IM COOKED T2

slow transforming viruses RNA causing neoplasia

feline leukemia virus

simian leukemia virus

bovine leukemia virus

avian leukosis virus

fast transforming virus RNA causing neoplasia

rous sarcoma virus

murine leukemia virus

feline sarcoma virus

DNA viruses causing neoplasia

hepadna- sqiurrels, woodchuck, duck- hepatocellular carcinoma

papilloma-rabbit, dog, horse- papilloma

herpes- chicken,guinea pigs, rabbit, monkey, frog- lymphosarcoma

Pox- rabbit, monkey- fibrosarcoma, histiocytoma

direct effects of tumors

necrosis

obstruction

direct compression

chronic inflammation

hemorrhage

penetration/perforation of a tissue barrier

pathological bone fractures

not seen on abdominal radiographs

pancreas

adrenal glands

ovaries

ureters

lymph nodes

canine small intestine proper sizing

not wider than 1.6x the L5 and/or

2x the width of a rib

feline small intestine proper sizing

no wider than 12mm or

2x the height of mid-body L2

vitamins are essential for what two things in the body

enzyme activity

structural components

minerals are essential for what two things in the body

coenzymes

regulators of metabolism

barrow

castrated male pig

wether

castrated male goat

steer

castrated male bovine

hog

mature pig of 120+ lbs

colt

male horse that is younger than 4 years old

hepatocellular adenoma

benign neoplasm of hepatocytes

described in young ruminants

single variably sized, brown masses

compress adjacent parenchyma

hepatocellular carcinoma

malignant neoplasma of hepatocytes

not common in all domestic species

reported in dogs, ruminants, especially sheep

described as massive (single mass), nodular, and diffuse

cholangiocellular adenoma

single, firm, discrete, white mass

mass comprises tubules with well differentiated cuboidal epithelium separated by minimal stroma

common in cats

cholangiocellular carcinoma

all species

large single mass or multiple masses

gray-tan unencapsulated masses

often metastatic to to other tissues

hepatic metastatic tumors

lymphoma (focal or diffuse)

hemangiosarcoma

melanoma

mammary carcinoma

transitional cell carcinoma

anal sac gland carcinoma

malignant melanoma→ multifocal variable sized black masses

mild to moderate elevation in ALT (disorders leading to 5x increase)

vs

marked elevation in ALT (stimulus leading to up to 10x increases)

5x: diabetes

±feline hyperthyroidism

2ndary to passive congestion and GI disease

anticonvulsant drugs

steroid drugs

phenobarbitol can induce liver dz

10: THT : toxic, hypoxic, trauma,

acute severe hepatic injury/ necrosis or cell death

when does AST increase

anticonvulsants

exercise (30% increase)

NO steroids increase AST

(Race horses is increased typically)

most common hepatic neoplasms

carcinoma

lymphoma

in cats any increase in ALP is significant because it indicates what two things and what is its half life

primary liver disease and hyperthyroidism

half life is short less than 8 hours

GGT can be used as an alternative to ALP in small animals

calcium and phosphorus excess causes what in large breed dogs

growth deformities

lameness, motility issues, pain

what is the rate limiting step in the synthesis of catecholamines in the adrenal medulla?

tyrosine hydroxylase

regulated via a negative feedback loop (rising level of cytoplasmic norepinephrine)

pheochromocytomas

catecholamine secreting tumors of chromaffin cells more frequent in dogs than cats

what are the three causes of Cushing’s Dz?, what is the most common tumor by what percent? species differences? dog /cat /horse

intake of steroids, pituitary tumor, adrenal tumor

pituitary tumor 80-90%

dog: primary (adrenal dependent) & pituitary dependent

cat: less common than in dogs

horses: PPID caused by a pituitary tumor

what are the adrenal gland tumors involved in addisons and cushings

cortical adenomas or adenocarcinomas: includes pheochromocytomas (medulla)

contralateral atrophy

*carcinomas are ofter large and involve the kidneys

Cushing’s CBC findings and Chemistry findings/ urinalysis

CBC:

Stress leukogram ( mature netrophilia, lymphopenia, eosinopenia, monocytosis)

