PCS Exam 3

major functions of the kidneys

1. regulate water and ion balance

2. remove metabolic waste products

3. remove foreign chemicals from body

4. secrete hormones

input to the kidney

renal artery

outputs of the kidney

renal vein and ureter

How does processing take place to determine what leaves via renal vein and what is cleared as urine?

glomerular filtration, tubular reabsorption, and tubular secretion

functional units of the kidney

nephrons

key parts of nephron

- glomerulus and bowmans capsule

- proximal rubule

- descending loop of henle

- ascending loop of henle

- distal tubule

- medullary collecting duct

surrounded by capillaries

proximal, sidtal tubules, loop of henle, and collecting duct

(Ultra)filtration

pressure drives fluid into Bowman’s Capsule, total amount reflects balance of pressure with osmosis

what can enter filtrate in glomerular filtration

20% of plasma, glucose, ions, water

what CANNOT enter filtrate in glomerular filtration

cellas and proteins

if kidneys are functioning properly what should be found in urine

urea, water, Na+

if kidneys are functioning properly what should not be found in urine

glucose

Once fluid enters Bowman’s Capsule via filtration

it moves through all portions of tubule into collecting duct via bulk flow

apical membrane

next to the lumen

basolateral membrane

next to interstitial space

proximal tubule

65% of overall reabsorption occurs here

—> all glucose reabsorbed here when kidneys are healthy

Proximal Tubule Transport (Primary Active)

Na/K ATPase

Proximal Tubule Transport (Secondary Active)

SGLT1,2

Proximal Tubule Transport (Diffusion)

Glut 1,2 transport proteins, Cl- channels

Proximal Tubule Transport (Osmosis)

AQ1

Proximal Tubule Primarily _______

NOT under hormonal control

what is direct source of energy used for glucose to cross apical membrane to proximal tubule epithelial cells?

Na+ Concentration gradient

What is the direct source of energy use for glucose to cross the basolateral membrane of proximal tubule epithelial cells?

Glucose concentration gradient

What is ATP the direct source of energy for

Na/K pump which sets Na+ gradient

if removed what protein would drop water reabsorptions

AQ1 , can maybe be Cl- channels

descending loop of henle

water reabsorption (high AQ1 expression & salt concentration in interstitial space)

ascending loop of henle

reabsorption of salt (not water) —> concentrating medulla

ascending loop of henle differences from descending

- No aquaporins (much less osmosis)

- NKCC2 drives salt reabsorption, maintenance of high salt in interstitial space

- Note-K+ that enters filtrate is mostly recycled by NKCC2

Effect(s) on urine formation if you could inhibit the Na/K ATPase in the ascending loop of Henle

mimicking the action of potent loop diuretics

inhibiting Na/K ATPase in the ascending limb of the Loop of Henle would cause what?

increase water excreted as urine

inhibiting Na/K ATPase in the descending limb of the Loop of Henle would cause what?

decrease water excreted as urine

distal tubule

Na and Cl reabsorption under hormonal control

distal tubule expression level of _____

Na/K ATPase, ROMK, ENaC are all hormonally regulated

medullary collecting duct

water reabsorption under hormonal control

medullary collecting duct AQ2

under hormonal control, other aquaporins in nephron are NOT

hormones regulate reabsorption alone _____

distal tubule and collecting duct

salt reabsorption in distal tubule

some reabsorbed

apical AQ in medullary collecting duct

AQ2

basolateral AQ in medullary collecting duct

AQ3 + AQ4

Control of water retention/excretion by Antidiuretic Hormone (ADH)/Vasopressin

—> some AQ2 stored intracellularly across vesicle membranes

—> antidiuretic hormone (ADH)/Vasopressin stimulated water reabsorption by increasing AQ2 exocytosis

Application: Dehydration

1. When we are dehydrated, osmolarity in hypothalamus interstitial space increases.

2. This is sensed by osmoreceptor neurons, which excite neuronal control network in hypothalamus.

3. Error signal from high osmolarity causes vasopressin/ADH containing neuroendocrine cells in hypothalamus to release vasopressin/ADH via posterior pituitary.

4. Vasopressin/ADH binds receptors in medullary collecting duct.

5. AQ2 on apical membrane increases, which increases wate reabsorption.

Neurogenic

Loss of function mutation affecting hypothalamus, e.g. in ADH/vasopressin-releasing neurosecretory cells.

Nephrogenic

Mutation affecting collecting duct cells, e.g. making vasopressin receptor insensitive to vasopressin.

Rare genetic disorder

Diabetes Insipidus (not the same as Diabetes mellitus)

best description of a symptom of Diabetes Insipidus

production of a larger than typical volume of urine that is dilute

—> decrease water reabsorption

—> increase water in urine

what is treatment w/ ADH/Vasopressin a good treatment for

Neurogenis Diabetes

Macula Densa is important in _______

how we regulate salt content.

