Mark Nelligan BCS Flashcards
Classification of CKD
see slide 5 of 2- progressive kidney disease lecture
Define rapid deterioration of renal function
Rapid deterioration defined as a fall in GFR of
> 5mLs/min/1.73m2 in 1 year
or
> 10mLs/min/1.73m2 in 5 years
Cause of deterioration of kidneys
- Lose adaptability
- Fail to excrete fluid load promptly
3.Fail to reduce urine volume in hypovolaemia promptly = DEHYDRATION Haemorrhage Hypotension Surgery Reduced Cardiac Output Sepsis
- Nephrotoxicity (NSAID’s, IV Contrast, etc)
- Worse in Diseased Kidneys
- Reduced Ability to Recover
Ist line Mx of HTN to prevent renal failure
- Angiotensin blockade (unless CI) eg. hyperkalaemia
2. Then move to ACE or CCB
1st line Mx of diabetic neuropathy (CHECK THIS WITH GREY BOOK AND NICE)
- Control HTN (130/80)
Tx of acidosis and justification
Sodium biocarbonate
Reduces Hyperkalaemia
Reduces Calcium Loss from Bone
Improves Catabolic State
Tx of hyperphosphatemia and justification
- Deranged Calcium, VitD, PTH
Normal Serum Phosphate
Reduces Renal Osteodystrophy
Reduces Calcium Loss from Bone
Improves Catabolic State
Dietary modifications in renal failure
- Protein Restriction 0.8 g/kg/day
- Avoid Ultra-Low Protein
- Calorie Supplements
No-Added Salt
- Sodium 60-90 mmol/day, Sodium Chloride 3.5-5 g/day
Reduced Protein
- Chronic Renal Failure 0.8 g/day
- Haemodialysis/CAPD 1.2 g/day
Reduced Phosphate
- <1000 mg/day
Low-Potassium Diet
- Potassium 40 mmol/day
Options or end stage renal failure
- End of life care
- Transplanatation
- Haemodialysis
- Peritoneal dialysis
What does dialysis `achieve
- Removes nitrogenous wastes/toxins
- Corrects electrolytes
- Removes water
- Corrects acid base abnormalities
Difference between dialysis and haemofiltration
Haemofiltration Blood is filtered across
a highly permeable membrane, allowing
movement of large and small solutes by
convection at almost the same rate. The
ultrafi ltrate is replaced with an equal volume
of fl uid, so there is less haemodynamic
instability. It is used in critically ill patients
for this reason, but is impractical as longterm
RRT, as it takes much longer than HD to
achieve the same clearance.
Haemodialysis removes solutes by diffusion. As such, it is relatively inefficient for solutes of high molecular weight as clearance by diffusion is inversely related to the molecular weight of the solute.
Haemofiltration removes solutes by convection. As such, efficiency remains more constant for all solutes able to cross the semi-permeable membrane.
The choice between haemodialysis and haemofiltration can be difficult. Points in favour of haemofiltration include:
better control of blood pressure
less risk of hyperlipidaemia
Those in favour of haemodialysis:
less expensive
technically easier
toxicity of molecules of high molecular weight has yet to be demonstrated
haemofiltration can only reduce, not normalise, the concentration of larger solutes
Advantages of haemodialysis
Good Clearance of small molecules
Very Efficient and Adjustable
Patient Freedom between Sessions
Does not cause Domestic Strain (Centre HD)
Acceptable to Patients
Disadvantage of haemodialysis
Expensive, Labour-Intensive, Capital-Intensive
Vascular Access
Intermittent Fluid Overload
Haemodynamic Instability during Dialysis
Restricted Fluid Intake
Poor Clearance of Phosphate
Poor Clearance of Middle Molecules
Malnutrition
Restrictive Diet
Types of peritoneal dialysis
- Diffusion of Chemicals – ‘Dialysis’
- Concentration Gradient In Both Directions - Osmotic Gradient (hypertonic glucose) - Endothelial Membrane with larger pores - ‘Middle Molecules’
- Convection of Chemicals – ‘Ultrafiltration’
- Transmembrane Hydrostatic Pressure does not exist