Thrombocytosis (slightly increased)

Chem:

ALP increased

mild ALT increased

leads to vacuolar hepatopathy (glycogen)

increase in bile acids and cholestasis

hyperglycemia (cats may show insulin resistance bc of DM)

ELEVATED cholesterol/triglycerides

lipemia (due to altered lipid metabolism)

LOWERED UN associated with PU/PD

electrolytes: mild hypernatremia, hypokalemia

Urinalysis:

USG= dilute from PU/PD

proteinuria with albumin WNL (mild protein leakage)

UTIs are common without pyuria due to immunosuppression

what drugs interfere with assay for hyperadrenocorticism?

cortisol= 100%

prednisolone= 69%

Dexamethasone= 0.1%

Basal cortisol is helpful in the dx of what disease?

addisons it is helpful to rule out Addison (it will decrease)

NOT useful in hyperA because of pulsatile ACTH secretion resulting in variable cortisol levels throughout the day and may be affected via non-adrenal issues

testing for hyperA and hypoA what are the screen testings, the diagnostic tests, and differentiating tests?

Screening tests: UCCR (urine cortisol:creatinine ratio) (negatives rule out hyperA=low ratio is negative) (higher ratio is more likely cushings)

diagnostic test: LDDST (low dose dexamethasone supression test) and ACTH stim test

differentiating test: HDDST (high dose dexamethasone suppression test) (differentiates from PDH and ADH) and eACTH (endogenous ACTH) (differentiates PDH from ADH)

hyperA suppression tests

complete suppression at both 4 and 8 hours→ stressed animals may fail to suppress

pituitary dependent LDDST= lack of suppression at 8 hours, elevated endogenous ACTH levels, eACTH is high and ultrasound show bilaterally enlarged adrenals

adrenal dependent LDDST= lack of suppression at ANY time point, ONE enlarged adrenal gland with contralateral atrophy, eACTH levels suppressed (decreased for primary adrenal)

ACTH testing is used for these three things

dx of iatrogenic cushing’s, addison’s and monitors HAC tx:

cushings= >20-22 ug/dL

addisons= <6-17 ug/dL

what type of tube should be used for eACTH?

Plastic because ACTH adheres to glass

Pituitary dependent hyperadrenocorticism High dose dex stim test

not used much since ultrasound and eACth measurements are less invasive and more precise alternatives for PDH vs ADH differentiation

HDDST= suppresses cortisol secretion in 75% of PDH cases and 25% of PDH cases show no suppression often linked to larger pituitary tumors

supression supports PDH dx while resistance can be either PDH or AT

what dx test is used most commonly to confirm PPID in horses? what is the relationship between PPID and EMS?

baseline plasma ACTH measurement and/or Thyrotropin releasing hormone stimulation test

relationship= horses with EMS are at increased risk of developing PPID as they age

primary vs secondary addisons

primary: caused by adrenal cortical destruction or insufficiency→ electrolyte disturbances and cortisol insufficiency (90-95%) causes: neoplasia (carcinoma), autoimmune, iatrogenic (over tx of drugs), surgical removal

secondary: caused by pituitary ACTH deficiency usually without electrolyte disturbances

Addisons dz CBC, CHEM, URINE

CBC:

mild non-regenerative anemia, lymohocytosis or esosinophilia (LACK of stress leukogram)

CHEM:

electrolytes: hyperkalemia, hyponatremia, hypochloremia (ADDISON NEEDS SALT, NO MORE BANANAS, HATES BLEACH); mild hypercalcemia linked to reduced corticosteroids and altered renal calcium handling

NA:K ratio <15:1 → <23:1= suspect addisons

elevated UN

URINE:

dilute urine

Pseudo Addisons is caused by what organism

trichuris vulpis (whipworms)

what are the three main players of Ca-P homeostasis

GI: ca absorption from diet via active mech, P mostly passive absorption

kidney: ca filtered both passive and active reabsorbed, P filtered actively reabsorbed or excreted bc often high in intake

bone: deposition and resorption of Ca-P salts→ calcium buffer system

the three hormones that are in control of plasma calcium and P and which one is the most powerful regulator of Ca-P

