PBL Topic 4 Case 7 Flashcards
Identify 7 functions of the kidneys
- Excretion of waste products
- Water + Electrolyte balance
- Regulation of body fluid osmolality
- Regulation of arterial pressure
- Regulation of acid-base balance
- Secretion, metabolism and excretion of hormones
- Gluconeogenesis
Identify four waste products that are excreted by the kidneys
- Urea (from amino acid metabolism)
- Creatinine (from muscle creatine)
- Uric acid (nucleic acids)
- Bilirubin (from haemoglobin breakdown)
Why must water and electrolyte excretion precisely match intake?
- If intake exceeds excretion, the amount of substance in the body will increase
- If intake is less than excretion, the amount of substance in the body will decrease
Briefly identify 2 ways that the kidneys regulate arterial pressure
- By excreting variable amounts of sodium and water
- By secreting vasoactive factors, e.g. renin, that lead to formation of vasoactive products, e.g. angiotensin II
Briefly describe how the kidneys regulate erythrocyte production
- Fibroblasts secrete erythropoietin
- Especially during hypoxia
- Which stimulates the production of red blood cells
Briefly outline how the kidneys regulate vitamin D.
- Hydroxylate vitamin D to calcitriol
Identify 3 roles of vitamin D
- Calcium deposition in bone
- Calcium reabsorption in GI tract
- Calcium and phosphate regulation
Outline the kidneys role in gluconeogenesis
- Synthesise glucose from amino acids
Outline the physiological anatomy of the kidneys
- Surrounded by fibrous capsule
- Contains outer cortex and inner medulla
- Medulla is divided into pyramids by cortex columns
- Base of each pyramid terminates in the papilla
- Papilla projects into renal pelvis
- Urine from papilla is collected by minor calyces which is collected by major calyces
Outline the arterial supply of the kidneys
- Renal artery enters hilum and gives off lobar arteries
- Which give off interlobar arteries
- Which give off arcuate arteries
- Which give off interlobular arteries
- Which give off afferent arterioles
- Which lead to glomerular capillaries
- Distal end of glomerular capillaries forms efferent arterioles
- Which lead to peritubular capillaries
How does hydrostatic pressure differ in the glomerular and peritubular capillaries
- High hydrostatic pressure in glomerular capillaries, causing rapid filtration
- Low hydrostatic pressure in peritubular capillaries, causing fluid reabsorption
Outline the venous drainage of the kidneys
- Peritubular capillaries drain into interlobular veins
- Which drain into arcuate veins
- Which drain into interlobar veins
- Which drain into the renal vein which leaves the kidney through the hilum
Identify the two main parts of a nephron
- Glomerulus, through which large amounts of fluid are filtered from the blood
- Tubule, where the filtered fluid is converted into urine
How many nephrons are there in each kidney? Can the kidney regenerate new nephrons?
- 1 million nephrons
- No
Describe the hydrostatic pressure in the glomerular capillaries
- High (60 mm Hg)
What happens to fluid that is filtered from the glomerular capillaries?
- Flows into Bowman’s capsule which encases the glomerular capillaries
- Fluid then flows into PCT
Is the PCT in the cortex or medulla of the kidney?
- Cortex
What happens to fluid after it passes through the proximal tubule?
- Flows into the loop of Henle
- Which is formed from a descending and ascending loop
How does thickness change in the loop of Henle?
- Walls of descending limb and lower ascending limb are thin
- The ascending limb thickens as it enters the cortex
Is the loop of Henle located in the cortex or medulla of the kidney?
- Both
- Dips from cortex to medulla
- Ascending limb thickens as it enters the cortex
What happens to fluid after it passes through the ascending limb of the loop of Henle?
- Enters the DCT
Does the DCT lie in the cortex or medulla?
- Cortex
What happens to fluid after it passes through the DCT?
- Flows into connecting tubules
- Which flows into cortical collecting tubules
- Which leads to cortical collecting duct
- Which runs downward and becomes the medullary collecting duct
What happens to fluid after it passes through the collecting ducts?
