and water?
Salts in ascending limb
Water in descending
What causes secretion of K and reaborption of Na and water in the DCT?
Aldosterone
How can you change the plasma volume?
Must add or remove an isosmotic solution - not change osmolarity
Move osmoles, water follows
How much Na is reabsorbed in each region of the nephron?
PCT - 67%
Loop - 25%
DCT - 5%
Collecting duct - 2.5%
0.5% remains at the end approx
Where is no water reabsorbed?
Ascending limbs of loop of henle
DCT (vv little)
What is glomerulotubular balance?
Balance between glomerulous and PCT
2nd line of defence which blunts sodium excretion response to any GFR changes which occur despite autoregulation
Reabsorption of Na in the PCT is a % of filtered load not set amount (unless Tm exceeded)
Is Na reabsorption trans or paracellular?
Transcellular
Is chloride reabsorption trans or paracellular?
Both - trans i active, para is passive. Na ion reabsorption, Cl is implied
What are the 2 regions of the PCT?
S1 - Na reabsorption. No movement of Cl or urea - increase conc. Stabilises osmolarity.
S2 and 3 - Conc grad. of Cl and urea from S1
(Osmolarity of PCT is constant)
What transporters are in the membrane of S1/S2 and 3?
What are the tranasporters in the TAL?
Lmenal membrane - NakCC2 and ROMK
Basolateral - NAKATPase and Cl transporters
What is the most energy consuming area of teh nephron?
Thick ascending limb
Why is the ROMK on the lumenal membrane of the TAL necessary?
Maintain some K in the lumen to allow NaKCC2 transporter to work
Describe the structure of the descending limb of the loop of henle.
V few transporters. Lots of aquaporins
What is the ascending limb of the loop of henle known as?
Diluting segment - tubule fluid leaving the loop is hypo-osmotic compared to plasma
What is the importnat transporter in the DCT?
luminal - NCC transporter and calcium channel
basolateral - NCX, 3Na2K ATPase and chlorine channel - Ca removed, Na in (NCX) conc gradient established by NaKATPase.
What are the 2 types of cells in the DCT?
Principle - reabsorption of NA ions via ENaC
Type B intercalated cells - active reabsorption of Chloride. Intercalated cells (secrete H ions or HCO3 ions)
How do principle cells work?
Reabsorption of Na ions via ENA channel on apical membrane
3Na2KATPase in basolateral is the driving force
Active Na uon uptake through a channel and not a cotransporter means there is no accompanying anion
Produces a lumen with - charge providing a driving force for Cl ionuptake via paracellular route
This - charge in the lumen has an important role in K secretion into the lumen
Variable water uptake through ACP dependent on action of ADH
Where are baroreceptors?
Nerve endings in the carotd sinus and aortic arch
How are long term changes in blood pressure controled?
Complex interation of neurohumoral responses directed at controlling sodium balance and thus extracellular fluid volume. Plasma is part of this therefore volume of each is linked
- Renin-angiotensin-aldosterone system (RAAS)
- Sympathetic nervous system
- Antidiuretic hormone (ADH)
- Atrial natriuretic peptide (ANP)
Describe the RAAS.
Renin is released from granular cells of juxtaglomerular apparatus
3 factors
reduced NaCl delivery to distal tubule
reduced perfusion pressure in kidney causes the release of renin - baroreceptors in afferent arteriole
sympathetic stimulation to JGA increases release of renin
Where is renin stored?
Stored and released from granular cells of afferent arterioles
What causes the relerase of renin in the kidney?
Decreased circulating volume - decreased NaCl conc at macula densa causes sympathetic stimulation to JGA. Decreased renal perfusion pressure is sensed by renal baroreceptors.
Describe the formation of active angiotensin.
Angiotensinogen -> angiotensin I -> angiotensin II (active form)
converted by renin then ACE
What effect does angiotensin have on the kidney?
vasoconstriction
enhance action of Na-H exchanger in apical membrane
Stimulates Na reabsorption by causing the release of aldosterone from the adrenal cortex
Increase thirst sensation in hypothalamus and cause ADH release
How does aldosterone work in the kidney?
