Y2 Kidney Revision Flashcards
What is atrial natriuretic peptide?
Secreted by the atria in repsonse to stretch
Decreases renin production and promotes sodium and water excretion
What does frothy urine idicate?
Protein in the urine
What does brown/red urine indicate?
Rhadbomyolysis - muscle break down
What would the presence of nitrites in the urine indicate?
Bacterial infection
Discuss autosomal dominant polycystic kidney disease
PKD1 (chromosome 16) mutation - affects people aged 30-40
PKD2 (chromosome 4) mutation - affects people 70+
PKD1 is more severe
What is the glomerulus?
Tuft of capillaries within Bowmanns capsule
What is the renal corpuscle?
Bowmans capsule + glomerulus
What is nephroptosis?
Kidney drop - often due to fat loss
What is hydronephrosis?
Swelling of the kidney due to urine buildup
Most commonly due to kidey stones
Discuss the two types of nephrons
1) Cortical: 85%
- Short loop, efferent supplies peritubular capillaries, renal corpuscle in the cortex
2) Juxtamedullary: 15%
- Long loop, efferent supplies vasa recta, renal corpuscle closer to medulla
What should glomerular filtration be?
90-120 ml/min
180L plasma/day
What are the cellular layers of the filtration membrane of the glomerulus?
- Fenestrated endothelium: blocks RBCs
- Glomerular basement membrane: blocks plasma proteins
- Podocytes: blocks macromolecules
What is renal clearance?
How quickly a substane is removed from the kidney and excreted in the urine
Clearance = concentration of substance in urine x flow rate/ concentration of substance in plasma
What should the clearance of createnine be?
140ml/min
What is inulin?
Used to measure GFR accurately - it is freely filtered and not absorbed
Discuss comparison of filtration of a substance to that of inulin
Cx (calculated clearance of substance)/ Clearance of inulin
= 1: substance is freely filtered
= <1: substance is absorbed
= >1: freely filtered and secreted
Where do the kidneys sit?
T12 - L3 vertebrae
Partially protected by ribs 11&12
Retroperitoneal
What are macula densa cells?
Chemoreceptors in the DCT
Detect NaCl
Low NaCl = low BP - macula densa cells cause afferent arteriole to dilate and increase the hydrostatic pressure in the glomerulus
MD cells cause granular cells to secrete renin
What are juxtaglomerular cells?
Secrete renin to increase Na reabsorption
Receive signals from macula densa cells
Discuss peritubular capillaries and the vasa recta
Peritubular capilaries surround DCT and PCT
Vasa recta surrounds the loop of Henle
What is mannitol?
Osmotic diuretic
What is acetazolemide?
Carbonic anhydrase inhibutor - diuretic
Reduces Na/H+ exchange so more Na in filtrate and more water loss
What is furosemide?
Loop diuretic
NKCC2 inhibitor
How do thiazide diuretics work?
Blocks Na/Cl transporter in the DCT and causes more potassium excretion because more Na reaches the collecting duct
In the collecting duct, Na is absorbed in exchange for the secretion of K+
*amiloride blocks this exchanger
Discuss K+ sparing diuretics
Amiloride: blocks Na+/ K+ exchanger in collecting duct - means less Na+ is absorbed and therefore less K+ is excreted
Spirololactone: blocks the aldosterone receptor, the activation of the aldosterone receptor normally causes more Na/K channels to be placed in the membrane
How does anti diuretic hormone work?
AKA vasopressin, secreted by posterior pituitary
- Causes more AQP2 to be place in collecting duct membrane and promotes water uptake
Where is the majority of Na+ reabsorbed?
PCT
What is true of the thick ascending limb?
It is impermeable to water
Large simple squamous epithelial cells
Discuss countercurrent multiplication of the kidney
Descending limb: permeable to water, impermeable to ions
water flows into interstitium
Think ascending limb: impermeable to water, ions move into interstitium because of water loss from descending limb
- Ultimately we lose water and ions to the interstitium and therefore end up with a more concentrated urine
What is the epithelia of the DCT?
Cuboidal cells, no microvilli
Discuss the transporters of the DCT
- Basolateral Na/K exchanger - Na absorbed into blood and K secreted
- Apical Na/Cl co-transporter
- Apical Ca2+ transporter
*Ca2+ and Mg+ reabsorption is thought to occur passively
Discuss HCO3- reabsorption in the kidney
PCT: Na is absorbed in exchange for H+ secretion
H+ and HCO3- combine in lumen to form carbonic acid
Carbonic acid then converts into water and CO2
CO2 enters the cell from the lumen and combines with water to become H+ and HCO3-
HCO3- can then be absorbed along with Na+
DCT: same as above but HCO3- reabsorption requires Cl- instead of Na+
Where does most acid-base balance occur?