- Passes into the renal pelvis through the tips of the renal papillae
Identify two types of nephrons and how they differ from one another in their structure
- Cortical nephrons, located in outer cortex, short loop of Henle
- Juxtamedullary nephrons, located in medulla, long loop of Henle
How do the two types of nephrons differ from one another in their vascular supply
- Cortical nephrons, surrounded by peritubular capillaries
- Juxtamedullary nephrons, surrounded by vasa recta that loop downward like the loop of Henle
Express urinary excretion rate mathematically
- Filtration rate - reabsorption rate + secretion rate
Identify a substance that is not filtered from the glomerular capillaries into Bowman’s capsule
- Protein
- Since the glomerular capillaries are impermeable to protein
Identify 4 substances that are reabsorbed in the tubules
- Water
- Electrolytes
- Amino acids
- Glucose
Why are calcium and fatty acids sometimes not freely filtered in the glomerulus?
- They may be bound to plasma proteins
Identify two factors that determine glomerular filtration rate
- Balance of hydrostatic and colloid osmotic forces
- Capillary filtration coefficient (Kf)
Identify two factors that determine the capillary filtration coefficient
- Permeability
- Surface area
Identify two reasons that the glomerular capillaries have a much higher rate of filtration that most other capillaries
- High hydrostatic pressure
- High Kf
What is the average GFR in ml/min
- 125 ml/min
What is filtration fraction and what is its value in the kidneys?
- The fraction of plasma flow that is filtered
- 20% (of plasma flowing through kidney is filtered through glomerular capillaries)
How is filtration fraction calculated mathematically
- GFR / Renal Plasma Flow
Identify the structure of the glomerular capillary membrane and the features of each which increase filtration
- Endothelium (with fenestrations)
- Basement membrane (with proteoglycan fibrillae)
- Epithelial cells (podocytes) (with slit pores)
What is the importance of the negative charges in the endothelium, basement membrane and epithelial cells
- Hinders passage of plasma proteins
Identify two forces that promote filtration
- Hydrostatic pressure in glomerular capillaries, (glomerular hydrostatic pressure)
- Colloid osmotic pressure of the proteins in Bowman’s capsule
Identify two forces that opposes filtration
- Hydrostatic pressure in Bowman’s capsule outside the capillaries
- Colloid osmotic pressure of the glomerular capillary plasma proteins
Why does the plasma protein concentration increase from the afferent to efferent arterioles?
- 20% of fluid is filtered into Bowman’s capsule
- Concentrating the glomerular plasma proteins that are not filtered
Identify two factors that influence glomerular capillary colloid osmotic pressure
- Arterial plasma colloid osmotic pressure
- Filtration fraction
Identify two factors that would increase filtration fraction
- Increasing GFR
- Reducing renal plasma flow
Identify three factors that affect glomerular hydrostatic pressure
- Arterial pressure
- Afferent arteriolar resistance
- Efferent arteriolar resistance
Outline the biphasic effect of efferent arteriolar resistance on GFR
- Moderate constriction of efferent arterioles increase resistance to outflow
- Which raises GFR
- Severe constriction increases colloid pressure
- Which decreases GFR
How is renal blood flow determined?
- Difference between renal artery and vein hydrostatic pressure
- Divided by renal vascular resistance
Where does most renal vascular resistance take place? How is this resistance controlled?
- Interlobular arteries
- Afferent arterioles
- Efferent arterioles
- Sympathetic nervous system
What is autoregulation?
- Mechanism by which renal blood flow and GFR remains relatively constant
Outline the renal blood flow to the medulla
- Blood flow to medulla accounts for 1% of blood flow
- Supplied by vasa recta from peritubular capillary system
Identify hormones that constrict arterioles and reduces GFR
- Noradrenaline
- Adrenaline
- Endothelin
- Angiotensin II
Identify an autacoid that decreases vascular resistance and increases GFR
- Nitric oxide
Identify autacoids and hormones that cause vasodilation and increases GFR
- Prostaglandins E2 and I2
- Bradykinin
What is glomerulotubular balance?