Stimulates Na and H2O reabsorption
Acts on principal cells of collecting duct
Activates apical Na channel and apical K channel
Also increases basolateral Na extrusion viaNaKATPase
(increases expression of ENaC and NaKATPase in preinciple cells of collecting duct)
What is the effect of ACE inhibitors and when might they be used?
Reduce hypertension - prevent reabsorption of Na and water and prevent vasoconstriction by preventing the formation of angiotensin II
ACE also converts bradykinin to peptide fragments (breaks it down) which usually acts as a vasodilator
What effect does the sympathetic nervous system have on the renal blood flow?
High stimulation reduces renal blood flow - decrease GFR - decrease Na excretion
Activates apical Na/H exchanger and basolateral Na/KATPase in PCT
Stimulates renin release from JGcells - increase Ang II / increaes aldosterone
What is the role of ADH?
Formation of concentrated urine by retaining water and control plasma osmolarity
Release stimulated by increase in plasma osmolarity or severe hypovolaemia
Stimulates Na reabsorption
Acts on thick ascending limb
What do natriuretic peptides do and where is it?
Promote Na excretion
Synthesized and stored in atrial myocytes
Released from atrial cells in response to stretch
Low pressure sensors in the atria
Reduced effective circulating volume inhibits the release of ANP- reduced filling of heart - less stretch
What are the actions of NP on the kidney?
Vasodilation of afferent arterioles
Increased blood flow -> increases GFR
Inhibits Na reabsorption along the nephron
Acts in opposite direction to the other neurohumoral regulators
What do prostaglandins do?
Act as vasodilators
enhance glomerular filtration and reduce Na reabsorption
May have important protective function
Act as a buffer to excessive vasoconstriction produced by SNS and RAAS
Important when levels of Ang II are high
What do NASIDs do and when might this be a problem?
Inhibit cyclo-oxygenase (COX) pathway involved in formation of prostaglandins. Therefore if NSAIDs are administrated when renal perfusion is compromised can further decrease GFR -> acute renal failure.
What is classified as hypertension?
Systolic BP >140
diastolic > 90
What causes hypertenison?
In around 95% of cases the cause is unkown - essential hypertension. May be genetic factors, environmental.
If cause can be defind it is known as secondary hypertension - must treat primary cause
What might cause secondary hypertension?
Renovascular disease
Chronic renal disease
Aldosteronism
Cushings syndrome
How can renovascular disease cause hypertension?
Occlusion of the renal artery (stenosis) causes a fall in perfusion pressure in that kidney
Decreased perfusion pressure leads to increased renin production
Activation of the RAAS
Vasoconstriction and Na retention at other kidney
How can renal parenchymal disase cause secondary hypertension?
Earlier stage may be a loss of vasodilator substances
Later, Na and water retention due to inadequate glomerular filtration - volume-dependent hypertension
How does Conn’s syndrom cause hypertension?
Aldosterone secreting adenoma therefore causing an increased reabsorption of Na and water
How can Cushing’s syndrome cause hypertension?
Excess secretion of glucocorticoid cortisol - at high concs acts on aldosterone receptors - Na and water retention
What is a phaeochromocytoma and how can it cause hypertension?
Tumour of the adrenal medulla that secretes catacholamines (adrenaline and noradrenaline)
What can result from hypertension that makes it “the silent killer”?
How is hypertension treated?
Secondary - treat primary cause
ACE inhibitors, Ang II receptor antagonists - diuretic and vasodilator effects
Thiazide diuretics - inhibit Na-Cl co-transport on apical membrane of cells in distal tubule - other diuretics will but not first line choice
Vasodilators - L-type Ca channel blockers - reduce Ca entry to vascular smooth muscle cells -> relaxation of vascular smooth muscle. Alpha 1 receptor blockers reduce sympathetic tone
Beta blockers of B1 receptors in the heart will reduce effects of sympathetic output - reduce heart rate and contractility- not used in first line treatment but would be if there are other indications such as previous MI
Non-pharmacological approaches can be taken.
How is a disorder of water balance manifested?
Changes in body fluid osmolarity
How is a disorder in Na balance manifested?
