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Pathophysiology 17 • JP Advis DVM, Ph.D.
Bartlett Hall, Animal Sciences, Cook,
932 - 9240, [email protected]
• Course website: rci.rutgers.edu/~advis
• Lectures, tests, grades, office hours, textbook,
• Material to
be covered:
• About
lecture
slides:
• There are not intended to be the sole source for studying the course material !!!!!!!!!!!!!!!!
• Slides are good to review the course material after you have study your course textbook
• Slides are a good indicator of the relative importance of lecture topics (see slide # per topic
• Group slides by titles when using them to review course material. Match lectures and text.
Lectures 1-2: Introduction to Pathophysiology (2) Lectures 3-4: Mechanisms of Self-Defense and Stress (2)
Lectures 5-8: Endocrine and Nervous System Dysfunctions (4) Lecture 9: Alterations of Skeletal Muscle Function (1)
REVIEW AND TEST #1 Lectures 12-18: Cardiovascular, Respiratory and Renal Dysfunctions (7)
REVIEW AND TEST #2
Lectures 21-24: Alterations of Digestive Function and Intermediary Metabolism (4) Lectures 25-26: Alterations of the Reproductive System (2)
REVIEW AND TEST #3
Renal basic structure / function
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Overview of the structure / function of the kidney
The kidney’s primary function is to maintain a stable internal
environment for optimal cell and tissue metabolism. It also has
an endocrine function, and also perform gluconeogenesis.
The nephron, the functional unit of the kidney, has a glomerulus
and a tubular component (PCT, HL, DCT) and empty its content
into collecting ducts (CD),
The JGA-MD has pressure and chemical receptors, is the area
that produces renin, it is the target of renal inervation from the
sympathetic ANS, and is involved in the autoregulation of GFR.
About 20-25% of CO perfuse the kidneys every minute. A major hormonal regulator of RBF is the RAS. Aldosterone and ADH are
the main endocrine regulators of blood volume and thus, BP.
The counter-current mechanism, through NaCl secretion in the
ascending loop of Henle, is the driving force for reabsorption of water from the collecting ducts.
Page 2
Renal basic structure / function
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Urinary organs and kidney structure
Adrenal
gland
Liver
12th rib
Right kidney
Ureter
Urinary
bladder
Spleen
Renal artery
Renal vein
Left kidney
Abdominal
aorta
Inferior
vena cava
Common
iliac artery and vein
Urethra
Page 3
interlobular
artery
Renal column
Renal sinus
Hilium
Renal pelvis
Renal
papilla of pyramid
Urether
Capsule (fibrous)
Cortex
Minor
calices
Major
calices
Medullary
pyramids
Medulla
Renal basic structure / function
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
The nephron and its tubular epithelial cells
Page 4
DCT
CD
Papilla of
pyramid
PCT
Glomerulus
HL (descending)
HL (ascending)
HL
afferent
arteriole viceral wall
parietal wall
PCT
Bowman capsule
Bowman space
DCT
Glomerulus efferent
arteriole
MD
JGA
Glomerulus
Brush border
PCT
mitochondria
HL
(thin)
HL
(thick)
DCT
Intercalated
cells
Principal
cells
CD (medullary)
Page 5
Renal basic structure / function
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
The nephron unit and its blood vessels
PCT
Glomerulus
DCT
CD
Vasa
recta
Pyramid
(medulla)
Cortical
nephron
Juctamedullary
nephron
Efferent arteriole
Afferent arteriole
Interlobular
artery and vein
Arcuate artery
and vein
HL
HL (ascending)
HL (descending)
Page 6
Renal basic structure / function
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Anatomy of the glomerulus and of the juxtaglomerular apparatus
MD
DCT
JGA
Glomerulus
PCT
Efferent
arteriole
Afferent
arteriole
Bowman
capsule
Parietal
epithelial cell Podocytes
(viceral cell)
pores in
endothelium
parietal
epithelia cell
mesangial
cell mesangial
matrix
viceral
epithelium
(podocytes)
capillary
lumen
pseudofenestrations
with central knob
basement
membrane
podocyte
cell body
pedicel
cell process
capsular slits
(filtration)
capillary
endothelium
Page 7
Renal basic structure / function
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Structures of the urinary bladder
Ureter
Opening
of ureter
Rugae
Prostate gland
External
urinart sphincter
Cut edge of
peritoneum
Smooth
muscle
Trigone
Opening
of ureter
Internal
urinary sphincter
Prostatic
urethra
Bulbouretheral
gland
Page 8
Renal basic structure / function
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Renal autoregulation
Flo
w r
ate
(m
l /
min
)
Arterial blood pressure (mm Hg)
RBF
GFR
Page 9
Renal basic structure / function
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Cooperative roles of antidiuretic hormone and aldosterone in
regulating urine and plasma volume
sweating
decreases
plasma volume / BP detected by
detected
by
JGA
renin release
kidney
Ag I
lung
Ag II
adrenal gland
aldosterone
release
posterior
pituitary
ADH release
Na
K
H2O
increases
osmotic imbalance
increases H2O reabs.
