Renal physiology Flashcards
What are the 4 causes of metabolic acidosis with a normal anion gap?
Renal tubular acidosis
Diarrhoea
Ammonium chloride ingestion
Adrenal insufficiency
What are the 4 causes of metabolic acidosis with a raised anion gap?
Lactic acidosis (hypoxia, sepsis, infarction)
Ketoacidosis (DM, starvation, alcohol)
Renal failure
Poisoning (late stages aspirin OD, methanol, ethylene glycol)
Give 5 causes of metabolic alkalosis.
Vomiting
Cardiac arrest
Multi-organ failure
CF
Potassium depletion (diuretics)
Cushing’s syndrome
Conn’s syndrome
Give 5 causes of respiratory alkalosis.
Hyperventilation
PE
Pneumothorax
CNS disorders (CVA, SAH, encephalitis)
High altitude
Pregnancy
Early stages of aspirin OD
Give 5 causes of respiratory acidosis.
COPD
Life-threatening asthma
Pulmonary oedema
Respiratory depression (Opiates, BDZs)
Neuromuscular disease (GBS, muscular dystrophy)
Incorrect ventilatory settings (hypoventilation)
Obesity
What doe/s the anion gap represent
The concentration of all the unmeasured anions in the plasma.
How do you calculate the anion gap?
Na - Cl - HCO3
What are the causes of a high anion gap metabolic acidosis?
Mnemonic CAT MUD PILES:
Carbon monoxide
Alcoholic ketoacidosis
Toluene
Metformin/ Methanol
Uraemia
Diabetic Ketoacidosis
Propylene glycol
Iron/ Isoniazid
Lactic acidosis
Ethylene glycol
Salicylates
What are the causes of a normal anion gap metabolic acidosis?
Mnemonic CAGE:
Chloride excess
Acetazolomide/ Addison’s disease
GI causes (diarrhoea, vomiting, fistulae)
Extra (renal tubular acidosis)
A high anion gap metabolic acidosis normally occurs due to what?
Accumulation of organic acid or impaired excrete of H+.
A normal anion gap metabolic acidosis normally occurs due to what?
Loss of HCO3 from extracellular fluid.
How is lactic acidosis defined?
pH <7.35
AND
lactate >5
What happens to the anion gap in lactic acidosis?
It is raised
What is type A lactic acidosis due to?
Tissue hypoxia
What is type B lactic acidosis due to?
Non-hypoxic processed affecting production and elimination of lactate.
Give some causes of type A lactic acidosis.
Shock (sepsis)
LV failure
Severe anaemia
Asphyxia
Cardiac arrest
CO poisoning
Respiratory failure
Severe asthma
COPD
Regional hypoperfusion
Give some causes of type B lactic acidosis.
Renal failure
Liver failure
Sepsis (non-hypoxic sepsis)
Thiamine deficiency
Alcoholic ketoacidosis
Diabetic ketoacidosis
Cyanide poisoning
Methanol poisoning
Biguanide poisoning
What is the RAAS system responsible for?
Regulation of arterial BP
Concentration of sodium in the plasma
Where is renin released from?
Juxtaglomerular cells
Where are juxtaglomerular cells located?
Afferent arterioles of the kidney
Which 3 things can cause renin to be released?
Decreased arterial BP (reduced renal perfusion)
Decreased sodium load delivered to the DCT
Sympathetic nervous system stimulation
Where is angiotensinogen produced?
Liver
What 4 factors cause an increase of angiotensinogen?
Increased corticosteroid levels
Increased thyroid hormone levels
Increased oestrogen levels
Increased angiotensin II levels
What is the function of renin?
Cleaves the peptide bond between leucine and valine on angiotensinogen, converting it to angiotensin I.
What is the overall effect of the RAAS?
Increase mean arterial BP and restore perfusion to the kidneys
Release of renin is inhibited by what?
Atrial natriuretic peptide (ANP)
When is atrial natriuretic peptide (ANP) released?
In response to the atria being stretched during periods of high blood pressure
Where are macula dense cells located?
DCT
What does angiotensin converting enzyme do?
Removes 2 c-terminals from angiotensin I to form angiotensin II.
Where is ACE produced?
Lungs
Where is angiotensin I converted to angiotensin II?
Lungs
What is the main bioactive product of RAAS?
Angiotensin II
What does angiotensin II do to vascular smooth muscle?
Constricts it (increased BP)
What does angiotensin II do the efferent arteriole of the glomerulus?
Constricts it (increased filtration fraction)
What does angiotensin II stimulate the release of?
Aldosterone
ADH
Where is aldosterone released from?
Zona glomerulosa of the adrenal cortex
Were is ADH released from?
Posterior pituitary gland
Where is the thirst centre of the brain?
Hypothalamus
What exchanger does angiotensin II act on?
Na+/H+ exchanger in PCT = Na+ reabsorption and H+ secretion
What are the 3 effects of angiotensin II on renal measurements?
Decreased renal plasma flow
Increased filtration fraction
Increased GFR
What is the main mineralocorticoid hormone?
Aldosterone
What 3 things is aldosterone released in response to?
Increased angiotensin II levels
Increased potassium levels
Increased ACTH levels
What substances does aldosterone cause reabsorption of?
Reabsorption of Na+ from DCT
Reabsorption of water from DCT
Reabsorption of C- from DCT
Where is the majority of water reabsorbed in the nephron?
PCT
Which limb of the loop of henle is permeable to water?
Descending limb
Where is the majority of sodium reabsorbed in the nephron?