Changes in body fluid volume
On average, how much does a person urinate per day and how much water do they ingest? What does this mean for the osmolarity of urine?
1-1.5L/day urine
600-1000 mosm/day ingested
Excretion must match consumption therefore water lost is 1000mosmL in 1L
What senses changes in plasma osmolarity?
Osmoreceptors in the Organum Vasculoum of the Laminae Terminalis (OVLT) of the hypothalamus. (anterior and ventral to the 3rd ventricle). Fenestrated leaky endothelium exposed directly to the systemic circulation
What are the 2 efferent pathways that enable a changes in plasma osmolarity to be corrected?
thirst - brain alters drinking behaviour
ADH - Kidney excretes water
What is ADH?
Anti diuretic hormone. 9 AA long peptide.
When is osmolarity compromised?
When faced with circulatory collapse the kidneys continue to conserve water even though this will reduce osmolarity of body fluids
What are the effects of ADH on the body?
Vasoconstriction in glomerulus can decrease the effective filtering surface area
Increases Na, K and Cl reabsorption in ascending limb
Increases water absorption in the DCT and CD
Increased secretion of K into the CD
Increased urea reabsorption in the CD
How does ADH effect water reabsorption?
Inserts aquaporin 2 channels into the apical membrane making it permeable to water. The basolateral membrane already has aquaporin 3/4 in it so is already permeable. This allows water to move freely across the membrane. In the absence of ADH, aquaporin 2 is removed
Does an increase or decrease in osmolarity cause the release of ADH?
Increase - more water reabsorbed to create a more dilute ECF
Describe the osmolarity at the cortico-medullary border.
isosmotic
Describe the osmolarity of the medullary intersticium
Hyperosmotic - increasing gradient down to the papilla
How would the medullary intersticium be made isosmotic?
Block NaKCl transporters with a loop diuretic
How is a hyperosmotic interstitual fluid created at the tubular bend of the loop of henle if only passive transport is occuring?
Urea is also present. Na diffuses down its concentration gradient to increase the osmolarity further (200 mosm difference) - counter current multiplier by the loop of henle. Maintained by the vasa recta acting as a counter current exchanger
What is urea recycling?
Urea is moved out of the collecting duct (more so in the presence of ADH) into the surrounding interstitium. This increases the osmotic gradient and enables water to follow by diffusion. Urea is often taken up again by the ascending loop of henle and recycled back to the collecting duct to continue its journey towards excretion
How is the plasma pH controlled by the kidneys?
Filter and variably recover hydrogen carbonate and actively secrete hydrogen ions
What pH range in the blood is safe and normal?
7.38-7.42
<7.30 acidaemia
>7.42 alkalaemia
Why is alkalaemia dangerous?
Lowers free calcium - increases excitability of nerves - >7.45 - parasthesia and tetany
Why is acidaemia dangerous?
Increased plasma potassium
Affects many enzymes - reduced cardia and skeletal muscle contractility, reduced glycolysis in many tissues, reduced hepatic function
severe effects below 7.1, life threatening below 7
How much hydrogen carbonate is dissolved compared to CO2?
20 times as much hydrogen carbonate as dissolved CO2. This ratio determines the pH
How is the concentration of hydrogen carbonate controlled?
By the kidney. Disturbed by metabolic and renal disease
What is the difference between pH correction and compensation?
Correction - remove the original problem to fix it
Compensation - fix the problem by bringing the ratio back to normal using the other component. Eg. if CO2 is changed, use HCO3- to fix it
How is metabolic acidosis conpensated for?
Chnging ventilation:
- peripheral chemoreceptors
- increased ventilation lowers pCO2
- restores pH towards normal
What does acidosis mean?
Change in the buffer base - if conc. HCO3- changes, acid/alkalosis, CO2 changes - acidaemia…
Why can metabolic alkalosis only be partially compensated for by ventilation?
To keep more CO2 would mean reducing O2 intake which is not a viable option after a point. Therefore, generally, HCO3 conc is corrected and CO2 is compensated
How can HCO3 be created?
Metabolic activity of the kidneys produces large quantities of CO2 which can react with water to produce HCO3- to enter plasma and H+ to enter urine.