PTH and Vit D increases Ca in blood

calcitonin (activates Vit D3) decreases Ca in blood (peptide hormone produced in C cells in the thyroid gland stimulated by hypercalcemia, favors osteoblast formation/bone formation)

**PTH (peptide hormone) is the most powerful regulator of Ca-P which is secreted by chief cells within the Parathyroid gland and calcium sensing receptors on the cheif cells regulate PTH secretion

stimuli for release of PTH and what does PTH do?

low levels of ca and high levels of phosphorus

hypercalcemia inhibits the release of PTH

PTH stimulates bone= bone resorption which stimulates osteoclasts dissolving ca-p salts increasing them in blood;

kidneys= stimulates calcium reabsorption (ca-atpase pump) and phosphate excretion (inhibits via Na-dependent cotransporters) and activates Vit D to D hormone;

GI= D hormone stimulates Ca and P absorptions by stimulating calbindin (ca binding protein) (sodium phosphate cotransporter)

vitamin D/ D hormone and species differences

Vit D3 is animal derived and more effective; Vit D2 is plant derived and less effective

pro vit D3 is synthesized in the liver sent to the skin to get activated by the UVB turns into vit D3 back to the liver or kidney (with PTH stimuli) which gets turned into D hormone to be utilized in the gut to absorb Ca and P

dogs/ cats= dietary dependent

herbivores/reptiles/many birds/llamas/alpacas= UV-B dependent

PTHrP=

hypercalcemia of Malignancy tumors (anal sac tumors) release uncontrolled amounts of PTH-related protein which mimics the actions of PTH

mechanisms of hypercalcemia (4)

increased GI absorption

increased osteolysis

decreased renal excretion

protein binding

effects of hypercalcemia

kidneys: nephrogenic diabetes insipidus (PU/PD due to reduced response to ADH), renal damage, urinary tract infection

soft tissue: mineralization

muscle: decreased excitability

nervous system: coma, paresis. reduced neural excitability

heart: rare arrhythmias lead to ventricular fibrillation

PTHrP is most commonly secreted by which tumor types

Squamous cell carcinoma

anal sac adenoma

lymphoma

primary hyperparathyroidism, humoral hypercalcemia of malignancy

primary: PTH secreting tumors common in dogs→ signs: hypercalcemia, hypophospatemia, uroliths

humoral: most common cause in dogs (tcell lymphoma, apocrine glad adenocarcinoma)→ production of PTHrP

hyper D: sources rodenticides, dietary supplements, toxic plants

hypocalcemia mechanisms (5)

decreased absorption: GI dz, dietary imbalance

excessive losses: renal, GI, milk

PTH-related issues: hypoparathroidism, PTH resistance or pseudohypoparathroidism

protein binding: hypoalbuminemia lowers total ca but not free ionized calcium; total calcium may not correlate with ionized calcium

hypoalbuminemia: causes mild hypo-ca without clinical signs

other causes: toxicoses (oxalates, ethylene glycol), endocrine diseases (pancreatitis, cushings), sweat losses

hypoparathyroidism, nutritional secondary hyperparathyroidism, renal secondary hyperparathyroidism

hypoparathroidism: low ca, low ipth, hyperphosphatemia

nutrional: imbalanced ca:p →osteolysis

renal: vit D deficiency (rickets), hyperphosphatemia

Growth hormone

(Somatotropin) peptide hormone produced by the anterior pituitary gland controlled by the hypothalamic GH releasing hormone and GH inhibiting hormone

released in a pulsatile fashion with superimposed peaks caused by: hypoglycemia/starvation, ghrelin (hunger hormone), exercise, stress, trauma, sleep, progesterone

highest during adolescence and decline with age

IGF-1 has a negative feedback on the GH release

low vs high energy status changes dominance between GH and IGF-1

low energy= LOW INSULIN→ GH dominant bc igf receptors are down-regulated in the liver = direct effects on tissues; simulates lipolysis, gluconeogenesis, insulin resistance (diabetics)

