Urology - Abnormal urine Flashcards
What is an acid?
H+ donor (total dissociation)
What is a base
H+ acceptor
What is a weak acid
HA ⇌ H ⁺ + A⁻ (partial dissociation)
What is a weak base
B + H ⁺ ⇌ BH⁺ (partial dissociation)
What is a buffered solution
A solution in which the addition of an acid or base does not affect the pH of the solution
Give Examples of physiological buffers
Bicarbonate [HCO₃⁻]
Phosphate [H₂PO₄⁻], [HPO₄2-]
Plasma proteins
Haemoglobin
What is the pH range where life can exist
6.8-7.8
What is the normal pH of the body
7.3 -7.4
Why is pH so tightly regulated
Enzyme dysfunction and denaturation =- DEATH
How is acid and alkali generated in the body
Diet (high meat is more acidic) and cellular metabolism (main reason)
What is the Bicarbonate buffer system equation
CO2 + H2O ⇌ H2CO3 ⇌ H ⁺ + HCO3-
What happens if you add to a weak acid
The conjugate base [A ⁻] of the partially dissociated weak acid [HA] neutralises the acid
What happens if you add a weak base
The hydrogen ion [H⁺] from the partially dissociated weak base [BH ⁺ ] neutralises the weak alkali
Where is the bicarbonate buffer system in the body located
CO2 + H 2O (lungs - resp)⇌ H 2CO3 ⇌ H ⁺ + HCO 3- (kidneys - metabolic)
What enzyme catalyses CO2 + H 2O ⇌ H 2CO
carbonic anhydrase (SLOW reaction)
what causes the reaction in H 2CO3 ⇌ H ⁺ + HCO 3-
FAST ionisation reaction
What is the weak acid in the equation CO2 + H 2O ⇌ H 2CO3 ⇌ H ⁺ + HCO 3-
H2CO3
What is the conjugate base in the equation CO2 + H 2O ⇌ H 2CO3 ⇌ H ⁺ + HCO 3-
HCO3-
Where is CO2 excreted
Lungs
Define acidaemia
an arterial pH below the normal range (<7.35)
What does a disturbance in bicarbonate primarily
Metabolic disorder
What does a disturbance in
respiratory disorder
Define alkalaemia
an arterial pH above the normal range (>7.45)
Define alkalosis
A process that tends to raise the extracellular fluid pH
Define acidosis
process that tends to lower the extracellular fluid pH
Why is reclamation of filtered bicarbonate and generation of new bicarbonate needed
To neutralise the net endogenous acid production (NEAP) (approx 50-100mmol/day)
How is pH maintained in the kidney
NEAP = RNAE
What should RNAE be in a 70kg person
70mEq
3 ways to get rid of acid
Bicarbonate, lungs, excretion of H+ by kidneys
How does the renal tubular reabsorb bicarbonate an decrease H+
reabsorbed an H+ is secreted
What are the 2 things kidneys do to maintain pH
Reclamation of bicarbonate
Generate new bicarb
How is HCO3 reabsorbed in early and late segments
H+ moves into tubular lumen - forms H2CO3 (conjugate), then separated with an enzyme to CO2 and H2O.
CO2 and H2O diffuses back into cell.
Once again is split into HCO3 and H+ by carbolic anhydrase
The H+ generated is used again to move into the tubular lumen.
1 H+ out 1HCO3 in
how does urinary phosphate (Pi) buffers generate new bicarbonate
Acidosis stimulates excretion of urinary Pi
buffers as titratable acid
How does synthesis of NH4+ from NH3 generate new bicarb
Acidosis stimulates renal ammoniagenesis
from glutamine
What is the pH range of urine
4.5- 8.0
What is the concentration of free H+ in urine at pH 4
0.1mmol/L
What would happen if no bufferes were used in urine to eliminate 70mmol of H+
you would excrete 700L of urine a day
What are the 2 buffer systems
Phosphate buffer system
Ammonia buffer system
What is the phosphate buffer system
NaPO4- binds to the secreted H+ creating NaH2PO4 which is excreted in urine
What is the ammonia buffer system
making NH4- and Cl-, the amonium chloride is excreted.
