JP Advis DVM, Ph.D. Bartlett Hall, Animal Sciences, …advis/500_patho_PDFs/500_17_arenal_1.pptx.pdfBartlett Hall, Animal Sciences, Cook, 932 ... Alterations of Digestive Function

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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.

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causes and types



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

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interlobular

artery

Renal column

Renal sinus

Hilium

Renal pelvis

Renal

papilla of pyramid

Urether

Capsule (fibrous)

Cortex

Minor

calices

Major

calices

Medullary

pyramids

Medulla






causes and types



The nephron and its tubular epithelial cells

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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)

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causes and types



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)

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causes and types



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

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causes and types



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

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causes and types



Renal autoregulation

Flo

w r

ate

(m

l /

min

)

Arterial blood pressure (mm Hg)

RBF

GFR

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causes and types



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.

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causes and types



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

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Renal Dysfunctions





causes and types



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





causes and types



Major sites of urinary tract obstruction

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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






causes and types



Example of an upper urinary tract obstruction:

Hydronephrosis with renal stones in pelvis & calyces

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Renal

stones






causes and types



Example of an lower urinary tract obstruction:

Neurogenic detrusor overactivity with vesico-sphincter

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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






causes and types



Example of an urinary tract obstruction due to a tumor:

Renal cell carcinoma

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Renal Dysfunctions: Infections





causes and types



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.

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Renal Dysfunctions: Infections





causes and types



Pyelonephritis, an urinary tract infection (UTI) of

renal pelvis and interstitium

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Glomerular disorders





causes and types



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





causes and types



Chronic glomerulonephritis

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Renal Failures





causes and types



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.

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Acute Renal Failure





causes and types



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

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Chronic Renal Failure





causes and types



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

JP Advis DVM, Ph.D. Bartlett Hall, Animal Sciences, …advis/500_patho_PDFs/500_17_arenal_1.pptx.pdfBartlett Hall, Animal Sciences, Cook, 932 ... Alterations of Digestive Function

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