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Renal Failure Flashcards

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1
Q

Function of the kidneys

A

• Electrolyte and fluid balances • Acid-Base Balances
• Elimination of metabolic wastes
• Regulation of blood pressure: ➢Renin-Angiotensin system
➢ Prostaglandin Synthesis
• Endocrine functions: site of Vitamin D synthesis → Ca2+ homeostasis
• Red Blood Cell Production: site of erythropoietin synthesis (EPO)
• Metabolic: 2nd major site of gluconeogenesis

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2
Q

Facts about the kidney

A

Dimensions: 10-12 cm long; 5-7 cm wide; 3 cm thick Position: between 12th thoracic and 3rd lumbar
vertebrae, retroperitoneal (back of ribcage)
Weight: 135 – 150 g = ~ 0.5% of total body mass Receive 20 – 25% of resting cardiac output
=> 1.2 L of blood / min through both kidneys

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3
Q

Parts of the kidney

A

Renal cortex (outer)
(cortex = rind)
Function: Nephron glomeruli
→filtration of primary urine
Renal medulla (inner):
• renal pyramids • renal columns

Function: Nephron tubules and collecting ducts→concentration of urine

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4
Q

The nephron

A

Nephrons ~ 1 000 000 / kidney: functional units of the kidney which produce the urine
Consists of:
• Renal corpuscle (=tiny body)
• Tubules

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5
Q

The renal corpuscle

A

I) Renal corpuscle
1) Glomerulus (capillary network)
2) Glomerular (Bowman’s) capsule: single sheet of impermeable epithelial cells
Function: Formation of primary urine

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6
Q

Structure of the glomerulus

A

-Endothelium which consists of 2 parts
A)endothelial cells which contain large pores that everything goes through but blood cells
B)mesangial cells which can contract by narrowing the diameter and regulate glomerular filtration rate(GFR)

-Basal lamina
• glycoprotein matrix: collagen fibres and proteoglycans
• excludes large plasma proteins

-Podocytes
• pedicels (little feet):
• filtration slits
• slit diaphragm: cuts off molecules larger than 0.006–0.007 μm
•retain albumin
•wrap around capillaries
•retain albumin,if they die albumin found in urine

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7
Q

Mechanism of Glomerular filtration

A

1) Endothelial fenestrations allow plasma but not blood cells to be filtered in the glomerulus
2) Basal lamina prevents filtration of large proteins
3) Slit membranes between podocyte pedicles prevent filtration of medium sized proteins

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8
Q

Functions of the Renal Corpuscle

A

• The glomeruli filter ~180L/day of cell and protein free primary urine before it enters the proximal tubules:
~ men: 125 ml/min women: 105 ml/min
• Sustains normal blood pressure (80 – 120 mmHg) via:
✓ dilation of afferent arterioles and glomerular capillaries
✓ constriction of efferent arterioles
✓ the renin-angiotensin-aldosterone system (RAAS)

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9
Q

The renal tubules

A

-The function is reabsorption of electrolytes,nutrients and water and secretion of waste and toxins
-Consists of proximal convolutes tubule,loop of Henle which includes the descending and ascending limbs,distal convoluted tubule
-also has collecting ducts,papillary ducts,peritubular capillaries and vasa recta

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10
Q

Formation of urine

A

Glomeruli→Formation of glomerular filtrate:
• 16 – 20% of blood volume
• ~150 L/ day in females; 180 L/ day in
males
Tubules→Reabsorption of ~99% of the glomerular filtrate and secretion
• →~ 1-2 L urine/day

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11
Q

Tests to check renal function

A

-2 types of tests

1)urinalysis and disease markers eg:
• Gross appearance of urine
• Urine sediment
• Biochemical tests of renal function

2) Functional tests
• Glomerular function: Glomerular filtration rate (GFR) • Clearance tests
• Plasma creatinine

3)injecting substances to see how well they get cleared

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12
Q

Advantages of urinalysis

A

-Liquid biopsy of the urinary tract, which is painless, non- invasive, inexpensive
-Yields much information quickly

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13
Q

The 3 stages of urinalysis

A

-gross appearance =detects the volume and colour
-microscopy=detects cells,casts,crystals and bacteria
-biochemistry=detects/checks for ph,osmolality,protein,creatinine,glucose

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14
Q

Glucose and kidney disease

A

-glucose normally absent in urine
-glucosuria:present in diabetes,low renal threshold for glucose or other tubular disorders

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15
Q

Relationship between protein and kidney disease

A

-shouldn’t be detected in urine,if they are it indicates proteinuria which is caused by:

overflow (↑ low MW proteins in plasma, Bence Jones protein (Ig antibody chains), myoglobin)
• glomerular leak
• decreased tubular reabsorption of protein • protein with renal origin