How does the amonia buffer system generate bicarb
Glutamine is broken down in the cell to 2NH+4 and 2HCO3. Ammonia is actively transported into the lumen and excreted and sodium (Na+ is actively reabsorbed). Bicarb is generated
What would happen to urinary HCO 3- excretion if a drug that inhibits
carbonic anhydrase is administered?
What is the urine anion gap
(Urine sodium + urine potassium)- urine chloride
What happens if there is more chloride than cations
Negative UAG - it indicated another cation is being excreted (NR4+)
what is increase renal amonium excretion the correct response of
metabolic acidosis. Tubular function is intact
What are clinical examples of respiratory acidosis
Emphysema, hypoventilation
What are clinical examples of metabolic acidosis
Lactic acidosis, renal failure, ketoacidosis, renal tubular acidosis
What are clinical examples of respiratory alkalosis
Congestive cardiac failure, raised intracranial pressure, hyperventilation
What are examples of metabolic alkalosis
Vomiting, diuretics, Cohns syndrome
What is the equation for RNAE
RNAE = [(U NH4x V)] + (U TA x V)] – (U HCO3_ x V)
What is the Henderson-hasselbach equation
pH = pKₐ + log([A⁻]/[HA])
One way to determine the pH of a buffer is by using the Henderson–Hasselbalch equation. In this equation, [HA] and [A⁻] refer to the equilibrium concentrations of the conjugate acid–base pair used to create the buffer solution.
What is the structure of the glomerula
Learn image
What is the purpose of a nephrone
To be a sieve to form a filtrate
What allows filtrate to form
Fee started capilary
What does the glomerular filtration barrier look like (what layers form or)
Where does the filtrate form
Bowman’s space
Define focal
Affecting only some glomeruli
Define diffuse
Affecting all glomeruli
Define segmental
Affecting only part of glomeruluS
Define global
Affecting whole glomerulus
Define proliferation
Increase in number of cells
Define expansion
Increase in intercellular matrix
Define crescent
Proliferation of cells within Bowman’s space
What are the 4 immunological mechanisms underlying glomerulonephritis
Intrinsic
Planted
Circulating
Non-specific deposition
What is intrinsic immunological mechanism of GN
Antibody binding to intrinsic glomerular antigens
- eg Goodpasture’s Disease
What is planted immunological mechanism of GN
Antibody binding to “planted” glomerular antigens
- eg post-Streptococcal glomerulonephritis
What is circulating complexes immunological mechanism of GN
Deposition of circulating antigen-antibody complexes
- eg lupus nephritis
What is the non-specific deposition mechanism of GN
The heavy chain is non-specific and is ‘sticky’ binding
-eg IgA nephropathy
What is the vascular mechanism of GN
Pauci-immune” capillary inflammation (eg systemic vasculitis) - granulomatitis with polyangitis - inflammation leading to ischaemia and damage
Pauci - means poor
What are some of the indications for renal biopsy
Nephrotic syndrome (adults)
Renal dysfunction of unknown cause (particularly acute)
To guide treatment or assess prognosis where diagnosis known
Dysfunction of transplant kidney - rejection
(Haematuria)
(Proteinuria)
What are complications of renal biopsy
Pain
Bleeding - macroscopic haematuria (5%)
- blood transfusion (0.5%)
- embolisation 1 in 1000
- nephrectomy 1 in 2000
- death
What are key contraindications for renal biopsy
Abnormal clotting / thrombocytopenia
Drugs (aspirin , clopidogrel, warfarin, DOACs etc)
Uncontrolled hypertension (eg >170/100)
Single kidney
Hydronephrosis - obstruction to outflow
Urinary tract infection
What 3 ways would you use to interpret renal biopsy
Light microscope
Immunostaning
Electron microscopy
What would you see for light microscopy
Basic morphology / cellular infiltrate
What stain would you use on a renal biopsy in light microscopy
Special stains – eg silver highlights collagen
What would you be looking at/for in immunostaining
Immunoglobulin or complement components
What would you be looking at/for in electron microscopy
Ultrastructural detail, including immune deposits
What are some presentations of renal disease
Haematuria
Proteinuria
Hypertension
Nephrotic syndrome
Nephritic syndrome
Acute kidney injury
Chronic kidney disease
Diagnose and what are the features of the disease
45 year old man with frothy urine, generalised oedema Urine dipstick 4+ protein Investigations:
- Urine protein excretion 5g/24hrs
- Albumin 22
Nephrotic syndrome
Proteinuria Hypoalbuminaemia Oedema
What is the most common cause of nephrotic syndrome in children (>75%)
