renal Flashcards
what are 2 clinical parameters (from blood test) used to indicate kidney function
- serum creatinine
(from breakdown of muscle) - blood urea nitrogen
(from breakdwon of protein)
if kidney function declines -> accumulation of C and N -> elevated levels
why serum creatinine levels preferred as marker of kidney function
muscle breakdown occurs at relatively constant rate
-> steady SCr levels
=> reliable baseline to detect changes due to change in kidney function
limitations of serum creatinine as a kidney function marker
delayed rise (24-48 hrs) in levels
in AKI
limitations of blood urea nitrogen as a kidney function marker
affected by non-renal factors like
diet,
dehydration
and liver disease
diet: higher protein intake -> more urea production => increase in BUN
dehydration: increased reabsorption => increase in BUN
liver disease: reduced urea synthesis => decrease in BUN
Should you give diuretics (e.g. Furosemide [loop diuretic]) as treatment for low urine output if patient has a low BP?
No
- worsens hypotension
- lowered BP FURTHER reduces renal blood flow
=> worsening oliguria
and worsening of AKI
Which of the following statements about the kidneys is true?
A) The right kidney is positioned higher than the left kidney.
B) The kidneys are located in the peritoneal cavity.
C) The left kidney is related to the 12th rib and diaphragm.
D) The kidneys are supplied by the femoral artery.
C) The left kidney is related to the 12th rib and diaphragm.
(A) is wrong due to presence of liver above R side
=> R kidney is lower than L kidney
(B) is wrong as kidneys are located in retroperitoneal cavity (i.e. posterior to peritoneal cavity)
(D) is wrong as kidneys are supplied by renal artery,
arising from abdominal aorta at L1-2
Which of the following structures provides cushioning and protection to the kidneys?
A) Renal capsule
B) Perinephric fat
C) Renal fascia
D) All of the above
D) All of the above
Protective layers (from innermost to outermost):
Renal capsule -> Perinephric fat -> Renal fascia
* Renal capsule: fibrous membrane (consists of collagen fibres) which provides barrier against infections and physical trauma
* Perinephric fat: fatty layer which acts as a cushion to absorb mechanical shocks
* Renal fascia: dense connective tissue which anchors kidneys to surrounding structures, thus preventing excess movements
Perinephric fat also known as perirenal fat
medial -> lateral
muscles in posterior abdominal wall
Psoas major -> quadratus lumborum -> transversus abdominus
quadratus lumborum is a deep posterior muscle
-> not visible from anterior side
Which nerve is not related to the posterior surface of the kidney?
A) Subcostal nerve (T12)
B) Ilioinguinal nerve (L1)
C) Phrenic nerve (C3-C5)
D) Iliohypogastric nerve (L1)
C) Phrenic nerve (C3-C5)
recall! phrenic nerve provides
- motor innervation to diaphragm + sensory innervation to pleura (CVS)
- sensory innervation to pleura (resp)
Which statement about the renal arteries is TRUE?
A) The right renal artery is shorter than the left renal artery.
B) The left renal artery is shorter than the right renal artery.
C) Both renal arteries are equal in length.
D) The renal arteries arise from the inferior vena cava.
B) The left renal artery is shorter than the right renal artery.
due to aorta being on L side and IVC being on R side
=> R renal vein is also shorter than L renal vein
i.e. pathway
what is the venous circulation in the kidney like
peritubular capillaries (PCT and DCT)
AND vasa recta (loop of Henle)
-> intermediary veins which eventually merge to form
-> renal veins
=> empty into IVC
NOT about their length
diff bet R and L gonadal veins
R gonadal vein drains DIRECTLY into IVC,
while L gonadal vein drains into left renal vein before reaching IVC
what has the symptom of “loin to groin” pain and follows renal colic pattern
urolithiasis
(i.e. renal/kidney stone)
what disease
when is KUB CT used
renal calculi
i.e. urolithiasis or renal/kidney stones
non-contrast
as stones are visible w/o contrast
plus contrast may actually obscure smaller stones
what is the most impt thing to look out for when doing urinalysis for patient w/ urolithiasis
i.e. levels of what
Levels of calcium, uric acid and other substances which might form stones
What to check for in blood tests for renal disease
- Serum Cr, BUN, electrolytes, etc
-> check kidney function -
Calcium and phosphorus levels
-> check if bone metabolism has been affected -
RBC count
-> check for secondary anemia due to decreased EPO production
What is one thing that a cystogram is used to check for
Vesicoureteral Reflux (VUR) in children
cystogram checks if urine flows backward from bladder into ureter
Which of the following correctly describes the anatomical course of the ureter?