PCT
Which part of the loop of Henle reabsorbs 25% sodium?
Thick ascending limb
How is water reabsorbed in the PCT?
Osmosis
How is sodium reabsorbed in the PCT?
Active transport
How is sodium reabsorbed in the thick ascending limb of the loop of henle?
Active transport
Where is 65% (majority) of chloride reabsorbed in the nephron?
PCT
How is chloride reabsorbed in the PCT?
Via a symporter with Na+
How is chloride reabsorbed in the ascending loop of henle?
Diffusion (in thick and think ascending LoH)
How is chloride reabsorbed in the DCT?
Diffusion
How is chloride reabsorbed in the collecting duct?
Symporter
Which part of the nephron are proteins reabsorbed?
PCT (almost 100%)
Where is 65% potassium reabsorbed in the nephron?
PCT by diffusion
Where is almost 100% glucose reabsorbed in the nephron?
PCT
How is glucose reabsorbed in the PCT?
Secondary active transport with Na+
What is the basic functional unit of the kidney?
Nephron
How many nephrons are in each kidney?
~1 million
In which part of the kidney does plasma undergo filtration?
Renal corpuscle (glomerulus + bowman’s capsule)
Where does the majority of solute reabsorption occur?
PCT
What are the adaptations of the PCT?
Cuboidal
Abundant mitochondria
Brush border
Which part of the kidney does the loop of henle lie in?
Renal medulla
Which part of the loop go henle allows water to move via osmosis but does not take part in solute transport?
Descending loop of henle
What happens in the thick ascending loop henle?
NO water reabsorption
NaK2Cl transporters absorb solutes
What happens in the DCT?
Fine control of urine composition
Where are macula dense cells?
Wall of DCT
Where are juxtaglomerular cells?
Wall of afferent arteriole
High sodium concentration in the DCT means what has happened to the GFR?
Increased (faster flow = less sodium reabsorbed)
What volume of plasma is filtered per minute at the glomerulus?
125ml
What is arterial supply to the kidneys?
Renal arteries
What vertebral levels do the renal arteries come off the aorta at?
L2
Which renal artery is longer?
Right renal artery
Where does the right renal artery pass in relation to the IVC?
Behind it
What does the right renal artery pass behind on route to the kidney?
IVC
Right renal vein
Head of pancreas
Second part of duodenum
What does the left renal artery pass behind on route to the left kidney?
Left renal vein
Body of pancreas
Splenic vein
At what vertebral level do the hila of the kidneys lie?
L1 (transpyloric plane)
What are the 3 layers of the glomeruli filtration membrane?
Fenestrated capillary endothelium
Basement membrane
Filtration slits formed by foot processes of podocytes
What charge does the basement membrane in the glomerulus have?
Negative
What is the mean GFR in men and women?
130ml in men
120ml in women
Reabsorption in the PCT is driven by what?
ATP-dependent transporters
What is the main way that reabsorption occurs in the PCT?
Bulk transport (solvent drag).
Means solutes are transported by the flow of water.
What percentage of the following substances is reabsorbed in the PCT?
Glucose
Amino acids
Sodium
Water
Potassium
Chloride
Glucose = 100%
Amino acids = 100%
Sodium = 67%
Water = 65%
Potassium = 65%
Chloride = 65%
What acts as the driving force for reabsorption in the PCT?
Sodium
How does glucose reabsorption occur at the PCT?
Sodium-glucose co-transporters (one glucose molecule with 2 sodium molecules)
How are amino acids transported across the PCT?
Co-transport (Na/amino acid symporters)
Where does acetazolamide act?
PCT
What does acetazolamide inhibit?
Carbonic annhydrase
What is the overall effect of acetazolamide?
Reduces sodium and water resorption.
Where is erythropoietin produced?
PCT
Which cells produce erythropoietin in the PCT?
Interstitial fibroblasts
What percentage of sodium is reabsorbed in the loop of henle?
20-25%
Which part of the loop of henle is highly permeable to water?
Thin descending limb
What is reabsorbed in the descending limb of the loop of henle?
Water (aquaporin 1 channels)
What is reabsorbed in the thin ascending limb of the loop of henle?
Ions - sodium, chloride, urea
NO water
How does ion reabsorption occur in the thin ascending loop of henle?
Paracellularly
What is reabsorbed in the thick ascending limb of the loop of henle?
Ions - sodium, chloride, potassium
NO water
Why does the interstitial around the loop of henle become concentrated with ions as the fluid descends?
Counter current mechanism creates an osmotic gradient
Which type of diuretics act on the loop of henle?
Loop diuretics
How do loop diuretics act?
Inhibit NaK2Cl transporter = urine less concentrated.
What percentage of water is reabsorbed in the DCT?
10-15%
What are the 2 sections of the DCT?
Early DCT (1)
Late DCT (2)
Where does the DCT start?
Just after the macula dense.
Sodium reabsorption is driven by which proteins in the primary DCT?
Na+/K+ ATPase
How does the movement of sodium ions occurs in the late DCT?
ENAC (epithelial sodium channel)
What do intercalated cells do in the DCT?
Assist with the acid-base balance
Which diuretics act on the DCT?
Thiazide diuretics
Aldosterone antagonists
Where do thiazide diuretics work?
DCT
What do thiazide diuretics inhibit?
NaCl co-transportters (reduce sodium and water reabsorption)
Where do aldosterone antagonists work?
DCT
What do aldosterone antagonists do?
Inhibit aldosterone.