minimal change disease
What would you expect to see on a light microscope biopsy of minimal change disease
Would be normal
What would you expect to see on an electron microscope biopsy of minimal change disease
fusion of podocyte foot processes (non- specific result of proteinuria)
What is the causes of MCD
IDIOPATHIC
Drugs - NSAIDS
Lymphoma
How do you treat MCD
Steroids
May relapse later and need more immunosuppression
What does FSGS stand for
Focal Segmental Glomerulosclerosis
How does FSGS present
Presents with nephrotic sydrome ± renal impairment Patchy (focal) involvement of kidney: may miss on biopsy
What would you see on immunoflourescence
Segmental sclerotic lesions with C3 and IgM deposition
How to treat FSGS
Not as responsive to steroids than MCD. Need very high dose
May get renal failure
May need transplant
What are the primary and secondary causes of FSGS
Obesity - IV heroin use - HIV - Drugs (eg pamidronate)
What is the most common cause of nephrotic syndrome in adults
MN membranous nephropathy
What would you see on histology for MN
spikes” on basement membranes, IgG deposition
What is MN associated with
Malignancy → careful history, consider investigation Drugs (eg gold, penicillamine, captopril) - Infections (eg hepatitis, malaria)
What will occur if you don’t treat (rule of 1/3)
- 1/3 improve spontaneously - 1/3 remain the same - 1/3 develop progressive disease
How to treat MN
Immunosuppression
If use steroids its in association with other immunosuppression (e.g. retuximab)
How does Mesangiocapillary Glomerulonephritis (aka Membranoproliferative GN) present
several ways, including nephrotic or nephritic syndromes Mesangial proliferation (often “lobular”)
For MGN how would it appear in histology
Thickened capillary walls, “double contouring” of basement membrane Positive immunofluorescence (eg C3)
What is MGN associated with
Infections (eg hepatitis, malaria, endocarditis, shunt nephritis) - Cryoglobulinaemia - Malignancy
Can occur post transplant
How does diabetic nephropathy present
microvascular complications (eg retinopathy, peripheral neuropathy)
low level proteinuria – “microalbuminuria” Proteinuria then becomes heavier (± nephrotic syndrome)
Progressive decline in GFR (often supranormal early in disease)
What would histology show in diabetic nephropathy
Kimmelstiel-Wilson lesions (nodular glomerulosclerosis)
Darker purple spoons on image
How does amyloidosis present
heavy proteinuria ± nephrotic syndrome ± renal failure
What is amyloidosis
Deposition of amyloid within multiple organs, including kidneys
AL – light chain deposition (eg myeloma)
AA – chronic inflammation (eg infection, connective tissue disorders)
What stain would you use for amyloidosis
Stains with congo red (apple green birefringence under polarized light)
What would you expect to see in electron microscopy of amyloidosis
Fibrils
What are the common causes of nephrotic syndrome according to age
Diagnose
24 year old man presents with macroscopic haematuria Had developed a sore throat the previous day General examination and blood pressure normal Settled spontaneously, but persistent microscopic haematuria 4 weeks later
IgA Nephropathy (Berger’s Disease)
What is the most common cause of glomerulonephristis
IgA nephropathy
What is burgers disease
Deposition of circulating IgA within mesangium leading to expansion of mesangial matrix and mesangial cell proliferation
How does burgers disease present
Asymptomatic microscopic haematuria
- Episodic macroscopic haematuria (eg exercise, respiratory tract infection)
- Progressive renal impairment, end stage renal failure
What are other associations with burgers disease
Liver disease
Henloch-schonlein purpurin (abdo and joint pain, skin rash)
Diagnose and state likely presentation
30 year old man presents feeling unwell Sore throat 2 weeks ago Ankle swelling and dark urine for the last few days
Urine dipstick positive for blood
BP 160/100
Creatinine 170
NEPHRITIC” PATTERN
Hypertension Haematuria Renal impairment
What is post infectious glomerulonephritis
2-3 weeks after Group A Streptococcal infection (throat, skin)
Damage due to post immune responce
How does post infectious glomerulonephritis present
Nephrotic illness
What would immunology show for PIG
Often low C3, normal C4 (alternate complement pathway activation) ?Antibody binding to planted Streptococcal antigens
What would you see on biopsy
neutrophil infiltration, mesangial and epithelial cell, proliferation, IgG and C3 deposition, subepithelial deposits
How do you treat PIG?