- Convection - Solvent Drag
- Endothelial Membrane with larger pores
- Middle Molecules’
Advantages of peritoneal dialysis
Preserves Residual Renal Function (8 ml/min virtual GFR)
Haemodynamically Stable, less challenging
Better Clearance of Middle Molecules
No Potassium Restriction
Liberal Diet
Lesser/No Fluid Restriction
Home-Based, No Travelling, More ‘Own’ time
Bloodless, Painless
Disadvantages of peritoneal dialysis
Self-Administered or Dependent on Trained Helper
Peritonitis and its Complications
Sclerosing Peritonitis
Often Chronic Fluid Overload
Poor Clearance of Phosphate
Obesity
Technique Failure after a few years
How is kidney function measured
MDRD equations gives eGFR
Causes of end stage renal failure
Diabetic Nephropathy
Glomerulonephritis
Idiopathic
Systemic (SLE, Vasculitis, Blood Dyscrasia, other)
Hypertension
Adult Polycystic Kidney Disease
Reno-Vascular Disease
Vesico-Ureteric Reflux Nephropathy and Congenital Renal Malformations CAKUT (‘Chronic Pyelonephritis’)
Other Hereditary Renal Diseases
Uremia related CV risk factors
- increased ECF
- Calcification
- PTH
- Anaemia
- ROS
- Malnutrition
- Pulse pressure
- TG’s and LP remnants
- Thrombogenic factors
Haemostatic Fx of the kidney
Fluid Balance & Euvolaemia
Excretion of Metabolic ByProducts
Degradation of Metabolic ByProducts, Peptides
Regulation of Chemical Composition of Plasma/ECF
Maintenance of Normal Osmolality
Acid-Base Balance
Hormonal Fx of the kidney
HORMONAL
- Endocrine
- Renin secretion
- Erythropoietin (HIF, Peritubular Cells)
- 1-α Hydroxylation of 25(OH)VitD3 - Paracrine
- Angiotensin II production
- Prostaglandin (PGI2, PGE2)
Haemostatic pathogenesis in renal failure
Accumulation of ‘Middle Molecules’ – ‘Uraemia’
Accumulation of Metabolic ByProducts (potassium,
phosphate, urate, oxalate, urea, creatinine)
Electrolyte Abnormalities
Acidosis
Oedema (Peripheral/Pulmonary) or Dehydration
Hyperlipidaemia
Compications of chronic renal failure
CKD1
No complications
CKD2
Increased CVD
CKD3
Increased CVD; Bone disease - raised PTH
CKD4
CVD, Anaemia, Bone disease - low Ca, high PO4
CKD5
CVD, Anaemia, Bone disease, Pruritus, Bleeding, Malnutrition
Symptoms of chronic renal failure
- Uraemic Muddy Colour:‘Urochrome’
- Severe Hypertension: Cardiac Failure, Headache, cerebrovascular Events,
- Fluid Overload : Peripheral Oedema, Ascites
- Pulmonary Oedema: Dyspnoea, Orthopnoea
- Hyperkalaemia: Cardiac Arrest, Diarrhoea,Peripheral Paralysis
- Diarrhoea, Vomiting: Gastritis, Hypermotility
- Peripheral Neuropathy :‘Middle Molecules’
- Encephalopathy, Coma: ‘Middle Molecules’, Urea
Cause of failure of hormonal control in CRF
- Hypertension
Renin-Driven - Anaemia
Erythropoietin deficiency
3.Proximal Myopathy
↓ 1,25(OH)2VitaminD3, ↑ PTH
- Pruritus
↑ PTH, ↑ PO4, Iron deficiency
Importance of potassium in CRF
Hyperkalaemia in CRF
- Reduced GFR
- Acidosis (competition with H cations at Collecting Duct)
- Acidosis (competition with H cations as ICF cation)
- Fluid Overload Suppresses Aldosterone Release
- ANP Digitalis-like Effect on the Na/K CounterTransporter
Iatrogenic Hyperkalaemia
- ACE Inhibitors
- Angiotensin II Receptor Blockers
- Aldosterone Antagonists
- β-Blockers
Causes of acidosis in CRF
Reduced GFR
►►Retained Acids (Phosphate)
Low Serum Bicarbonate
- Reduced Renal Mass – Tubular Cells
►►Reduced HCO3 Regeneration in Proximal Tubule
►►Reduced H Cation Secretion in Proximal Tubule
►►Reduced Hydrogen Secretion in Collecting Duct
►►Reduced Ammonia Production
Reduced Buffering
- Reduced Haemoglobin
- `High Phosphate
Consequences of acidosis
Hyperkalaemia
Hydrogen Cations Replace and Expel Calcium from Bone
Protein Catabolic Effect
Dyspnoea
What does the presence of casts in the urine indicate?