PCT
What is the role of type B intercalated cells?
Express a chloride-bicarbonate exchanger, pendrin, at their apical membrane and express H+-ATPase at their basolateral membrane
Essentially they secrete HCO3- and reabsorb H+
What is the role of type a intercalated cells?
Acid secretion - damage to these cells causes distal renal tubular acidosis
What are the renal tubule buffers?
Phosphate (HPO4-) + H+ = H2PO4
Glutamine breakdown = Ammonia (NH3) + H+ = NH4 (ammonium)
*stop the urine being too acidic
What could cause metabolic acidosis?
- Diabetes: ketone bodies
- Too much protein in diet
- Diarrhoea
- Antifreeze
- Aspirin
What could cause metabolic alkalosis?
- Vomiting
- Too many rennies
- Too much fruit
- Thiazide and loop diuretics - K+ and H+ loss
- Loss of function of type B intercalated cells (spit out bases)
- Hyperfunction of type A intercalated cells (spit out acid)
Where is arterial blood usually taken from for blood gases?
Radial
What is the normal level of HCO3-?
22-26mEq
What is the normal range of CO2?
34-45mmHg
What is the key intracellular and plasma buffer?
Hb - forms HHb when combined with H+
Discuss buffering in the body
- 52% of the buffering capacity is in cells
- 5% is in RBCs
- 43% of the buffering capacity is in the extracellular space
- of which 40% by bicarbonate buffer, 1% by proteins and 1% by phosphate buffer system
What could cause a respiratory alkalosis?
Depression of respiratory centres by narcotics
- Restrictive lung disease
- Paralysis of respiratory muscles
Where are the majoirty of drug components secreted in the kidney?
PCT
Discuss the role of urine pH in drug excretion
Acidic urine: alklaine drug more readily ionised and therefore more easily excreted
Alkaline urine: acidic drug more easily excreted
What would be given in the case of an aspirin overdose?
Sodium bicarbonate - makes urine more alkaline and promotes loss of salicylic acid (aspirin metabolite)
Which drug has a 25x increased half life in renal failure?
Aminoglycosides (30s inhibitors)
- Can also cause ototoxicity
Which diuretics are associated with gout
Thiazides - promote uptake of urea
What does nosocomial mean?
Originating in hospital
What is the most common UTI causing bacteria?
E.Coli UPEC
*E.Coli 0157 causes intestinal disease
What pathogen rarely causes UTIs?
M.Tuberculosis
Discuss E.Coli UPEC
Uropathogenic E.Coli
- Type 1 fimbriae bind to mannose residues on host cells
- Type P frimbriae adhere to urinary tract cells and prevent phagocytosis
What are the risks of UTIs in pregnancy?
- Low birth weight
- Prematurity
What is pyelonephritis?
Kidney inflammation usually due to infection
Uncomplicated vs. Complicated UTI
Uncomplicated: not pregnant, no evidence of kidney spread, normal urinary system, normal pathogen
Complicated: opposite of above
Name a commonly used antibacterial for UTIs
Trimethoprim: stops DHF - THF, prevents folate production and inhibits DNA
What is nitrofurantoin?
Used to treat UTIs
Inhibits the synthesis of DNA, RNA, protein and cell wall synthesis
- ineffective for kidney infection
- highly stable against resistant bacteria due to number of MOA
How would UTIs be treated in children?
Lower: amoxicillin, trimethoprim
Upper: Co-amoxiclav (combination consisting of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor)
Which drugs are commonly used for pyelonephritis?
Co-amoxiclav and ciproflaxin
Sometimes trimethoprim
How is chronic kidney disease defined?
Structural damage
GFR <60mL/min/1.73m2 for 3 months
How is acute kidney disease defined?
Creatinine >26mmol/L
Urine <0.5mL/Kg/day
Discuss causes of renal failure
Pre renal: HF, hypovolemia
Renal: Tubular necrosis, trauma, sepsis
Post renal: bladder obstuction, stones
Discuss stages of kidney disease
Per GFR
Stage 1 >90
Stage 2 <90
Stage 3 <60
Stage 4 <30
Stage 5 <15 or dialysis
What is nephrotic syndrome?