high energy= HIGH INSULIN→ IGF-1 dominant= indirect effects on tissues= stimulates protein anabolism affects all tissues most obvious in cartilage/ bones (stimulates bone length and width growth) and muscles (increases muscle mass)

juvenile onset panhypopituitarism (dwarfism) and acromegaly

panhypopituitarism= deficiency at birth low GH, TSH, FSH/LH, ACTH→ delayed growth, retained puppy coat, bilateral alopecia, delayed dentition, small sex organs, infertility

acromegaly= functional pituitary tumors secreting excess growth hormone→ joint problems, increased body weight, facial broadening, paw enlargement, prognathia with increased spacing in teeth, laryngeal hypertrophy, tongue enlargement, organomegaly (DIABETIC CATS)

hyperphosphatemia causes

intake: excess intake, hypervitaminosis D, decreased GI motility

physiologic: young animals

decreased excretion: reduced renal excretion, hypoparathyrodism

shifting: hemolysis, excess muscle damage

hyperthyroidism: 21% of cats show elevated phosphate

hypophosphatemia causes

decreased intake: starvation, malabsorption, vomiting, diarrhea, tube feeding

increased intake: renal losses, hyperparathyroidism, pseudohyperparathroidism, osmotic diuresis

shifting ICF: insulin therapy (rapid uptake into cells)

defective mobilization: post parturient states (milk fever, eclampsia)

ovaries are made up of two regions:

cortex→ follicular growth and corpora luteal location

medulla→ very irrigated and rich in nerve endings

estrous cycle and the stages

cyclical pattern of ovarian activity that transitions from reproductive receptivity to non receptivity

PEMDA (protestus, estrus, metestrus, diestrus, anestrus) (Please excuse my dear aunt)

P: very short (non existent in queens) Active follicular growth and estrogen production follicular phase

E: sexual receptivity to the male (estrogen is very high and induce estrus); follicular phase

M: some species (mare, ruminants, sow) transitional phase between estrus and diestrus were the corpus lutea are developing

D: longest period of the cycle: presence of corpora letea and high levels of progesterone; luteal phase

A: reproductive quiescence

ovarian follicles

follicles contain the oocyte and develop from primordial or more mature, pre-ovulatory stages→ produce increasing amounts of estrogen

ovulation: local inflammatory process that results in the release of a mature oocyte (expect dogs release immature)

corpus luteum produces progesterone; some species can have multiple corpus luteum with multiple ovulations (bitch, queen ewe, sow)

folliculogenesis and oogenesis, and progesterone

depends on FSH and LH from the pituitary/ hypothalamus

oocyte matures inside the follicle

progesterone= has strong negative feedback on the hypothalamic pituitary axis during the luteal phase, high levels of P4 reduce GnRH and FSH/LH pulses and surges, inhibits estrus behavior

two cells of estrogen production

theca cells: stimulated by LH produce androstenedione (precursor to estrogen)

granulosa cells: stimulated by FSH convert androstenedione into estrogen (estradiol)

ovulation: spontaneous vs induced

high levels of estrogen stimulate brain centers (surge center) that induce sexual receptivity, mating posture, phonation and increased physical activity= very high levels of estrogen creates a strong positive feedback on the hypothalamic pituitary axis during estrus leading to a massive release of GnRH and surge of LH inducing ovulation

LH stimulates histamine, proteolytic enzymes, and prostaglandins, causing follicular swelling, pressure increase, and rupture releasing the oocyte= spontaneous ovulation

follicular wall collapse bleeding occurs then lutenization begins producing progesterone

lack of estrogen terminates estrous behavior

induced ovulation= (queens, rabbits, camels) vaginal mechanoreceptors in the wall of the vagina need to be stimulated by physical copulation with the male and once recptors are stimulated impulses sent to hypothalamus for GnRH and LH surge

luteinization

folliular granulosa and theca cells transform into luteal cells forming corpus luteum producing progesterone