Haematuria/pyuria is of glomerular or renal tubular origin
Would bladder cancer or kidney stones have casts?
No cast but would have haematuria
Would acute cystitis have casts?
No casts, but would have pyuria
What do RBC casts indicate?
- Glomerulonephritis
2. Malignant HTN
What do Fatty casts (oval fat bodies) indicate?
Nephrotic syndrome (assoc. with maltese cross sign)
What do WBC casts indicate?
- Tubulointerstitial inflammation
- Acute pyelonephritis
- Transplant rejection
What do brown muddle casts indicate?
Acute tubular necrosis
What do waxy casts indicate?
1.ESRD/CRF
Normal and nephrotic range for 24 hour urinary protein
Normal <150 mg
(pregnancy <300 mg)
Nephrotic range >3g
Treatment of hyperkalemia?
Treatment in non-urgent cases
• Treat the underlying cause; review medications.
• Polystyrene sulfonate resin (eg Calcium Resonium® 15g/8h PO) binds K+ in the gut,
preventing absorption and bringing K+ levels down over a few days. If vomiting
prevents PO administration, give a 30g enema, followed at 9h by colonic irrigation.
If there is evidence of myocardial hyperexcitability, or K+ is >6.5mmol/L, get senior
assistance, and treat as an emergency (see p849).
Treatment for urgent hyperkalaemia:
1 Stabilize cardiac membrane with 10mL 10% calcium gluconate
2 Drive K+ into cells with 10units actrapid in 50mL 20% glucose
- Stop all potassium-retaining/containing drugs where possible and arrange dietary
review of potassium in diet where appropriate.
Treatment for anaemia
EPO and Iron
What are the causes and features of uremic syndrome
Cause:
Accumulated products of protein catabolism, Urea usually excreted from the kidney - in renal failure it is not so builds up in the blood
Features:
- Pruritus
- Peripheral Neuropathy
- Encephalopathy
Cause of platlelet dysfunction and haemorrhage in CRF
Uremia interrupts the binding of platlets resulting in haemorrhagic state
Platelet dysfunction and haemorrhage
Inhibition of platelet adhesion
Defective vWF receptor ligand
Bleeding time is useful
Cause of prothrombotic tendency in CRF
Protein C/S functional deficiency
Increased homocysteine
Inadequate tPA
wHAT TYPE OF CONDITION EFFECTING pth DOES crf LEAD TO?
Secondary hyperparathyroidism
Consequences of calcium dysregulation
Periarticular calcification
Blood vessel wall calcification
Proximal Myopathy
Calciphylaxis
Calcification of the heart
Symptoms of bone changes due to calcium dysregulation
Proximal Myopathy
Bone pain – backs, hips, legs
Joint pain
Fractures
Poor mobility
Growth retardation, deformities, child
Features of osteodystrophy
Osteitis Fibrosa Cystica: increased PTH
Osteomalacia: defective Mineralisation
Adynamic Bone Disease: low bone Turnover (low PTH)
Osteoporosis: defective bone Formation
Aluminium-Induced Calcification Failure (Newcastle
Disease – Pathological Fractures)
Mx of bone disease in CKD 3/4
- High PTH: Start 1a caldiol then repeat Ca2+, phospahte and PTH
- If still high Calcium and Low PTH stop 1a calcidiol
- If High PO4: PO4 restriction or calcium based PO4 binders
- If low Vit D: Start Vit D
What is the vertebral level of the kidneys?
T12 - L3 - they are protected by the thoracic ribs but or not in thoracic cavity as they are below the level of the diaphragm
How many lobes per kidney?
5-11
What are the origins of the renal pelvis?
Superior part of the ureter. Branches to firn two or three major calices - each of which divide again to form minor calices which collect urine from papillae of kidneys
Innervation of the kidney
Vagus (PNS) through coeliac plexus - allows RA and RV dilation
T10-L1 (SNS) - constricts RA and RV
Location of nephrons in the kidney
See slide 12 of renal anatomy lecture
Significance of septum between adrenal gland and kidneys?
Prevents damage to adrenal gland in renal transplantation
Site for transplanting a kidney?
Iliac fossa of the greater renal pelvis
Which structure joins the ext. iliac a.
RA
Which structure joins the ext. iliac vein
RV
What does the ureter pass over anteriorly?
- Psoas major
2. Genitofemoral nerve
Which structures is the left ureter related to?
- sigmoid colon,
gonadal vessels - left colic branches of inferior
mesenteric artery.