supportive case only
What systemic vascular most commonly affects kidneys
Wegener’s granulomatosis (GPA), microscopic polyangiitis (MPA)
How does vascular is cause glomerulonephritis
Inflammation of blood vessels leading to multiorgan involvement
What would vasculitis show on biopsy
Focal necrotising glomerulonephritis ± crescents on biopsy, but pauci-immune
How do you treat vascular glomerulonephritis
immunosuppression +/- plasma exchange
What is the clinical presentation of cresent nephritis
nephritic illness with rapidly deteriorating renal function
What is crescent nephritis
Rapidly progressive glomerulonephritis
What would renal biopsy show for crescent nephritis
shows acute inflammatory process with crescent formation – cellular proliferation in Bowman’s space
What is the WHO classification of lupus nephritis
I: Normal glomeruli (including minimal change) II: Mesangial disease
III: Focal proliferation (<50%)
IV: Diffuse proliferation (>50%)
V: Membranous nephropathy
VI: Advanced sclerosis
What MUST you do if you suspect lupus nephritis
Renal biopsy
What urine tests can be done for patients with glomerular disease
Dipstick (blood, protein, leucocytes, nitrites)
Microscopy (cells, casts, crystals)
Culture
Protein quantification
What blood tests can be done for patients with glomerular disease
Haematology (FBC, ESR, coagulation, blood film) - Biochemistry (U&E, LFT, Ca, PO4, CRP)
Immunology: autoantibodies (ANA, ANCA, anti-GBM etc), serum immunoglobulins and electrophoresis serum free light chains, cryoglobulins, complement levels
Microbiology:blood cultures, serology (eg hepatitis B/C, HIV, ASO titre)
What imaging can be done for patients with glomerular disease
Chest radiograph
Renal ultrasound
Other (eg CT, MRI, angiography, nuclear medicine)
define proteinuria
Excessive protein in the urine
Normal urine protein <150mg/day (usually 40-80 mg/day)
how does proteinuria present?
Asymptomatic and incidental detection on urine dipstick
Heavy proteinuria —> peripheral oedema, frothy urine
What are the 6 mechanisms of Proteinuria
GTOPPP
- Glomerular
- Tubular
- Overflow
- Post-renal
- Physiological or Benign
- Pathological
what is benign proteinuria (primary and secondary cause)
Orthostatic proteinuria – children and adolescents. Usually <3.5g/day
Transient proteinuria secondary to fever, heavy exercise, vasopressor, intravenous albumin. Usually <1g/day
what is pathological glomerular proteinuria
Disruption of the filtration barrier
Can be associated with microscopic haematuria - Usually >1g/day
Give some examples of primary causes of glomerulonephritis
Minimal change disease
Primary Focal Segmental glomerulosclerosis
Idiopathic membranous nephropathy
IgA nephropathy
Idiopathic membranoproliferative glomerulonephritis (MPGN)
Give some examples of secondary causes of glomerulonephritis
Diabetes Mellitus
Systemic Amyloidosis
Secondary Focal Segmental glomerulosclerosis eg: Obesity, Hypertension, HIV infection
Autoimmune disease – eg: SLE
Secondary membranous nephropathy eg: cancer, drugs
MPGN – Hepatitis B or C
Define glomerulonephritis
Glomerulonephritis is damage to your glomeruli, tiny filters inside your kidneys.