- Adaptive mechanisms in renal tubules
- That allow them to increase their reabsorption rate when GFR rises
Where are macula densa cells located and what is their role?
- DCT
- Sense changes in volume delivery to the distal tubule
Outline the effect of a reduced GFR on macula densa cells
- Reduced GFR slows the flow rate in the loop of Henle
- Causing increased reabsorption of NaCl in the ascending loop of Henle
- Reducing concentration of NaCl at macula densa cells
- Decreasing resistance to blood flow (increasing GFR)
- And increasing release of renin from juxtaglomerular cells (increasing GFR)
Identify the role of renin in raising GFR
- Increases formation of angiotensin I
- Which is converted to angiotensin II
- Which constricts efferent arterioles
- Increasing hydrostatic pressure and returning GFR to normal
Outline the purpose myogenic mechanism of renal blood flow
- Ability of blood vessels to resist stretching during increased arterial pressure
- To maintain a constant renal blood flow and GFR
Outline the role of calcium ions in the myogenic mechanism of renal blood flow
- Stretch of vascular walls increases movement of calcium ions into cells from extracellular fluid
- Which causes them to contract
- Which prevents over-distension of the vessel
- And increases vascular resistance
- Which helps prevent excessive increases in renal blood flow and GFR
Why does a high protein intake increase renal blood flow / GFR?
- Increased release of amino acids into blood
- Which are reabsorbed in proximal tubule
- Which causes reabsorption of sodium in proximal tubule
- Decreased sodium to macula densa
- Which causes a decrease in resistance of the afferent arterioles
- Which raises renal blood flow and GFR
Why does a high glucose intake increase renal blood flow / GFR?
- Glucose causes reabsorption of sodium
- Reduced delivery of sodium to macula densa
- Activating tubuloglomerular feedback-mediate dilation of afferent arterioles
- With increase in renal blood flow and GFR
Describe the tubular absorption of:
[A] Glucose and amino acids
[B] Ions in plasma
[C] Waste products
- [A] Completely reabsorbed
- [B] Variable absorption
- [C] Poorly reabsorbed
Identify two ways in which water and solutes can be reabsorbed
- Transcellular route through the cell membrane
- Paracellular route, through the tight junctions
What is ultra-filtration?
- Reabsorption from interstitial fluid into peritubular capillaries
- Passive process
- Driven by hydrostatic and colloid osmotic pressure gradients
What is primary active transport?
- Movement of solutes against an electrochemical gradient
- Requiring energy from hydrolysis of ATP by ATPase
Give an example of the primary activate transport ysstem
- Reabsorption of sodium ions
- Hydrolysis of ATP moves sodium out of cell
- At same time potassium is transported to inside of cell
Identify two provisions for moving large amounts of sodium into the cell
- Brush border increases surface area
- Sodium carrier proteins for facilitated diffusion
Identify two mechanisms of secondary active reabsorption
- Co transport, interaction with carrier protein and transport together (e.g. sodium and glucose)
- Counter-transport, diffusion of sodium into cell liberates energy to secrete hydrogen ions into tubule
Identify a substance that is reabsorbed by pinocytosis. Outline the process of pinocytosis
- Protein
- Attaches to brush border of luminal membrane
- This portion invaginates to interior of cell and pinched off to form a vesicle
- Once in cell, protein is digested into amino acids
- Which are reabsorbed through basolateral membrane
What is meant by transport maximum? Identify an example of this
- Limit to rate at which solute can be actively transported
- Due to saturation of carrier proteins when amount of solute exceeds capacity
- Glucose transport system in uncontrolled diabetes
What is gradient time transport
- Limit to rate at which solute can be passively reabsorbed
- Increased by high diffusion gradient, high permeability increased time that the substance remains in the tubule
How does reabsorption of water occur and how does it change throughout the nephron
- Active transport of solutes decreases their concentration
- Which increases osmosis of water
- Reduces throughout nephron as tight junctions become tighter
What is solvent drag?