A) The ureter exits the renal pelvis, descends medially, and enters the bladder anteriorly.
B) The ureter exits the renal pelvis, runs along the transverse processes of the vertebrae, crosses in front of the sacroiliac joint, and enters the bladder posteriorly.
C) The ureter runs anterior to the transverse processes of the vertebrae and crosses behind the sacroiliac joint before reaching the bladder.
D) The ureter runs parallel to the abdominal aorta before entering the bladder from the front.
B) The ureter EXITS the renal pelvis,
runs ALONG the transverse processes of the vertebrae,
crosses IN FRONT of the sacroiliac joint
and ENTERS the bladder posteriorly.
here are the 3 points of constriction in the ureters where stones are most likely found
- Pelviureteric junction
(i.e. right after ureter EXITS kidney) - Pelvic brim
(i.e. where ureter descends into pelvic cavity through pelvic inlet) - Vesicoureteric junction
(i.e. right before ureter ENTERS bladder)
pelvic brim is anterior to sacroiliac joint
what are the potential complications of urolithiasis
i.e. renal calculi
4Bs
* Bleed: Hematuria
<- stones damage urothelium
* Block:
UTI
due to partial or complete obstruction of urine flow by stone
-> urine stasis
-> ideal envt for bacterial overgrowth
and/or hydroureter/hydronephrosis
due to stone blocking urine flow
-> increased (back)pressure
=> dilation of ureter (hydroureter)
-> over time increased pressure in kidney
=> swelling of kidneys (hydronephrosis)
* Burst: Ulceration
due to stone being lodged at one location
-> repeated mechanical trauma
-> erosion of urothelium
* Burrow: Fistula formation
due to chronic irritation from the stone
-> weakened walls bet organs
=> tissue breakdown and abnormal connections bet the organs
which measurements to look out for
what are the markers of Acute Kidney Injury (AKI)
- Urine output: oliguria / anuria
- Creatinine clearance: azotaemia
azotaemia = progressive, usually rapid, rise of serum creatinine
which measurements to look out for
what are the markers of Chronic Kidney Disease (CKD)
- GFR
- presence of albuminuria
(as a marker of kidney damage)
over >3 months
cause of pre-renal kidney damage
(and examples)
inadequate perfusion or blood flow to kidneys,
e.g. from
* decreased circulatory vol (e.g. dehydration, severe vomiting)
* decreased CO
* decreased renal vascular supply,
i.e. constriction of afferent arteriole OR dilation of efferent arteriole
(e.g. drugs like ACEi)
cause of post-renal kidney damage
(and examples)
obstruction of urinary tract
-> urine backflow
-> increased pressure in renal parenchyma
* acute urinary tract obstruction (e.g. kidney stones, blood clots)
* external compression (e.g. BPH, tumours, fibrosis)
cause of intrinsic kidney damage
(and examples)
Issue with
* glomerulus (e.g. glomerulonephritis)
* tubules/interstitium (e.g. acute tubular necrosis, acute interstitial nephritis)
* vascular supply (e.g. haemolytic uraemic syndrome, vasculitis)
OR just everything (e.g. severe infections)
ATN: necrosis of TUBULAR cells,
either due to ischaemia
or nephrotoxic causes (e.g. drugs, infections)
AIN: inflammation of renal INTERSTITIUM
(i.e. tissue surrounding tubules and glomerulus),
often due to allergic rxn to meds
or infections
or autoimmune diseases
definition of acute on chronic kidney disease
acute worsening of previously stable chronic kidney disease
How does diabetes mellitus (DM) lead to CKD
i.e. diabetic nephropathy
high blood sugar
-> hyperfiltration (to get rid of excess sugar)
-> increased pressure inside glomeruli
-> thickening of glomerular basement membrane (GBM)
-> over time there is scarring (glomerulosclerosis)
most common cause of CKD
<-> other common causes include glomerulonephritis and HTN
histological changes of diabetic nephropathy
- Diffuse mesangial expansion
due to excess glucose
-> glycosylation of proteins
-> triggers mesangial cell proliferation and matrix accumulation - Nodular mesangial expansion
due to chronic mesangial expansion and ECM deposition
-> localised nodules - Afferent AND efferent arteriolar hyalinosis
due to excess glucose damaging endothelial cells
-> leakage of plasma proteins into vessel wall
-> hyaline deposits which cause narrowing and stiffening of blood vessels
histological features of hypertensive nephrosclerosis
- arteriolar hyalinosis
due to chronic hypertension
-> persistent high BP damaging endothelial cells
-> leakage of plasma proteins into vessel wall
-> hyaline deposits which cause narrowing and stiffening of blood vessels
=> ischaemia and CKD -
hyperplastic arteriolosclerosis
due to malignant hypertension
-> extreme BP triggers smooth muscle prolieration
-> formation of layers of smooth muscle
-> “onion skin” thickening of arterioles and narrowing of lumen
=> severe ischaemia and renal failure
arteriolar hyalinosis ONLY seen in afferent arteriole
what is affected in nephrItic syndromes
Inflammation disrupting
glomerular basement membrane (GBM)
what is affected in nephrotic syndromes
podocyte damage
leading to disruption of glomerular charge-barrier
Which of the following is a characteristic feature of nephritic syndrome?