What structures is the right ureter related to?
- descending (2nd
part) duodenum, - terminal ileum,
- root of the
mesentery, - gonadal vessels,
- right colic and
ileocolic branches - terminal part of the
superior mesenteric artery.
At which landmark does the ureter cross medially
into the pelvis?
Ext. iliac or common iliac vessels
Blood supply of the ureters
Proximal (near renal pelvis): Ureteric
branches from renal artery.
• Middle (most of abdomen) Ureteric
branches from gonadal arteries.
• Distal (near urinary bladder) ureteric
branches off inferior vesical artery (which
is a branch of the internal iliac artery).
Ureteric anatomical constriction sites and their clinical significance
- ureteropelvic junction (UPJ)
- crossing of the common iliac/external iliac
vessels at pelvic brim - where the ureters enter the wall
- Ureteric calculi may cause complete or
intermittent obstruction of urinary flow at these
sites.
Layers of the ureters
MUCOSA – Transitional epithelium (for expansion) – Lamina propria (has elastic tissue to recoil)
• MUSCULAR LAYER (smooth muscle) – Inner longitudinal – Outer circular • ADVENTITIA – Provides protection, strength for organs, and attaches ureters to surrounding structures
Features of ureteric calculus pain
severe rhythmic pain (ureteric colic) as it
is gradually forced down the ureter by waves of contraction.
• Depending on the level of obstruction, the pain may be referred to
the: lumbar region, hypogastric region, external genitalia or testis.
• The pain is referred to the cutaneous areas innervated by spinal
cord segments and sensory ganglia, which also supply the ureter
(mainly T11-L2).
Difference in histology in ureter and bladder
Same except ureter has rugae in its mucosal layer to allow for expansion
What is the trigone composed of and what is its fx?
the triangular region formed by the two ureteral orifices and the
internal urethral orifice. It is very sensitive to expansion (is always smooth to
limit expansion) and once stretched to a certain degree, the urinary bladder
signals the brain of its need to empty.
Describe the anti-reflux mechanism of the bladder
The ureters pass obliquely through the bladder wall in an inferomedial direction.
An increase in bladder pressure presses the walls of the ureters together,
preventing the pressure in the bladder from forcing urine up the ureters.
Blood supply of the bladder?
The bladder primarily receives its vasculature from the internal iliac vessels.
Arterial supply is delivered by the superior vesical branch of the internal iliac artery. In males, this is supplemented by the inferior vesical artery, and in females by the vaginal arteries. In both sexes, the obturator and inferior gluteal arteries also contribute small branches.
Venous drainage is achieved by the vesical venous plexus, which empty into the internal iliac vein (also known as the hypogastric vein).
Nerve supply of the bladder
• Parasympathetic (S2-S4) are motor to detrusor muscle and
inhibitory to the internal sphincter.
• Sympathetic (T11-12, L1-2) cause constriction of internal
sphincter and inhibit the detrusor muscle.
Histology and dx of urethra between men and women
Smooth muscle with inner mucosa
– Changes from transitional through stages to stratified squamous
near end
– Drains urine out of the bladder and body
• Male: about 20 cm (8”) long
• Female: 3-4 cm (1.5”) long
– Short length is why females have more urinary tract infections
than males - ascending bacteria from stool contamination
• Urethral sphincters
– Internal: involuntary sphincter of smooth muscle
– External: skeletal muscle inhibits urination voluntarily until proper
time (levator anni muscle also helps voluntary constriction)
Go through case studies of Renal anatomy lectures - stavros
Go through case studies of Renal anatomy lectures - stavros
Describe Paroxysmal Nocturnal Haemoglobinuria
Acquired life threatening disease where C’ attacks RBC’S. It may develop on its own (“primary PNH”) or in the context of other bone marrow disorders such as aplastic anemia (“secondary PNH”). Presents as blood in the urine in the morning in 26% of pts. (hence the name)
What is located in the renal cortex?
Renal corpuscle (glomerulus and bowmans capsule) and tubules apart from the LOH. Also contain cortical collecting ducts
What are the renal columns and what are their fx
The renal column (or Bertin column, or column of Bertin) is a medullary extension of the renal cortex in between the renal pyramids. It allows the cortex to be better anchored.
Each column consists of lines of blood vessels and urinary tubes and a fibrous material.
Why do the pyramids have a striped appearance
The pyramids appear striped because they are formed by straight parallel segments of nephrons and collecting ducts.