- As water is reabsorbed
- It carries solvents with it
Outline the process of chloride reabsorption
- Sodium reabsorption causes transport of chloride ions due to electrical potentials
- Water reabsorption increases chloride ion concentration which creates a concentration gradient
- Chloride ions can be co-transported with sodium ions
Identify three features of the PCT that allow for reabsorption
- Highly metabolic, lots of mitochondria for active transport
- Apical brush border
- Carrier proteins
Explain how bicarbonate ions are removed from the PCT
- Secretion of H+ (by counter transport)
- Which combines with bicarbonate ions
- To form carbonic acid
- Which dissociates into water and carbon dioxide
Outline substances that are secreted by the PCT
- Bile salts
- Oxalate
- Urate
- Catecholamines
- Harmful drugs and toxins
- PAH
What is the function of the descending part of the loop of Henle?
- Simple diffusion of water
- Ascending part is impermeable to water
Which section of the ascending part of the loop of Henle is adapted for reabsorption?
- Thick segment
- ATPase
- Due to high metabolic activity and surface area
Which part of the loop of Henle reabsorbs calcium, bicarbonate and magensium?
- Thick ascending part
Outline the process of sodium reabsorption in the thick ascending part of the loop of Henle
- ATPase provides energy
- To move sodium through the Na-K-Cl co-transporter across the luminal membrane
- This releases energy which moves chloride and potassium ions into the cell against a concentration gradient
- In a ratio of (1Na:1K:2Cl)
Why is the distal tubule referred to as the diluting segment?
- Reabsorption of ions via the Na-K-Cl transporter
- Impermeable to water and urea
Identify the two cell types in the late distal tubule and cortical collecting tubule
- Principal cells: Sodium and water reabsorption, potassium secretion
- Intercalated cells: Potassium reabsorption and hydrogen secretion
Describe the process of potassium secretion by principal cells
- Potassium enters cell through sodium potassium ATPase pump
- Diffuses across luminal membrane into tubular fluid down concentration gradient
Describe the process of hydrogen ion secretion by intercalated cells
- Carbonic anhydrase catalyses reaction of H2O and CO2
- To form carbonic acid
- Which dissociated into hydrogen and bicarbonate ions
- Hydrogen ions secreted into lumen by hydrogen-ATPase transport mechanism
Outline the special characteristics of the medullary collecting duct
- Its permeability is controlled by ADH
- It is permeable to urea
- Secretes protons against a large concentration gradient
What is glomerulotubular balance?
- Rate of reabsorption changes in response to tubular inflow
- To help prevent overloading of the distal tubular segments
How is reabsorption calculated?
- Kf x Net Reabsorptive Force
Identify the four osmotic forces that represent the net reabsorptive force
- Hydrostatic pressure in peritubular capillaires
- Hydrostatic pressure in renal interstitium
- Colloid pressure in peritubular capillary
- Colloid pressure in renal interstitium
Identify factors that increase the peritubular capillary hydrostatic pressure and the effect on reabsorption
- Increased arterial pressure
- Increase in resistance of afferent and efferent arterioles
- Both of which decrease reabsorption
Identify factors that influence the peritubular capillary colloid pressure
- Increase in plasma protein concentration
- Increase in filtration fraction
- Both of which increase reabsorption
What is meant by pressure natriuresis and diuresis?
- Increase in arterial pressure
- Causes marked increase in urinary excretion of sodium and water
Where is aldosterone secreted from?
- Zone glomerulosa
- Of adrenal cortex
What is the primary site of aldosterone action?
- Principal cells
- Cortical collecting tubule
What is the action of aldosterone?
- Increased sodium reabsorption
- Increased potassium secretion
- By stimulating sodium-potassium ATPase pump on basolateral side of cortical collecting tubule
Outline two clinical conditions in which aldosterone is affected?
- Addison’s disease: absence of aldosterone so marked natriuresis and accumulation of potassium
- Conn’s syndrome: excess aldosterone so sodium retention and potassium depletion
When is angiotensin II secreted?
- Low blood pressure or extracellular fluid volume
What is the general action of angiotensin II?
