1. Renal Physiology
Nandinii Ramasenderan (K1)

2. A. Renal Vein
B. Renal Artery
C. Ureter
D. Medulla
E. Renal Pelvis
F. Cortex
1. Ascending loop of
Henle
2. Descending loop of
Henle
3. Peritubular capillaries
4. Proximal tubule
5. Glomerulus
6. Distal tubule
The Kidney and the Nephron

3. •Glomerulus
•Afferent and
Efferent arterioles
•Proximal Tubule
•Loop of Henle
•Distal Tubule
•Collecting Duct
Components of
the nephron

4. Functions of the Kidney:
Maintaining balance
• Regulation of body fluid volume and osmolality
• Regulation of electrolyte balance
• Regulation of acid-base balance
• Excretion of waste products (urea, ammonia, drugs, toxins)
• Production and secretion of hormones
• Regulation of blood pressure

5. From http://www.emc.maricopa.edu/faculty/farabee/BIOBK/BioBookEXCRET.html
Overview of nephron function

6. Filtration

7. Reabsorption
and secretion

8. Reabsorption
• Active Transport –requires ATP
• Na+, K+ ATP pumps
• Passive Transport-
• Na+ symporters (glucose, a.a., etc)
• Na+ antiporters (H+)
• Ion channels
• Osmosis

9. What is Reabsorbed- Where?
Proximal tubule - reabsorbs 65 % of filtered Na+ as well
as Cl-
, Ca2+
, PO4, HCO3
-
. 75-90% of H20. Glucose,
carbohydrates, amino acids, and small proteins are
also reabsorbed here.
Loop of Henle - reabsorbs 25% of filtered Na+.
Distal tubule - reabsorbs 8% of filtered Na+. Reabsorbs
HCO3-.
Collecting duct - reabsorbs the remaining 2% of Na+
only if the hormone aldosterone is present. H20
depending on hormone ADH.

10. Secretion
• Proximal tubule – uric acid, bile salts, metabolites, some drugs, some
creatinine
• Distal tubule – Most active secretion takes place here including
organic acids, K+, H+, drugs, Tamm-Horsfall protein (main
component of hyaline casts).

11. Hormones Produced by the Kidney
• Renin:
• Released from juxtaglomerular apparatus when low blood flow or low Na+. Renin leads to
production of angiotensin II, which in turn ultimately leads to retention of salt and water.
• Erythropoietin:
• Stimulates red blood cell development in bone marrow. Will increase when blood oxygen
low and anemia (low hemoglobin).
• Vitamin D3:
• Enzyme converts Vit D to active form 1,25(OH)2VitD. Involved in calcium homeostasis.

12. Renin, Angiotensin, Aldosterone:
Regulation of Salt/Water Balance

13. Aldosterone
• Secreted by the adrenal glands in response
to angiotensin II or high potassium
• Acts in distal nephron to increase resorption
of Na+ and Cl- and the secretion of K+ and
H+
• NaCl resorption causes passive retention of
H2O

14. Anti-Diuretic Hormone (ADH)
• Osmoreceptors in the brain (hypothalamus) sense
Na+ concentration of blood.
• High Na+ (blood is highly concentrated) stimulates
posterior pituitary to secrete ADH.
• ADH upregulates water channels on the collecting
ducts of the nephrons in the kidneys.
• This leads to increased water resorption and
decrease in Na concentration by dilution

15. Anatomic Changes in Pregnancy
• Kidney’s increased size (can increase up to 2cm in length),
• Increased vascular volume,
• Increased interstitial space and increased glomerular size (not number).
• The greatest changes are seen in the collecting system, where calyces, renal
pelvises and ureters dilate and elongate.
• These changes are evident by the 3rd
gestational month and persist until the
12th week post partum

16. • Pregnancy induces increased synthesis of prostaglandin E2 (PGE2) which
inhibits ureteral peristalsis and may be responsible for the hypomotility
and distension.
• Increased oestrogen and progesterone production causes muscular and
hypertrophic changes in the urinary tract resulting in hypomotility of the
urinary tract.
• Increased production of chorionic growth hormone may cause some
renal hypertrophy.
• Mechanical obstruction by the enlarged uterus can contribute to
ureteral distension as well as changes to surrounding structures.

17. Functional Changes
• Early in pregnancy increased RBF, secondary to increased CO and
renal vasodilatation
• This has been shown to be up to 40% above nongravid values.
• Usually a decrease in systolic pressure is seen, due to the decrease in
vascular resistance from vasodilation.
• This increased RBF  increased glomerular filtration rate (GFR). This
begins during the first few weeks after conception, is at its greatest at
the beginning of the 2nd
trimester and remains until after delivery.
• Creatinine, urea and uric acid clearances increase, therefore serum
levels decrease during pregnancy.

18. • Acid base regulation altered decrease in the bicarbonate threshold. Early morning
urine specimen is more alkaline.
• Pregnant women tend to hyperventilate and subsequently mild alkalosis is often
present.
• Glucose, water-soluble vitamins, protein and amino acids are excreted during normal
pregnancy (increase in GFR  filtered load of nutrients to surpass the reabsorptive
capacity of the kidney, therefore these substances spill into the urine)
• Intermittent glycosuria is normal and makes screening for diabetes more difficult.
• Volume regulation ch.  gradual accumulation and retention of water and sodium.
• Most healthy women gain an average of 12.5 kilograms and most of this is fluid.
• The plasma volume doubles and this results in a fall in the plasma sodium
concentration (dilution).

