Pathophysiology: Chronic Kidney Disease Flashcards
Functions of the kidney
- Excretory
- Endocrine/Metabolic
Excretory function of the kidney
- blood is filtered through glomerulus -> tubules fine tune solutes -> urine output
- homeostasis of: water, electrolytes, acid-base, toxins
- via: filtration (passive), secretion (active), reabsorption
Endocrine/metabolic function of kidney
- renin production
- erythropoetin production
- vitamin D activation
Chronic Kidney Disease (CKD)
- abnormalities of kidney structure or function
- must be present for more than 3 months!
- classified based on cause, GFR category, and albuminuria category (CGA)
CKD Workup
- Urinalysis
- Labs: CMP
- Biopsy
- US, CT, nuclear flow scan
What percentage of kidney loss to get to late stage CKD?
- 90% kidney function
CKD Prevalence
- More than 1 out of 10 adults has some level of CKD
Primary cause of ESRD
- Diabetes Mellitus (49%) and Hypertension (28%)
- pts in hemodialysis are the most common
ESRD incidence and prevalence in CKD
- more pts going on dialysis and CKD as time goes on
- pts with CKD have a higher mortality
- heart disease is the number 1 disease in the US
What is used for staging CKD?
- Modification for Diet in Renal Disease (MDRD)
Modification for Diet in Renal Disease (MDRD)
- estimates GFR
- preferred for staging CKD
- more accurate than Cockcroft-Gault when staging CKD
Cockcroft-Gault Equation
- estimates Creatinine Clearance
- preferred for drug dosing in CKD
- no longer used for staging CKD
CKD Epidemiology Study group (CKD-EPI)
- also estimates eGFR
- more accurate in pts with GFR >60mL/min/1.73m²
- is the preferred formula since there is no race variable
Stage 3 CKD
- is subdivided to 3a and 3b
What is the relationship between GFR and the staging of CKD?
- depending on how low the GFR is, the higher or worse the staging for CKD is
Which stage of CKD do symptoms start?
- Stage 3 CKD
Stage 1 and Stage 2 CKD
- asymptomatic
- best time for preventative care
Stage 5 CKD
- when pts are on dialysis
- almost all pts have NO urine output
CKD Staging: Albuminuria
- aka proteinuria
- 24-hour urine collection
“Spot” urine sample
- Albumin-to-Creatinine Ratio (ACR)
- most accurate way to measure albumin
- often provided with laboratory test results
- used as an estimate
Urine dipstick
- NOT reliable
- done in 5 minutes
- Yes or No if you have proteinuria
- does NOT quantify AER or ACR
- NOT used
Stage A1: Albuminuria
- AER: <30 mg
- ACR: <30 mg/g
- Normal to mildly
Stage A2: Albuminuria
- AER: 30-300 mg
- ACR: 30-300 mg/g
- Description: Moderately
Stage A3: Albuminuria
- AER: >300 mg
- ACR: >300 mg/g
- Description: Severely
Why do we need to stage someone with CKD?
- the worst staging of CKD and higher A3 means the higher the proteinuria
- so we can keep track overtime
Efferent arteriole
- blood flow outward
Afferent arteriole
- blood flow inward
The loss of nephron mass results in?
- changes in the efferent and afferent side which changes the surface area
- reduced GFR
- compensatory hypertrophy
Key elements of CKD
1) Loss of nephron mass
2) Glomerular capillary hypertension
3) Proteinuria
4) Progressive nephron loss
Glomerular capillary hypertension
- mediated by angiotensin II
- increased filtration fraction
- altered membrane permeability
Proteinuria
- promotes inflammatory and vasoactive cytokines and complement
- direct tubular toxicity
Progressive nephron loss
- Glomerulosclerosis
- Interstitial fibrosis
- Reduced GFR
What is not a risk factor for CKD?
- alcohol use
CKD Risk factors: Susceptibility to CKD
- advanced age
- reduced kidney mass
- low birth weight
- racial/ethnic minority
- family history
- low income or education
- systemic inflammation
- previous acute kidney injury
- exposure to certain drugs or chemicals
CKD risk factors: progression of CKD
- Diabetes
- Hypertension
- Proteinuria
- Obesity (BMI: equal or more than 30)
- smoking
- Dyslipidemia
What is the number one leading cause of CKD?