What is tubular proteinuria
Usually < 1-2 g/day
Low molecular weight proteins are filtered at the glomerulus and reabsorbed by proximal tubules
Tubulo-interstitial nephritis:
What are the 3 causes of tubulo-interstitial nephritis. Give examples for each
Drugs - eg: Antibiotics, NSAIDs, PPIs
Autoimmune disease - eg: Crohn’s disease, Sarcoidosis, Sjogren’s disease
Infections - eg: Tuberculosis, CMV infection, Leptospirosis
What is overflow proteinuria
Excess production of low molecular weight proteins exceeds resorptive capacity of tubules
What are 3 examples of overflow proteinuria and the excess proteins they produce
Myeloma (free light chains)
Rhabdomyolysis (myoglobin)
Haemolysis (haemoglobin)
what is post-renal proteinuria
Inflammation or lower urinary tract – infection, stones
what are the 3 key clinical features of nephrotic syndrome
Hypoalbuminaemia – serum albumin < 3g/dL
Oedema
Hyperlipidemia
what are the 3 key clinical things that will occur if nephrotic syndrome is left untreated
Infection
Thrombosis
Established renal failure
- High mortality
True of False:
Nephrotic syndrome is always caused by glomerular disease
True
What are the general management and treatments for nephrotic syndrome
Low sodium diet and fluid restriction
Diuretics
Renin Angiotensin Aldosterone Inhibition and BP control
- Angiotensin constricts efferent arteriole and increases GFR
- Inhibition of angiotensin dilates efferent arteriole and decreases GFR – decreasing proteinuria
Statin
Anticoagulation
How does Minimal Change disease look on a microscope and how is it treated
Normal glomerulus on light microscopy
90% of NS in children
Steroid responsive
Uncommonly associated with renal impairment
What is Focal Segmental Glomerulosclerosis what are some of the primary and secondary causes
Focal (<50% glomeruli), Segmental (part of the glomerulus)
Primary or Idiopathic – Steroid and immunosuppression
Secondary – Obesity, Hypertension, HIV infection, Bisphosphonates
what is mebranous nephropathy and give primary and secondary causes
- ~30% of nondiabetic adult NS
- Glomerular basement membrane immune deposits
- Primary or Idiopathic – Anti PLA2R – Immunosuppression
- Secondary – hepatitis, malignancy, autoimmune, drugs
What is diabetic nephropathy what does it look like under a microscope and how is it treated
- Type 1 or Type 2 DM
- Progressive CKD and ERF
- Glycaemic control, BP control and RAAS inhibition
- Glomerulosclerosis – Kimmelstein Wilson nodules
what is amyloidosis
- Extracellular deposition of beta sheet fibrils
- Systemic disorder
what are the 2 types of amyloidosis
- AL Amyloid – Ig light chains
- AA Amyloid – Amyloid A. Chronic Inflammation.
label the renal corpuscle
label the ultrafiltration barrier
what cahrge is the ultrafiltration barrier
-ve
therefore -ve charged albumin is not filtered even though it would fit.
what is hydrostatic pressure
o Force a fluid exerts on the walls of its compartment (capillaries and bowmans capsule) – pushing out
o Main force – glomerulus forcing fluid out of glomerulus
what is oncotic pressure
pressure exerted by plasma proteins on the wall of the compartment – sucking in
what is the equation to calculate Net Filtration Pressure (NFP)
Net Filtration Pressure (NFP) (10mmHg) = HPg (55mmHg) – HPbc (15mmHg) – OPgcp (30mmHg)
HP glomerulus opposed by HP bowman’s capsule and OP glomerular capillary protein
-Ignore OP bowman’s capsule as not enough protein present
what is the GFR
Glomerular Filtration Rate (GFR) is the total amount of filtrate formed by all the renal corpuscles by both kidneys per minute
- Indication of kidney impairment
- Takes into account NFP, surface area available, and permeability of glomeruli
GFR = (surface area + permeability) x NFP
GFR – Kf x NFP
Which of the following would cause the greatest decrease in GFR in a person with
otherwise normal kidneys?
- Decrease in renal arterial pressure from 100 to 80 mm Hg
- 50% increase in proximal tubular sodium reabsorption
- 50% decrease in afferent arteriolar resistance
- 50% decrease in efferent arteriolar resistance
- 5 mm Hg decrease in Bowman’s capsule pressure
50% decrease in afferent arteriolar resistance
A 50% decrease in efferent arteriolar resistance would cause a substantial decrease in GFR.