19. • Osmolarity levels decrease  stimulate a diuresis by suppressing ADH.
However, in pregnancy this does not appear to happen.
• It appears as though the osmoreceptors are ‘reset’ at a lower level to
avoid a continuous diuresis.
• Mean BP decreases by around 10 mmHg in early pregnancy  decrease in
peripheral vascular resistance; effects of progesterone (smooth muscle
relaxant).
• Renin concentration is 5 - 10 times greater in pregnancy, however the
pregnant women is extremely resistant to the vasoconstriction effects of
angiotensin II. Related to elevated levels of aminopeptidase which
destroys angiotensin II.
• Erythropoietic activity increases during pregnancy. This is possibly due to
an increase in erythropoietin levels from an increase in renal tissue

20. Normal Renal Alterations in Pregnancy

21. Normal Changes in Pregnancy
 Systemic Vasodilation
 Lower BP
 Increased Aldosterone
 Volume expansion / edema
 Increased GFR / RBF
 Angiogenesis

22. Progesterone
 Stimulates Nitric Oxide Synthase
 Decreased response to Angiotensin

23. Progesterone
 Stimulates Nitric Oxide Synthase
 Leads to systemic Vasodilation
 Which causes lower BP,
 Which stimulates Aldosterone
 Which leads to volume expansion
 Which increases GFR/RBF
 Decreased response to Angiotensin

24. Pregnancy in women with
existing renal disease

26. Why don’t uremic women
get pregnant?
• Most beyond child bearing age
• Libido/ frequency of intercourse reduced
• Don’t ovulate
• Absence of increase in basal body temperature during the luteal
phase of cycle
• Elevated circulating prolactin concentrations
• Elevated PRL impairs hypothalamic-pit function

27. Course of Renal Disease in Pregnancy
• Baseline azotemia = more rapid deterioration
• As renal dz progresses, ability to maintain nl pregnancy deteriorates,
and presence of HTN incr likelihood of renal deterioration
• Renal dysfunction - greater risk for complications incl preeclapsia,
premature delivery, IUGR

28. Chronic Renal Failure
• CRF is defined as a permanent reduction in glomerular filtration rate
(GFR) sufficient to produce detectable alterations in well-being and
organ function. This usually occurs at GFR below 25 ml/min.
Clinical practice Guidelines:Clinical practice Guidelines:
•Pregnancy may be considered in women with chronic kidney disease (CKD) having mild renal
impairment (serum creatinine <124 μmol/L) and well controlled blood pressure. (Grade C)
•Women with moderate to severe renal impairment should be counselled to avoid pregnancy
due to greater adverse maternal and fetal outcomes. (Grade C)
•All pregnant women with CKD should be co-managed by a multidisciplinary team. (Grade C)

29. Stages of chronic kidney disease:
Cockroft Gault Formula: [(140-age) x weight] / [PCr x 72] x 0.75 (women)

30. Risk factor:
• Family history of kidney disease
• Age - chronic kidney disease is much more common among people over 60 years of age
• Atherosclerosis
• Bladder obstruction
• Chronic glomerulonephritis
• Congenital kidney disease (kidney disease which is present at birth)
• Diabetes Hypertension
• Lupus erythematosus
• Overexposure to some toxins
• Sickle cell disease
• Some medications

31. Uremic Syndrome
• Uremia occurs in stage 3 & 4 of CRF:
• Changes in mental status
• Fever, Malaise
• Anorexia, Nausea, vomiting, LOW
• Mild neural dysfunction
• Uremic pruritus (itching)

32. Associated problems with
CRF
• Immunosuppression
• Increased risk of infection
• People with CFR should be vaccinated regularly
• Anemia
• Due to reduced erythropoietin production by kidney. Usually
doesn’t occur until 6-12 mos prior to dialysis
• Hyperuricemia (Gout)
• Increased uric acid in system
• Pain in joints, may contribute to renal dysfunction
• Hyperphosphatemia
• Increased parathyroid hormone levels
• Increased phosphate load from bone metabolism
• Hypertension
• Poor coagulation
• Proteinuria

33. How CKD should be managed in
pregnancy?
• All women with chronic kidney disease should be referred early in
pregnancy to an obstetrician and other specialist as necessary, to plan
subsequent antenatal care.
• However, with a few exceptions, the most important aspects of managing
chronic kidney disease in pregnancy relate to managing associated clinical
features, rather than the type of kidney disease.
• Regular monitoring of maternal renal function (serum creatinine and
serum urea), blood pressure, midstream urine (for infection), proteinuria,
and when appropriate ultrasound (to detect urological obstruction) should
identify pathological changes and allow timely intervention to optimise
perinatal outcome and maternal renal outcome.

34. Before pregnancy:
• Ideally, all women with chronic kidney disease should be made aware of the risks
to their long term renal function and to the fetus before they conceive.
• Women with chronic kidney disease often have amenorrhoea but may still
occasionally ovulate and thus conceive.
• Contraceptive measures that consider clinical comorbidities should be taken by
those who do not wish to become pregnant.
• Folic acid 400 μg daily should be given as usual before conception until 12 weeks’
gestation.
• Low dose aspirin (50-150 mg/day) should be started in early pregnancy to reduce
the risk of pre-eclampsia and improve perinatal outcome.
• Fetotoxic drugs—such as ACE inhibitors and angiotensin II receptor blockers—
should be stopped before pregnancy if equally effective drugs are available, or as
soon as pregnancy is confirmed, if they are thought to be important for protecting
maternal renal function.

35. During pregnancy:

36. Management:
• Dialysis
• Kidney transplantation

37. Common Themes in Dialysing Pregnant
Patients
1. Keeping BUN < 50
2. Increasing dialysis time and frequency
3. BP control
4. Managing anemia with increasing doses of ESA
5. Fetal monitoring once viability reached