LH is essential for CL development and is needed to keep the luteal phase viable

high progesterone levels suppress the surge center in the hypothalamus , reducing LH pulses, preventing further ovulation

progesterone main targets: uterus, mammary glands (prepares for pregnancy)

luteolysis

process whereby the corpus luteum undergoes regression and cell death

most species= induced physiologically by prostaglandin F2 alpha

cows, sows, mares= have active luteal destruction activated to end the cycle and start a new estrous cycle

end of diestrus= oxytocin initiates the PGF2a release from the ednometrium closer to diestrus the amplitude and frequency of PGF2a increases and inhibits progesterone synthesis and opens calcium channels leading to apoptosis

declining progeserone activates the HPaxis starting new cycle

pregnancy

to maintain pregnancy the corpus luteum must be sustained for pregnancy to continue meaning progesterone is crucial

in some species placenta takes over progesterone production in later stages of pregnancy

the embryo must prevent the release of endometrial PGF2alpha to avoid luteolysis

PGF2a triggers luteolysis which leads to CL degeneration and pregnancy loss

site of spermatogenesis, testis functions what plexus supplies the testies

seminiferous tubules (sperm production)→ straight→rete→efferent ductus→ epididymus head→ body→ tail → ductus deferenes

functions: gametogenic and testosterone production

pampiniform plexus: for temperature regulation and counter current exchange of testosterone (forms around the testicular artery)

epididymis is the site of what two things

fluid absorption and sperm maturation (final steps)

accessory sex organs

ampulla of the ductus deferens, seminal vesicles, prostate, bulbourethral glands; provide: optimal environment and nourishment for the spermatozoa

male hormone crucial nuclei in the brain

hormone production cycle is fully functional after puberty (reproductive competence)

fetal testosterone abolishes the males fetus’s surge center and males only remain with the tonic center

male fetus testosterone freely enters the brain it is transformed in estradiol which minimizes the function of the surge center

tonic center produces: GnRH

after puberty the hypothalamus starts to release GnRH in a pulsatile fashion every few hours which then induces pulse of LH and FSH release from the anterior pituitary gland →circulation (FSH has longer ½ life)

male hormones with testosterone and spermatogenesis production

testosterone: LH stimulates Leydig cells which produce testosterone

sperm: FSH stimulates the steroli cells which are responsible for spermatogenesis

*testosterone from leydig cells diffuse into the steroli cells where its converted into dihydrotestosterone and estradiol which is essential for spermatogenesis production

testosterone also released into circulation for metabolism and behavior and suppresses further release of GnRH

**FSH produces spermatogenic substances (androgen binding protein) maintains higher tubular testosterone concentration despite pulsatile release and INHIBIN (selectively inhibits FSH release)

spermatogenesis

within the seminiferous tubules

requires 40-60 days for spermatogenesis; most immature are at the periphery of a seminiferous tubule near the basement membrane

divided into three phases mitosis, meiosis, differentiation

mitosis: proliferation phase; contains all mitotic divisions A-spermatogonia→B-spermatogonia→primary spermatocyte *stem cell renewal is important part here allows some sperm to revert to stem cells providing continual renewal which new spermatogonia can develop (loss of intercellular bridges)

meiosis: meiosis 1 ensures DNA diversity and crossing over, primary spermatocytes → secondary spermatocytes; meiotic phase produces haploid spermatids forming the secondary spermatocyte secondary spermatocytes→ spermatids

differentiation: evolvement stage (no more cell division) commonly called spermiogenesis: golgi phase, cap phase, acrosomal phase, maturation phase→ turns into fully differentiated spermatozoon containing head and flagellum including mid-piece(mitochondrial helix) and principle piece (tail)

capacitation

in tail of epididymus, sperm require certain degree of maturity but in order to acquire maximum fertility the spermatozoa must spend time in the female reproductive tract

final functional enhancement of the flagellar activity (hyper activation) and acrosome reaction

capacitation is completed in the isthmus of the oviduct

all sperm are not capacitate at the same time

structures of the abdominal cavity/wall superficial to deep

skin→ subcutaneous connective tissue→ cutaneous trunci muscles→ external abdominal m→ internal abdominal m→rectus abdominis m→ transversalis facia→ parietal peritoneum

internal vs external rectus sheaths what muscles make them up

internal- transverse muscle (forms internal lamina of sheath of rectus abdominis)