A) Massive proteinuria with fatty casts
B) Isolated hyperlipidemia
C) Hematuria with dysmorphic RBCs and RBC casts
D) Severe hypoalbuminemia
C) Hematuria with dysmorphic RBCs and RBC casts
nephrItic syndrome
= Inflammation disrupting GBM
-> glomerular capillary damage
=> increased passage of RBCs into urine
increased bcos pliability of RBCs -> can squeeze through GBM usuall
- GROSS hematuria (i.e. HIGH RBC in urine)
=> cola coloured urine - diff from mild proteinuria which is due to increased glomerular capillary permeability
compare edema seen in nephrotic vs nephritic syndrome
- nephrotic is due to disruption of glomerular charge-barrier
-> excessive protein leakage into urine (proteinuria)
-> which exceeds hepatic albumin synthesis,
thus resulting in hypoalbuminemia
-> decreased plasma oncotic pressure
-> fluid leakage into interstitial space
=> anasarca (generalised, but esp pedal, periorbital and abdominal swelling) - nephritic is due to inflammation of glomerulus
-> reduce filtration surface area
-> decrease GFR
-> RAAS activation
-> sodium and water retention
-> increased intravascular vol
-> increased hydrostatic pressure
=> edema
Edema in nephritic not as bad as nephrotic
Normal filtering of proteins:
Proteins are filtered based on molecular size and charge
(LMW and (+)-charged proteins can be filtered, since glomerular charge barrier is (+)-charged)
-> ALL LMW and some albumin cross glomerular barrier
-> then completely reabsorbed in tubule
Which of the following best explains why nephritic syndrome often presents with hypertension?
A) Massive protein loss causing a decrease in plasma volume
B) Unable to filter sodium and water due to glomeruli damage
C) Increased capillary permeability leading to fluid loss
D) Direct injury to the sympathetic nervous system
B) Unable to filter sodium and water due to glomeruli damage
inflammation of glomerulus
-> reduce filtration surface area
-> decrease GFR
-> RAAS activation
-> sodium and water retention
=> HTN
urine vol in nephrotic vs nephritic syndrome
- nephrotic: no significant change in urine vol
- nephritic: oliguria
due to inflammation of glomerulus
-> reduce filtration surface area
=> reduce GFR
note: proteinuria -> foamy urine in nephrotic syndrome
is hyperlipidaemia seen in nephrotic or nephritic syndrome
nephrotic
due to massive protein loss
-> exceed hepatic albumin synthesis,
thus resulting in hypoalbuminemia
=> triggers increased synthesis of lipoPROTEINS by liver as compensatory mechanism
will also see lipiduria
as increased hepatic lipoprotein production leads to spill into urine
is proteinuria seen in nephritic syndrome
yes, but MILD
due to glomerular barrier inflammation
-> increased capillary permeability
-> proteins leak
what is a patient with nephrotic syndrome more susceptible to
-
infections
<- loss of proteins include antibodies (IgG)
AND altered production
(defect in switch from IgM -> IgG synthesis) -
thrombotic disorders
<- loss of proteins include anticoagulants
Which of the following is the most common cause of nephrotic syndrome in children?
A) Focal Segmental Glomerulosclerosis (FSGS)
B) Membranous Nephropathy
C) Minimal Change Disease (MCD)
D) Diabetic Nephropathy
E) Lupus Nephritis
C) Minimal Change Disease (MCD)
where there is effacement (i.e. flattening) of podocyte foot processes
-> loss of podocyte integrity
=> disruption of glomerular charge barrer
in contrast, membranous glomerulopathy is the most common cause of nephrotic syndrome in adults
Which nephrotic syndrome is curable with steroids?
Minimal Change Disease
do so by
* reducing inflammation
* suppressing immune response that is damaging the filtration barrier
thus have good prognosis
in contrast, Focal Segmental Glomerulosclerosis is steroid resistant
Which of the following nephrotic syndromes is most likely to present with subepithelial immune complex deposits on electron microscopy?