What is formed by the apex of a renal pyramid? What does this structure empty into?
Papilla. Drains into the minor calcyes then into the major calyces then to the renal pelvis then to the ureter
What is the normal position for right and left kidneys?
T12-L3 - Right slightly lower than the left due to the presence of the liver
Origin of the renal arteries
The kidneys are supplied with blood via the renal arteries, which arise directly from the abdominal aorta, immediately distal to the origin of the superior mesenteric artery.
Due to the anatomical position of the abdominal aorta (slightly to the left of the midline), the right renal artery is longer, and crosses the vena cava posteriorly.
Each renal artery enters the kidney via the renal hilum, dividing into segmental branches.
Venous drainage of the kidney
The kidneys are drained of venous blood by the left and right renal veins. They leave the renal hilum anteriorly to the renal arteries, and empty directly into the inferior vena cava.
As the vena cava lies slightly to the right, the left renal vein is longer, and travels anteriorly to the abdominal aorta.
Anomoly of renal pelves location in horseshoe kidney?
Normal posterior rotation of the kidney is prevented by the fusion resulting in the renal pelves becoming orientated anteriorly.
What are areas do interlobar and interlobular arteries supply?
interlobar are between pyramids in the renal columns. Interlobular are the smaller branches in the renal cortex
What structures are located within a renal lobe?
The renal lobe is a portion of a kidney consisting of a renal pyramidand the renal cortex above it
Difference between normal and ectopic kidneys
Ectopic kidneys have blood vessels derived from the distal aorta and iliac artery, are smaller in size and have a short ureter. Prevalence is between 1:500 and 1:1200 cases.
While the pelvic placement of the kidney in the above case was abnormal, the typical site for transplanting a kidney is in the iliac fossa. Why is this the case?
Shorter ureter and can connect transplanted kidney to iliac artery and vein
To which parts of the skeleton are the kidneys normally related?
left = 11th and 12th rib
right 12th rib
In a lumbar surgical approach to a normal kidney, which posterior abdominal muscles must the surgeon go through?
Psoas major
Quadratus lamborum
Transverse abdominis
Which nerves are related posteriorly to kidneys in a normal position?
Subcostal
Iliohypogastric
ilioinguinal
Significance of P wave and normal length
- Atrial depolarisation
- Waves travels inferiorly from right to left therefore lead II is positive whereas AvR is negative
- Determines HR
- Should not exceed 0.12 secs (3 small sq.)
Significance of PR interval and normal length
- Wave traveling from artia to ventricles via AV node and HIS-Purkinje fibres
- Should be between 0.12-0.2 sec (3-5 small sq.)
- If > this it suggests AV heart block
- If < suggests extra conduction tissue
Significance of QRS wave
- Ventricular depolarisation
- Determines axis
- Should be 0.12 sec (3 small sq.)
- If > suggests BBB
- If in leads V1 and V2 (septal leads) more suggestive of RBBB
- If in V5 and V6 (lateral left view) more suggestive of LBBB
sIGNIFICANCE OF st SEGEMENT
- Repolarisation
- Elevation = infarction
- Depression = ischaemia
Significance of the T wave
Represents rapid phase of ventricular repolarisation
Normally positive in leads I, II, (III), aVL, aVF,V2-6 (i.e.
QRS-T concordance).
Most sensitive area for looking at ventricular disease
processes
If inverted = ischaemia.
If peaked = hyperkalaemia (potassium).
Significance of QT interval
Length of interval varies with rate!
