US Lecture 8 - What happened when the kidneys stop working? Flashcards
What happens when the kidneys stop working?
Loss of excretory, homeostatic, endocrine function and abnormality of glucose homeostasis NB: clinical features are determined by rate of deterioration
Why is excretory function lost when the kidneys stop working?
Accumulation of waste products
Why is homeostatic function lost when the kidneys stop working?
Disturbance of electrolyte balance, loss of acid-base control, inability to control volume homeostasis
Why is endocrine function lost when the kidneys stop working?
Loss of erythropoetin production, failure to synthesise 1 alpha hydroxylase vitamin D
Why is there abnormality of glucose homeostasis when the kidneys stop working?
Decreased glucogenesis
What are some symptoms of renal failure?
Extreme lethargy, weakness and anorexia; clinically volume depleted -> severe hypotension, elevated plasma urea and creatinine and it is complicated by hyperkalaemia, hyponatraemia, metabolic acidosis and anaemia. NB: kidneys become small and shrunken
What causes the symptoms of lethargy and anorexia in renal dysfunction?
Accumulation of nitrogenous waste products, hormones, peptides, acidosis, hyponatraemia, volume depletion (low BP), anaemia, chronic neurological damage (peripheral neuropathy)
In patients with renal dysfunction what occurs to the water and salt retention?
Usually difficulty excreting salt and water, leading to tendency to retain Na causing hypertension, peripheral/pulmonary oedema BUT salt and water loss can be found in patients with tubulointerstitial disorders where the concentrating mechanisms have been damaged
What causes the salt and water imbalance in renal dysfunction?
Inability to decrease Na excretion when Na depleted, osmotic diuresis caused by conc of small waste substances, inappropriately high loss of salt and water results in volume depletion which causes low BP
What are the implications of acidosis?
Caused by decreased excretion of H+ and by retention of acid bases; buffered by H+ passing into cells in exchange for K+, so ^ tendency of hyperkalaemia; compensation mechanism inc. increasing CO2 loss through lungs (Kussmahl resp); exacerbates anorexia and increases muscle catabolism
What are the implications of hyperkalaemia?
Caused by failure of DCT to secrete K and is exacerbated by acidosis which causes shift of K from IC to EC space
What does hyperkalaemia cause?
Cardiac arrhythmias and arrest; can affect neural and muscular activity and clinical features of hyperkalaemia are dependent on the chronicity of the hyperkalaemia
What are the features of an ECG of a person with hyperkalaemia?
T waves peak, then T waves disappear > bradycardia > QRS broadens
What are the kidney’s metabolic functions and what happens if they are not carried out?
Decreased erythropoietin production in renal failure results in anaemia. Low 1-25 Vit D levels result in poor intestinal Ca absorption, hypocalcaemia and hyperparathyroidism
What is the mechanism by which phosphate retention decreases Ca2+?
What is a major outcome for patients with CKD?
CV disease
What does an increased CV risk lead to?
Hypertension, secondary cardiac effects, endothelial effects and lipid abnormalities
How can you tell the difference between acute/chronic loss of kidney function?
Acute: Renal size is unchanged and previously normal creatinine levels. Chronic: Renal size often reduced, chronic uraemic symptoms and previously abnormal creatinine levels
What are the initial forms of management of loss of kidney function?
IV normal saline to correct fluid depletion, IV sodium bicarbonate to correct acidosis, IV insulin and dextrose to lower plasma K and dialysis
What are the traditional methods of assessing GFR?
Urea -> poor indicator as it is confounded by diet, catabolic state, GI bleeding. Creatinine -> affected by muscle mass, sex, age, race. Creatinine Clearance -> difficult for elderly patients and overestimates GFR at low GFR. Inulin clearance -> laborious used for research only. Radionuclide studies -> EDTA clearance, reliance but expensive
How is GFR assessed now?
Eqn which automatically calculates estimated GFR from serum creatinine and result is normalised for race -> MDRD but it is unreliable in GFR>60ml/min and in very obese/thin patients
What is the long term management of kidney failure?