A) Minimal Change Disease
B) Focal Segmental Glomerulosclerosis
C) Membranous Glomerulopathy
D) Diabetic Nephropathy
E) Lupus Nephritis
deposition of immune complexes
-> complement activation
-> podocyte injury
=> disruption of glomerular charge barrer
C) Membranous Glomerulopathy
deposition of immune complexes on basement membrane (IgG and C3)
-> thickening of the GBM
Which nephritic syndromes is the most common cause of glomerulonephritis?
IgA nephropathy
where there is IgA deposits in glomeruli
commonly associated with URTI
Which of the following is a key histological feature of Focal Segmental Glomerulosclerosis (FSGS)?
A) Diffuse thickening of the glomerular basement membrane
B) Podocyte foot process effacement with no scarring
C) Focal and segmental sclerosis of some glomeruli
D) Subepithelial immune complex deposits
E) Crescent formation in glomeruli
C) Focal and segmental sclerosis of some glomeruli
sclerosis is due to podocyte injury
<- idiopathic or secondary to factors like obesity, hypertension, etc
example of a thiazide diuretic
hydrochlorothiazide
which organs (or parts of them) is lined by transitional epithelium
i.e. urothelium
- renal pelvis (of kidneys)
- ureters
- urinary bladder
- proximal urethra
found in these areas
as urothelium can stretch and adapt to varying urine volumes
what are the 3 layers which form the ureters and the urinary bladder
from innermost to outermost:
* lamina propria
(connective tissue containing blood vessels, nerves and lymphatics)
* muscularis propria
(smooth muscle)
* adventitia (or serosa in parts of kidneys covered by peritoneum)
(connective tissue)
in ureter, smooth muscle consists of 3 layers:
inner longitudinal, middle circular, outer longitudinal
-> facilitate peristaltic contractions to move urine
in bladder, smooth muscle consists of layer
which are collectively known as detrusor muscle
Post-infectious glomerulonephritis (PIGN) most commonly occurs after an infection with which organism?
a) Staphylococcus aureus
b) Group A Streptococcus
c) Escherichia coli
d) Mycobacterium tuberculosis
b) Group A Streptococcus
immune complexes (strep antigens + antibodies) deposit in GBM
-> trigger complement activation
=> inflammation
- A patient with systemic lupus erythematosus (SLE) develops nephritis. Which of the following is the most likely immunofluorescence finding in his kidney biopsy?
A) IgG and C3 deposits with a “lumpy-bumpy” appearance
B) “Full house” immunofluorescence with IgG, IgA, IgM, C3, and C1q
C) Linear IgG deposits along the basement membrane
D) Apple-green birefringence under polarized light with Congo red staining
B) “Full house” immunofluorescence with IgG, IgA, IgM, C3, and C1q
nephritic syndrome associated w/ SLE
= lupus nephritis
Which of the following statements about IgA nephropathy (Berger’s disease) is true?
A) It usually follows a streptococcal throat infection by 1-3 weeks
B) It is associated with normal serum complement levels
C) It causes diffuse subepithelial deposits on electron microscopy
D) It is always associated with Henoch-Schönlein purpura
B) It is associated with normal serum complement levels
forms IgA immune complexes instead of usual ones which involves C3 and C4
-> normal serum complement levels
(in contrast to PIGN which has low C3 lvls
and lupus nephritis which has low C3 and C4)
(A) is Post-infectious glomerulonephritis
which follows infection by certain strains of streptococci, usually strep pharyngitis
complications if CKD is left untreated
- Fluid and electrolytes related
e.g. Dehydation
due to kidney being unable to concentrate urine
-> generate more urine to excrete solutes
e.g. HyperKalemia and hypoNatremia - Bone related
e.g. Osteoporosis
due to hyperphosphataemia
<- less phosphate excretion
and hypocalcaemia
<- less vit D produced due to kidney damage - Haematologic (i.e. Blood related)
e.g. Anaemia
due to less EPO produced
-> decreased RBC
Vit D increase calcium levels when they are low by
* increasing calcium absorption in intestine
* promoting calcium release from bone breakdown
* reducing calcium excretion by kidneys
which of the following is not a superior relation of the kidneys?