Prolongation can be:
Due to inherited conditions
Acquired e.g. due to drugs
When prolonged can cause of life-threatening arrhythmias
Immune mechanisms underlie most forms of glomerular injury
Antibody-mediated injury
Cell-mediated immune injury
Activation of alternate complement pathway
Glomerular response to injury
- Cellular proliferation
Mesangial or endothelial cells
Leukocytic infiltration
Formation of ‘crescents’ (accumulations of proliferating epithelial
cells and infiltrating leukocytes) - Basement membrane thickening
Light Microscopy: Thickening of the capillary walls (PAS stain)
Electron Microscopy:
Deposition of amorphous electron dense material (most often
immune complexes) on the endo- or epithelial side of the BM or
within the glomerular BM itself. - Glomerular scarring = ‘Sclerosis’
Definition of diffuse glomerular injury
> 50% of glomeruli are involved
Definition of focal glomerular injury
<50% of glomeruli are involved
Definition of global glomerular injury
A whole glomerulus is involved
Definition of segmental glomerular injury
Part of a glomerulus is involved (e.g. focal
and segmental glomerular sclerosis)
Categories of glomerular diseases
1. Primary Glomerulonephritis Kidney is the only or the predominant organ involved Termed Glomerulopathies when no cellular inflammatory component is involved
- Secondary Glomerulonephritis
Glomeruli are injured as a
secondary consequence of
another systemic disease
Name the primary glomerular disease
- Membranous Glomerulonephritis
- Focal Segmental Glomerulosclerosis
- Membranoproliferative
Glomerulonephritis - IgA Nephropathy
- Chronic Glomerulonephritis
- Acute Diffuse Proliferative
Glomerulonephritis - Crescentic Glomerulonephritis
- Minimal Change Disease
- Alport Syndrome
- TBMN (thin basement membrane nephropathy
Types of secondary glomerular diseases
- SLE
- DM
- Amyloidosis
- Polyarteritis nodosa
Features of MCD
Normal Light Microscopy Negative ImmunoFluorescence Fusion of Foot Processes of Podocytes Commonest cause of Nephrotic Syndrome in Children (>95%) Heavy Proteinuria Steroid-Responsive Good prognosis, without permanent injury
Features of membranous nephropathy/glomerulonephritis
Most common cause of nephrotic syndrome in caucasian adults Form of chronic Ag-Ab-mediated disease Diffuse thickening of the glomerular capillary walls Basement membrane projections (“spikes”) [Silver stains] Immunofluorescence: Granular and linear pattern of IgG and C3 Electron Microscopy: Subepithelial deposits along the BMs, with effacement of podocyte foot processes
Progression of membranous glomerulonephritis
- Proteinuria
- Spontaneous complete remission 5%-30% at 5 yrs
- Spontaneous partial remission 25%-40% at 5yrs
- End Stage Renal Disease (ESRD)
14% 5 years
35% 10 years
41% 15 years
Tx for membranous glomerulonephritis
Immunosuppression 6 to 12 months
Cyclophosphamide
Steroids
Feautures of FSGS
This lesion is characterized by sclerosis of some (but not all)
glomeruli (focal) and in the affected glomeruli, only a portion is
involved (segmental)
FSGS occurs in the following settings:
As idiopathic (primary) disease
In association with other known conditions e.g. HIV, sickle cell
disease, massive obesity
As a secondary event, reflecting glomerular scarring, in other
forms of focal glomerulonephritis e.g. IgA nephropathy
As a component of the adaptive glomerular ablation response in
advance stages of renal disorders
- In sclerotic segments there is: Collapse of the basement membranes Increase in matrix Deposition of hyaline masses (hyalinosis)
IF of FSGS?
iGm OR c3 (THIS DIFFERS FROM FIRST AID WHICH SAYS THERE WOULD BE NO IF DEPOSITS
EM of FSGS
diffuse loss of podocytes foot processes and focal detachment of podocytes from the underlying GBM Note the capillary collapse and mesangial sclerosis
Naural Hx of FSGS
- Proteinuria
Nephrotic Syndrome ‘Lipoid Nephrosis’, similar to MCNS
Low Proteinuria suggests secondary to familial abnormality - Prognosis
Dependent on diagnosis and response to treatment
High rate of recurrence in renal transplants
Tx of FSGS
Immunosuppression
Steroids Responsive 50%, sustained 25%
Cyclophosphamide For steroid-dependent
Cyclosporine For steroid-dependent
Features of IgA nephropathy
Berger’s disease Probably the most common glomerular disease worldwide Presence of prominent IgA deposits in the mesangial regions, detected by IF microscopy Genetic or acquired abnormality of immune regulation leading to increased mucosal IgA synthesis Presents invariably with episodic haematuria +/- nephrotic syndrome or proteinuria
Microscopic findings of IgA nephropathy
Mesangial cell proliferation
Segmental endo-capillary proliferation