A decrease in renal arterial pressure from 100-80 mm Hg in a normal kidney would only
cause a slight reduction in GFR because of autoregulation. The other options would tend to
increase GFR.
Fill in the gap
Net contribution by the kidneys to whole-body glucose production is minimal
(<10%) except under conditions of ___________, when they can contribute
up to 30% to 40%.
Net contribution by the kidneys to whole-body glucose production is minimal
(<10%) except under conditions of PROLONGED FASTING, when they can contribute
up to 30% to 40%.
Which of the following, compared with normal, might you expect to find 3 weeks
after a patient ingested a toxin that caused sustained impairment of proximal tubular
NaCl reabsorption? Assuming no change in diet or ingestion of electrolytes.
- No change in GFR, no change in afferent arteriolar resistance
- Decreased GFR, increased afferent arteriolar resistance
- Increased GFR, increased afferent arteriolar resistance
- Increased GFR, decrease afferent arteriolar resistance
Decreased GFR, increased afferent arteriolar resistance
Impairment of proximal tubular NaCl reabsorption would increase NaCl delivery to the
macular densa, which in turn would cause a tubuloglomerular feedback-mediated increase in afferent arteriolar resistance. The increased afferent arteriolar resistance would decrease GFR.
Which mediator acts to selectively modulate the sympathetic vasoconstrictive
effects on the afferent arterioles to prevent sustained damage
- Brain natriuretic peptide
- Prostaglandin
- Angiotensin II
prostaglandin
Fill in the gap with INCREASE or DECREASE
A selective decrease in efferent arteriolar resistance would ______ glomerular
hydrostatic pressure, ______ GFR, and ______ renal blood flow
A selective decrease in efferent arteriolar resistance would decrease glomerular
hydrostatic pressure, decrease GFR, and increase renal blood flow
- Add increase or decrease
What are the 2 renal circulation capillary beds called
glomerular and peritubular capillaries
what separated these 2 capillary beds
the efferent arteriole
what is the renal pelvis
a large and wider cavity where the urine collects before the tube narrows into the ureter.
what is the renal blood flow in order from the aorta to the vena cava
what % of cardiac output does the kidney recieve
20%
what is the normal volume and concentraton of urine
1.5L of water is excreted daily with 600miliomoles of solute
how much blood evers the glomerulus’s every minute
1L/min
what are the 6 functions of the kisneys (VCpMEE)
Volume, Concentration, pH, Metabolic, Excretory and Endocrine
What role do the kidneys have in maintaining volume
BLOOD PRESSURE
Kidney are key to maintain blood volume
Directed by excretion or retention
Blood volume mediates blood pressure
BP = amount of blood + size of blood vessel
what are the key ions that need to be regulated to maintain correct concentrations in the urine and blood
(SPCMHBC)
o Sodium
o Potassium
o Chloride
o Magnesium
o Hydrogen
o Bicarbonate
o Calcium
how does the kidney regulate pH
Regulation of acid/base balance
Modulation of hydrogen and bicarbonate (respiratory/metabolic acidosis/alkalosis)
what role does the kidneys have in maintaining metabolism
Kidneys produce glucose through glucogenesis
Glucose production is minimal (~<10%) except under prolonged fasting (30-40%).
What roles does the kidney have in excretion
peeing :)
urea, creatinine, water soluble drugs and toxins
what 4 ways do the kidneys have a role in endocrine maintenance and production
- Renin production – linked back with regulation of blood volume
- RAAS 1 of 4 pathways to correct low volume
- EPO – new RBC production
- Vitamin D – controls calcium and phosphorus metabolism
true or false
Blood flow is linked to rate of renal filtration and excretion.