Protein loss due to dysfunction of podocytes
Causes frothy urine and oedema
Adults: Focal segmental glomerulosclerosis
In children: most common cause is minimal change disease - so called because the damage is so small it cant be seen using a microscope
What are the consequences of nephrotic syndrome?
- Oedema
- Hypoalbuminemia
- Proteinuria
- Hyperlipidemia
- Hypercoaguability
What is Berger’s disease?
Nephritic disease: IgA neuropathy
- Hematuria (gross, frank, microscopic)
- Oedema in hands and feet
- Cola- or tea-colored urine
What is nephritic syndrome?
Immune cmplexes build up and elecit an immune response that damages the filtration membrane
- Loss of RBCs
- Proteinuria
- Oliguria
- Hypertension
Henloch-Schonlein and Goodpasture’s
What is Goodpasture’s syndrome?
Immune system attacks the basement membrane in kidney and allows blood through into the urine
What is the first sign of kidney damage?
Oliguria
What is used to treat BPH?
Finasteride - 5a reductase inhibitor, prevents DHT production from testosterone
What is tamulosin?
Alpha 1a blocker, relaxes muscle fibres in prostate and bladder neck and allows for easier micturition
Discuss renal cell cancer
- Clear cell (most common - treated with surgical resection) AKA renal adenocarcinoma
- Papillary types 1&2
- Chromophobe (similar appearance to clear cell but cells are larger)
- Oncocytic
- Collecting duct: rare, seen in young adults, aggressive
Discuss bladder cancer
- Transitional cell (most common)
- SCC
- Adenocarcinoma
- 7th most common in UK
What is the blood supply to the bladder?
Superior and inferior vesical arteries, which arise directly or indirectly from the internal iliac artery
Which nerve supplies the external urethral sphincter?
Pundendal
Discuss micturition
Pelvic nerve: parasympathetic, ACh release, causes contraction of detrusor muscle
Pudendal nerve: parasympathetic, ACh release, contraction of external urethral sphincter
Hypogastric nerve: sympathetic, noradrenaline release, relaxes detrusor and contracts internal spincter
What is the difference between nicotinic and muscarinic receptors?
Both are ACh receptors
Nicotinic: ionotropic
All are excitatory
Muscarinic: GPCRs
Discuss the three layers of the bladder
Outer: adventitial connective tissue
Middle: smooth muscle detrusor)
Inner: Transitional epithelium
What is acute urinary retention?
Painful inability to void with relief following catheterisation
>800mL
Discuss drug interactions with spironolactone
ACE inhibitors: dangerous hyperkalemia because ACE inhibitors also increase potassium retention - Since aldosterone is responsible for increasing the excretion of potassium, ACE inhibitors can cause retention of potassium
Aspirin: defecreases spironolactone effectiveness
Which drugs increase GFR?
Afferent dilators: Atrial natriuretic peptide, prostaglandins
Efferent constrictors: angiotensin II and ANP (by blocking affect of noradrenaline)
How do NSAIDs affect the kidney?
Contrict the afferent arteriole and therefore reduce GFR
Why are ACEi and ARB contraindicated in renal artery stenosis?
Renal artery stenosis = GFR low
ACEi and ARB = dilate efferent arteriole and decrease GFR even further
What would be the result of a dilated efferent arteriole?
GFR would decrease because blood can easily flow out via the efferent
What would happen to the GFR if the efferent arteriole was constricted?
GFR would increase
What are the consequences of renal artery stenosis?
Stenosis causes hypoperfusion of kidney
Kidney senses low BP and release renin
Renin causes increase BP systemically but this can’t get past the renal stenosis and thus more renin is released etc etc
Causes hypertension
What affect does noradrenaline have on GFR?
Increases GFR by constricting the efferent arteriole
Discuss causes of nephritic syndrome in adults and children
Children: Haemolytic uraemic syndrome
Henloch-Scholein purpura
Post-streptococcal GN
Adults: Goodpasture’s, ANCA associated vasculitis, lupus (SLE)
What is ANCA associated vasculitis?
(ANCA)-associated vasculitis (AAV) is a group of diseases (granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and microscopic polyangiitis), characterized by destruction and inflammation of small vessels
Discuss various causes of nephritic disease
Immune complex trapping: Systemic lupus erythematosus
In situ antigen: Goodpasture’s - circulating anti-glomerular basement membrane antibody
Post infectious: bacterial antigen sits in the membrane
