renal Flashcards
(123 cards)
1
Q
what are 2 clinical parameters (from blood test) used to indicate kidney function
A
- serum creatinine
(from breakdown of muscle) - blood urea nitrogen
(from breakdwon of protein)
if kidney function declines -> accumulation of C and N -> elevated levels
2
Q
why serum creatinine levels preferred as marker of kidney function
A
muscle breakdown occurs at relatively constant rate
-> steady SCr levels
=> reliable baseline to detect changes due to change in kidney function
3
Q
limitations of serum creatinine as a kidney function marker
A
delayed rise (24-48 hrs) in levels
in AKI
4
Q
limitations of blood urea nitrogen as a kidney function marker
A
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
5
Q
Should you give diuretics (e.g. Furosemide [loop diuretic]) as treatment for low urine output if patient has a low BP?
A
No
- worsens hypotension
- lowered BP FURTHER reduces renal blood flow
=> worsening oliguria
and worsening of AKI
6
Q
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.
A
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
7
Q
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
A
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
8
Q
medial -> lateral
muscles in posterior abdominal wall
A
Psoas major -> quadratus lumborum -> transversus abdominus
quadratus lumborum is a deep posterior muscle
-> not visible from anterior side
9
Q
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)
A
C) Phrenic nerve (C3-C5)
recall! phrenic nerve provides
- motor innervation to diaphragm + sensory innervation to pleura (CVS)
- sensory innervation to pleura (resp)
10
Q
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.
A
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
11
Q
i.e. pathway
what is the venous circulation in the kidney like
A
peritubular capillaries (PCT and DCT)
AND vasa recta (loop of Henle)
-> intermediary veins which eventually merge to form
-> renal veins
=> empty into IVC
12
Q
NOT about their length
diff bet R and L gonadal veins
A
R gonadal vein drains DIRECTLY into IVC,
while L gonadal vein drains into left renal vein before reaching IVC
13
Q
what has the symptom of “loin to groin” pain and follows renal colic pattern
A
urolithiasis
(i.e. renal/kidney stone)
14
Q
what disease
when is KUB CT used
A
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
15
Q
what is the most impt thing to look out for when doing urinalysis for patient w/ urolithiasis
i.e. levels of what
A
Levels of calcium, uric acid and other substances which might form stones
16
Q
What to check for in blood tests for renal disease
A
- 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
17
Q
What is one thing that a cystogram is used to check for
A
Vesicoureteral Reflux (VUR) in children
cystogram checks if urine flows backward from bladder into ureter
18
Q
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.
A
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.
19
Q
here are the 3 points of constriction in the ureters where stones are most likely found
A
- 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
20
Q
what are the potential complications of urolithiasis
i.e. renal calculi
A
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
21
Q
which measurements to look out for
what are the markers of Acute Kidney Injury (AKI)
A
- Urine output: oliguria / anuria
- Creatinine clearance: azotaemia
azotaemia = progressive, usually rapid, rise of serum creatinine
22
Q
which measurements to look out for
what are the markers of Chronic Kidney Disease (CKD)
A
- GFR
- presence of albuminuria
(as a marker of kidney damage)
over >3 months
23
Q
cause of pre-renal kidney damage
(and examples)
A
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)
24
Q
cause of post-renal kidney damage
(and examples)
A
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)
25
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)
## Footnote
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
26
definition of **acute on chronic** kidney disease
**acute** worsening of previously stable **chronic** kidney disease
27
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)
## Footnote
most common cause of CKD
<-> other common causes include glomerulonephritis and HTN
28
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
29
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
## Footnote
arteriolar hyalinosis ONLY seen in **afferent** arteriole
30
what is affected in nephr**I**tic syndromes
**I**nflammation disrupting
glomerular **basement membrane** (GBM)
31
what is affected in nephr**o**tic syndromes
p**o**docyte damage
leading to disruption of glomerular **charge-barrier**
32
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
nephr**I**tic syndrome
= **I**nflammation disrupting GBM
-> glomerular capillary **damage**
=> **increased** passage of RBCs into urine
| increased bcos **pliability** of RBCs -> can squeeze through GBM usuall
## Footnote
* GROSS hematuria (i.e. HIGH RBC in urine)
=> **cola coloured** urine
* diff from mild proteinuria which is due to increased glomerular capillary **permeability**
33
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
## Footnote
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
34
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
35
urine vol in nephrotic vs nephritic syndrome
* nephrotic: no significant change in urine vol
* nephritic: **olig**uria
due to **inflammation** of glomerulus
-> reduce **filtration surface area**
=> reduce **GFR**
## Footnote
note: proteinuria -> **foamy** urine in nephrotic syndrome
36
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**
## Footnote
will also see **lipiduria**
as increased hepatic lipoprotein production leads to **spill into urine**
37
is proteinuria seen in nephritic syndrome
yes, but **MILD**
due to glomerular barrier **inflammation**
-> increased capillary **permeability**
-> proteins leak
38
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**
39
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
## Footnote
in contrast, **membranous glomerulopathy** is the most common cause of nephrotic syndrome in **adults**
40
Which nephrotic syndrome is curable with steroids?