Remain on haemodialysis 4h, 3x/week, low K diet and fluid restriction, erythropoietin injections to correct anaemia, 1,25 Vit D supplements to prevent hyperparathyroid bone disease
How is respiratory alkalosis/acidosis reached and compensated for?
How is metabolic alkalosis/acidosis reached and compensated for?
What is the difference in renal and pulmonary compensation?
Renal compensation takes a long time - from hours to weeks. Pulmonary compensation takes minutes as they both use different compensation mechanisms
What is the normal range in pH for blood and urine and how is it kept constant?
Urine is the regulator as any excess acid from meals or respiration can be excreted in the urine, so urine pH can change in response to diet
What is normal plasma HCO3- concentration?
22-26 mEq/L
Where and how much HCO3- is absorbed in the nephron?
What is HCO3-?
Important high capacity chemical buffer that can respond rapidly to changes in metabolic acid and can be produced from volatile respiratory acid
What is the Henderson-Hasselbach equation?
How is HCO3- reabsorbed in the PCT?
HCO3- has no transporters to carry it across the membrane so H+ from IC is transported out H+/ATPase and combines with HCO3- and CA to form CO2 which diffuses down conc grad into cell, where it turns back into HCO3- (H+ transported out via H/ATPase or Na/H antiporter). HCO3- is then removed from the cell via Chloride bicarbonate exchangers, Na/3HCO3- cotransporter where it moves from IF to the capillary -> 3Na/2K ATPase keeps Na conc grad and K in the cell
How are bicarbonate levels regulated by the intercalating cells of the collecting duct?
CA converts HCO3- to CO2 so it diffuses across the membrane and is converted again into HCO3- by CA where H+ is removed into filtrate via H/K ATPase and H/ATPase (excess of acid in filtrate) and HCO3- is removed by HCO3/Cl exchanger (AE1) to IF and the Cl then diffuses back out into IF. OR HCO3- in cell is removed via Cl/HCO3 exchanger into filtrate and H+ is removed into IF via H/ATPase to reduce pH
How is HCO3- removed in cuboidal epithelial cells of PCT?
CO2 + H2O form H+ and HCO3-, w/H being removed into filtrate via H+ ATPase where it reacts with HPO4(2-) to form H2PO4-. HCO3- is transported into IF via AE1 (Cl/HCO3- exchanger)
How is HCO3- generated in cuboidal epithelial cells of PCT?
Glutamine is deaminated into 2NH4 and 2HCO3-. NH4 are excreted from cell into filtrate via Na/NH4 exchangers and HCO3- is exchanged with Cl into IF. Na/K ATPase removes Na from cell into blood. Na is also moved into the cell from filtrate via Na/Glu SGLT-1 transporter
Why is the Na/K ATPase important in the nephron cells when making/removing HCO3- from the cell?
Na/K ATPase pumps are needed when the cell relies on Na to aid transportation of a substance from external environment into the cell. By removing Na from basal membrane of cell, Na enters the circulation in high concentrations, meaning that it will be filtered into the nephron again, entering a cycle
What are the compensatory mechanisms of metabolic/respiratory alkalosis/acidosis?
What happens if there is respiratory acidosis?
Hypoventilation leads to accumulation of CO2 in arterial blood, so subsequent fall in arterial blood pH, PCO2 stimulus and acidaemia effect plateau. Kidneys increase HCO3- retention/production and H+ secretion, so pH begins to normalise, leading to full compensation
What happens if there is respiratory alkalosis?
Hyperventilation so CO2 reduces, so there is an increase in pH and kidneys decrease HCO3- retention/production and H+ secretion into blood increases to reduce the alkalosis
What happens if there is metabolic acidosis?
Problem with Base excess -> BE decreases, so pH decreases, which causes increased ventilation to reduce CO2 levels in blood
What happens if there is metabolic alkalosis?
BE increases, so pH increases > compensatory mechanism is to reduce ventilation, to increase CO2 levels and bring up the pH
What is partial compensation?
Changing the action of an organ to deal with the action of a different organ