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16
Q

Normal urinary protein excretion

A

• In normal adult, normal urinary protein excretion should be < 150 mg/day
• Normal rate of albumin excretion is < 20 mg/day (15 μg/min), increases with age and higher body weight

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17
Q

Abnormal urinary protein excretion (proteinuria)

A

Microalbuminuria: Persistent albumin excretion between 30 and 300 mg/day (20 to 200 μg/min):
• Overt proteinuria: Albumin excretion > 300 mg/day (200 μg/min):

18
Q

Signs that suggest proteinuria

A

Excessive foaming and cloudiness

19
Q

Albuminuria

A

• Appr 1.3 g of albumin / day is filtered by the glomerulus
• Majority reclaimed by endocytosis
• Normally we lose appr. 15 mg of albumin in the urine / day
Microalbuminuria: pathological increase in the rate of albumin loss in urine below detection limit of dipsticks
Macroalbuminuria: albumin detected by dipsticks e.g. in diabetic nephropathy

20
Q

Glomerula filtration rate

A

-GFR is a measure of the clearance of an ideal substance by the kidney

-Characteristics of an ideal substance for GFR measurements:
• Stable concentration in plasma
• Physiologically inert
• Freely filtered at the glomerulus
• Not secreted, reabsorbed, synthesized or metabolised by kidneys

Equation :
GFR=(UXV)\P
P is plasma concentration of substance
V is the the rate of urine formation
U is the urinary concentration of substance

21
Q

Estimated GFR (eGFR)

A

Modified Diet in Renal Diseases study equation (MDRD formula)
eGFR = 175 x (SCr)-1.154 x (age)-0.203 x 0.742 [if female] x 1.212 [if Black]
SCr - standardised serum creatinine (mg/dL) Age - years
▪MDRD formula:
• Derived for CKD
• Not reliable if near normal function or for AKI

22
Q

Advantages and Disadvantages of serum creatinine as a marker of renal function

A

-Advantages: readily available and easy to measure

  • Disadvantages: proportional to Muscle mass/Age/Sex/ Race/Diet
23
Q

Urine Albumin:Creatinine ratio (uACR)

A

uACR - Adult reference range (NICE guidelines CG182)
• <3 mg/mmol: normal to mildly increased
• 3-30mg/mmol:moderatelyincreased
• >30.0mg/mmol:severelyincreased,includingnephroticsyndrome(uACR usually >220 mg/mmol)
Sample collection: Early morning or random mid-stream urine sample
Limitation:uACR is specific for albumin→possible to lose significant amounts of proteins of lower molecular size (e.g. in renal tubular disease or in light chain disease) without seeing an increase in albumin loss.

24
Q

Problems with using Plasma Creatinine & eGFR

A

▪Formulae only apply in steady state. Not good for Acute renal failure • Stable renal function for 4 days
▪Plasma creatinine can increase following protein loads
• Goulash effect. 80% rise in creatinine after 300g of cooked beef
• Less variability in early morning creatinine
▪ Strenuous exercise may increase creatinine by 14%
▪ Muscle mass more difficult to predict in oedematous patients and late pregnancy
▪ Patients with muscle wasting
▪ Patients with liver disease
▪ Drugs inhibiting tubular secretion can raise creatinine concentration

25
Q

Renal failure

A

Result of Acute Kidney Injury (AKI) or Chronic kidney disease (CKD) (called End-Stage Renal Disease (ESRD) when the cause is CKD)

26
Q

Signs and symptoms of kidney disease

A

Symptoms of Uraemia (elevated blood urea + fluid, electrolyte and
hormone imbalances): nausea, vomiting, lethargy
Disorders of Micturition (urination): decreased frequency, nocturia, urine retention
Disorders of Urine volume: polyuria, oliguria, anuria
Alterations in urine composition (haematuria, proteinuria, bacteriuria,
leukocyturia, calculi)
Oedema: (hypoalbuminaemia, salt and water retention)
Pain, Fatigue, Confusion Anaemia

27
Q

Causes of renal failure

A

•Impaired blood flow to the kidneys: severe dehydration, blood or fluid loss, heart attack, infection, sepsis, liver failure, anaphylaxis, renal artery stenosis, hyperperfusion, etc.
• Damage to the kidneys: toxins, drugs, infections, autoimmune diseases, glomerulonephritis, muscle tissue breakdown (rhabdomyolysis), etc.
•Urinary obstructions: kidney stones, prostate, bladder, cervical or colon cancer, etc.