A) Abdominal muscles
B) Ribs
C) Diaphragm
D) Liver
A) Abdominal muscles
anterior to the kidney
(B) Floating ribs (12th and/or 11th) lie anterior and posterior to kidneys
(C) Diaphragm is located superior to kidneys
3
where does fluid enter after passing through collecting ducts
minor calyces
-> major calyces
-> renal pelvis
3 types
what epithelium lines urethra
- proximal urethra: urothelium
- membranous and spongy urethra: psuedostratified columnar epithelium
- distal urethra: stratified squamous epithelium
<- wear and tear due to contact w/ external envt
name the specific part of the bladder which is smooth
trigone area
(between the 2 ureteric orifices and the internal urethral opening)
differences between internal and external urethral sphincter
- location:
internal is at junction of bladder and urethra,
while external is further down urethra - structure and control:
internal is smooth muscle and is thus under autonomic control,
while external is skeletal muscle and can be controlled via pudendal nerve
and its location
function of macula densa (MD) cells
- located at distal end of thick ascending limb of Loop of Henle
- monitors the NaCl conc within lumen of DCT
type of cell, location
function of juxtaglomerular (JG) cells
- modified smooth muscle cells located in afferent arteriole
- synthesise and secrete renin
2 mechanisms
what results in the constriction or dilation of afferent arteriole
- change in BP:
when BP increases
-> arterial wall is stretched more
-> trigger myogenic mechanism
-> contraction of afferent arteriole - change in NaCl in filtrate:
when NaCl conc in DCT increases
-> change is sensed by MD cells
-> which will then release vasoactive substances (e.g. adenosine)
-> resulting in contraction of afferent ateriole
different mechanism for
when NaCl conc in DCT decreases
-> change is sensed by MD cells
which will send a signal to JG cells
to secrete more renin
-> activation of RAAS system
-> increase in Ang II which will increase GFR through contraction of efferent arteriole
AND increase in aldosterone will increase blood volume and thus BP through Na+ and water retention
limitations of creatinine clearance as an estimation of GFR
creatinine is moderately secreted by renal tubules
-> greater conc of creatinine in urine than estimated
=> GFR will be slightly overestimated
previously used marker is inulin
which is freely filtered and NOT reabsorbed or secrete
where does the majority of reabsorption occur
PCT
“after pushing out everything (filtration),
try to take back as much as possible first (reabsorption)
then slowly throw out stuff (secretion)”
and how much of it
what substances are reabsorbed in PCT
- glucose and amino acids: 100%
<- important building blocks - water: majority
- NaCl: majority
- bicarbonate: majority
how is sodium reabsorbed in PCT
- moves from tubule lumen into PCT
by moving down its electrical gradient (passive transport)
via various membrane proteins (e.g. ENaC) - then actively pumped out from basolateral side of PCT into interstitial fluid
by Na+/K+ ATPase
how is glucose reabsorbed in PCT
- sodium reabsorption pathway,
but instead of ENaC,
sodium is absorbed through sodium-glucose linked transporters (SGLT),
thus helping to pull glucose into cell against its conc gradient - glucose then diffuses out of basolateral side of PCT via glucose transporters (GLUT)
function of vasa recta
minimise dissipation of conc gradient via countercurrent exchange where
* lying parallel to loop of Henle and being in close associtation
* having a very slow flow
* equilibrate with medullary osmolarity:
(e.g. in descending limb of tubule, water is reabsorbed into renal medulla
-> ascending limb of vasa recta then absorbs this water
=> allowing more water to be reabsorbed into renal medulla)
what is the main function of DCT
secretion of K+, bicarbonate and H+
“after throwing out everything (filtration),
take back first (reabsorption)
then slowly filter (secretion)”
and where it acts
MOA of aldosterone
- acts on DCT cells
- transcription, translation and protein synthesis to form
1. proteins which modulate EXISTING channels and pumps
2. NEW protein channels and pumps
describe process of organic anion secretion in PCT
just a vague description, don’t need to go into details (e.g. specific transporters)
-
accumulate Na+ and aKG- from urine
(i.e. movement from tubule lumen into PCT cell) -
throw away Na+ into body so that can get more aKG-
(i.e. movement of Na+ from PCT cell into interstitial fluid
-> movement of aKG- from interstitial fluid into PCT) - excess aKG- allows up to take organic anions from body through OAT transporters
(i.e. movement of aKG- from PCT cell into interstitial fluid in exchange for OA-) - trade out OA- for other anions
(i.e. movement of OA- from PCT cell into tubule lumen in exchange for A-)
which part of the nephron has the highest osmolarity
Loop of Henle
<- water reabsorption at descending limb
refers only to the LOOP part
and NOT the ascending or descending limb
CORRECT UR MISCONCEPTION!
reabsorption = moving of substance from urine (in tubules) to blood plasma
Why can a solution be hyperosmotic but hypertonic?