- Helps to increase blood pressure
- By increasing sodium and water reabsorption from renal tubules
Identify three effects of angiotensin II secretion
- Stimulates aldosterone secretion,
- Constricting efferent arterioles
- Stimulates sodium-potassium ATPase pump
What is the general action of ADH?
- Increases water permeability of distal tubule, collecting tubule and collecting duct epithelia
- Causing reabsorption of water
- To conserve water e.g. dehydration
Outline the cellular action of ADH
- Binds to V2 receptors in distal tubules, collecting tubules and duct
- Which increases cAMP formation and PKA
- Which stimulates movement of aquaporin-2 to luminal side of cell membrane
- Which fuse with the cell membrane by exocytosis
- To form water channels that permit rapid diffusion of water through the cells
When is atrial natriuretic peptide released and what is its action?
- Distension of atria
- Reduces reabsorption of sodium and water in collecting ducts
- Which increases urinary excretion
- Helping to return blood volume back to normal
Outline the principal action of PTH in the kidneys
- Increases calcium reabsorption in DCT
- Decreases phosphate and magnesium reabsorption in loop of Henle
Outline three effects of the sympathetic nervous system on reabsorption
- Constricts renal arterioles, reducing GFR
- Increased reabsorption in proximal tubule
- Increased renin release and angiotensin II formation
Outline the renal mechanism for excreting a dilute urine
- Dilution in ascending limb of loop of Henle
- Due to reabsorption of ions (impermeable to water)
- Absence of ADH so reduces reabsorption in collecting ducts
Outline the two basic requirements for forming a concentrated urine
- High level of ADH in collecting ducts (to increase permeability for water absorption)
- High osmolarity of renal medullary interstitial fluid (providing an osmotic gradient)
What is the importance of urea recycling?
- Absorption of urea into medullary interstitium from collecting ducts
- Increases osmolarity in renal medulla
- To increase reabsorption of water to produce concentrated urine
Outline the countercurrent mechanism
- Blood enters and leaves medulla through vasa recta
- It is concentrated as it descends in due to solute entry and loss of water
- It is diluted as it ascends due to solute loss and gain of water
- Resulting in little net dilution
- Preventing loss of hyperosmolarity in medullary interstitial fluid
Outline two mechanisms for controlling extracellular fluid osmolarity and sodium concentration
- Osmoreceptor ADH system
- Thirst mechanism
Where are osmoreceptor cells located and how does their activation cause increase ADH release?
- Anterior hypothalamus near supraoptic nuclei
- They shrink when osmolarity ([Na]) increase above normal
- Which causes them to fire signal down pituitary stalk to posterior pituitary gland
- Causing secretion of granular ADH into bloodstream
How is ADH synthesised?
- By magnocellular neurons in the supraoptic and paraventricular nuclei
Where is the AV3V region located?
- Anteroventral region of third ventricle
Identify the structures of the AV3V region
- Subfornical organ superiorly
- Organum vasculosum inferiorly
- Median preoptic nuclei (which connects to both organs as well as the supraoptic nuclei)
Why can the subfornical organ and organum vasculosum respond to changes in osmolarity?
- They lack the typical blood brain barrier
- Allowing for diffusion of ions from the blood into the brain tissue
Outline the two cardiovascular reflexes involving in stimulating ADH release
- Arterial baroreceptor reflexes
- Cardiopulmonary reflexes
- Which originate in high pressure regions (aortic arch and carotid sinus)
- Afferent stimuli are carried by CN9 and CN10 to tractus solitarius
- Which relays signals to hypothalamic nuclei controlling ADH synthesis and secretion
- E.g. increased ADH secretion in haemorrhage
Outline 3 additional factors that increase ADH secretion
- Nausea
- Hypoxia
- Drugs: morphine, nicotine, cyclophosphoamide
Outline three drugs that decrease ADH secretion
- Alcohol
- Clonidine
- Haloperidol
Outline 3 stimuli for thirst
- Extracellular fluid osmolarity
- Angiotensin II
- Dryness of mouth
Identify the three determinants of potassium excretion
- Rate of potassium filtration
- Rate of potassium reabsorption
- Rate of potassium secretion
Where is the majority of potassium reabsorbed?