28
Q

2 causes of renal failure

A

Acute(temporary):

• Myocardial infarction
• Cardiac arrest (→impaired kidney
oxygenation)
• Rhabdomyolysis
• Decreased perfusion of the kidneys (e.g. blood loss or shock)
• Obstruction along the urinary tract
• Haemolytic uremic syndrome (E. coli infection)
• Toxins
• Glomerulonephritis

Chronic kidney disease(permanent damage):

• Diabetic nephropathy
• Hypertension
• Lupus (autoimmune disease)
• Prolonged urinary tract obstruction
• Alport syndrome (genetic)
• Nephrotic syndrome
• Polycystic kidney disease (genetic)
• Cystinosis (genetic)
• Interstitial nephritis or pyelonephritis

29
Q

Causes of acute kidney diease(in detail)

A

3 types(prerenal=affecting blood supply,intrarenal=intrinsic kidney disease,postrenal(affecting lower urinary tract )

30
Q

Pre renal causes of AKI

A

-Decreased blood flow to the kidneys
-dehydration
-hypotension
-haemorrhage
-sepsis
-low cardiac output
-burns
-Postoperative fluid and blood losses

31
Q

Post renal causes of AKI

A

-urinary tract obstruction
-bilateral obstructing kidney stones
-prostatic enlargement
-urinary tract neoplasms
-neurogenic bladder
-retropritoneal fibrosis involving both ureters

32
Q

Intrinsic renal causes of AKI

A

-intrinsic damage to the kidneys
-diseases:glomerular,micro vascular ,systemic lupus etc
-neprhotoxins:plant toxins,x ray contrast Media,NSAIDs

-intrarenal obstruction eg bence jones protein

33
Q

Diagnosis of AKI

A

Stage 1:
Creatinine concentration :≥ 26 μmol/L increase within 48 h
Or
1.5-1.9-fold increase from baseline within 7 days
Urine output:< 0.5 ml/kg/h for > 6 h

Stage 2:
Creatinine concentration: 2-3 fold increase from baseline within 7 days
Urine output: < 0.5 ml/kg/h for > 12 h

Stage 3:
Creatinine concentration: ≥ 354 μmol/L
Or
≥ 3-fold increase form baseline within 7 days
Urine output: < 0.3 ml/kg/h for > 24 h or anuria for 12 h

Biochemical changes In plasma :
Increased: potassium
urea
creatinine
phosphate
magnesium
hydrogen ion
urate

Decreased:
Sodium
Bicarbonate
Calcium

34
Q

Treatment of AKI

A

• depends on the cause and stage of AKI
• May require renal replacement therapy (dialysis)

35
Q

Chronic kidney disease

A

CKD:
Abnormal kidney structure or function, present for more than 3 months, with a gradual loss of kidney function over months and years

5 stages:
1=kidney damage with normal kidney function
2=kidney damage with mild loss of kidney function
3a=mild to moderate loss of kidney function
3b=moderate to severe loss of kidney function
4=severe loss of kidney function
5=kidney failure

36
Q

Symptoms of ckd

A

Early CKD stages (1-3): mostly asymptomatic
Later CKD stages:
• weight loss and poor appetite
• swollen ankles, feet or hands – as a result of
water retention (oedema)
• shortness of breath
• tiredness
• blood in the urine
• an increased need to pee – particularly at night • difficulty sleeping (insomnia)
• itchy skin
• muscle cramps
• feeling sick
• headaches
• erectile dysfunction in men

37
Q

Nephrotic Syndrome

A

• Massive proteinuria—at least 3.5 g/day→frothy urine
• Hypoalbuminemia (albumin < 3.5 mg/dL)
• Generalized edema (e.g. peri-orbital, lower limb, ascites)
• Shortness of breath (with associated chest signs of pleural effusion – e.g. stony dullness in lung bases)
• Hyperlipidemia, hyperlipiduria (↑lipids in the urine –e.g. HDL)

38
Q

Nephritic Syndrome

A

• Causes: e.g. glomerulonephritis (inflammation of the glomeruli) • Mild to moderate proteinuria— less than 3.5g/L/day
• Generalized edema
• Low urine output
• Associated with hypertension
• Hematuria (presence of red blood cells in the urine)
• RBC casts – symptom of glomerular damage
• Uraemic symptoms (e.g. reduced appetite, fatigue, pruritus, nausea) • Poorer prognosis than nephrotic syndrome

39
Q

Management of CDK

A

Aim:

➢ Reduce rate of disease progression to stage 5 CKD (renal failure) ➢ Alleviate symptoms in stage 4 and 5
Management:
• Blood glucose control (if diabetes is a leading factor for CKD)
• Diuretics to promote sodium excretion
• Anti-hypertensive drugs (e.g. targeting the Renin-Angiotensin system: ACEIs and ARBs)
• Bicarbonate to control metabolic acidosis
• Appropriatenutrition
• Treatment of anaemia in the later CKD stages
• Renal replacement therapy (dialysis of kidney transplantation) at stage 5 CKD

40
Q

Renal Failure following CKD

A

RF (Stage 5 CKD) begins when >90% of nephrons lost, corresponding to eGFR <15 ml/min/1.73m2 for more than 3 months

Treatment: dialysis or transplantation

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