Solution can have HIGHER total conc of solutes,
and a HIGHER conc of non-penetrating solutes
=> water moves into solution
and what is it released by
where is anti-diuretic hormone (ADH) synthesised
- synthesised in hypothalamus
- released by posterior pituitary
can rmb as pituitary GLAND -> thus release ADH hormone
plus since kidneys are located in posterior part of body -> posterior pituitary
MOA of ADH
a.k.a. vasopressin
triggers G-protein signalling
-> increases insertion of aquaporin-2 water pores into APICAL membrane of collecting duct cells via exocytosis
=> increase permeability of collecting duct to water
and thus increase water reabsorption
recall! apical = side facing tubular lumen
related to ADH
what is diabetes insipidus
insufficient ADH
-> excessive H2O loss
=> polyruria (w/ low urine osmolarity),
hypovolaemia
and polydipsia
polydipsia = increased thirst in response to volume loss
related to ADH
what is SIADH
excessive ADH release
-> excessive H2O retention
=> high urine osmolarity,
hyponatraemia
and volume overload
sodium conc drop
as water retention occurs WITHOUT sodium retention
unlike effect of aldosterone
3 mechanisms
how is RAAS activated when BP is low
- decrease in renal perfusion secondary to decrease in SV and CO
-> JG cells in afferent arteriole detect less stretch
=> release renin - decrease in renal perfusion secondary to decrease in SV and CO
-> decrease in GFR
-> decrease in sodium reaching DCT
-> MD cells in DCT detect lower sodium levels
=> send signals to JG cells to release renin - drop in BP is detected by baroreceptors (in carotid sinus and aortic arch)
-> increase in adrenergic activity (sympathetic tone)
-> stimulation of B1-adrenergic receptors on JG cells
=> release of renin
MOA of aldosterone
- diffuses into principal cells of collecting duct
-> binds to cytoplasmic receptor
-> triggers increased expression and activity of
1. NEW protein channels and pumps
2. proteins which modulate EXISTINF protein channels and pumps
what is the main stimuli of aldosterone synthesis and release
- decreased BP
- hyperkalaemia
where is aldosterone synthesised
adrenal cortex
upon activation of RAAS
in contrast, adrenal medulla releases catecholamines
(epinephrine and norepinephrine)
Which of the following is NOT an effect of Angiotensin II?
A. Vasoconstriction of systemic arterioles
B. Increased Na⁺ reabsorption in the proximal tubule
C. Direct stimulation of aldosterone release from the adrenal cortex
D. Increased K⁺ excretion in the kidneys
E. Increased ADH release
D. Increased K⁺ excretion in the kidneys
increased K+ excretion
(with increased Na+ and H2O retention)
is effect of aldosterone
on DCT and collecting duct
- other than vasoconstriction of systemic arterioles (A),
there is also vasoconstriction of efferent arteriole
-> decrease net renal blood flow and increase intraglomerular pressure
=> increase and thus maintain GFR - Ang II results in increased Na+ and H2O reabsorption at PCT (B)
- Ang II also has central effects,
which includes stimulating pituitary gland to release more ADH (E)
as well as acting on hypothalamus to increase thirst
what receptors detect changes in plasma osmolarity
- osmoreceptors in hypothalamus
- regulates ADH release and thirst
how does BODY respond to increased blood volume
atrial natriuretic peptide system
* where increased blood vol triggers atria and ventricular stretch receptors
-> release of ANP and BNP
* inhibits sodium reabsorption and aldosterone release via
(i.e. opp of RAAS)
1. vasodilation in kidneys
-> increase GFR
=> reduce renin secretion
2. inhibit aldosterone secretion in adrenal cortex
3. inhibit ADH secretion in hypothalamus
4. reduce sympathetic output in medulla oblongata
how does potassium levels affect muscles
- hyperkalaemia:
increased [K+] in cells
-> resting membrane potential is less (-)
-> increase likelihood of spontaneous depolarisation
=> increased excitability - hypokalaemia:
decreased [K+] in cells
-> resting membrane potential is more (-)
-> stronger stimulus required to trigger action potential and depolarisation
=> muscle weakness
thus another side effect of hyperkalaemia is cardiac arrhythmias,
while another side effect of hypokalaemia is failure of respiratory muscles and heart
given pH, CO2 and HCO3-
interpretation of arterial blood gas
- Does pH indicate acidosis or alkalosis?
(normal pH range = 7.35-7.45) - Does the change in CO2 or HCO3- account for the acidosis/alkalosis?