Why is Macula Densa important for how we regulate salt content

Low salt in filtrate indicates low salt in plasma (i.e. ultimate source of filtrate).

what happens when low salt is sensed

a feedbackloop initiates to increase salt reabsorption. Feedback loop involves local signaling from macula densa cells to juxtaglomerular cells. Macula Densa cells release prostaglandin (PG), which stimulates juxtaglomerular cells to release renin into blood

Macula Densa cells release

prostaglandin (PG)

prostaglandin (PG)

stimulates juxtaglomerular cells to release renin into blood

singaling molecules that binds to a receptor

prostoaglandins, angiotensin II, aldosterone, etc

Angiotensinogen and Angiotensin I are

inactive

Renin

angiotensinogen to produce Angiotensin I

Angiotensin converting enzyme (ACE)

cleaves angiotensin I to produce angiotensin II

Angiotensin II is a

signaling molecule

Adrenal cortex cells express

angiotensin II receptors

Aldosterone is a steroid hormone that

stimulates Na+ reabsorption and K+ secretion in Distal Tubule and Cortical Collecting Duct

ENaC activity

dramatically increases Na+ reabsorption, both ROMK and Cl channels keep effect electrically neutral

Aldosterone activity

indirectly leads to more water being reabsorbed

Vasopressin and aldosterone’s effects on water reabsorption

increase blood pressure because of increased volume of plasma

how does aldosterone cause an increase in water absoprtion

it stimulates water reabsorption because increased Na (and Cl) reabsorption leads to more water reabsorption by increasing osmotic gradient

Motility

Movement of substances from mouth to anus, process along the way

Secretion of digestive enzymes

Into the lumen of the GI tract

Digestion of food

Enzymes break down large molecules into small molecules for absorption

Absorption

Of small molecules from lumen of GI tract to the circulatory system so they can be delivered to body cells

functions of GI tract

- motility

- secretion of digestive enzymes

- digestion of food

- absorption

GI (gastrointestinal tract)

long, muscular tube from mouth to anus

GI main organs

Oral cavity (mouth), pharynx, esophagus, stomach, small/large intestine, anus

GI accessory organs

Salivary glands, liver, gallbladder, pancreas

everything within GI tract is

external to our body tissues

general structure of GI tract

- mucosa layer

- submucosa

- muscularis extrena

mucosa layer

a. Epithelial layer, across which absorption occurs, also includes endocrine and exocrine cells

b. Loose connective tissue with capillaries, lymphatic vessels, neuronal processes

c. Thin layer of smooth muscle

Submucosa

blood and lymphatic vessels, neuronal network that links to mucosa

Muscularis externa

Muscles that control motility, neuron network links to inner layer of neurons, smooth muscle, autonomic nervous system.

Mouth/jaw and top 1/3 of esophagus

Skeletal muscle – combination of voluntary and involuntary control (i.e. involved in swallowing)

Rest of esophagus, stomach, small/large intestines

Lined by smooth muscle involuntary control

External anal sphincter

Skeletal muscle – under voluntary control (after toilet training) Mostly in a contracted state Relaxed during excretion

Swallowing

oral phase, pharyngeal phase, and esophageal phase

Oral phase

Voluntary. Bolus of food forced into pharynx. Soft palate lodges against pharynx

Pharyngeal phase

Involuntary. Mechanoreceptors initiate reflex involving “swallowing center” in brainstem. Bolus moved to esophagus. Epiglottis closes and upper esophageal sphincter relaxes

Esophageal phase

Involuntary. Upper esophageal sphincter contracts. Peristaltic contractions move bolus to stomach

Movement of Food through most of GI tract

Peristalsis & Segmentation

Peristalsis

• Rhythmic wave of smooth muscle contraction that results in the movement of bolus through the GI tract

• Occurs in the esophagus, stomach small intestine, and large intestine

Segmentation (mixing movements)

• Is the pinching of the intestine into compartments and subsequent mixing of undigested materials with intestinal secretions.

• Ensures chemical digestion and absorption are both completed

• There is no net movement as in peristalsis

• Occurs in the small intestine and large intestine

Autonomic nervous system can affect contractions

• The contraction of the smooth muscles in GI tract occurs without CNS motor input

• Sympathetic and Parasympathetic input affect GI tract contractions

how will increased rate of parasympathetic input on the GI tract muscles affect the intensiyu of GI tract smooth muscle contraction?

increased contraction intensity

Parasympathetic system =

REST and DIGEST

Parasympathetic system = REST and DIGEST

↑ rate of parasympathetic input leads to ↑ intensity of smooth muscle contraction

Sympathetic system = FIGHT or FLIGHT

↑ rate of sympathetic input leads to ↓ intensity of smooth muscle contraction

Sympathetic system =

FIGHT or FLIGHT

Saliva

• Enzymes, mucus, water

• Moistens food

• Amylase and lipase begin digestion of carbohydrates and triglycerides

• Lysozyme-an antimicrobial enzyme

Lysozyme

an antimicrobial enzyme

basic stomach anatomy

—> stomach secretes about 2L of HCl per day

—> pH is around 1.5-3

Functions of the Stomach

• Holds ingested food (at this point called chyme)

• Passes chyme in small increments to the small intestine

• Kills most microbes that we ingest

• Degrades food physically

• Begins digestion of proteins using enzyme called pepsin

• Secretes intrinsic factor required for absorption of vitamin B12

chyme

ingested food

Roles of HCl

• Acidity kills most microorganisms ingested on food

• Acidity denatures proteins and inactivates most enzymes in food

• Acidity helps break down plant cell walls and connective tissue in meat

• HCl is necessary for the activation of pepsin, the enzyme necessary to digest proteins

how do cells in the stomach secrete HCl

H/K ATPase pumps one H+ ion out for every one K+ into cell

Prilosec and other similar drugs decrease stomach acid production to decrease their symptoms of heartburn and acid reflux. what is the most likely mechanism by which these drugs act?

reduced proton pump (H+/K+ ATPase pump) activity

If a patient’s stomach acid pH was too high, what issues might they have?

increased bouts w/ food poisoning

—> decreased ability to absorb proteins