What is erythropoeitin?
It is a glycoprotein hormone secreted from the peritubular endothelial cells and interstitial fibroblasts.
It acts on the bone marrow to produce RBC and WBC.
Mechanism of EPO
- Binds to erythropoeitin receptor
- Then JAK2 kinase is activated
- This activates other pathways such as STAT, PIK AND MAPK
- This leads to differentiation, proliferation and survival of red blood cells
Erythropoeitin stimulating agents (ESAs)
Also known as recombinant human EPO
There are two types: alpha and beta
Uses are:
- Anemia in CKD
- Anemia in MDS
- Anemia in cancer patients
- Used by athletes
Side effects of EPO
- Myocardial infarction
- Stroke
- Venous thromboembolism (VTE)
- Tumour recurrence
Acute renal failure
- Damage to kidneys lowering GFR
- Reversible
Prerenal
- Sudden or severe decrease in blood pressure
- Flow obstruction to kidney via ischemia or athersclerosis
Intrarenal
- Direct damage to kidney
- Inflammation of kidney
- Infection
- Drug
- Autoimmune disease
Most common form of acute renal failure
Post renal
Obstruction of urine flow
- Benign prostatic hyperplasia, kidney stones, bladder injury, tumour
Risk factors of AKI
- Age over 65
- CKD
- Cardiac failure
- Hypovolemia
- Diabetes mellitus
- Nephrotoxic drugs (NSAIDs, ARBs, ACE inhibitors and cyclosporin)
Erythrocyte
Life span of erythrocyte is 100-200 days.
Old RBC become rigid and hemoglobin degenerates. When RBC is engulfed by macrophage the heme and globin separate. Iron is removed from heme and salvaged for reuse - stored as hemociderin or ferritin in tissues.
Erythrocytes contain spectrin which provide flexibility.
Causes of hypoxia
- Haemorrhage or increased destruction of RBC
- Abnormality of hemoglobin - iron deficiency
- Reduced oxygen
What is anemia?
Functional inability of the blood to supply tissues with adequate oxygen for metabolic functions due to:
- Erythrocyte loss
- Decreased erythrocyte production
- Increased erythrocyte destruction
Types of anemia
- Iron deficiency
- Vitamin B12 or folic acid deficiency - DNA synthesis impaired and no cell division just cell growth
- Aplastic anemia - Stem cells in bone marrow damaged and affect all blood cells
- Abnormal haemoglobin
- Haemolytic anemia - Breakdown of RBC in blood vessels/spleen
- Renal anemia - Low renal blood flow, low EPO
What is CKD?
Decrease in kidney function/ structural damage or both for greater than 3 months
GFR
Normal GFR rate is 100-120ml/min/1.73m2 and slightly less in women
Causes of CKD
- Hypertension
- Macrophage and foam cells get into the glomeruli and this secretes growth factor TGF-beta1 causing mesangial cells to regress back to immature mesangioblasts which release extracellular matrix leading to glomerulisclerosis causing hardening and scarring
- Diabetes - excess glucose attach to arteriolar walls by glycation and cause the narrowing/stiffening of efferent arteriolar walls
What is azotemia?
When the GFR is low, the urea excreted is decreased and it begins to build up in the blood leading to AZOTEMIA.
Causing nause and loss of appetite.
Can lead to encephelopathy, coma, death, pericarditis
Problems associated with CKD
- Azotemia
- Potassium excretion is reduced and this causes hyperkalemia resulting in cardiac arrythmias (ST elongation)
- Less activated vitamin D resulting in hypocalcemia causing release of parathyroid hormone which causes bones to lose Ca2+ leads to renal osteodystrophy
- Releases renin to increase blood pressure leading to hypertension
- EPO levels fall and there is lower production of RBC leading to anemia
Diagnosis of CKD
- GFR less than 90ml/min/1.73m2
- Irreversible kidney damage occurs at less than 60ml/min/1.73m2