true
true or false
it is vital local renal blood flow is autoregulated to prevent damage
true
how is bp maintained across the kidneys
dilation and constriction of the afferent and efferent arterioles
what are the 2 key vasoconstrictors
sympathetic nerves and RAAS (ANGII)
what are the 2 key vasodilators
prostaglandins and natriuretic peptides (ANP, BNP)
how do the sympathetic nerves cause vasoconstriction
- Sympathetic tone increases as part of flight-flight response or low extracellular volume
- Sympathetic nerve terminals release norepinephrine into the interstitial space
- At high levels of nerve stimulation, BOTH afferent and efferent arteriolar resistances rise (constrict), thus generally decreasing both RBF and GFR
o ALL above prevent fluid loss and maintain BP for response (fight or flight)
what effect does RAAS have on blood flow and how does it work
RAAS – Increased Efferent
* Angiotensin II – response to low extracellular volume
* Multiple actions depending on conc.:
* Constricts efferent and afferent arterioles
* Works with PROSTAGLANDINS to constrict efferent more than afferent – maintaining GFR with reduced renal perfusion. Maintaining fluid in capillaries
what effect does prostaglandins have and how does it work at changing bp
- Dampen renal vasoconstrictor effects of sympathetic nerves or angiotensin II – particular the afferent arteriole
- Prevents severe vasoconstriction and renal ischaemia
what effect do natriuretic peptides have on bp control and how des it work
- ANP and BNP released from heart from increased pressure and circulating volume
- Act mainly on afferent arteriole – increases renal blood flow and GFR
- ANP – inhibits secretion of renin – lowering ANG II
what 2 factors need to be controlled to maintain stable renal blood flow
renal blood flow and mean arterial pressure
what is the stable blood flow in mmHg
60-160mmHg
what are the 2 mechanisms for maintaining a stable blood flow
myogenic response and tubuloglomerular feedback mechanism
explain the myogenic response
- Can constrict in response to pressure – prevents overstretching – increasing vascular resistance – helps prevent excessive increase in renal blood flow and GFR when BP rises
Explain the tubuloglomerular feedback mechanism
- Increase arterial pressure increases filtration and ultimately Na+ and Cl- in proximal tubule.
- Sensed by macula densa cells of the JGA
- Macula densa cell to release paracrine agents which triggers contraction of nearby vascular smooth-muscle cells in afferent arteriole
- Increased afferent arteriolar resistance decreases GFR, counteracting the initial increase in GFR
what is autoimmunity
when your immune system thinks your body is a pathogen
What is type 1 hupersensitivity
Immediate hypersensitivity - Allergy NOT autoimmunity
* IgE secreted by B cells into blood and bind IgE receptors on mast cells and eosinophils
* IgE bound to antigen causes histamine release from mast cells to open ‘holes’ in a parasite for the rest of the immune system to recognise.
* IgE is important for allergies e.g. asthma
what is anaphylaxis
potentially fatal shock response where large amounts of histamine is released narrowing the airways and reducing blood pressure through vasodilation.
what is autoimmunity anti-body mediated type 2 reaction
cell bound antigen
* Antibodies (IgG, IgM bind self-antigen on tissue. Fc domains activate complement and recruit NK calls, macrophages, neutrophils etc leading to tissue damage and inflammation
Give some examples of diseases the self antigen and the target for type 2 reactions
what is the self antigen and target for goodpastures disease, pemphigus vulgaris and graves disease
Good pastures disease - collagen type IV - kidney, lungs
pemphigus vulgaris - cadhedrin - skin rash
graves disease- thyroid stimulating hormone - hyperthyroidism
specifically how is graves disease type II
Antibodies bind thyroid stimulating (THS) hormone receptors stimulate thyroxine release. Hyperthyroidism
specifically how is hashimotos disease type II
Antibody binds to thyroid stimulating hormone (TSH) receptors. antibodies damage the thyroid - hypothyroidism
specifically how is antiglomerular basement membrane disease type II
Autoantibodies bind collagen in the glomerulus basement membrane
Often follows damage to the lungs (smoking) which reveals cryptic antigens
specifically how is goodpastures syndrome type II
autoantibodies to collagen in the kidneys and lungs
what is Autoimmunity Antibody-mediated Type III
Immune Complex Disease
* Antibodies bind soluble self-antigen and form immune complexes.
* Immune complexes get stuck in small blood vessels
* Fc domains activate complement recruiting NK cells, neutrophils etc leading to inflammation and damage.
* IgA is made by B cells in response to infection of mucosal surfaces.