- PCT
In which part of the loop of Henle does most potassium reabsorption take place?
- Thick ascending part
Identify the three main factors that control potassium secretion by the principal cells
- Na+-K+ ATPase activity
- Electrochemical gradient fro potassium secretion
- Permeability of luminal membrane for potassium
Which cells reabsorb potassium in severe potassium depletion?
- Intercalated cells
What is hypocalcaemic tetany?
- Increased excitability of nerve and muscle cells
- As a result of hypocalcaemia
- Characterised by spastic skeletal muscle contractions
How does plasma [H+] affect calcium binding to plasma proteins
- Acidosis: Less calcium is bound to plasma proteins (possible role of denaturation?)
- Alkalosis: More calcium bound to plasma proteins
How does calcium excretion differ to other ions?
- Excretion also occurs in faeces
Outline the role of the parathyroid glands when extracellular [Ca2+] falls
- Promote secretion of PTH
- Which increases calcium resorption from bone
- And stimulates intestinal resorption of calcium via Vitamin D
- Elevating extracellular [Ca2+]
Why is only 50% of plasma calcium filtered at the glomerulus?
- The other 50% is bound to plasma proteins
- Or forms complex anions with phosphate
Identify five factors that increase calcium excretion
- Decreased PTH
- Increased extracellular fluid volume
- Increased blood pressure
- Decrease plasma phosphate
- Metabolic acidosis
Identify two ways in which PTH regulates plasma phosphate concentration
- High PTH increases bone resorption, releasing phosphate ions into extracellular fluid
- High PTH decreases transport maximum of phosphate, decreasing tubular absorption and increasing excretion
What is the primary site of magnesium reabsorption?
- Loop of Henle
Identify 3 factors that cause increased magnesium excretion
- Increased extracellular magnesium concentration
- Extracellular volume expansion
- Increased extracellular fluid calcium concentration
What are nonvolatile acids?
- Acids produced from protein metabolism
- That cannot be excreted by the lungs
- So must be removed via the kidneys
Outline the process of H+ secretion in the PCT
- Secondary active secretion
- Reabsorption of Na+ into cell
- Provides energy for H+ secretion against a concentration gradient
Outline the process of HCO3- reabsoprtion in the PCT
- CO2 diffuses into tubular cells
- Combines with water to form H2CO3 (catalysed by CA)
- Which dissociates into HCO3- and H+
- H+ secretion against a concentration gradient via secondary active secretion with sodium
- HCO3- crosses basolateral membrane into renal interstitium
Outline the process of H+ secretion in the DCT
- Primary active transport
- H+ is transported through ATPase protein in intercalated cells
Outline the phosphate buffer system
- Depletion of HCO3-
- So H+ combines with HPo42- to form H2PO4-
- Which is excreted as NaH2PO4 in the urine
Outline the ammonia buffer system
- Glutamine enters epithelial cells
- Metabolised to NH4+ and HCO3-
- NH4+ is secreted into lumen by a counter transport mechanism with sodium
- HCO3- is transported across basolateral membrane with sodium
How does the ammonia buffer system differ in the collecting tubules?
- Collecting ducts are permeable to NH3
- Which diffuses into tubular lumen
- And combines with secreted H+ to form NH4+
- Which is eliminated in urine
When does acidosis occur?
- When ratio of HCO3- to CO2 decreases
- Decreasing pH
What is the difference between metabolic and respiratory acidosis?
- Metabolic: Decrease in HCO3-
- Respiratory: Increase in PCO2
What is the affect of acidosis on the renal tubular fluids?
- Decreased ratio of HCO3- to H+
- Resulting in an excess of H+ in the tubule
- Which combines with urinary buffers
- HCO3- is reabsorbed
When does alkalosis occur?
- When ratio of HCO3- to CO2 increases
- Increasing pH
What is the difference between metabolic and respiratory alkalosis?