Page 10
Renal basic structure / function
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Major functions of nephron segments
glomerulus in
Bowman’s
capsule
filtration Reabsorption of:
Na (majority)
glucose K
aminoacids
HCO3
PO4
H2O
Secretion of:
H
foreign
Substances
isotonic
Concentration
of urine
Descending
loop:
H2O
reabsorbed
Na diffuses in
Ascending
loop:
Na secretion
H2O stays in
Isotonis
Hypertonic
Hypotonic
PCT HL DCT CD
Reabsorption
of:
Na H2O
HCO3
Secretion of:
K Urea
H
NH3
Some drugs
Isotonic or
hypertonic
Reabsorption
of:
H2O
Reabsorption
or secretion of:
Na
K H
NH3
Final
concentration
STRUCTURE
FUNCTION
TONICITY OF
FLUID WITHIN
DUCTS
Page 11
Renal Dysfunctions
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Examples of major renal dysfunctions
Urinary tract obstruction is an interference with the flow of urine
along the urinary tract. It might be anatomical or functional.
Upper urinary tract obstructions include compression of a calyx,
ureteropelvic or ureterovesical junction (stones); compression
from an aberrant vessel, tumor, or abdominal inflammation and
scarring (retroperitoneal fibrosis); or ureteral blockage by stones
or a malignancy of the renal pelvis, ureter, bladder, or prostate. Calculi or kidney stones are masses of crystals, proteins, or other
substances that are a common cause or urinary tract obstruction.
Lower urinary tract obstructions are primarily related to storage of
urine in bladder or emptying of urine through the bladder outlet. It might have a neurogenic and/or an anatomic origin (neurogenic
bladder, overactive bladder syndrome, obstructions to urine flow).
Renal tumors, such as renal adenomas and renal cell carcinoma,
and bladder tumors are often silent in onset and metastized to lung, lymph nodes, liver, bone, thyroid, and CNS.
Renal Dysfunctions: Obstructions
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Major sites of urinary tract obstruction
Page 12
Ureteropelvic valve
Ureteropelvic
structure
Fibrous band
Stenosis
Ureteral orifice
Ureteral sphincter
muscle in urogenital diaphragm
Hydronephrosis
Polycystic
kidney
Dysplacia – agenesis
of ureter
Posterior
vesicoureteral valve (reflux)
Prostate hypertrophy
Posterior
vesicouretheral valve
Uretheral stenosis
Renal Dysfunctions: Obstructions
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Example of an upper urinary tract obstruction:
Hydronephrosis with renal stones in pelvis & calyces
Page 13
Renal
stones
Renal Dysfunctions: Obstructions
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Example of an lower urinary tract obstruction:
Neurogenic detrusor overactivity with vesico-sphincter
Page 14
Neurogenic Detrusor overactivity with Vesico-
Spincter: narrowing of the sphincter (arrow) is
consistent with EMG (line 6). See low urine flow (line 1) and volume (line 2), and high abdominal
pressure (line 3). Pressure inside bladder (line
4) and in the detrusor muscle (line 5).