* IgA binds and IgA receptor and is secreted across epithelial cells to protect mucosal surfaces
what are some examples with their self antigen and target for type 3
How is SLE type 3
Antibodies against DNA form immune complexes that deposit in small blood vessels. The complexes bind complement, induce recruitment of neutrophils leading to inflammation
How is Post-steptococcal glomerulonephritis type 3
how is glomerulonephritis type 3
what causes IgA nephropathy
infection - frequent coughs and colds
IgA is recognised by autoantibodies and incorportaed into immune complexes that lodge in the glomerulus - mesangial deposits of IgA in biopsy of glomerulus
The is Tcell mediated damage Type 4
Delayed Type
* Cell mediated type 4 hypersensitivity
* Activated autoreactive cytotoxic T cells that are not destroyed in the thymus release cytotoxic cytokines (TNF) and perforins - kill cells
* Cell mediated type IV hypersensitivity does not involve antibodies
what are some examples of type 4 reactions with the self antigen and target
why is typ4 called the delayed type
how is type 1 diabetes a type 4 reaction
cytotoxic t cells recognising islet cells proteins contribute to type 1 diabetes
activated cytotoxic t cells release perforins and kill islet cells
what is genetic autoantibody formation
antibodies recognise HLA
self reactive T cells are released from the thymus.
they can also be stimulated by cytokines during infections
give some examples of different conditions and the HLA target
how does autoimmunity occur after infection
cytokines generated during infection can stimulate low numbers of self-reactive T cells. These provide help to self reactive B cells
give some examples of autoimmune conditions and the infections that can cause them
which 3 conditions are treated with removal of the antibody by plasmapheresis or IgG therapy
- Guilian-Barre
- Myasthenia gravis
- Thrombotic thrombocytopenia purpura
what autoimmune conditon is treated with anti-inflammatory drugs and NSAIDs, steroids and/or biologics
RA
which 3 conditions have treatment to restore/reverse specific damge
Type 1 diabetes - insulin
Graves disease - carbimazole
hashimotos - thyroxine
What antibiotic would you prescribe for an uncomplicated lower UTI for a patient taking methotrexate
Nitrofurantoin
dose 50mg QDS PO for 3 days (7 if pregnant or male)
OR
100mg modified release BD PO 3/7 days
wahat antibiotic would you prescribe for a patient with a Lower UTI - no other notable issues
Trimethoprim (AKA Septrin
*200mg BD PO for 3/7 days) – 7/7 if complicated (male)
what is co-amixicalv
amoxicillin and clavulanic acid
how do you differentiate between lower and upper UTI
presenting symptoms:
U UTI - Rigors, vomiting, flank pain, high grade 38
what antibiotic can you not use in Upper UTI
Nitrofuratoin - it cant act on kidneys
what is 3rd line treatment for UTI
cephalexin
what is the main complication of ciprofloxacin
achilis tendonitis
what is a kidney stone usualy made of
calcium oxulate
what 3 areas usually block with a kidney stone
Uretoesical junction UVJ, ureter and renal pelvis
how do you image for kidney stones in females and males
- Female – ultrasound plus x ray (don’t get high dose radiation of ovaries)
- Male – CT KUB (kidneys, ureter and bladder)
4 year old boy presents with generalised swelling
Urine dipstick testing shows 4+ protein
Blood tests: albumin 23, creatinine 40
What is the name of the syndrome?
Nephrotic syndrome
Proteinuria (>3.5g/24hrs)
Oedema Hypoalbuminaemia
what is the most likely diagnosis?
Minimal change disease is commonest childhood cause (>75%)
What is the management of minimal change disease
Empirical steroid therapy usually given to children; if no response consider further investigation for alternative cause
- Prednisolone 1-2mg/Kg
what is the prognosis of Minimal change disease
Remission with treatment is usually the norm in minimal change disease; may relapse, but should not affect renal function
65 year old woman presents with generalised swelling Urine dipstick testing shows 4+ protein Serum albumin 23
What is the differntial diagnosis
Membranous nephropathy
Minimal change disease
Focal segmental glomerulosclerosis (FSGS)
Amyloid
Diabetes
Mesangiocapillary glomerulonephritis (MCGN)
To determine the diagnosis what further information and examination would be necessary
- Drugs
- Infection
- Malignancy
- Other systemic disorders