- Metabolic: Increase in HCO3
- Respiratory: Decrease in PCO2
Outline the renal response to respiratory alkalosis
- Decrease in PCO2 leads to a decrease in H+ secreted by renal tubules
- Not enough H+ to react with HCO3- that is filtered
- HCO3- that cannot react with H+ is excreted in urine
Outline the mechanism of action of loop diuretics
- Act on thick ascending limb
- Combine with Cl- binding site on Na+/K+/2Cl-
- Inhibit Na+ reabsorption
- Also have vasodilatory effect
Identify two loop diuretics
- Furosemide
- Bumetanide
Loop diuretics increase excretion of [A] and [B] and decrease excretion of [C]
- [A] Ca2+
- [B] Mg2+
- [C] Uric acid
Identify unwanted effects of loop diuretics
- Hypovolaemia and hypotension
- Hypokalaemia and metabolic acidosis
- Hypomagnesaemia and hyperuricaemia (gout)
- Hearing loss
- Allergic reactions
Outline the mechanism of action of thiazide diuretics
- Act on DCT
- Bind to Cl- site on Na+/Cl- co transport system
- Inhibiting its action
- Resulting in natriuresis with loss of sodium and chloride into urine
- Vasodilatory action (useful in hypertension)
Why are thiazide diuretics advantageous over loop diuretics in older patients?
- They reduce Ca2+ excretion
- So reduced bone resorption in older patients at risk of osteoporosis
Identify unwanted effects of thiazide diuretics
- Increased urinary frequency
- Erectile dysfunction
- Impaired glucose tolerance (activation of KATP channels)
- Hyponatraemia
- Hypokalaemia (adverse drug reaction which precipitates encephalopathy)
- Allergic reactions
Identify two thiazide diuretics and three related drugs
- Bendroflumethiazide
- Hydrochlorothiazide
- Chlortalidone
- Indapamide
- Metolazone
Identify two aldosterone antagonists
- Spironolactone
- Eplerenone
What is the active metabolite of spironolactone
- Canrenone
Identify unwanted effects of aldosterone antagonists
- Fatal hyperkalaemia
- GI disturbances
- Gynaecomastia (actions on progesterone/androgen receptors)
How is cardiac toxicity of hyperkalaemia counteracted?
- Intravenous calcium gluconate
- Glucose + Insulin (to shift K+ into cell)
Outline the mechanism of action of triamterene and amiloride
- Act on collecting tubules and ducts
- Inhibit Na+ reabsorption by blocking luminal sodium channels
- Decreases K+ excretion
Identify the unwanted effects of triamterene and amiloride
- Hyperkalaemia
- GI disturbances
- Kidney stones (triamterene only)
- Skin reactions
Identify a carbonic anhydrase inhibitor
- Acetazolamide
Identify the mechanism of action of carbonic anhydrase inhibitors
- Acts on PCT
- Increases excretion of bicarbonate
- With accompanying Na+, K+ and water
- Resulting in an increased flow of alkaline urine and metabolic acidosis
Identify a use of acetazolamide
- Glaucoma for reduction of aqueous humor formation
Identify an osmotic diureitc
- Mannitol
Identify the mechanism of action of mannitol
- Reduces passive water reabsorption
What is diabetic nephropathy?
- Manifestation of diabetic microvascular disease
- Involving renal arterioles and glomeruli
Outline the pathophysiology of diabetic nephropathy
- Glucose combines with amino acids forming advanced glycosylation end products
- Which accumulate in tissues by cross-linking with collagen molecules
- Stimulation of mesangial cell proliferation and matrix production
- Which produces thicker more permeable glomerular basement membrane
What causes glomerular hyperperfusion and hyperfiltration in diabetic nephropathy?
- Defective autoregulation and albumin leakage
Identify the clinical features of diabetic nephropathy
- Microalbuminuria (30-300 mg/day)
- Followed by more severe proteinuria
- Commonest cause of end-stage kidney disease
Which type of diabetes is most associated with the development of diabetic nephropathy?