(normal pCO2 range = 35-45mmHg,
normal [HCO3-] = 22-28 mEq/L)
1. If due to CO2 => respiratory
2. If due to HCO3- => metabolic - Deduce compensatory action
cause of respiratory acidosis
hypoventilation
-> CO2 retention
-> accumulation of CO2 resulting in increased PaCO2
-> more CO2 reacting with H2O
-> increased H+
=> decrease in pH and acidosis
most common cause is COPD
other possible causes are
* other obstructive lung diseases (e.g. pneumonia, asthma)
* airway obstruction
* respiratory depression (opioids, alcohol)
cause of metabolic alkalosis
excess HCO3- or loss of H+
-> increased HCO3-
-> increased pH and thus alkalosis
most common causes are
* excess HCO3-: excessive antacid use
* loss of H+: vomiting, diuretics (NOT diarrhoea)
what compensation is seen in metabolic acidosis/alkalosis
- fast: respiratory compensation
(hypo/hyperventilation) - slow (i.e. hours to days): renal compensation
(HCO3- excretion to lower pH/HCO3- reabsorption to BUFFER acidity)
common cause of metabolic acidosis
- excess H+: diabetic ketoacidosis, lactic acidosis
- loss of HCO3-: diarrhoea
what does anion gap check for
- used when there is metabolic acidosis
-
high AG (>12) indicates
AG metabolic acidosis
(e.g. DKA)
formula for AG = Na+ - (Cl- + HCO3-)
for respiratory or metabolic acidosis/alkalosis
what formulas can be used to check compensation
- respiratory acidosis and alkalosis: acute/chronic formulas
- metabolic acidosis: Winter’s formula
- metabolic alkalosis: expected PaCO2 formula
If actual is different from expected,
there is a mixed acid-base disorder
w/ concomitant metabolic or respiratory acidosis/alkalosis
definition of glomerulonephritis
- inflammation of glomerulus,
leading to increasing glomerular cellularity
(i.e. abnormal increase in no of cells) - consequence: disruption of filtration barrier
-> nephrotic OR nephritic syndromes
- can lead to both nephrotic and nephritic
as it encompasses all types of disruption to filtration barrier,
including podocytes (nephrotic) or endothelium and mesangium (nephritic) - but more commonly associated with nephritic
Which of the following bacterial infections is most commonly associated with the formation of struvite (i.e. triple) stones?
A) Escherichia coli
B) Proteus mirabilis
C) Streptococcus pyogenes
D) Mycobacterium tuberculosis
triple = magnesium, ammonium, phosphate
B) Proteus mirabilis
UTI is a secondary cause of urolithiasis
as proteus is a urease-producing bacteria
-> breaks down urea into ammonia (which is basic)
-> increases urine pH
=> favours triple stone formation
Why does vitamin A deficiency increase the risk of urolithiasis?
A) It decreases calcium absorption in the intestines
B) It leads to squamous metaplasia of the urinary tract epithelium
C) It causes an overproduction of ammonium ions in the urine
D) It leads to hypercalcemia, which increases stone formation
B) It leads to squamous metaplasia of the urinary tract epithelium
bcos vit A is essential for maintaining normal epithelial lining
-> deficiency leads to squamous metaplasia
-> keratinisation of epithelium
-> provides abnormal surface for crystals to adhere to
=> increase risk of stone formation
Which type of kidney stone formation is most favored by high urine pH?
A) Calcium oxalate stones
B) Calcium phosphate stones
C) Struvite (i.e. triple) stones
D) Uric acid and cystine stones
B) Calcium phosphate stones and
C) Struvite (i.e. triple) stones
in contrast, low urine pH favours formation of uric acid and cystine stones (D)
order the following stones according to their prevalence:
(most prevalent -> least prevalent)
* calcium stones,
* cystine stones,
* triple stones,
* urate stones
- Calcium stones
- triple stones
- urate stones
- Cystine stones
CalCuli = C-dominated (2 Cs) so C at top and C at bottom
cause of calcium stones
hyperCalciuria
(i.e. high levels of calcium in URINE)
* hyperabsorption of calcium from intestine
OR intrinsic impairment in renal tubular reabsorption of calcium
* NO hypercalcemia
(i.e. high levels of calcium in blood)
as kidneys effectively filter any excess calcium
what are some conditions associated with urate stones
- GOUT
- leukemia
what is associated with cystine stones
genetic defects
CTUC
what type of stones are staghorn calculi usually
triple stones
key associations of acute interstitial nephritis
- immune-mediated inflammation
(classic triad: fever, rash, eosinophilia) - occurs 1-2 weeks after starting drug
difference between acute and chronic pyelonephritis
- acute: acute bacterial infection of kidney
- chronic: repeated/persistent infections
=> scarring, atrophy, renal dysfunction
what are the causes of chronic pyelonephritis
- vesicoureteric reflex
- obstruction
(at any level below kidney)
more long-term conditions
which predisposes patient to kidney infection/inflammation
=> progressive scarring
causes of acute tubular necrosis