Minimal Change Disease
do so by
* reducing **inflammation**
* **suppressing immune response** that is damaging the filtration barrier
## Footnote
thus have good prognosis
in contrast, Focal Segmental Glomerulosclerosis is **steroid resistant**
41
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
## Footnote
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
42
Which nephritic syndromes is the most common cause of glomerulonephritis?
IgA nephropathy
where there is IgA deposits in **glomeruli**
## Footnote
commonly associated with URTI
43
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
44
example of a thiazide diuretic
hydrochloro**thiazide**
45
which organs (or parts of them) is lined by transitional epithelium
| i.e. urothelium
* renal pelvis (of kidneys)
* ureters
* urinary bladder
* **proximal** urethra
## Footnote
found in these areas
as urothelium can **stretch** and adapt to **varying urine volumes**
46
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**)
## Footnote
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**
47
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
48
3. 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**
49
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)
## Footnote
(A) is Post-infectious glomerulonephritis
which follows **infection** by certain strains of **streptococci**, usually **strep pharyngitis**
50
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. Hyper**K**alemia and hypo**Na**tremia
* 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**
## Footnote
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
51
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
## Footnote
(B) Floating ribs (12th and/or 11th) lie anterior and posterior to kidneys
(C) Diaphragm is located superior to kidneys
52
# 3
where does fluid enter after passing through collecting ducts
minor calyces
-> major calyces
-> renal pelvis
53
# 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
54
name the specific part of the bladder which is **smooth**
**trigone** area
(between the 2 ureteric orifices and the internal urethral opening)
55
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**
56
# 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**
57
# type of cell, location
function of juxtaglomerular (JG) cells
* modified **smooth muscle** cells located in **afferent arteriole**
* synthesise and secrete **renin**
58
# 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
## Footnote
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**
59
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**
## Footnote
previously used marker is **inulin**
which is **freely filtered** and NOT reabsorbed or secrete
60
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)"
61
# 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
62
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**
63
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)**
64
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)
65
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)**"
66
# 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**
67
describe process of organic anion secretion in PCT
## Footnote
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-)
68
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
## Footnote
CORRECT UR MISCONCEPTION!
reabsorption = moving of substance **from urine (in tubules) to blood plasma**
69
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
70
# and what is it released by
where is anti-diuretic hormone (ADH) synthesised
* synthesised in **hypothalamus**
* released by **posterior pituitary**
## Footnote
can rmb as pituitary GLAND -> thus release ADH hormone
plus since kidneys are located in posterior part of body -> posterior pituitary
71
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
72
# 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
73
# related to ADH
what is SIADH
**excessive ADH** release
-> excessive **H2O retention**
=> high urine osmolarity,
hyponatraemia
and volume overload
## Footnote
sodium conc drop
as water retention occurs WITHOUT sodium retention
unlike effect of aldosterone
74
# 3 mechanisms
how is RAAS activated when BP is low
1. decrease in renal perfusion secondary to decrease in SV and CO
-> **JG cells** in **afferent arteriole** detect **less stretch**
=> release **renin**
2. 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**
3. 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**
75
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
76
what is the main stimuli of aldosterone synthesis and release
* decreased BP
* **hyperkalaemia**
77
where is aldosterone synthesised
adrenal **cortex**
| upon activation of RAAS
## Footnote
in contrast, adrenal **medulla** releases catecholamines
(epinephrine and norepinephrine)
78
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**
## Footnote
* 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**
79
what receptors detect changes in **plasma osmolarity**
* **osmo**receptors in **hypothalamus**
* regulates **ADH** release and thirst
80
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**
81
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**
## Footnote
thus another side effect of hyperkalaemia is **cardiac arrhythmias**,
while another side effect of hypokalaemia is **failure of respiratory muscles and heart**
82
# 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 = **35-45**mmHg,
normal [HCO3-] = **22-28** mEq/L)
1. If due to CO2 => respiratory
2. If due to HCO3- => metabolic
* Deduce compensatory action
83