Segmental glomerulosclerosis and adhesion
Focal accumulation of hyaline
Focal presence of glomerular crescents
Tubular atrophy with interstitial fibrosis
Natural Hx of IgA nephropathy
Most patients do well without treatment
End Stage Renal Disease: 30% at 20 years
What indicates a poor prognosis in IgA nephropathy
Elevated serum Creatinine concentration
Hypertension (>140/90 mmHg)
Nephrotic/Persistent protein excretion above 1000 mg/day
Crescentic Nephritis
Tubular Atrophy
Tx of IgA nephropathy
Angiotensin Blockade : ACEI preferable Omega-3 Fish Oils, in large dose - Immunosuppression for Acute Glomerulonephritis Cyclophosphamide Azathioprine Steroids
Relationship between SLE and renal disease
- Clinical evidence of renal disease seen in 50-70%
- SLE causes a heterogeneous group of lesions and clinical
presentations - Glomerular changes are classified into:
1. Class I Minimal Mesangial Lupus Glomerulo-Nephritis (LGN)
- Class II Mesangial Proliferative LGN
- Class III Focal LGN (<50% of glomeruli)
Class IV Diffuse LGN (>50% of glomeruli; subdivide into IV-S and IV-G) - Class V Membranous LGN
- Class VI Advanced Sclerotic LGN (>90% sclerotic glomeruli)
Features of Class I (Minimal Mesangial LGN):
Mild disease with small
amount of swelling
- Mesangial deposits of Immunoglobulins and/or complement (mainly in the mesangium), without morphologic changes identified in Light Microscopy
Features of Class II (Mesangial Proliferative LGN):
Still fairly mild
disease but more swelling than Class I. Mesangial deposits of
Immunoglobulin
- Mesangial hypercellularity or mesangial matrix expansion (Light Microscopy) Few isolated subepithelial or subendothelial deposits (IF or EM)
Features of Class III focal LGN
Moderate degree of swelling with less than 50% of the glomeruli affected Proliferation of endothelial and mesangial cells Infiltration with neutrophils - Association with focal subendothelial deposits (EM)
Features of Class IV (Diffuse LGN)
Severe degree of swelling with greater than 50% filtering units affected Proliferation Necrosis and hyaline thrombi Subendothelial deposits (wire-loops) - Segmental thickening of capillary walls by wire-loop deposits
Features of Class V (Membranous LGN):
Most of the swelling is
confined to the outer layer surrounding the filter unit
Widespread thickening of the capillary wall (LM)
Sub-epithelial IgG deposits (IF or EM)
Features of class VI Advanced Sclerotic LGN)
Sclerosis of ≥90% of the filter units
show scarring
Renal Tx of SLE
Dependent on Histological Class Class IV Cyclophosphamide & Steroids Class V Azathioprine & Steroids All - Mycophenolate Resistant - Rituximab
Features of Alport Syndrome
X-linked Alport (80%): Mutations on COL4A5 gene; α5 chain
of collagen type IV
Autosomal Alport (20%): Mutations on COL4A3 and
COL4A4 genes; α3 and α4 chains of collagen type IV
Mutations interfere with the structure and function of collagen
IV and thus with the GBM ultra-structure. Mechanism is not
well understood
Often associated with sensorineural hearing loss and ocular
abnormalities
Initial renal manifestation of Alport syndrome is asymptomatic
persistent microscopic hematuria, which is present in early
childhood in affected patients
Morphological features of Alport
Presence of irregular foci of thickening and thinning, with pronounced splitting and lamellation of the GBM
Features of CFHR5 Nephropathy (Troodos Nephropathy)
Inherited (autos. dominant) kidney disease; endemic in Cyprus
Caused by a mutation in the gene CFHR5 (duplication of exons
2 and 3 of CFHR5)
Estimated that 1:6500 Cypriots carry the mutation
CFHR5: Synthesized in the liver
CFHR5-Function: Inhibits C3 Convertase activity and binds
Heparin and CRP
Clinical picture: Persistent microscopic hematuria and episodes
of synpharyngitic macroscopic hematuria (1-2 days after upper
respiratory tract infection)
Subendothelial and mesangial C3-deposits and occasionally
subepithelial basement membrane C3-deposits
What is the uteropelvic junction
The point at which the renal pelvis narrows to form the ureter
The ureter is in contact with which structures of the posterior abdominal wall?
psoas major
How do the ureters enter the pelvic area
At the area of the sacroiliac joints, the ureters cross the pelvic brim, thus entering the pelvic cavity. At this point, they also cross the bifurcation of the common iliac arteries.
At the level of the ischial spines, they turn anteromedially, moving in a transverse plane towards the bladder.
Which structures pass anterior to the ureter? Does this differ in males and females?
ureters run in close proximity to ovaries so need to take care when performing an ovariectomy esp. during ligation of the ovarian arteries.