- Type 1
- With a clear relationship between duration of diabetes (15 years) and histological changes
Identify the morphological changes in diabetic nephropathy
- Thickening of glomerular basement membrane
- Depletion of podocytes
- Increase in mesangial matrix
- Nodular glomerulosclerosis (Kimmelstiel-Wilson nodules) of collagen and other matrix proteins
How is diabetic nephropathy managed?
- Lifestyle changes
- Control of hypertension and poor metabolic regulation
- ACE inhibitors and ARAs following microalbuminuria
- Paricalcitol (vitamin D receptor activator)
Identify three clinical findings that suggest acute pyelonephritis
- Fever
- Loin pain
- Tenderness
Outline the structural changes in acute pyelonephritis
- Renal cortical abscesses
- Steaks of puss
- Infiltration of leucocytes in tubular lamina
What is the treatment for acute pyelonephritis
- Amoxicillin
- Co-amoxiclav and ciprofloxacin in resistant organisms
Outline the basic principles of haemodialysis
- Blood is pumped through semi-permeable membrane (dialyser)
- Blood comes into contact with dialysate
- Causing diffusion of molecules down their concentration gradient
What is the blood flow during dialysis and the flow of dialysate?
- Blood: 200-300 ml/min
- Dialysate: 500 ml/min
What is the best way to achieve a blood flow of 200ml for dialysis?
- Arteriovenous fistula
- Usually the radial or brachial artery and the cephalic vein
- Resulting in distension and thickening of the vein
What is the frequency and duration of haemodialysis?
- 4-5 hours three times a week
- Optimal dialysis is adjusted to individual patient needs
Why are patients anticoagulated during haemodialysis tretment?
- Contact with foreign surfaces activates the clotting cascade
Identify complications of haemodialysis
- Hypotension
- Anaphylactic reactions to ethylene oxide used to sterilise dialysers
- Hard water syndrome (nausea and vomiting)
- Haemolytic reactions
- Air embolism
Outline the basic principles of peritoneal dialysis
- A tube is placed in peritoneal cavity through AAW
- Dialysate is run into peritoneal cavity
- Urea, creatine and phosphate pass into dialysate down concentration gradients
- Water is attracted into peritoneal cavity by osmosis
- The fluid is changes regularly to repeat the process
What is the role of glucose or polymer (icodextrin) in peritoneal dialysis?
- Determines osmolarity of dialysate
Outline the main complication of peritoneal dialysis
- Bacterial peritonitis
- With abdominal pain, guarding, rebound tenderness
- And a cloudy peritoneal effluent (diagnostic)
Identify a second complication of peritoneal dialysis
- Constipation
Outline the Human Tissue Act 2004
- Permits opt in donation post mortem
- Allows family members to refuse if donor not on ODR
- Permits live organ donation to be target to specific individuals
- Makes paid donations illegal
- Allows 12 years olds and above to make their own decision
What does the Amends Organ Donation Bill state?
- Person concerned is deemed to have consented to transplantation
- Unless a person who stands in a qualifying relationship to the person provides information
- That would lead to a reasonable person to conclude that the person concerned would not have consented.
Identify factors for assessing allocation policies in organ donation
- Patient benefit
- Transparency
- Equity of access
- Geographical equity
What is motivational interviewing?
- Collaborative conversation
- That elicits and strengthens peoples good motivations
- For making lifestyle and behaviour changes
Identify four aspects within the spirit of motivational interviewing
- Compassion
- Collaborative
- Evoking
- Supporting autonomy
What is sustain talk?
- Patients talk about why they should stay the same
- Helps to identify obstacles the individual should overcome
What is change talk?
- Patients talk about changing
- Including their reasons, motivations and self-efficacy
- Helps an individual move towards change
Identify four skills required for motivational interviewing
- Open questions
- Affirmations
- Reflective listening
- Summarising
Identify four reasons why motivational interviewing is important
- Understand patient perspective
- Builds relationship with patients
- Helps individuals take more responsibility for their health
- May assist individuals in self-management