- Diabetes
Diabetes Mellitus 1 (DM1):
- 80% will develop overt nephropathy
Diabetes Mellitus 2 (DM2)
- 20-40% will progress to CKD
Diabetes MOA in CKD
- risk increases with mean glucose (A1C) and proteinuria
- Mechanism: hyperglycemia -> mesangial expansion, glomerular basement membrane thickening, podocytopathy, impaired filtration/proteinuria
Hypertension in CKD
- # 2 leading cause of CKD
- result of CKD (fluid overload)
- risk of CKD increase with BP and proteinuria
- Mechanism: increased intraglomerular pressure -> glomerular injury -> impaired filtration/proteinuria
Cause of Kidney disease with chronic use of:
- NSAIDs
- Salicylates
- Lithium
- Calcineurin inhibitors
Clinical Manifestation of CKD
- Fluid and Electrolyte Disturbances
- Acid-base disturbances
- Osteodystrophy
- Calcium Homeostasis
- Mineral and Bone disorder
- Calcium, Phosphorus & the Cardiovascular System
- Calciphylaxis (uremic arteriolopathy)
- Cardiovascular abnormalities
- Anemia of CKD
- Other
Impaired tubular excretion of Na+
- results in extracellular fluid volume expansion
- influenced by dietary sodium intake
- hypertension, peripheral and pleural edema, weight gain
Impaired reabsorption of Na+ (when needed for extrarenal fluid losses)
- prone to ECFV depletion
- acute-on-chronic kidney failure
Impaired tubular excretion of K+
- hyperkalemia
- risk for life threatening arrythmias
- influenced by diet, drugs, transfusion, hemolysis and acidosis
Impaired tubular excretion of Mag++
- mild hypermagnesemia
Impaired tubular excretion of [PO4-]
- contributes to development of mineral-bone-disorder and hyperparathyroidism
Acid-Base disturbances
- decreased GFR leads to retention of organic acids
- hyperkalemia decreases ammonia production, reducing urinary buffer and bicarbonate regeneration
= Anion-gap metabolic acidosis
= Protein catabolism
How is Ca++ maintained?
-by Calcitonin and PTH
- needs to maintain [Ca++] 10mg/100mL
What happens when there is too much Ca++?
- will trigger calcitonin secretion
Calcitonin role in the bone
- will continue to produce until [Ca++] levels are in homeostasis
PTH role in calcium homeostasis
- tells kidneys to activate Vitamin D
- stimulate Ca++ release from bones
- increase Ca++ uptake in the intestines
Overtime, the release of PTH
- will cause increase Ca++ mobilization from the bone
- increase renal Ca++ reabsorption
- decrease phosphate
What occurs in the later stages of CKD?
- secondary hyperparathyroidism = hypocalcemia
- the result of another condition that lowers the blood calcium, which then affects the gland’s function
- result in kidney failure and Vit D deficiency
Progressive kidney disease leads to
- decrease phosphate excretion = hypocalcemia
- decrease Calcitriol (Vitamin D3) production = hypocalcemia
- increased PTH
What happens when there is decreased phosphate excretion?
- there will be phosphate retention which can lead to hypocalcemia
- OR increased calcium phosphate crystals which leads to Soft Tissue Calcification
increased PTH
- is caused by hypocalcemia
- which leads to:
1) increased Ca++ mobilization from bone
2) increased renal Ca++ reabsorption
3) decreased renal phosphate reabsorption
Decreased Calcitriol
- decreased GI Ca++ absorption = Hypocalcemia or impaired bone mineralization
impaired bone mineralization
- Osteomalacia
Calciphylaxis
- blood vessel occlusions with extreme vascular and soft tissue calcification: skin necrosis and poor wound healing
- associated with Warfarin therapy and calcium-based phosphorus binders
- very poor prognostic factor
- stops blood flow altogether
Anemia of CKD
- low hemoglobin
- reduce transport of blood oxygen
- decreased erythropoietin
- Folate(B9) and/or Cobalamin (B12) deficiencies
- pernicious anemia
- iron deficiency
- megaloblastic anemia
Other clinical manifestation of CKD
- uremic bleeding (platelet dysfunction)
- reduced insulin elimination
- reduced estrogen, testosterone
- dry, itchy skin
Decreased levels of ____ is the cause of this anemia.
a) Erythropoietin
b) Iron
c) PTH
d) Vitamin D
Erythropoietin
______ levels of _______ would cause bone disease in CKD.
a) increased; calcitonin
b) decreased; calcitonin
c) increased; PTH
d) decreased; PTH
increased; PTH