Can also make HCO3- from amino acids (particularly glutamine) producing NH4- to enter the urine
Where is HCO3 recovered in teh kidneys?
80-90% in prox con tubule
remainder in thick ascending imb of the loop of henle
How is HCO3- recovered in the loop of henle?
Coupled to the movement of Na+ out and H+ in. Reactes with H+ -> H2O + CO2 which moves into the tubular cell and reformed to HCO3- by reaction again with H2O
How is HCO3- created in the prox con tubule?
Glutamine broken down to produce alphaketoglutarate which makes HCO3- and ammonium (ammonia + hydrogen first, then reaction to ammonium). HCO3- is moved into ECF and NH4+ into lumen.
How is HCO3- created in the distal convoluted tubule?
By this poit all filteres HCO3= is usually recovered, Na gradient insufficient to drive H+ secretion so need active secretion of H+ into lumen. Here it is buffered by filtered phosphate and excreted ammonia. H+ is generated from metabolic CO2 and HCO3- is produced which enters the ECF
What is the minimum urine pH?
4.5 - no HCO3=, some H+ buffered by phosphate (titratable acid), rest attached to ammonia as ammonium
Total acid excretion 50-100mmol H+ per day. This keeps plasma [HCO3] normal
What are the cellular responses to acidosis?
Enhanced H+/Na+ exchange - full recovery of all filtered HCO3-
Enhanced ammonium productin in prox tube
Increased activity of H+ ATPase in distal tubule
Increased capacity to export HCO3- from tubular cells to ECF
What is the cellular response to metabolic acidosis?
Acids produced metabolically produce H+ and an ion. H+ reacts with HCO3- producing CO2 which is breathed out. So some HCO3- is replaced by anion from acid
What is the anion gap?
Indicates whether any HCO3- has been replaced with something other than Cl-
= ([Na+]+[K+]) - ([Cl-]+[HCO3-]) (unaccounted anions)
Normally 10-15mmol/l. Increased if anions from metabolic acid has replaced plasma HCO3-
Sometimes renal problems can reduce [HCO3-] without increaseing the anion gap as it is replaced with Cl-
If the anion gap does not change but the blood is acid, what is the cause?
Disease of the kidney - HCO3- replaced with Cl-
When might metabolic alkalosis occur and why might this be particularly difficult to correct?
Increase HCO3- after persistant comiting. Should be easy to correct as HCO3- infusions excreted extremely rapidly (rise in intra-cellular pH reduces H+ excretion and HCO3- recovery
However, if there is also volume depletion, capacity to lose HCO3- is less, because of high rates of recovery of Na+ favouring HCO3- recovery and H+ secretion as well
How do acid base disturbances effect potassium?
Metabolic acidosis associated with hyperkalaemia as K+ moves out of cells and more K+ is reabsorbed in the nephron. These conditions favour H+ excretion and HCO3- recovery and therefore metabolic alkalosis
Metabolic alkalosis is associated with hypokalaemia as K+ moves into cells and less K+ is reabsorbed. This causes HCO3- excretion to be favoured and can therefore cause metabolic acidosis
What % of body weight is water?
60%
How much of the body’s water is ICF/ECF?
2/3 ICF
1/3 ECF
Where is K+ measured to determine hypo/hyperkalaemia?
Intertitial fluid
How much potassium is in the ICF?
98% of the bodies ICF
How is the ICF & ECF [K+] maintained?
Na-K ATPase moves out of ECF into cells
K+ channels move K+ out of cells into ECF
What is the resting membrane potential?
-90mV (ICF more negative)
Why is the regulation of K+ so importatn?
The resting membrane potential of cells is dependent on the [K+] in ICF and ECF
(Increase ECF [K+] depolarizes the cell membrane potential, decrease causes hyperpolarization of the cell)
These changes have a profound effect on excitability of cardia and neuromuscular tissues and hence their function. (IC K+ important in cellular function)
How much K+ is lost in the GI tract?
5-10%
What is responsible for the long term control of K+?
Kidneys
Slow to act. Approx 6-12 hrs to excrete a load of potassium
What factors promote the uptake of K+ into cells?