Also, 2cm superior to ischial spine, ureters run underneath the uterine artery (take care during hysterectomy) In men, the uterine arteries are the vas deferens
Which layers does the suprapubic catheter pass through?
The bladder is an extraperitoneal organ, The suprapubic catheter would pass superior to the pubis through the layers of the anterior abdominal wall.
If the bladder is distended at the time of the procedure, the tube can then continue through the bladder wall into the bladder. As the bladder fills with urine, it rises into the abdomen between the peritoneum and the transversalis fascia of the anterior abdominal wall.
Consequence of bladder rupture in males vs. females
in men the bladder is intra and extra peritoneal whereas in women it is extraperitoneal. So a rupture of the bladder in women is very rarely intraperitoneal, this is more common in men however
In most cases the superior surface ruptures since it is the thinnest wall and becomes increasingly thinner as distension increases.
The term ‘‘superior surface’’ actually refers to the relatively flat roof of a non-distended bladder;
however, it becomes increasingly convex with filling, developing superolateral and posterosuperior surfaces.
Rupture of the thinned-out wall also tears the peritoneum that covers it, so that the urine and blood escape into the peritoneal cavity.
Relationship between urethra and anterior vaginal wall
Urethra is fused to the anterior vaginal wall
Paraurethral gland homologue
prostate gland
Why is the passage of cystoscopes or catheters easier in the female than the male?
Urethra is shorter and less curved in females.
Systematic approach to a sick patient?
History
Examination
Differential
Investigations
Diagnosis
Treatment
Order to assess the systems
- Call for help early
- Priority of Tx
- Complete initial assessment and then reassess
- Pt. responsiveness to Tx
A: airway (with C-spine protection in trauma)
B: breathing
C: circulation
D: deficits in neurological status
E: environment (exposure)
(O2, IV access and fluids ± specific treatment can be repeated as many time as possible
Should not take more than 5 minutes
How to recognize an obstructed airway
Can the patient talk?
Does the patient sound distressed?
Shortness of breath
Noisy breathing
stridor, wheeze, gurgling
See-saw respiratory pattern,
Common causes of airway problems
CNS depression
Blood
Vomit
Foreign body
Trauma
Infection
Inflammation
Laryngospasm
Approach to assessment of breathing problems
- Look
- Inspect respiratory distress, accessory muscles, cyanosis, Respiratory rate very
important. RR>20 sign of a sick patient - Listen
- Auscultate breath sounds, noisy breathing - Feel
- palpate expansion, percussion, tracheal position
- Pulse oxymetry: Saturation 94%: on oxygen ?
Tx of breathing problems
- Airway
- Oxygen
- Treat underlying cause
- e.g. drain pneumothorax
- e.g . Nebulizers - Support breathing if inadequate
- e.g. ventilate with bag valve mask
How to assess circulation
- Look at the patient
- Pulse – central pulse (carotid)
- peripheral pulse
- Peripheral perfusion
- capillary refill time
( normally <2 sec) - Blood pressure
- Monitor
Primary causes of circulatory problems
- Acute coronary syndromes
- Dysrhythmias
- Hypertensive heart disease
- Valve disease
- Drugs
- Electrolyte / acid base
abnormalities
Secondary cause of circulatory problems?
- Hypoxaemia
- Blood loss
- Hypothermia
- Septic shock
Tx of circulatory problems
- Airway, Breathing
- Oxygen
- IV access, take blood sample and lab
investigations - Treat cause
- Give fluids
- Haemodynamic monitoring
What is a fluid challenge?
A positive response is an increase in cardiac output in
response to the increased volume.
Heart rate decreases
Mean arterial pressure increases
Arterial pulse pressure increases
Urine output increases
Lactate clearance increases
Cardiac output or stroke volume increase
Know how to do a glasgow coma score
see slight 33 on recognising a sick patient lecture
What is AVPU
Used to measure consciousness.
Alert – a fully awake patient (not necessarily orientated)
Voice –Responds to voice or confused/agitated
Pain – Makes a response when mild pain is inflicted e.g. trapezius pinch
Unresponsive – No response to voice or pain
A fall in the AVPU score should always be considered
significant
More detailed conscious level and neurological data should
be recorded on ‘neurological observations’ chart if required
This should include a ‘Glasgow Coma Scale’ assessment
What is the significance of urine output in a sick patient?
Urine output is one of the few signs of end-organ
perfusion
In a sick patient catheterisation should be considered to
allow measurement (and documentation) of hourly urine
volume The weight is essential to get an accurate urine
output.