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
## Footnote
most common cause is **COPD**
other possible causes are
* other obstructive lung diseases (e.g. pneumonia, asthma)
* airway obstruction
* respiratory depression (opioids, alcohol)
84
cause of metabolic alkalosis
**excess HCO3-** or **loss of H+**
-> increased HCO3-
-> increased pH and thus alkalosis
## Footnote
most common causes are
* excess HCO3-: excessive **antacid** use
* loss of H+: **vomiting**, diuretics (NOT diarrhoea)
85
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**)
86
common cause of metabolic acidosis
* excess H+: **diabetic ketoacidosis**, lactic acidosis
* loss of HCO3-: **diarrhoea**
87
what does anion gap check for
* used when there is **metabolic acidosis**
* **high** AG (>12) indicates
**AG metabolic acidosis**
(e.g. **DKA**)
## Footnote
formula for AG = Na+ - (Cl- + HCO3-)
88
# 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**
89
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
## Footnote
* 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
90
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
91
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
92
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
## Footnote
in contrast, **low** urine pH favours formation of uric acid and cystine stones (D)
93
order the following stones according to their prevalence:
(most prevalent -> least prevalent)
* calcium stones,
* cystine stones,
* triple stones,
* urate stones
* **C**alcium stones
* triple stones
* urate stones
* **C**ystine stones
| **C**al**C**uli = C-dominated (2 Cs) so C at top and C at bottom
94
cause of calcium stones
hyper**Ca**lci**uria**
(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
95
what are some conditions associated with urate stones
* **GOUT**
* leukemia
96
what is associated with cystine stones
**genetic** defects
97
# CTUC
what type of stones are staghorn calculi usually
triple stones
98
key associations of acute interstitial nephritis
* immune-mediated **inflammation**
(classic triad: fever, rash, eosinophilia)
* occurs 1-2 weeks after **starting drug**
99
difference between acute and chronic pyelonephritis
* acute: acute **bacterial infection** of kidney
* chronic: **repeated**/persistent infections
=> **scarring, atrophy, renal dysfunction**
100
what are the causes of chronic pyelonephritis
* vesicoureteric reflex
* obstruction
(at any level below kidney)
## Footnote
more long-term conditions
which predisposes patient to kidney infection/inflammation
=> progressive scarring
101
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**
102
is acute tubular necrosis reversible
yes, in fact there are 3 stages
* oliguric:
tubular epithelial **cell death**
-> **no urine** being produced
* polyuric: **regeneration**of tubular cells
-> **too much urine** being produced
* recovery: gradually **back to normal**
103
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**
104
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**
## Footnote
first 2 characteristics result in BILATERAL **ballotable** kidneys
105
# 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**
106
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)
107
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**)
## Footnote
angio = blood vessels (blood cells)
myo = smooth muscle (myoid spindle cells)
lipo = fat (adipose cells)
108
what imaging method to use for angiomyolipoma
CT imaging
due to its **FATTY** areas
which will appear **dark grey to black** on imaging
109
clinical presentation of renal cell carcinoma (RCC)
* painless **haematuria**
* **mass** in FLANK
* pain in FLANk
* fever
110
# 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
## Footnote
due to RCC arising from **tubular epithelium**
which is responsible for REGULATED EPO production
111
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)
112
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**
113
# 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**)
114
gross morphology and histology of nephroblastoma
(Wilms tumour)
* gross morphology: well circumscribed,
**grayish, white, soft** mass
* histology: sheets of **small blue cells**
115
# genetics
what is clear cell RCC associated with
Von Hippel Lindau (VHL) syndrome
(chromosome 3p deletions)
116
MOA of carbonic anhydrase inhibitors
inhibits **carbonic anhydrase** in **PCT**
=> increased excretion of **HCO3-** (main),
**H2O, K+ and Na+**
## Footnote
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
117
# hint: not diuretic haha
clinical indications of carbonic anhydrase inhibitor
* glaucoma
* metabolic alkalosis
## Footnote
not really used as diuretic due to its **low efficacy**
118
example of carbonic anhydrase inhibitor
acetazolamide
## Footnote
don't get it mixed up with indapamide (also ends with -ide)
which is a thiazide diuretic
119
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**)
## Footnote
freely filtered by glomerules but **NOT reabsorbed**
120
example of osmotic diuretic
mannitol
121
clinical indication of osmotic diuretic
used in **emergency** situations to reduce pressure
(e.g. reduce acute rise of **intracranial pressure** in neurologic conditions)
122
onset of action
of loop diuretics vs potassium-sparing diuretics
* loop diuretics: **very rapid**
* potassium-sparing: **slow**
## Footnote
can rmb as among the 3 main diuretics,
* loop diuretics has the **highest efficacy** => **fast** onset
* potassium-sparing has the **lowest efficacy** => **slow** onset
123
identify which ones are MD cells
and which ones are JG cells