Hormones
Alkalosis (decrease ECF H+)
Increased K+ in ECF
What hormones promote the uptake of K+ into cells?
Insulin - K+ in splanchnic blood stimulated insulin secretion by pancreas and in return insulin stimulates K+ uptake by muscle cells and the liver via increase in Na-K-ATPase
Aldosterone - K+ stimultaes aldosterone secretion…
Catecholamines - acts via beta 2 adrenoreceptors which in turn stimulate Na-K-ATPase which stimulates teh cell uptake of K+
What factors promote the K+ shift out of cells
Low WCF [K+]
Exercise
Cell lysis
Increase in ECF osmolarity
Acidosis - increase ECF [H+] shift of H+ into cells, reciprocal K+ shift out
How does excercise affect ICF and ECF K+?
How does cell lysis effect K+ ICF and ECF?
How does plasma tonicity affect K+ ICF and ECF?
How does acid base disturbance affect the ECF K+?
Where in the nephron is K+ reabsorbed and secreted?
What tubular factors affect K+ secretion by principal cells?
Aldosterone
K+ in EFC
Acid base status
What luminal factors affect K+ secretion by principal cells?
increase DCT flow rate, increaes K+ loss
Increase sodium delivery to distal tubule results in more K+ loss
What cells in the DCT and collecting duct absorb K+?
Intercalated cells via an active process. Mediated by H+ K+ ATPase in apical membrane
When may hyperkalcaemia be expected to occur?
Untreate diabetic ketoacidosis
Treatment with ACEI
Addisons disease
Kidney failure
Cushings syndrom
Poor perfusion of the kidney due to renal artery stenosis
What effects does changes in ECF {K+] have?
Alter cell membrane resting potential
Alter neuro muscular excitability
Result in arrhthmias, cardiac arrest, muscle paralysis
What might hyperkalaemia be due to?
Problems of external balance - increased intake (only causes problems in the presence of renal dysfunction unless inappropriate doses given IV),
Inadequate renal excretion - acute/chronic kidney injury or reduced aldosterone with normally functioning kidneys
Internal shifts - diabetic ketoacidosis, other metabolic acidosis, cell lysis (muscle cruch injury)
When might there be reduced aldosterone?
Adrenal insufficiency
Drugs which reduce/block aldosterone action
K sparing diuretics
ACEI
What effect does hyperkalaemia have on cardia tissue?
Depolarizes it -> more Na channels remain in inactive form, heart less excitable
What are the clinical features of hyperkalaemia?
Heart - altered excitability -> arrhythmias, heart block
GI - neuromuscular dysfunction -> paralytic ileus
Acidosis
What ECG changes may be brought about by hyperkalaemia?
Ventricular fibrillation
Atrial standstill, intraventicular block
Prolonged PR interval, depressed ST segment, high T wave
What is the emergency treatment for hyperkalcaemia?
Reduce K+ effect on heart - IV calcium gluconate
Shift K+ into ICF - glucose +insulin IV/nebulised beta agonists (salbutamol)
Remove excess K+ - dialysis
What are the long term treatments of hyperkalcaemia?
Treat cause
Reduce intake
Measures to remove excess K+ (dialysis, oral K+ binding resins to bind K+ in gut)
What might hypokalaemia be due to?
Problems of external balance - excessive loss (GI/kidney)
Problems of internal balance - shifts of K into ICF eg metabolic alkalosis
What effect does hypokalaemia have on the resting membrane potential of cardiac cells?
Hyoerpolarises -> more fast Na channels available in active form -> heart more excitable
What are the clinical features of hypokalaemia?
Heart - altered excitability -> arrhythmias
GI - neuromuscular dysfunction -> paralytic ileus
Skeletal muscle - neuromuscular dysfunction -> muscle weakness
Renal - dysfunction of collecting duct cells -> unresponsive to ADH -> nephrogenic diabetes insipidus
What are the ECG changes associated with hypokalaemia?
Low T wave
High U wave
Low ST segment
What is the treatment of hypokalaemia?
Treat cause
Potassium replacement - IV/oral
If due to increased mineralocorticoid activity, potassium sparing diuretics which block action of aldosterone on principle cells
