US Lecture 8 - What happened when the kidneys stop working?

Question 1

What happens when the kidneys stop working?

Answer 1

Loss of excretory, homeostatic, endocrine function and abnormality of glucose homeostasis NB: clinical features are determined by rate of deterioration

Question 2

Why is excretory function lost when the kidneys stop working?

Answer 2

Accumulation of waste products

Question 3

Why is homeostatic function lost when the kidneys stop working?

Answer 3

Disturbance of electrolyte balance, loss of acid-base control, inability to control volume homeostasis

Question 4

Why is endocrine function lost when the kidneys stop working?

Answer 4

Loss of erythropoetin production, failure to synthesise 1 alpha hydroxylase vitamin D

Question 5

Why is there abnormality of glucose homeostasis when the kidneys stop working?

Answer 5

Decreased glucogenesis

Question 6

What are some symptoms of renal failure?

Answer 6

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

Question 7

What causes the symptoms of lethargy and anorexia in renal dysfunction?

Answer 7

Accumulation of nitrogenous waste products, hormones, peptides, acidosis, hyponatraemia, volume depletion (low BP), anaemia, chronic neurological damage (peripheral neuropathy)

Question 8

In patients with renal dysfunction what occurs to the water and salt retention?

Answer 8

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

Question 9

What causes the salt and water imbalance in renal dysfunction?

Answer 9

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

Question 10

What are the implications of acidosis?

Answer 10

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

Question 11

What are the implications of hyperkalaemia?

Answer 11

Caused by failure of DCT to secrete K and is exacerbated by acidosis which causes shift of K from IC to EC space

Question 12

What does hyperkalaemia cause?

Answer 12

Cardiac arrhythmias and arrest; can affect neural and muscular activity and clinical features of hyperkalaemia are dependent on the chronicity of the hyperkalaemia

Question 13

What are the features of an ECG of a person with hyperkalaemia?

Answer 13

T waves peak, then T waves disappear > bradycardia > QRS broadens

Question 14

What are the kidney’s metabolic functions and what happens if they are not carried out?

Answer 14

Decreased erythropoietin production in renal failure results in anaemia. Low 1-25 Vit D levels result in poor intestinal Ca absorption, hypocalcaemia and hyperparathyroidism

Question 15

What is the mechanism by which phosphate retention decreases Ca2+?

Answer 15

Question 16

What is a major outcome for patients with CKD?

Answer 16

CV disease

Question 17

What does an increased CV risk lead to?

Answer 17

Hypertension, secondary cardiac effects, endothelial effects and lipid abnormalities

Question 18

How can you tell the difference between acute/chronic loss of kidney function?

Answer 18

Acute: Renal size is unchanged and previously normal creatinine levels. Chronic: Renal size often reduced, chronic uraemic symptoms and previously abnormal creatinine levels

Question 19

What are the initial forms of management of loss of kidney function?

Answer 19

IV normal saline to correct fluid depletion, IV sodium bicarbonate to correct acidosis, IV insulin and dextrose to lower plasma K and dialysis

Question 20

What are the traditional methods of assessing GFR?

Answer 20

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

Question 21

How is GFR assessed now?

Answer 21

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

Question 22

What is the long term management of kidney failure?

Answer 22

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

Question 23

How is respiratory alkalosis/acidosis reached and compensated for?

Answer 23

Question 24

How is metabolic alkalosis/acidosis reached and compensated for?

Answer 24

Question 25

What is the difference in renal and pulmonary compensation?

Answer 25

Renal compensation takes a long time - from hours to weeks. Pulmonary compensation takes minutes as they both use different compensation mechanisms

Question 26

What is the normal range in pH for blood and urine and how is it kept constant?

Answer 26

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

Question 27

What is normal plasma HCO3- concentration?

Answer 27

22-26 mEq/L

Question 28

Where and how much HCO3- is absorbed in the nephron?

Answer 28

Question 29

What is HCO3-?

Answer 29

Important high capacity chemical buffer that can respond rapidly to changes in metabolic acid and can be produced from volatile respiratory acid

Question 30

What is the Henderson-Hasselbach equation?

Answer 30

Question 31

How is HCO3- reabsorbed in the PCT?

Answer 31

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

Question 32

How are bicarbonate levels regulated by the intercalating cells of the collecting duct?

Answer 32

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

Question 33

How is HCO3- removed in cuboidal epithelial cells of PCT?

Answer 33

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)

Question 34

How is HCO3- generated in cuboidal epithelial cells of PCT?

Answer 34

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

Question 35

Why is the Na/K ATPase important in the nephron cells when making/removing HCO3- from the cell?

Answer 35

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

Question 36

What are the compensatory mechanisms of metabolic/respiratory alkalosis/acidosis?

Answer 36

Question 37

What happens if there is respiratory acidosis?

Answer 37

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

Question 38

What happens if there is respiratory alkalosis?

Answer 38

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

Question 39

What happens if there is metabolic acidosis?

Answer 39

Problem with Base excess -\> BE decreases, so pH decreases, which causes increased ventilation to reduce CO2 levels in blood

Question 40

What happens if there is metabolic alkalosis?

Answer 40

BE increases, so pH increases \> compensatory mechanism is to reduce ventilation, to increase CO2 levels and bring up the pH

Question 41

What is partial compensation?

Answer 41

Changing the action of an organ to deal with the action of a different organ