1
2
3
4
5
6
Renal Dysfunctions: Obstructions
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Example of an urinary tract obstruction due to a tumor:
Renal cell carcinoma
Page 15
Renal Dysfunctions: Infections
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Examples of urinary tract infection (UTI)
Urinary tract infection (UTI) is an inflammation of the urinary
epithelium usually caused by bacteria from gut flora. It can occur
anywhere along the tract (urethra, prostate, bladder, ureter, kidney).
Acute cystitis, is an inflammation of the bladder, the most common
site of UTI. It may occur alone or in association with pyelonephritis
or prostatitis.
Painful bladder syndrome / intertitial cystitis (PBS/IC), is a condition
that includes non-bacterial infectious cystitis (viral, mycobacterial,
chlamydial, fungal), non-infectious cystitis (radiation, chemical,
autoimmune, hypersensitivity), and intertitiak cystitis (of unknown
origin, a persistent and chronic form of non-bacterial cystitis, with mast cell activation, altered epithelial permeability, and rise sensory
nerve sensitivity).
Acute pyelonephritis is an infection of renal pelvis and intertitium.
Chronic pyelonephritis is a persistent or recurrent infection leading to scarring of the kidney.
Page 16
Renal Dysfunctions: Infections
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Pyelonephritis, an urinary tract infection (UTI) of
renal pelvis and interstitium
Page 17
Glomerular disorders
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Examples of glomerular disorders
Glomerular disease might have a sudden or insidious origin.
It is caused by an inflammatory process initiated by immune
responses, metabolic disorders, or circulatory disturbances. It is the most common cause of chronic and end-stage renal failure.
Glomerulonephritis is an inflammation of the glomerulus caused by
immunologic abnormalities, ischemia, free radicals, drugs, toxins,
vascular disorders, and systemic diseases including diabetes mellitus and lupus erythermatosus.
Acute glomerulonephritis is often associated with streptococal or
staphilococal infection. Sporadic occurrence have been observed
after bacterial endocarditis, viral diseases (varicella, hepatitis B & C). Injury to glomeruli is immune mediated with Ag-Ab complex
depositing on the glomerular basement membrane. It can evolve
into a rapidly progressive glomerulonephrits (RPGN) and even to a
chronic glomerulonephritis.
Nephrotic syndrome is the excertion of >3.5 g of protein per day
and is a characteristic of glomerular injury.
Glomerulonephritis
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Chronic glomerulonephritis
Page 18
Renal Failures
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Examples of renal failures
Acute renal failure (ARF) occurs over days or weeks, with low
GFR, BUN, plasma creatinin and cystatin C levels. It might be
associated with oliguria. There is an alteration in tubular function. They might be reversible if treated early. They are
classified as: prerenal (low renal perfusion and GFR, ischemia
and tubular necrosis); intrarenal (associated with several
systemic diseases but commonly with acute tubular necrosis);
and postrenal (associated with diseases that obstruct the flow of urine from the kidneys).
Chronic renal failure (CRF) represents a progressive loss of renal
function. Plasma creatinin levels gradually become elevated as
GFR decreases; Na is lost in the urine; K is retained; acidosis develops; Ca and phosphate metabolism are altered and EPO
production is disminished. All organ systems are affected by
CRF.
Page 19
Acute Renal Failure
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Mechanism of oliguria in acute renal failure
Ischemia or nephrotoxins
Possible
glomerular injury
Decreased
permeability and
decreased surface
area
Cellular cast formation
Obstruction Tubular back leak
Decreased GFR
OLIGURIA
Intrarenal
vasoconstriction
Tubular injury
(e.g. acute tubular necrosis)
Increased intraluminal
pressure
Page 20
Chronic Renal Failure
Structure / Function kidney and urinary tract, renal blood flow, nephron, renal hormones, clearance
Urinary tract obstruction
upper, lower, tumors
Urinary tract infection
causes and types
Glomerular disorders glomerulonephrits, nephrotic syndrome
Renal failure types of renal failure
Mechanism related to the progression of chronic renal failure
Renal injury
Loss of nephrons
Glomerular capillary hypertension
Increased glomerular
permeability and filtration
Proteinuria
Increased tubular protein
reabsorption
Tubulointertitial
inflammation and fibrosis
Renal scarring
Increased
Ag II
Systemic
hypertension