external-external and internal abdominal oblique muscles forms external lamina of the sheath of the rectus abdominis

abdominal wall nerve supply

T13- costo-abdominal n

L1- cranial lliohypogastric n

L2- caudual lliohypogastric n

L3-llioinguinal n

L4-lateral cutaneous femoral n

farquharson method vs magda method of nerve blocks vs inverted L block

farquharson= proximal paravertebral nerve block

magda= distal paravertebral nerve black

inverted L= for obese or aggressive cows

boundaries of the pelvic cavity

borders of the anal triangle and urogenital triangle

Pelvic diaphragm is composed of what muscles

coccygeus muscle

levator ani muscle

external and internal fascia

some consider the external anal sphincter m

urogenital diaphragm closed off by these muscles

retractor clitoridis muscles

constrictor vulvae muscles

constrictor vestibuli muscles

compartments of the pelvic cavity

renal recesses vs renal sinus

recesses= depressions in the renal pelvis

sinus= fat filled space surrounding the renal vessels and ureters

ultrasound of the kidneys echogenictiy

renal cortex: hypoechoic or isoechoic

renal medulla: hypoechoic or anechoic

renal pelvis: hyperechoic bc of the fat/fibrous tissue

species variations kidneys

dog- fused both cortex and medulla

bovine- unfused both cortex and medulla, 18-20 lobes, NO crest or pelvis right kidney= flattened and oval left kidney= slightly twisted displaced to the right by rumen; contains renal calices (major (2) and minor(lobe #))

porcine= no external lobation bc cortex fused but internal lobation present; kidneys at same level T-13-L4; no contact with liver; calyces present (10 minor and two major); cranial of both associated with pancreas (left/body)

goats/sheep= similar to canine species fused cortex/medulla, bean shaped (color slightly lighter than canine)

equine= right kidney: T16-L1 touches liver heart shaped; left: T17-L2 figure of 6; has a unipyramidal (fused pyramids with a common renal crest); renal pelvis is expanded with two polar terminal recesses with papillary ducts that open into the terminal recesses

internal kidney supply

afferent into glomerulus then out via efferent then into peritubular capillaries

pars convoluta vs pars radiata

convoluta= proximal and distal convoluted tubules

radiata= collecting ducts (part of cortex part in medulla)

cortical nephron vs juxtamedullary nephron

Juxtaglomerular apparatus= distal tubule is connected to afferent arteriole with macula densa cells within the distal tubule and sensitive to chloride ions to help regulate the filtration rate

Juxtaglomerular cells are in the afferent arteriole which produce RENIN

juxtaglomerular nephrons are known to conserve more water (camels have more of this type of nephron

capillary network within the glomerulus: what are the three barriers for filtrate

100 liters of blood are circulated through the kidney producing 1 liter f urine

the three barriers:

1. porous capillaries

2. basement membrane

3. podocytes= cells surround glomerular fenestrated capillaries forms the visceral layer of the bowman’s space, controls amount of filtrate produced primary and secondary processes (form filtration slits)

the nephron tubule micro anatomy

proximal: simple columnar with microvilli (for reabsorption)

henle: simple squamous epithelium nuclei flattened and nuclei protrude into lumen

distal: simple cuboidal epithelium lumen in larger with no brush border

papillary duct: epithelium two layered and later transitional epithelium

renal calices and pelvis: lined by transitional epithelium and undergoes loose connective tissue layer (in horse the mucous glands are present under the epithelium responsible for the mucous in the equine urine)

toxins and hypoxia affects which parts of the kidneys

cortex= toxins reach this more bc more perfusion

medulla=hypoxia bc its main job is to maintain hyperosmolarity

renal circulation-pressures

glomerulus is high pressure while peritubular capillaries is low pressure to promote reabsorption

1-2% of total renal blood flow is flowing through the vasa recta and promotes reabsorption

PROMOTES CONTINUOUS FLOW

glomerular filtration offers filtration to what and happens during dz?