- ischaemia
(commonly due to prolonged hypotension or blood loss) - toxic substances
which result in tubular epithelial cell death/injury
=> loss of tubular function
is acute tubular necrosis reversible
yes, in fact there are 3 stages
* oliguric:
tubular epithelial cell death
-> no urine being produced
* polyuric: regenerationof tubular cells
-> too much urine being produced
* recovery: gradually back to normal
histological findings of acute tubular necrosis
- sloughing
due to cell death
-> dead cells then detach from tubular walls - muddy brown casts
due to detached dead cells
accumulating to form casts
and then adhering to protein matrix
characteristics of autosomal dominant polycystic kidney disease
- affect BOTH kidneys
- starts with multiple cysts which gradually enlarge until very little parenchyma remaining
-
detoriation in renal function
=> eventually renal failure
first 2 characteristics result in BILATERAL ballotable kidneys
genes and conditions
what is autosomal dominant polycystic kidney disease associated with
- associated with mutations in polycystin-1 (PKD1) and polycystin-2 (PKD2) genes
- associated with hypertension
characteristics of cystic renal dysplasia / multicystic dysplastic kidney (MCDK)
- multiple cysts
- usually one kidney, which is non-functioning
-
abnormal tissues
(due to abnormal metanephric differentiation and persistence of primitive structures)
features of angiomyolipoma
-
benign
(usually well-circumscribed, no calcifications or irregular features) - but can rupture and bleed
- variegated cut surfaces w/ yellow FATTY areas
(will look non-uniform (multiple diff colours and tetures), and have fatty areas w/ soft, greasy texture)
angio = blood vessels (blood cells)
myo = smooth muscle (myoid spindle cells)
lipo = fat (adipose cells)
what imaging method to use for angiomyolipoma
CT imaging
due to its FATTY areas
which will appear dark grey to black on imaging
clinical presentation of renal cell carcinoma (RCC)
- painless haematuria
- mass in FLANK
- pain in FLANk
- fever
what’s the change, reason behind it
important lab finding of RCC
elevated haematocrit
ectopic EPO
(i.e. tumour secretes EPO regardless of oxygen levels)
-> increased EPO production
-> increased RBC production
haematocrit = proportion of RBCs in blood
due to RCC arising from tubular epithelium
which is responsible for REGULATED EPO production
gross morphology and histology of RCC
- gross morphology: cirumscribed,
yellowish cut surfaces w/ foci of necrosis and haemorrhage - histology: polygonal cells with clear cytoplasm
above histology is only for clear cell type
(most common type of RCC)
characteristics of urothelial carcinoma
affects urothelium
-> thus can be found in any structure lined by urothelium
=> confirm have in kidney,
but can be multifocal and also found in
ureter and bladder
associated with who, clinical presentation, prognosis
characteristics of nephroblastoma
(Wilms tumour)
- associated with children
(congenital malformations) - clinical presentation: large mass in abdomen, fever
- prognosis: good
(can be treated nephrectomy and chemotherapy)
gross morphology and histology of nephroblastoma
(Wilms tumour)
- gross morphology: well circumscribed,
grayish, white, soft mass - histology: sheets of small blue cells
genetics
what is clear cell RCC associated with
Von Hippel Lindau (VHL) syndrome
(chromosome 3p deletions)
MOA of carbonic anhydrase inhibitors
inhibits carbonic anhydrase in PCT
=> increased excretion of HCO3- (main),
H2O, K+ and Na+
carbonic anhydrase facilitates conversion of CO2 and H2O into H2CO3
thus inhibition of CA results in less H2CO3 formed
-> less H+ formed via dissociation of H2CO3 into H+ and HCO3-
-> reduced activity of Na+/H+ exchanger
=> more Na+ and HCO3- excreted in urine
hint: not diuretic haha
clinical indications of carbonic anhydrase inhibitor
- glaucoma
- metabolic alkalosis
not really used as diuretic due to its low efficacy
example of carbonic anhydrase inhibitor
acetazolamide
don’t get it mixed up with indapamide (also ends with -ide)
which is a thiazide diuretic
MOA of osmotic diuretics
physical presence results in higher osmolarity of tubular fluid in descending limb of Loop of Henle and PCT
-> reduce water reabsorption which usually occurs in these parts
=> osmotic diuresis (i.e. increased urine output)
freely filtered by glomerules but NOT reabsorbed
example of osmotic diuretic
mannitol
clinical indication of osmotic diuretic
used in emergency situations to reduce pressure
(e.g. reduce acute rise of intracranial pressure in neurologic conditions)
onset of action
of loop diuretics vs potassium-sparing diuretics
- loop diuretics: very rapid
- potassium-sparing: slow
can rmb as among the 3 main diuretics,
* loop diuretics has the highest efficacy => fast onset
* potassium-sparing has the lowest efficacy => slow onset