glomerular basement membrane offers high permeability for the filtration of water and small solutes

molecular weight= <5,200; almost impermeable to plasma proteins

molecular charge= glom pores lined with negative charges and reject neagtively charged molecules like proteins (even of a smaller diameter of the pore)

In glomerulonephritis the negative charges are neutralized and allows negative macromolecules like albumin to increase resulting in proteins in the urine= proteinuria

filtrate = ?; and what is the glomerular filtration rate

plasma without proteins bc the glomerulus filters everything except over 5.2weight and negative charged molecules

glomerular filtration rate= volume of filtrate into bowman’s capsules by both the kidneys each minute

slow speed= increased absorption of waste products

fast speed= reabsorption decreases and miss valuable substances are lost

filtration speed depends on glomerular filtration rate which si controlled by increasing and decreasing resistance of the afferent and efferent arteriole blood flow

pressures altering flow of glomerular filtration

angiotensin 2 regulates the vasocontriction of the efferent arteriole

severe vasoconstriction of the efferent arteriole has paradoxical effect decreases flow GCOP counters the increased GHP which decreases GFR

afferent vasoconstrict= low pressure and filtration

afferent vasodilate=high pressure and filtration

how does NSAIDS, tying up in horses, and lower urinary tract obstruction affect GFR?

NSAID= decrease GFR because it causes severe vasocontriction in efferent arteriole

tying up= decrease GFR myoglobin released from muscles into the urine cause tubular obstruction and reduced filtration efficiency (earthquake survivors)

obstruction= decrease GFR causes pressure changes lowering GFR backward pressure cascade

pressure diuresis

GFR is almost but not perfectly constant so an increase in blood pressure will increase GFR resulting in higher urine output

autoregulation

autoregulation maintains the GFR within a 5% deviation any more too high or too low causes wither excess waste absorption or excess excretion of valuable solutes

myogenic reflex: baroreceptors in the arterioles cause an auto regulation stretch=vasoconstrict no stretch= vasodilation in order to maintain adequate pressures this system works for a specific range of pressures (80-189 mmhg) if out of these ranges then myogenic reflex is limited

tubulogomerular feedback=

GFR low→ afferent arteriole vasodilates and efferent vasocontricts (more NaCl are reabsorbed and in the distal tubules the macula densa cells detect that NaCl is too low in the filtrate and responds by DILATION of the AFFERENT arteriole with NITRIC OXIDE; in the EFFERENT arteriole that angiotensin 2 (formed from the release of renin from the JG cells) is used to constrict the efferent arterioles

GFR high→ leads to an increase in NaCl delivery to Macula densa cells so macula release ADENOSINE which diffuses through the interstitial fluid to the afferent arteriole causing vasoconstriction and also signal to REDUCE the release of renin causing efferent vasodilation

RAAS stumli and short/long term effects

short= increase blood pressure

long= aldosterone increases blood volume

stimuli= hypotension, hyponatremia, increase sympathetic activation, hyperkalemia

effects of angiotensin

reabsorption of substances in the proximal tubule

GLUCOSE= Na and glucose CO-transporter with the NaK+ATPase pump on basolateral border is SATURABLE facilitated diffusion into the peritubular capillary

SODIUM and BICARBONATE:

CALCIUM/WATER: 2/3rds is absorbed in the proximal tubule; 90% being paracellular by solvent drag driven by the active transcellular reabsorption of sodium provides a driving force for the osmotic reabsorption of water; small amount is transcellular mediated by the voltage gated calcium channel sensitive to hormones (PTH)

PHOSPHATE: 80% of filtered phosphate is reabsorbed from prox. tubule but is exclusively transcellular process with 3 sodium coupled phosphate transporters mediate phosphate influx; apical phosphate entry is driven by the inward gradient for sodium maintained by the activity of the basolateral Na-K-ATPase→ PTH INHIBITS tubular phosphate reabsorption by decreasing the apical membrane expression of sodium-phosphate transporters

MAGNESIUM: is unusual because it is primarily reabsorbed along the thick ascending limb (50-70%) rather than proximal tubule which only reabsorbs 10-25% of the filtered load but plays an important role in fine tuning mg2+ homeostasis; paracellular mechanism that is likely to be largely unregulated